Population-based survival estimates for childhood cancer in Australia during the period 1997–2006

Background: This study provides the latest available relative survival data for Australian childhood cancer patients. Methods: Data from the population-based Australian Paediatric Cancer Registry were used to describe relative survival outcomes using the period method for 11 903 children diagnosed with cancer between 1983 and 2006 and prevalent at any time between 1997 and 2006. Results: The overall relative survival was 90.4% after 1 year, 79.5% after 5 years and 74.7% after 20 years. Where information onstage at diagnosis was available (lymphomas, neuroblastoma, renal tumours and rhabdomyosarcomas), survival was significantly poorer for more-advanced stage. Survival was lower among infants compared with other children for those diagnosed with leukaemia, tumours of the central nervous system and renal tumours but higher for neuroblastoma. Recent improvements in overall childhood cancer survival over time are mainly because of improvements among leukaemia patients. Conclusion: The high and improving survival prognosis for children diagnosed with cancer in Australia is consistent with various international estimates. However, a 5-year survival estimate of 79% still means that many children who are diagnosed with cancer will die within 5 years, whereas others have long-term health morbidities and complications associated with their treatments. It is hoped that continued developments in treatment protocols will result in further improvements in survival.

Modelling of operating theatres using simulation

This paper describes the development of a simulation model for operating theatres. Elective patient scheduling is complicated by several factors; stochastic demand for resources due to variation in the nature and severity of a patient’s illness, unexpected complications in a patient’s course of treatment and the arrival of non-scheduled emergency patients which compete for resources. Extend simulation software was used for its ability to represent highly complex systems and analyse model outputs. Patient arrivals and lengths of surgery are determined by analysis of historical data. The model was used to explore the effects increasing patient arrivals and alternative elective patient admission disciplines would have on the performance measures. The model can be used as a decision support system for hospital planners.

Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

What aspects of the scoliosis correction are most important to the teenager who has keyhole scoliosis correction surgery? A prospective series of 100 patients

Introduction. Surgical treatment of scoliosis is assessed in the spine clinic by the surgeon making numerous measurements on X-Rays as well as the rib hump. But it is important to understand which of these measures correlate with self-reported improvements in patients’ quality of life following surgery. The objective of this study was to examine the relationship between patient satisfaction after thoracoscopic (keyhole) anterior scoliosis surgery and standard deformity correction measures using the Scoliosis Research Society (SRS) adolescent questionnaire. Methods. A series of 100 consecutive adolescent idiopathic scoliosis patients received a single anterior rod via a keyhole approach at the Mater Children’s Hospital, Brisbane. Patients completed SRS outcomes questionnaires before surgery and again at 24 months after surgery. Multiple regression and t-tests were used to investigate the relationship between SRS scores and deformity correction achieved after surgery. Results. There were 94 females and 6 males with a mean age of 16.1 years. The mean Cobb angle improved from 52º pre-operatively to 21º for the instrumented levels post-operatively (59% correction) and the mean rib hump improved from 16º to 8º (51% correction). The mean total SRS score for the cohort was 99.4/120 which indicated a high level of satisfaction with the results of their scoliosis surgery. None of the deformity related parameters in the multiple regressions were significant. However, the twenty patients with the smallest Cobb angles after surgery reported significantly higher SRS scores than the twenty patients with the largest Cobb angles after surgery, but there was no difference on the basis of rib hump correction. Discussion. Patients undergoing thoracoscopic (keyhole) anterior scoliosis correction report good SRS scores which are comparable to those in previous studies. We suggest that the absence of any statistically significant difference in SRS scores between patients with and without rod or screw complications is because these complications are not associated with any clinically significant loss of correction in our patient group. The Cobb angle after surgery was the only significant predictor of patient satisfaction when comparing subgroups of patients with the largest and smallest Cobb angles after surgery.

The measurement of applied forces during anterior single rod surgical correction of adolescent idiopathic scoliosis

INTRODUCTION. Following anterior thoracoscopic instrumentation and fusion for the treatment of thoracic AIS, implant related complications have been reported as high as 20.8%. Currently the magnitudes of the forces applied to the spine during anterior scoliosis surgery are unknown. The aim of this study was to measure the segmental compressive forces applied during anterior single rod instrumentation in a series of adolescent idiopathic scoliosis patients. METHODS. A force transducer was designed, constructed and retrofitted to a surgical cable compression tool, routinely used to apply segmental compression during anterior scoliosis correction. Transducer output was continuously logged during the compression of each spinal joint, the output at completion converted to an applied compression force using calibration data. The angle between adjacent vertebral body screws was also measured on intra-operative frontal plane fluoroscope images taken both before and after each joint compression. The difference in angle between the two images was calculated as an estimate for the achieved correction at each spinal joint. RESULTS. Force measurements were obtained for 15 scoliosis patients (Aged 11-19 years) with single thoracic curves (Cobb angles 47˚- 67˚). In total, 95 spinal joints were instrumented. The average force applied for a single joint was 540 N (± 229 N)ranging between 88 N and 1018 N. Experimental error in the force measurement, determined from transducer calibration was ± 43 N. A trend for higher forces applied at joints close to the apex of the scoliosis was observed. The average joint correction angle measured by fluoroscope imaging was 4.8˚ (±2.6˚, range 0˚-12.6˚). CONCLUSION. This study has quantified in-vivo, the intra-operative correction forces applied by the surgeon during anterior single rod instrumentation. This data provides a useful contribution towards an improved understanding of the biomechanics of scoliosis correction. In particular, this data will be used as input for developing patient-specific finite element simulations of scoliosis correction surgery.

Development and evaluation of an integrated clinical learning model to inform continuing education for acute care nurses

Background Significant ongoing learning needs for nurses have occurred as a direct result of the continuous introduction of technological innovations and research developments in the healthcare environment. Despite an increased worldwide emphasis on the importance of continuing education, there continues to be an absence of empirical evidence of program and session effectiveness. Few studies determine whether continuing education enhances or develops practice and the relative cost benefits of health professionals’ participation in professional development. The implications for future clinical practice and associated educational approaches to meet the needs of an increasingly diverse multigenerational and multicultural workforce are also not well documented. There is minimal research confirming that continuing education programs contribute to improved patient outcomes, nurses’ earlier detection of patient deterioration or that standards of continuing competence are maintained. Crucially, evidence-based practice is demonstrated and international quality and safety benchmarks are adhered to. An integrated clinical learning model was developed to inform ongoing education for acute care nurses. Educational strategies included the use of integrated learning approaches, interactive teaching concepts and learner-centred pedagogies. A Respiratory Skills Update education (ReSKU) program was used as the content for the educational intervention to inform surgical nurses’ clinical practice in the area of respiratory assessment. The aim of the research was to evaluate the effectiveness of implementing the ReSKU program using teaching and learning strategies, in the context of organisational utility, on improving surgical nurses’ practice in the area of respiratory assessment. The education program aimed to facilitate better awareness, knowledge and understanding of respiratory dysfunction in the postoperative clinical environment. This research was guided by the work of Forneris (2004), who developed a theoretical framework to operationalise a critical thinking process incorporating the complexities of the clinical context. The framework used educational strategies that are learner-centred and participatory. These strategies aimed to engage the clinician in dynamic thinking processes in clinical practice situations guided by coaches and educators. Methods A quasi experimental pre test, post test non–equivalent control group design was used to evaluate the impact of the ReSKU program on the clinical practice of surgical nurses. The research tested the hypothesis that participation in the ReSKU program improves the reported beliefs and attitudes of surgical nurses, increases their knowledge and reported use of respiratory assessment skills. The study was conducted in a 400 bed regional referral public hospital, the central hub of three smaller hospitals, in a health district servicing the coastal and hinterland areas north of Brisbane. The sample included 90 nurses working in the three surgical wards eligible for inclusion in the study. The experimental group consisted of 36 surgical nurses who had chosen to attend the ReSKU program and consented to be part of the study intervention group. The comparison group included the 39 surgical nurses who elected not to attend the ReSKU program, but agreed to participate in the study. Findings One of the most notable findings was that nurses choosing not to participate were older, more experienced and less well educated. The data demonstrated that there was a barrier for training which impacted on educational strategies as this mature aged cohort was less likely to take up educational opportunities. The study demonstrated statistically significant differences between groups regarding reported use of respiratory skills, three months after ReSKU program attendance. Between group data analysis indicated that the intervention group’s reported beliefs and attitudes pertaining to subscale descriptors showed statistically significant differences in three of the six subscales following attendance at the ReSKU program. These subscales included influence on nursing care, educational preparation and clinical development. Findings suggest that the use of an integrated educational model underpinned by a robust theoretical framework is a strong factor in some perceptions of the ReSKU program relating to attitudes and behaviour. There were minimal differences in knowledge between groups across time. Conclusions This study was consistent with contemporary educational approaches using multi-modal, interactive teaching strategies and a robust overarching theoretical framework to support study concepts. The construct of critical thinking in the clinical context, combined with clinical reasoning and purposeful and collective reflection, was a powerful educational strategy to enhance competency and capability in clinicians.

The factor V HR2 haplotype: Prevalence and association of the A4070G and A6755G polymorphisms

Recently, a polymorphism was identified in exon 25 of the factor V gene that is possibly a functional candidate for the HR2 haplotype. This haplotype is characterized by a single base substitution named R2 (A4070G) in the B domain of the protein. A mutation (A6755G; 2194Asp→Gly) located near the C terminus has been hypothesized to influence protein folding and glycosylation, and might be responsible for the shift in factor V isoform (FV1 / FV2) ratio. This study investigated the prevalence of these two factor V HR2 haplotype polymorphisms in a cohort of normal blood donors, patients with osteoarthritis and women with complications during pregnancy, and in families of factor V Leiden individuals. A high allele frequency for the two polymorphisms was found in the blood donor group (6.2% R2, 5.6% A6755G). No significant difference in allele frequency was observed in the clinical groups (obstetric complications and osteoarthritis, 4.1-4.9% for the two polymorphisms) when compared with that of healthy blood donors. We confirm that the factor V A6755G polymorphism shows strong linkage to the R2 allele, although it is not exclusively inherited with the exon 13 A4070G variant and can occur independently. © 2001 Lippincott Williams & Wilkins.

A pilot study assessing the feasibility of a home-based progressive resistance exercise program and trend toward healing rates for patients with venous leg ulcers

Venous leg ulceration is a serious condition affecting 1 – 3% of the population. Decline in the function of the calf muscle pump is correlated with venous ulceration. Many previous studies have reported an improvement in the function of the calf muscle pump, endurance of the calf muscle and increased range of ankle motion after structured exercise programs. However, there is a paucity of published research that assesses if these improvements result in an improvement in the healing rates of venous ulcers. The primary purpose of this pilot study was to establish the feasibility of a homebased progressive resistance exercise program and examine if there was any clinical significance or trend toward healing. The secondary aims were to examine the benefit of a home-based progressive resistance exercise program on calf muscle pump function and physical parameters. The methodology used was a randomised controlled trial where eleven participants were randomised into an intervention (n = 6) or control group (n = 5). Participants who were randomised to receive a 12-week home-based progressive resistance exercise program were instructed through weekly face-to-face consultations during their wound clinic appointment by the author. Control group participants received standard wound care and compression therapy. Changes in ulcer parameters were measured fortnightly at the clinic (number healed at 12 weeks, percentage change in area and pressure ulcer score healing score). An air plethysmography test was performed at baseline and following the 12 weeks of training to determine changes in calf muscle pump function. Functional measures included maximum number of heel raises (endurance), maximal isometric plantar flexion (strength) and range of ankle motion (ROAM); these tests were conducted at baseline, week 6 and week 12. The sample for the study was drawn from the Princess Alexandra Hospital in Brisbane, Australia. Participants with venous leg ulceration who met the inclusion criteria were recruited. The participants were screened via duplex scanning and ankle brachial pressure index (ABPI) to ensure they did not have any arterial complications. Participants were excluded if there was evidence of cellulitis. Demographic data were obtained from each participant and details regarding medical history, quality of life and geriatric depression scores were collected at baseline. Both the intervention and control group were required to complete a weekly exercise diary to monitor activity levels between groups. To test for the effect of the intervention over time, a repeated measures analysis of variance was conducted on the major outcome variables. Group (intervention versus control) was the between subject factor and time (baseline, week 6, week 12) was the within subject or repeated measures factor. Due to the small sample size, further tests were conducted to check the assumptions of the statistical test to be used. The results showed that Mauchly.s Test, the Sphericity assumptions of repeated measures for ANOVA were met. Further tests of homogeneity of variance assumptions also confirmed that this assumption was met. Data analysis was conducted using the software package SPSS for Windows Release 17.0. The pilot study proved feasible with all of the intervention (n=6) participants continuing with the resistance program for the 12 week duration and no deleterious effects noted. Clinical significance was observed in the intervention group with a 32% greater change in ulcer size (p= 0.26) than the control group, and a 10% (p = 0.74) greater difference between the numbers healed compared to the control group. Statistical significance was observed for the ejection fraction (p = 0.05), residual volume fraction (p = 0.04) and ROAM (p = 0.01), which all improved significantly in the intervention group over time. These results are encouraging, nevertheless, further investigations seem warranted to examine the effect exercise has on the healing rates of venous leg ulcers, with a multistudy site, larger sample size and longer follow up period.

An economic evaluation of the Safe Motherhood programme in Guangxi, China

Maternal and infant mortality is a global health issue with a significant social and economic impact. Each year, over half a million women worldwide die due to complications related to pregnancy or childbirth, four million infants die in the first 28 days of life, and eight million infants die in the first year. Ninety-nine percent of maternal and infant deaths are in developing countries. Reducing maternal and infant mortality is among the key international development goals. In China, the national maternal mortality ratio and infant mortality rate were reduced greatly in the past two decades, yet a large discrepancy remains between urban and rural areas. To address this problem, a large-scale Safe Motherhood Programme was initiated in 2000. The programme was implemented in Guangxi in 2003. Interventions in the programme included both demand-side and supply side-interventions focusing on increasing health service use and improving birth outcomes. Little is known about the effects and economic outcomes of the Safe Motherhood Programme in Guangxi, although it has been implemented for seven years. The aim of this research is to estimate the effectiveness and cost-effectiveness of the interventions in the Safe Motherhood Programme in Guangxi, China. The objectives of this research include: 1. To evaluate whether the changes of health service use and birth outcomes are associated with the interventions in the Safe Motherhood Programme. 2. To estimate the cost-effectiveness of the interventions in the Safe Motherhood Programme and quantify the uncertainty surrounding the decision. 3. To assess the expected value of perfect information associated with both the whole decision and individual parameters, and interpret the findings to inform priority setting in further research and policy making in this area. A quasi-experimental study design was used in this research to assess the effectiveness of the programme in increasing health service use and improving birth outcomes. The study subjects were 51 intervention counties and 30 control counties. Data on the health service use, birth outcomes and socio-economic factors from 2001 to 2007 were collected from the programme database and statistical yearbooks. Based on the profile plots of the data, general linear mixed models were used to evaluate the effectiveness of the programme while controlling for the effects of baseline levels of the response variables, change of socio-economic factors over time and correlations among repeated measurements from the same county. Redundant multicollinear variables were deleted from the mixed model using the results of the multicollinearity diagnoses. For each response variable, the best covariance structure was selected from 15 alternatives according to the fit statistics including Akaike information criterion, Finite-population corrected Akaike information criterion, and Schwarz.s Bayesian information criterion. Residual diagnostics were used to validate the model assumptions. Statistical inferences were made to show the effect of the programme on health service use and birth outcomes. A decision analytic model was developed to evaluate the cost-effectiveness of the programme, quantify the decision uncertainty, and estimate the expected value of perfect information associated with the decision. The model was used to describe the transitions between health states for women and infants and reflect the change of both costs and health benefits associated with implementing the programme. Result gained from the mixed models and other relevant evidence identified were synthesised appropriately to inform the input parameters of the model. Incremental cost-effectiveness ratios of the programme were calculated for the two groups of intervention counties over time. Uncertainty surrounding the parameters was dealt with using probabilistic sensitivity analysis, and uncertainty relating to model assumptions was handled using scenario analysis. Finally the expected value of perfect information for both the whole model and individual parameters in the model were estimated to inform priority setting in further research in this area.The annual change rates of the antenatal care rate and the institutionalised delivery rate were improved significantly in the intervention counties after the programme was implemented. Significant improvements were also found in the annual change rates of the maternal mortality ratio, the infant mortality rate, the incidence rate of neonatal tetanus and the mortality rate of neonatal tetanus in the intervention counties after the implementation of the programme. The annual change rate of the neonatal mortality rate was also improved, although the improvement was only close to statistical significance. The influences of the socio-economic factors on the health service use indicators and birth outcomes were identified. The rural income per capita had a significant positive impact on the health service use indicators, and a significant negative impact on the birth outcomes. The number of beds in healthcare institutions per 1,000 population and the number of rural telephone subscribers per 1,000 were found to be positively significantly related to the institutionalised delivery rate. The length of highway per square kilometre negatively influenced the maternal mortality ratio. The percentage of employed persons in the primary industry had a significant negative impact on the institutionalised delivery rate, and a significant positive impact on the infant mortality rate and neonatal mortality rate. The incremental costs of implementing the programme over the existing practice were US $11.1 million from the societal perspective, and US $13.8 million from the perspective of the Ministry of Health. Overall, 28,711 life years were generated by the programme, producing an overall incremental cost-effectiveness ratio of US $386 from the societal perspective, and US $480 from the perspective of the Ministry of Health, both of which were below the threshold willingness-to-pay ratio of US $675. The expected net monetary benefit generated by the programme was US $8.3 million from the societal perspective, and US $5.5 million from the perspective of the Ministry of Health. The overall probability that the programme was cost-effective was 0.93 and 0.89 from the two perspectives, respectively. The incremental cost-effectiveness ratio of the programme was insensitive to the different estimates of the three parameters relating to the model assumptions. Further research could be conducted to reduce the uncertainty surrounding the decision, in which the upper limit of investment was US $0.6 million from the societal perspective, and US $1.3 million from the perspective of the Ministry of Health. It is also worthwhile to get a more precise estimate of the improvement of infant mortality rate. The population expected value of perfect information for individual parameters associated with this parameter was US $0.99 million from the societal perspective, and US $1.14 million from the perspective of the Ministry of Health. The findings from this study have shown that the interventions in the Safe Motherhood Programme were both effective and cost-effective in increasing health service use and improving birth outcomes in rural areas of Guangxi, China. Therefore, the programme represents a good public health investment and should be adopted and further expanded to an even broader area if possible. This research provides economic evidence to inform efficient decision making in improving maternal and infant health in developing countries.

Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.

Predictive factors of contact lens case contamination

PURPOSE: To examine the relationship between contact lens (CL) case contamination and various potential predictive factors. METHODS: 74 subjects were fitted with lotrafilcon B (CIBA Vision) CLs on a daily wear basis for 1 month. Subjects were randomly assigned one of two polyhexamethylene biguanide (PHMB) preserved disinfecting solutions with the corresponding regular lens case. Clinical evaluations were conducted at lens delivery and after 1 month, when cases were collected for microbial culture. A CL care non-compliance score was determined through administration of a questionnaire and the volume of solution used was calculated for each subject. Data was examined using backward stepwise binary logistic regression. RESULTS: 68% of cases were contaminated. 35% were moderately or heavily contaminated and 36% contained gram-negative bacteria. Case contamination was significantly associated with subjective dryness symptoms (OR 4.22, CI 1.37–13.01) (P<0.05). There was no association between contamination and subject age, ethnicity, gender, average wearing time, amount of solution used, non-compliance score, CL power and subjective redness (P>0.05). The effect of lens care system on case contamination approached significance (P=0.07). Failure to rinse the case with disinfecting solution following CL insertion (OR 2.51, CI 0.52–12.09) and not air drying the case (OR 2.31, CI 0.39–13.35) were positively correlated with contamination; however, did not reach statistical significance. CONCLUSIONS: Our results suggest that case contamination may influence subjective comfort. It is difficult to predict the development of case contamination from a variety of clinical factors. The efficacy of CL solutions, bacterial resistance to disinfection and biofilm formation are likely to play a role. Further evaluation of these factors will improve our understanding of the development of case contamination and its clinical impact.

Quantitative fit assessment of a precontoured fracture fixation plate : its automation and an investigation on the borderline cases

Virtual methods to assess the fitting of a fracture fixation plate were proposed recently, however with limitations such as simplified fit criteria or manual data processing. This study aims to automate a fit analysis procedure using clinical-based criteria, and then to analyse the results further for borderline fit cases. Three dimensional (3D) models of 45 bones and of a precontoured distal tibial plate were utilized to assess the fitting of the plate automatically. A Matlab program was developed to automatically measure the shortest distance between the bone and the plate at three regions of interest and a plate-bone angle. The measured values including the fit assessment results were recorded in a spreadsheet as part of the batch-process routine. An automated fit analysis procedure will enable the processing of larger bone datasets in a significantly shorter time, which will provide more representative data of the target population for plate shape design and validation. As a result, better fitting plates can be manufactured and made available to surgeons, thereby reducing the risk and cost associated with complications or corrective procedures. This in turn, is expected to translate into improving patients' quality of life.

Country of Origin and Internet Publication : Applying the Berne Convention in the Digital Age

Historically, determining the country of origin of a published work presented few challenges, because works were generally published physically – whether in print or otherwise – in a distinct location or few locations. However, publishing opportunities presented by new technologies mean that we now live in a world of simultaneous publication – works that are first published online are published simultaneously to every country in world in which there is Internet connectivity. While this is certainly advantageous for the dissemination and impact of information and creative works, it creates potential complications under the Berne Convention for the Protection of Literary and Artistic Works (“Berne Convention”), an international intellectual property agreement to which most countries in the world now subscribe. Under the Berne Convention’s national treatment provisions, rights accorded to foreign copyright works may not be subject to any formality, such as registration requirements (although member countries are free to impose formalities in relation to domestic copyright works). In Kernel Records Oy v. Timothy Mosley p/k/a Timbaland, et al. however, the Florida Southern District Court of the United States ruled that first publication of a work on the Internet via an Australian website constituted “simultaneous publication all over the world,” and therefore rendered the work a “United States work” under the definition in section 101 of the U.S. Copyright Act, subjecting the work to registration formality under section 411. This ruling is in sharp contrast with an earlier decision delivered by the Delaware District Court in Håkan Moberg v. 33T LLC, et al. which arrived at an opposite conclusion. The conflicting rulings of the U.S. courts reveal the problems posed by new forms of publishing online and demonstrate a compelling need for further harmonization between the Berne Convention, domestic laws and the practical realities of digital publishing. In this article, we argue that even if a work first published online can be considered to be simultaneously published all over the world it does not follow that any country can assert itself as the “country of origin” of the work for the purpose of imposing domestic copyright formalities. More specifically, we argue that the meaning of “United States work” under the U.S. Copyright Act should be interpreted in line with the presumption against extraterritorial application of domestic law to limit its application to only those works with a real and substantial connection to the United States. There are gaps in the Berne Convention’s articulation of “country of origin” which provide scope for judicial interpretation, at a national level, of the most pragmatic way forward in reconciling the goals of the Berne Convention with the practical requirements of domestic law. We believe that the uncertainties arising under the Berne Convention created by new forms of online publishing can be resolved at a national level by the sensible application of principles of statutory interpretation by the courts. While at the international level we may need a clearer consensus on what amounts to “simultaneous publication” in the digital age, state practice may mean that we do not yet need to explore textual changes to the Berne Convention.

something 2.0

In ‘something 2.0’, a section of a Hollywood film is re-edited to include textual elements that appear as ‘Pinocchio-ish’ protrusions from the actors faces. As they sit in what appears to be an interview or therapy session, this re-editing and looping imposes a new fictionalized narrative upon the characters. The histrionic yet vague nature of the text, and its imperfect integration into the footage, can be read as both a comical imposition and a failed critical gesture, both speaking to the complications involved in the relationship of the artist and the fan as they engage with popular culture. Thw work was included in the group show 'Perfection' part of the Metro Arts Artistic Program 2008.