Numerical simulation of anomalous diffusion with application to medical imaging

The first objective of this project is to develop new efficient numerical methods and supporting error and convergence analysis for solving fractional partial differential equations to study anomalous diffusion in biological tissue such as the human brain. The second objective is to develop a new efficient fractional differential-based approach for texture enhancement in image processing. The results of the thesis highlight that the fractional order analysis captured important features of nuclear magnetic resonance (NMR) relaxation and can be used to improve the quality of medical imaging.

Pharmacokinetics-based elucidation on disparity in clinical effectiveness between varieties of Zhi Zhu Wan, a traditional Chinese medical formula

AIM: Zhi Zhu Wan (ZZW) is a classical Chinese medical formulation used for the treatment of functional dyspepsia that attributed to Spleen-deficiency Syndrome. ZZW contains Atractylodes Rhizome and Fructus Citrus Immaturus, the later originates from both Citrus aurantium L. (BZZW) and Citrus sinensis Osbeck (RZZW). The present study is designed to elucidate disparities in the clinical efficacy of two ZZW varieties based on the pharmacokinetics of naringenin and hesperetin. MEHTOD: After oral administration of ZZWs, blood sample was collected from healthy volunteers at designed time points. Naringenin and hesperetin were detected in plasma by RP-HPLC, pharmacokinetic parameters were processed using mode-independent methods with WINNONLIN. RESULTS: After oral administration of BZZW, both naringenin and hesperetin were detected in plasma, and demonstrated similar pharmacokinetic parameters. Ka was 0.384+/-0.165 and 0.401+/-0.159, T(1/2(ke))(h) was 5.491+/-3.926 and 5.824+/-3.067, the AUC (mg/Lh) was 34.886+/-22.199 and 39.407+/-19.535 for naringenin and hesperetin, respectively. However, in the case of RZZW, only hesperetin was found in plasma, but the pharmacokinetic properties for hesperetin in RZZW was different from that in BZZW. T(max) for hesperetin in RZZW is about 8.515h, and its C(max) is much larger than that of BZZW. Moreover, it was eliminated slowly as it possessed a much larger AUC value. CONCLUSION: The distinct therapeutic orientations of the Chinese medical formula ZZWs with different Fructus Citrus Immaturus could be elucidated based on the pharmacokinetic parameters of constituents after oral administration.

Double standards in special medical research : questioning the discrepancy between requirements for medical research involving incompetent adults and medical research involving children

Medical research represents a substantial departure from conventional medical care. Medical care is patient-orientated, with decisions based on the best interests and/or wishes of the person receiving the care. In contrast, medical research is future-directed. Primarily it aims to contribute new knowledge about illness or disease, or new knowledge about interventions, such as drugs, that impact upon some human condition. Current State and Territory laws and research ethics guidelines in Australia relating to the review of medical research appropriately acknowledge that the functions of medical care and medical research differ. Prior to a medical research project commencing, the study must be reviewed and approved by a Human Research Ethics Committee (HREC). For medical research involving incompetent adults, some jurisdictions require an additional, independent safeguard by way of tribunal or court approval of medical research protocols. This extra review process reflects the uncertainty of medical research involvement, and the difficulties surrogate decision-makers of incompetent adults face in making decisions about others, and deliberating about the risks and benefits of research involvement. Parents of children also face the same difficulties when making decisions about their child’s research involvement. However, unlike the position concerning incompetent adults, there are no similar safeguards under Australian law in relation to the approval of medical research involving children. This column questions why this discrepancy exists with a view to generating further dialogue on the topic.

Utilizing least significant bit-planes of RONI pixels for medical image watermarking

We propose a computationally efficient image border pixel based watermark embedding scheme for medical images. We considered the border pixels of a medical image as RONI (region of non-interest), since those pixels have no or little interest to doctors and medical professionals irrespective of the image modalities. Although RONI is used for embedding, our proposed scheme still keeps distortion at a minimum level in the embedding region using the optimum number of least significant bit-planes for the border pixels. All these not only ensure that a watermarked image is safe for diagnosis, but also help minimize the legal and ethical concerns of altering all pixels of medical images in any manner (e.g, reversible or irreversible). The proposed scheme avoids the need for RONI segmentation, which incurs capacity and computational overheads. The performance of the proposed scheme has been compared with a relevant scheme in terms of embedding capacity, image perceptual quality (measured by SSIM and PSNR), and computational efficiency. Our experimental results show that the proposed scheme is computationally efficient, offers an image-content-independent embedding capacity, and maintains a good image quality

Towards a translational medical research ecosystem

In this paper we introduce a novel design for a translational medical research ecosystem. Translational medical research is an emerging field of work, which aims to bridge the gap between basic medical science research and clinical research/patient care. We analyze the key challenges of digital ecosystems for translational research, based on real world scenarios posed by the Lab for Translational Research at the Harvard Medical School and the Genomics Research Centre of the Griffith University, and show how traditional IT approaches fail to fulfill these challenges. We then introduce our design for a translational research ecosystem. Several key contributions are made: A novel approach to managing ad-hoc research ecosystems is introduced; a new security approach for translational research is proposed which allows each participating site to retain control over its data and define its own policies to ensure legal and ethical compliance; and a design for a novel interactive access control framework which allows users to easily share data, while adhering to their organization's policies is presented.

Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula: Liuwei Dihuang Wan

Liuwei Dihuang Wan (LWD), a classic Chinese medicinal formulae, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. It has attracted increasingly much attention as one of the most popular and valuable herbal medicines. However, the systematic analysis of the chemical constituents of LDW is difficult and thus has not been well established. In this paper, a rapid, sensitive and reliable ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) method with automated MetaboLynx analysis in positive and negative ion mode was established to characterize the chemical constituents of LDW. The analysis was performed on a Waters UPLCTM HSS T3 using a gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. Under the optimized conditions, a total of 50 peaks were tentatively characterized by comparing the retention time and MS data. It is concluded that a rapid and robust platform based on UPLC-ESI-Q-TOF-MS has been successfully developed for globally identifying multiple-constituents of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of the chemical constituents of LDW. This article is protected by copyright. All rights reserved.

Competency and capacity : the legal and medical interface

Balancing the competing interests of autonomy and protection of individuals is an escalating challenge confronting an ageing Australian society. Legal and medical professionals are increasingly being asked to determine whether individuals are legally competent/capable to make their own testamentary and substitute decision-making, that is financial and/or personal/health care, decisions. No consistent and transparent competency/capacity assessment paradigm currently exists in Australia. Consequently, assessments are currently being undertaken on an ad hoc basis which is concerning as Australia’s population ages and issues of competency/capacity increase. The absence of nationally accepted competency/capacity assessment guidelines and supporting principles results in legal and medical professionals involved with competency/capacity assessment implementing individual processes tailored to their own abilities. Legal and medical approaches differ both between and within the professions. The terminology used also varies. The legal practitioner is concerned with whether the individual has the legal ability to make the decision. A medical practitioner assesses fluctuations in physical and mental abilities. The problem is that the terms competency and capacity are used interchangeably resulting in confusion about what is actually being assessed. The terminological and methodological differences subsequently create miscommunication and misunderstanding between the professions. Consequently, it is not necessarily a simple solution for a legal professional to seek the opinion of a medical practitioner when assessing testamentary and/or substitute decision-making competency/capacity. This research investigates the effects of the current inadequate testamentary and substitute decision-making assessment paradigm and whether there is a more satisfactory approach. This exploration is undertaken within a framework of therapeutic jurisprudence which promotes principles fundamentally important in this context. Empirical research has been undertaken to first, explore the effects of the current process with practising legal and medical professionals; and second, to determine whether miscommunication and misunderstanding actually exist between the professions such that it gives rise to a tense relationship which is not conducive to satisfactory competency/capacity assessments. The necessity of reviewing the adequacy of the existing competency/capacity assessment methodology in the testamentary and substitute decision-making domain will be demonstrated and recommendations for the development of a suitable process made.

Writing the visible page : a multimodal approach to graphic devices in literary fiction

This practice-led project has two outcomes: a collection of short stories titled 'Corkscrew Section', and an exegesis. The short stories combine written narrative with visual elements such as images and typographic devices, while the exegesis analyses the function of these graphic devices within adult literary fiction. My creative writing explores a variety of genres and literary styles, but almost all of the stories are concerned with fusing verbal and visual modes of communication. The exegesis adopts the interpretive paradigm of multimodal stylistics, which aims to analyse graphic devices with the same level of detail as linguistic analysis. Within this framework, the exegesis compares and extends previous studies to develop a systematic method for analysing how the interactions between language, images and typography create meaning within multimodal literature.

Medical nutrition therapy and simple interventions can improve intake in patients who eat poorly in hospital

The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients in Australian and New Zealand hospitals consume ≤50% of the offered food. The ANCDS found a significant association between poor food intake and increased in-hospital mortality after controlling for confounders (nutritional status, age, disease type and severity)1. Evidence for the effectiveness of medical nutrition therapy (MNT) in hospital patients eating poorly is lacking. An exploratory study was conducted in respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, 24-hour food intake (0%, 25%, 50%, 75%, 100% of offered meals) was evaluated for patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT with food intake re-evaluated on day-7. 184 patients were observed over four weeks. Sixty-two patients (34%) consumed ≤50% of the offered meals. Simple interventions (feeding/menu assistance, diet texture modifications) improved intake to ≥75% in 30 patients who did not require further MNT. Of the 32 patients referred for MNT, baseline and day-7 data were available for 20 patients (68±17years, 65% females, BMI: 22±5kg/m2, median energy, protein intake: 2250kJ, 25g respectively). On day-7, 17 participants (85%) demonstrated significantly higher consumption (4300kJ, 53g; p<0.01). Three participants demonstrated no improvement due to ongoing nutrition-impact symptoms. “Percentage food intake” was a quick tool to identify patients in whom simple interventions could enhance intake. MNT was associated with improved dietary intake in hospital patients. Further research is needed to establish a causal relationship.

Education higher degree research students writing for publication

Higher Degree Research (HDR) student publications are increasingly valued by students, by professional communities and by research institutions. Peer-reviewed publications form the HDR student writer's publication track record and increase competitiveness in employment and research funding opportunities. These publications also make the results of HDR student research available to the community in accessible formats. HDR student publications are also valued by universities because they provide evidence of institutional research activity within a field and attract a return on research performance. However, although publications are important to multiple stakeholders, many Education HDR students do not publish the results of their research. Hence, an investigation of Education HDR graduates who submitted work for publication during their candidacy was undertaken. This multiple, explanatory case study investigated six recent Education HDR graduates who had submitted work to peer-reviewed outlets during their candidacy. The conceptual framework supported an analysis of the development of Education HDR student writing using Alexander's (2003, 2004) Model of Domain Learning which focuses on expertise, and Lave and Wenger's (1991) situated learning within a community of practice. Within this framework, the study investigated how these graduates were able to submit or publish their research despite their relative lack of writing expertise. Case data were gathered through interviews and from graduate publication records. Contextual data were collected through graduate interviews, from Faculty and university documents, and through interviews with two Education HDR supervisors. Directed content analysis was applied to all data to ascertain the support available in the research training environment. Thematic analysis of graduate and supervisor interviews was then undertaken to reveal further information on training opportunities accessed by the HDR graduates. Pattern matching of all interview transcripts provided information on how the HDR graduates developed writing expertise. Finally, explanation building was used to determine causal links between the training accessed by the graduates and their writing expertise. The results demonstrated that Education HDR graduates developed publications and some level of expertise simultaneously within communities of practice. Students were largely supported by supervisors who played a critical role. They facilitated communities of practice and largely mediated HDR engagement in other training opportunities. However, supervisor support alone did not ensure that the HDR graduates developed writing expertise. Graduates who appeared to develop the most expertise, and produce a number of publications reported experiencing both a sustained period of engagement within one community of practice, and participation in multiple communities of practice. The implications for the MDL theory, as applied to academic writing, suggests that communities of practice can assist learners to progress from initial contact with a new domain of interest through to competence. The implications for research training include the suggestion that supervisors as potentially crucial supporters of HDR student writing for publication should themselves be active publishers. Also, Faculty or university sponsorship of communities of practice focussed on HDR student writing for publication could provide effective support for the development of HDR student writing expertise and potentially increase the number of their peer-reviewed publications.

Writing eBooks to support first year students

A potential use of eBooks is to write them to specifically support first year students. Such eBooks have many advantages over published books, including tailored content and flexibility. One initiative was to write an eBook called “Getting Started” as part of a bridging course for 100-200 accelerated students in Nursing, who were about to have their first year at University at second year level. This was a formative activity to be undertaken by the students prior to the start of study. Another initiative was the writing of an eBook called “Pharmacology in One Semester”, which is available to all students, including the accelerated students, in a second year Unit. This is a plain English language version of pharmacology, which has been unpacked from the standard textbooks to improve the learning of the students. Both of these initiatives have been welcomed by the accelerated students.

The life course of Australian researchers : experiences of applying for research funding

The life course of Australian researchers includes regular funding applications, which incur large personal and time costs. We previously estimated that Australian researchers spent 550 years preparing 3,727 proposals for the 2012 NHMRC Project Grant funding round, at an estimated annual salary cost of AU$66 million. Despite the worldwide importance of funding rounds, there is little evidence on what researchers think of the application process. We conducted a web-based survey of Australian researchers (May–July 2013) asking about their experience with NHMRC Project Grants. Almost all researchers (n=224 at 31 May) supported changes to the application (96%) and peer-review (88%) processes; 73% supported the introduction of shorter initial Expressions of Interest; and half (50%) provided extensive comments on the NHMRC processes. Researchers agreed preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. More than half (57%) provided extensive comments on the ongoing personal impact of concurrent grant-writing and holiday seasons on family, children and other relationships. Researchers with experience on Grant Review Panels (34%) or as External Reviewers (78%) reported many sections of the proposals were rarely or never read, which suggests these sections could be cut with no impact on the quality of peer review. Our findings provide evidence on the experience of Australian researchers as applicants. The process of preparing, submitting and reviewing proposals could be streamlined to minimise the burden on applicants and peer reviewers, giving Australian researchers more time to work on actual research and be with their families.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

Encouraging, assisting, and time to eat : comparison of mealtime assistance interventions in elderly medical inpatients

BACKGROUND: The prevalence of protein-energy malnutrition in older adults is reported to be as high as 60% and is associated with poor health outcomes. Inadequate feeding assistance and mealtime interruptions may contribute to malnutrition and poor nutritional intake during hospitalisation. Despite being widely implemented in practice in the United Kingdom and increasingly in Australia, there have been few studies examining the impact of strategies such as Protected Mealtimes and dedicated feeding assistant roles on nutritional outcomes of elderly inpatients. AIMS: The aim of this research was to implement and compare three system-level interventions designed to specifically address mealtime barriers and improve energy intakes of medical inpatients aged ≥65 years. This research also aimed to evaluate the sustainability of any changes to mealtime routines six months post-intervention and to gain an understanding of staff perceptions of the post-intervention mealtime experience. METHODS: Three mealtime assistance interventions were implemented in three medical wards at Royal Brisbane and Women's Hospital: AIN-only: Additional assistant-in-nursing (AIN) with dedicated nutrition role. PM-only: Multidisciplinary approach to meals, including Protected Mealtimes. PM+AIN: Combined intervention: AIN + multidisciplinary approach to meals. An action research approach was used to carefully design and implement the three interventions in partnership with ward staff and managers. Significant time was spent in consultation with staff throughout the implementation period to facilitate ownership of the interventions and increase likelihood of successful implementation. A pre-post design was used to compare the implementation and nutritional outcomes of each intervention to a pre-intervention group. Using the same wards, eligible participants (medical inpatients aged ≥65 years) were recruited to the preintervention group between November 2007 and March 2008 and to the intervention groups between January and June 2009. The primary nutritional outcome was daily energy and protein intake, which was determined by visually estimating plate waste at each meal and mid-meal on Day 4 of admission. Energy and protein intakes were compared between the pre and post intervention groups. Data were collected on a range of covariates (demographics, nutritional status and known risk factors for poor food intake), which allowed for multivariate analysis of the impact of the interventions on nutritional intake. The provision of mealtime assistance to participants and activities of ward staff (including mealtime interruptions) were observed in the pre-intervention and intervention groups, with staff observations repeated six months post-intervention. Focus groups were conducted with nursing and allied health staff in June 2009 to explore their attitudes and behaviours in response to the three mealtime interventions. These focus group discussions were analysed using thematic analysis. RESULTS: A total of 254 participants were recruited to the study (pre-intervention: n=115, AIN-only: n=58, PM-only: n=39, PM+AIN: n=42). Participants had a mean age of 80 years (SD 8), and 40% (n=101) were malnourished on hospital admission, 50% (n=108) had anorexia and 38% (n=97) required some assistance at mealtimes. Occasions of mealtime assistance significantly increased in all interventions (p<0.01). However, no change was seen in mealtime interruptions. No significant difference was seen in mean total energy and protein intake between the preintervention and intervention groups. However, when total kilojoule intake was compared with estimated requirements at the individual level, participants in the intervention groups were more likely to achieve adequate energy intake (OR=3.4, p=0.01), with no difference noted between interventions (p=0.29). Despite small improvements in nutritional adequacy, the majority of participants in the intervention groups (76%, n=103) had inadequate energy intakes to meet their estimated energy requirements. Patients with cognitive impairment or feeding dependency appeared to gain substantial benefit from mealtime assistance interventions. The increase in occasions of mealtime assistance by nursing staff during the intervention period was maintained six-months post-intervention. Staff focus groups highlighted the importance of clearly designating and defining mealtime responsibilities in order to provide adequate mealtime care. While the purpose of the dedicated feeding assistant was to increase levels of mealtime assistance, staff indicated that responsibility for mealtime duties may have merely shifted from nursing staff to the assistant. Implementing the multidisciplinary interventions empowered nursing staff to "protect" the mealtime from external interruptions, but further work is required to empower nurses to prioritise mealtime activities within their own work schedules. Staff reported an increase in the profile of nutritional care on all wards, with additional non-nutritional benefits noted including improved mobility and functional independence, and better identification of swallowing difficulties. IMPLICATIONS: The PhD research provides clinicians with practical strategies to immediately introduce change to deliver better mealtime care in the hospital setting, and, as such, has initiated local and state-wide roll-out of mealtime assistance programs. Improved nutritional intakes of elderly inpatients was observed; however given the modest effect size and reducing lengths of hospital stays, better nutritional outcomes may be achieved by targeting the hospital-to-home transition period. Findings from this study suggest that mealtime assistance interventions for elderly inpatients with cognitive impairment and/or functional dependency show promise.

Writing the oriental woman : an examination of the representation of Japanese women in contemporary Australian crime fiction

This study considers the challenges in representing women from other cultures in the crime fiction genre. The study is presented in two parts; an exegesis and a creative practice component consisting of a full length crime fiction novel, Batafurai. The exegesis examines the historical period of a section of the novel—post-war Japan—and how the area of research known as Occupation Studies provides an insight into the conditions of women during this period. The exegesis also examines selected postcolonial theory and its exposition of representations of the 'other' as a western construct designed to serve Eurocentric ends. The genre of crime fiction is reviewed, also, to determine how characters purportedly representing Oriental cultures are constricted by established stereotypes. Two case studies are examined to investigate whether these stereotypes are still apparent in contemporary Australian crime fiction. Finally, I discuss my own novel, Batafurai, to review how I represented people of Asian background, and whether my attempts to resist stereotype were successful. My conclusion illustrates how novels written in the crime fiction genre are reliant on strategies that are action-focused, rather than character-based, and thus often use easily recognizable types to quickly establish frameworks for their stories. As a sub-set of popular fiction, crime fiction has a tendency to replicate rather than challenge established stereotypes. Where it does challenge stereotypes, it reflects a territory that popular culture has already visited, such as the 'female', 'black' or 'gay' detective. Crime fiction also has, as one of its central concerns, an interest in examining and reinforcing the notion of societal order. It repeatedly demonstrates that crime either does not pay or should not pay. One of the ways it does this is to contrast what is 'good', known and understood with what is 'bad', unknown, foreign or beyond our normal comprehension. In western culture, the east has traditionally been employed as the site of difference, and has been constantly used as a setting of contrast, excitement or fear. Crime fiction conforms to this pattern, using the east to add a richness and depth to what otherwise might become a 'dry' tale. However, when used in such a way, what is variously eastern, 'other' or Oriental can never be paramount, always falling to secondary side of the binary opposites (good/evil, known/unknown, redeemed/doomed) at work. In an age of globalisation, the challenge for contemporary writers of popular fiction is to be responsive to an audience that demands respect for all cultures. Writers must demonstrate that they are sensitive to such concerns and can skillfully manage the tensions caused by the need to deliver work that operates within the parameters of the genre, and the desire to avoid offence to any cultural or ethnic group. In my work, my strategy to manage these tensions has been to create a back-story for my characters of Asian background, developing them above mere genre types, and to situate them with credibility in time and place through appropriate historical research.