Regulating IVF and pre-implantation tissue-typing for the creation of "saviour siblings" : a harm analysis

Scientific discoveries, developments in medicine and health issues are the constant focus of media attention and the principles surrounding the creation of so called ‘saviour siblings’ are of no exception. The development in the field of reproductive techniques has provided the ability to genetically analyse embryos created in the laboratory to enable parents to implant selected embryos to create a tissue-matched child who may be able to cure an existing sick child. The research undertaken in this thesis examines the regulatory frameworks overseeing the delivery of assisted reproductive technologies (ART) in Australia and the United Kingdom and considers how those frameworks impact on the accessibility of in vitro fertilisation (IVF) procedures for the creation of ‘saviour siblings’. In some jurisdictions, the accessibility of such techniques is limited by statutory requirements. The limitations and restrictions imposed by the state in relation to the technology are analysed in order to establish whether such restrictions are justified. The analysis is conducted on the basis of a harm framework. The framework seeks to establish whether those affected by the use of the technology (including the child who will be created) are harmed. In order to undertake such evaluation, the concept of harm is considered under the scope of John Stuart Mill’s liberal theory and the Harm Principle is used as a normative tool to judge whether the level of harm that may result, justifies state intervention or restriction with the reproductive decision-making of parents in this context. The harm analysis conducted in this thesis seeks to determine an appropriate regulatory response in relation to the use of pre-implantation tissue-typing for the creation of ‘saviour siblings’. The proposals outlined in the last part of this thesis seek to address the concern that harm may result from the practice of pre-implantation tissue-typing. The current regulatory frameworks in place are also analysed on the basis of the harm framework established in this thesis. The material referred to in this thesis reflects the law and policy in place in Australia and the UK at the time the thesis was submitted for examination (December 2009).

Pretreatment malnutrition and quality of life - association with prolonged length of hospital stay among patients with gynecological cancer: A cohort study

Background Length of hospital stay (LOS) is a surrogate marker for patients' well-being during hospital treatment and is associated with health care costs. Identifying pretreatment factors associated with LOS in surgical patients may enable early intervention in order to reduce postoperative LOS. Methods This cohort study enrolled 157 patients with suspected or proven gynecological cancer at a tertiary cancer centre (2004-2006). Before commencing treatment, the scored Patient Generated - Subjective Global Assessment (PG-SGA) measuring nutritional status and the Functional Assessment of Cancer Therapy-General (FACT-G) scale measuring quality of life (QOL) were completed. Clinical and demographic patient characteristics were prospectively obtained. Patients were grouped into those with prolonged LOS if their hospital stay was greater than the median LOS and those with average or below average LOS. Results Patients' mean age was 58 years (SD 14 years). Preoperatively, 81 (52%) patients presented with suspected benign disease/pelvic mass, 23 (15%) with suspected advanced ovarian cancer, 36 (23%) patients with suspected endometrial and 17 (11%) with cervical cancer, respectively. In univariate models prolonged LOS was associated with low serum albumin or hemoglobin, malnutrition (PG-SGA score and PG-SGA group B or C), low pretreatment FACT-G score, and suspected diagnosis of cancer. In multivariable models, PG-SGA group B or C, FACT-G score and suspected diagnosis of advanced ovarian cancer independently predicted LOS. Conclusions Malnutrition, low quality of life scores and being diagnosed with advanced ovarian cancer are the major determinants of prolonged LOS amongst gynecological cancer patients. Interventions addressing malnutrition and poor QOL may decrease LOS in gynecological cancer patients.

An egg apparatus-specific enhancer of Arabidopsis, identified by enhancer detection

Despite a central role in angiosperm reproduction, few gametophyte-specific genes and promoters have been isolated, particularly for the inaccessible female gametophyte (embryo sac). Using the Ds-based enhancer-detector line ET253, we have cloned an egg apparatus-specific enhancer (EASE) from Arabidopsis (Arabidopsis thaliana). The genomic region flanking the Ds insertion site was further analyzed by examining its capability to control gusA and GFP reporter gene expression in the embryo sac in a transgenic context. Through analysis of a 5' and 3' deletion series in transgenic Arabidopsis, the sequence responsible for egg apparatus-specific expression was delineated to 77 bp. Our data showed that this enhancer is unique in the Arabidopsis genome, is conserved among different accessions, and shows an unusual pattern of sequence variation. This EASE works independently of position and orientation in Arabidopsis but is probably not associated with any nearby gene, suggesting either that it acts over a large distance or that a cryptic element was detected. Embryo-specific ablation in Arabidopsis was achieved by transactivation of a diphtheria toxin gene under the control of the EASE. The potential application of the EASE element and similar control elements as part of an open-source biotechnology toolkit for apomixis is discussed.

Development and validation of a novel approach to work sampling : a study of nurse practitioner work patterns

Objectives: This methodological paper reports on the development and validation of a work sampling instrument and data collection processes to conduct a national study of nurse practitioners’ work patterns. ---------- Design: Published work sampling instruments provided the basis for development and validation of a tool for use in a national study of nurse practitioner work activities across diverse contextual and clinical service models. Steps taken in the approach included design of a nurse practitioner-specific data collection tool and development of an innovative web-based program to train and establish inter rater reliability of a team of data collectors who were geographically dispersed across metropolitan, rural and remote health care settings. ---------- Setting: The study is part of a large funded study into nurse practitioner service. The Australian Nurse Practitioner Study is a national study phased over three years and was designed to provide essential information for Australian health service planners, regulators and consumer groups on the profile, process and outcome of nurse practitioner service. ---------- Results: The outcome if this phase of the study is empirically tested instruments, process and training materials for use in an international context by investigators interested in conducting a national study of nurse practitioner work practices. ---------- Conclusion: Development and preparation of a new approach to describing nurse practitioner practices using work sampling methods provides the groundwork for international collaboration in evaluation of nurse practitioner service.

Stability and convergence of an effective numerical method for the time-space fractional Fokker-Planck equation with a nonlinear source term

Fractional Fokker-Planck equations (FFPEs) have gained much interest recently for describing transport dynamics in complex systems that are governed by anomalous diffusion and nonexponential relaxation patterns. However, effective numerical methods and analytic techniques for the FFPE are still in their embryonic state. In this paper, we consider a class of time-space fractional Fokker-Planck equations with a nonlinear source term (TSFFPE-NST), which involve the Caputo time fractional derivative (CTFD) of order α ∈ (0, 1) and the symmetric Riesz space fractional derivative (RSFD) of order μ ∈ (1, 2). Approximating the CTFD and RSFD using the L1-algorithm and shifted Grunwald method, respectively, a computationally effective numerical method is presented to solve the TSFFPE-NST. The stability and convergence of the proposed numerical method are investigated. Finally, numerical experiments are carried out to support the theoretical claims.

Comparing exercise prescribed with exercise completed : effects of gender and mode of exercise

The purpose of this study was to compare the amount of exercise prescribed with the amount completed between two different modes of training intervention and between the sexes. Thirty-two men (mean age = 39.1 years, body mass index = 32.9 kg · m-2) and women (mean age = 39.6 years, body mass index = 32.1 kg · m-2) were prescribed traditional resistance training or light-resistance circuit training for 16 weeks. Lean mass and fat mass were determined by dual-energy X-ray absorptiometry at weeks 1 and 16. A completion index was calculated to provide a measure of the extent to which participants completed exercise training relative to the amount of exercise prescribed. The absolute amount of exercise completed by the circuit training group was significantly greater than the amount prescribed (P < 0.0001). The resistance training group consistently under-completed relative to the amount prescribed, but the difference was not significant. The completion index for the circuit training group (26 ± 21.7%) was significantly different from that of the resistance training group (-7.4 ± 3.0%). The completion index was not significantly different between men and women in either group. These data suggest that overweight and obese individuals participating in light-resistance circuit training complete more exercise than is prescribed. Men and women do not differ in the extent to which they over- or under-complete prescribed exercise.

Zoledronic acid once-yearly : what role in the prevention of non-vertebral osteoporotic fractures?

Osteoporosis is the most common bone disease. Low levels of oestrogens or testosterone are risk factors for primary osteoporosis. The most common cause of secondary osteoporosis is glucocorticoid treatment, but there are many other secondary causes of osteoporosis. Osteoporosis can be secondary to anti-oestrogen treatment for hormone-sensitive breast cancer and to androgen-deprivation therapy for prostate cancer. Zoledronic is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least a year after a single intravenous administration. The efficacy and safety of extended release (once-yearly) zoledronic acid in the treatment of osteoporosis is reviewed.

Lateral shearing interferometry, dynamic wavefront sensing, and high-speed videokeratoscopy for noninvasive assessment of tear film surface characteristics : a comparitive study

There are several noninvasive techniques for assessing the kinetics of tear film, but no comparative studies have been conducted to evaluate their efficacies. Our aim is to test and compare techniques based on high-speed videokeratoscopy (HSV), dynamic wavefront sensing (DWS), and lateral shearing interferometry (LSI). Algorithms are developed to estimate the tear film build-up time TBLD, and the average tear film surface quality in the stable phase of the interblink interval TFSQAv. Moderate but significant correlations are found between TBLD measured with LSI and DWS based on vertical coma (Pearson's r2=0.34, p<0.01) and higher order rms (r2=0.31, p<0.01), as well as between TFSQAv measured with LSI and HSV (r2=0.35, p<0.01), and between LSI and DWS based on the rms fit error (r2=0.40, p<0.01). No significant correlation is found between HSV and DWS. All three techniques estimate tear film build-up time to be below 2.5 sec, and they achieve a remarkably close median value of 0.7 sec. HSV appears to be the most precise method for measuring tear film surface quality. LSI appears to be the most sensitive method for analyzing tear film build-up.

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.

Diagnostic and treatment pathways for men with prostate cancer in Queensland : investigating spatial and demographic inequalities

Background: Patterns of diagnosis and management for men diagnosed with prostate cancer in Queensland, Australia, have not yet been systematically documented and so assumptions of equity are untested. This longitudinal study investigates the association between prostate cancer diagnostic and treatment outcomes and key area-level characteristics and individual-level demographic, clinical and psychosocial factors.---------- Methods/Design: A total of 1064 men diagnosed with prostate cancer between February 2005 and July 2007 were recruited through hospital-based urology outpatient clinics and private practices in the centres of Brisbane, Townsville and Mackay (82% of those referred). Additional clinical and diagnostic information for all 6609 men diagnosed with prostate cancer in Queensland during the study period was obtained via the population-based Queensland Cancer Registry. Respondent data are collected using telephone and self-administered questionnaires at pre-treatment and at 2 months, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months post-treatment. Assessments include demographics, medical history, patterns of care, disease and treatment characteristics together with outcomes associated with prostate cancer, as well as information about quality of life and psychological adjustment. Complementary detailed treatment information is abstracted from participants’ medical records held in hospitals and private treatment facilities and collated with health service utilisation data obtained from Medicare Australia. Information about the characteristics of geographical areas is being obtained from data custodians such as the Australian Bureau of Statistics. Geo-coding and spatial technology will be used to calculate road travel distances from patients’ residences to treatment centres. Analyses will be conducted using standard statistical methods along with multilevel regression models including individual and area-level components.---------- Conclusions: Information about the diagnostic and treatment patterns of men diagnosed with prostate cancer is crucial for rational planning and development of health delivery and supportive care services to ensure equitable access to health services, regardless of geographical location and individual characteristics. This study is a secondary outcome of the randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000233426)

Aboriginal public health and education : has it made a difference in practice?

Over the years, public health in relation to Australian Aboriginal people has involved many individuals and groups including health professionals, governments, politicians, special interest groups and corporate organisations. Since colonisation commenced until the1980s, public health relating to Aboriginal and Torres Strait Islander people was not necessarily in the best interests of Aboriginal and Torres Strait Islander people, but rather in the interests of the non-Aboriginal population. The attention that was paid focussed more generally around the subject of reproduction and issues of prostitution, exploitation, abuse and venereal diseases (Kidd, 1997). Since the late 1980s there has been a shift in the broader public health agenda (see Baum, 1998) along with public health in relation to Aboriginal and Torres Strait Islander people (NHMRC, 2003). This has been coupled with increasing calls to develop appropriate tertiary curriculum and to educate, train, and employ more Aboriginal and Torres Strait Islander and non-Aboriginal people in public health (Anderson et al., 2004; Genat, 2007; PHERP, 2008a, 2008b). Aboriginal and Torres Strait Islander people have been engaged in public health in ways in which they are in a position to influence the public health agenda (Anderson 2004; 2008; Anderson et al., 2004; NATSIHC, 2003). There have been numerous projects, programs and strategies that have sought to develop the Aboriginal and Torres Strait Islander Public Health workforce (AHMAC, 2002; Oldenburg et al., 2005; SCATSIH, 2002). In recent times the Aboriginal community controlled health sector has joined forces with other peak bodies and governments to find solutions and strategies to improve the health outcomes of Aboriginal and Torres Strait Islander peoples (NACCHO & Oxfam, 2007). This case study chapter will not address these broader activities. Instead it will explore the activities and roles of staff within the Public Health and Research Unit (PHRU) at the Victorian Aboriginal Community Controlled Health Organisation (VACCHO). It will focus on their experiences with education institutions, their work in public health and their thoughts on gaps and where improvements can be made in public health, research and education. What will be demonstrated is the diversity of education qualifications and experience. What will also be reflected is how people work within public health on a daily basis to enact change for equity in health and contribute to the improvement of future health outcomes of the Victorian Aboriginal community.

The use of economic evaluation in CAM : an introductory framework

Background For CAM to feature prominently in health care decision-making there is a need to expand the evidence-base and to further incorporate economic evaluation into research priorities. In a world of scarce health care resources and an emphasis on efficiency and clinical efficacy, CAM, as indeed do all other treatments, requires rigorous evaluation to be considered in budget decision-making. Methods Economic evaluation provides the tools to measure the costs and health consequences of CAM interventions and thereby inform decision making. This article offers CAM researchers an introductory framework for understanding, undertaking and disseminating economic evaluation. The types of economic evaluation available for the study of CAM are discussed, and decision modelling is introduced as a method for economic evaluation with much potential for use in CAM. Two types of decision models are introduced, decision trees and Markov models, along with a worked example of how each method is used to examine costs and health consequences. This is followed by a discussion of how this information is used by decision makers. Conclusions Undoubtedly, economic evaluation methods form an important part of health care decision making. Without formal training it can seem a daunting task to consider economic evaluation, however, multidisciplinary teams provide an opportunity for health economists, CAM practitioners and other interested researchers, to work together to further develop the economic evaluation of CAM.

Optimisation of a class of transportation problems using genetic algorithms

This paper presents a Genetic Algorithms (GA) approach to search the optimized path for a class of transportation problems. The formulation of the problems for suitable application of GA will be discussed. Exchanging genetic information in the sense of neighborhoods will be introduced for generation reproduction. The performance of the GA will be evaluated by computer simulation. The proposed algorithm use simple coding with population size 1 converged in reasonable optimality within several minutes.