Corneal confocal microscopy : a novel noninvasive means to diagnose neuropathy in patients with Fabry disease

ABSTRACT: Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal esthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS)and heat-induced pain (HIP) were only significantly increased in males onERT (P<0.01). However, corneal sensation assessed withNCCAwas significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QSTand CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Working memory correlates of three symptom clusters in schizophrenia

Examined whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. 52 outpatients (mean age 37.5 yrs) with schizophrenia were studied using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.

Vibrational spectroscopic studies of laboratory scale polymer melt processing : application to a thermoplastic polyurethane nanocomposite

A laboratory scale twin screw extruder has been interfaced with a near infrared (NIR) spectrometer via a fibre optic link so that NIR spectra can be collected continuously during the small scale experimental melt state processing of polymeric materials. This system can be used to investigate melt state processes such as reactive extrusion, in real time, in order to explore the kinetics and mechanism of the reaction. A further advantage of the system is that it has the capability to measure apparent viscosity simultaneously which gives important additional information about molecular weight changes and polymer degradation during processing. The system was used to study the melt processing of a nanocomposite consisting of a thermoplastic polyurethane and an organically modified layered silicate.

Age-related maculopathy : linking aetiology and pathophysiological changes to the ischaemia hypothesis

Age-related maculopathy (ARM) has remained a challenging topic with respect to its aetiology, pathomechanisms, early detection and treatment since the late 19th century when it was first described as its own entity. ARM was previously considered an inflammatory disease, a degenerative disease, a tumor and as the result of choroidal hemodynamic disturbances and ischaemia. The latter processes have been repeatedly suggested to have a key role in its development and progression. In vivo experiments under hypoxic conditions could be models for the ischaemic deficits in ARM. Recent research has also linked ARM with gene polymorphisms. It is however unclear what triggers a person's gene susceptibility. In this manuscript, a linking hypothesis between aetiological factors including ischaemia and genetics and the development of early clinicopathological changes in ARM is proposed. New clinical psychophysical and electrophysiological tests are introduced that can detect ARM at an early stage. Models of early ARM based upon hemodynamic, photoreceptor and post-receptoral deficits are described and the mechanisms by which ischaemia may be involved as a final common pathway are considered. In neovascular age-related macular degeneration (neovascular AMD), ischaemia is thought to promote release of vascular endothelial growth factor (VEGF) which induces chorioretinal neovascularisation. VEGF is critical in the maintenance of the healthy choriocapillaris. In the final section of the manuscript the documentation of the effect of new anti-VEGF treatments on retinal function in neovascular AMD is critically viewed.

Where the bloody hell does parody fit in Australian copyright law?

This article examines the role of the recently introduced fair dealing exception for the purposes of parody and satire in Australian copyright law. Parody and satire, while central to Australian expression, pose a substantial challenge for copyright policy. The law is asked to strike a delicate balance between an author’s right to exploit their work, the interests of the public in stimulating free speech and critical discussion, the rights of artists who rely on existing material in creating their own expression, and the rights of all artists in their reputation and the integrity of their works. This article highlights the difficulty parodists and satirists have historically faced in Australia and examines the potential of the new fair dealing exceptions to relieve this difficulty. This article concludes that the new exceptions have the potential, if read broadly, not only to bridge the gap between humorous and non-humorous criticism, but also to allow for the use of copyright material to critique figures other than the copyright owner or author, extending to society generally. This article will argue that the new exceptions should be read broadly to further this important policy goal while also being limited in their application so as to prevent mere substitutable uses of copyright material. To achieve these twin goals, I suggest that the primary indication of fairness of an unlicensed parody should be whether or not it adds significant new expression so as not to be substitutable for the original work.

From Sydney and Shanghai : Australian and Chinese women writing modernism

In the 1930s and 1940s, Australian women writers published novels, poems, and short stories that pushed the boundaries of their national literary culture. From their position in the Pacific, they entered into a dialogue with a European modernism that they reworked to invigorate their own writing and to make cross-continental connections. My interest in the work of Australian women prose writers of this period stems from an appreciation of the extent of their engagement with interwar modernism (an engagement that is generally under-acknowledged) and the realization that there are commonalities of approach with the ways in which contemporaneous Chinese authors negotiated this transnational cultural traffic. China and Australia, it has been argued, share an imaginative and literal association of many centuries, and this psychic history produces a situation in which ‘Australians feel drawn towards China: they cannot leave it alone.’1 Equally, Chinese exploration of the great southern land began in the fifteenth century, prior to European contact. In recent times, the intensity of Australia’s cultural and commercial connections with Asia has led to a repositioning of the Australian sense of regionalism in general and, in particular, has activated yet another stage in the history of its relationship with China. In this context, the association of Australian and Chinese writing is instructive because the commonalities of approach and areas of interest between certain authors indicate that Australian writers were not alone in either the content or style of their response to European modernism. This recognition, in turn, advances discussions of modernism in Australia and reveals an alternative way of looking at the world from the Pacific Rim through literature. The intent is to examine selective Australian and Chinese authors who are part of this continuous history and whose writing demonstrates common thematic and stylistic features via the vector of modernism. I focus on the 1930s and 1940s because these are the decades in which Australia and China experienced wideranging conflict in the Pacific, and it is significant that war, both forthcoming and actual, features as an ominous soundtrack in the writing of Chinese and Australian women. I argue that, given the immensity of cultural difference between Australia and China, there is an especially interesting juncture in the ways in which the authors interrogate modernist practices and the challenge of modernism. The process in which writing from the Pacific Rim jointly negotiates the twin desires of engaging with European literary form and representing one’s own culture may be seen as what Jessica Berman identifies as a geomodernism, one of the ‘new possible geographies’ of modernism.2 My discussion centres on the work of the Australian women, to which the Chinese material serves as a point of reference, albeit a critical one. The Chinese writing examined here is restricted to authors who wrote at least some material in English and whose work is available in translation.

Comparison of temporal processing and motion perception in emmetropes and myopes

While spatial determinants of emmetropization have been examined extensively in animal models and spatial processing of human myopes has also been studied, there have been few studies investigating temporal aspects of emmetropization and temporal processing in human myopia. The influence of temporal light modulation on eye growth and refractive compensation has been observed in animal models and there is evidence of temporal visual processing deficits in individuals with high myopia or other pathologies. Given this, the aims of this work were to examine the relationships between myopia (i.e. degree of myopia and progression status) and temporal visual performance and to consider any temporal processing deficits in terms of the parallel retinocortical pathways. Three psychophysical studies investigating temporal processing performance were conducted in young adult myopes and non-myopes: (1) backward visual masking, (2) dot motion perception and (3) phantom contour. For each experiment there were approximately 30 young emmetropes, 30 low myopes (myopia less than 5 D) and 30 high myopes (5 to 12 D). In the backward visual masking experiment, myopes were also classified according to their progression status (30 stable myopes and 30 progressing myopes). The first study was based on the observation that the visibility of a target is reduced by a second target, termed the mask, presented quickly after the first target. Myopes were more affected by the mask when the task was biased towards the magnocellular pathway; myopes had a 25% mean reduction in performance compared with emmetropes. However, there was no difference in the effect of the mask when the task was biased towards the parvocellular system. For all test conditions, there was no significant correlation between backward visual masking task performance and either the degree of myopia or myopia progression status. The dot motion perception study measured detection thresholds for the minimum displacement of moving dots, the maximum displacement of moving dots and degree of motion coherence required to correctly determine the direction of motion. The visual processing of these tasks is dominated by the magnocellular pathway. Compared with emmetropes, high myopes had reduced ability to detect the minimum displacement of moving dots for stimuli presented at the fovea (20% higher mean threshold) and possibly at the inferior nasal retina. The minimum displacement threshold was significantly and positively correlated to myopia magnitude and axial length, and significantly and negatively correlated with retinal thickness for the inferior nasal retina. The performance of emmetropes and myopes for all the other dot motion perception tasks were similar. In the phantom contour study, the highest temporal frequency of the flickering phantom pattern at which the contour was visible was determined. Myopes had significantly lower flicker detection limits (21.8 ± 7.1 Hz) than emmetropes (25.6 ± 8.8 Hz) for tasks biased towards the magnocellular pathway for both high (99%) and low (5%) contrast stimuli. There was no difference in flicker limits for a phantom contour task biased towards the parvocellular pathway. For all phantom contour tasks, there was no significant correlation between flicker detection thresholds and magnitude of myopia. Of the psychophysical temporal tasks studied here those primarily involving processing by the magnocellular pathway revealed differences in performance of the refractive error groups. While there are a number of interpretations for this data, this suggests that there may be a temporal processing deficit in some myopes that is selective for the magnocellular system. The minimum displacement dot motion perception task appears the most sensitive test, of those studied, for investigating changes in visual temporal processing in myopia. Data from the visual masking and phantom contour tasks suggest that the alterations to temporal processing occur at an early stage of myopia development. In addition, the link between increased minimum displacement threshold and decreasing retinal thickness suggests that there is a retinal component to the observed modifications in temporal processing.

Australian nursing informatics competency project

A study of Australian nurses on their use of information technology in the workplace was undertaken by the Australian Nursing Federation (ANF) in 2007. This study of over 4000 nurses highlighted that nurses recognise benefits to adopting more information technology in the workplace although there are significant barriers to their use. It also identified gross deficits in the capacity of the nursing workforce to engage in the digital processing of information. Following the release of the study last year, the ANF commenced work on a number of key recommendations from the report in order to overcome identified barriers and provide opportunities for nurses to better utilise information technology and information management systems. One of these recommendations was to seek research funding to develop national information technology and information management competency standards for nurses. This project has now received Federal Government funding to undertake this development. This project is being developed in collaboration with the ANF and the Queensland University of Technology. This paper will discuss the methodology, development and publication of the Australian Nursing Informatics Competency Standards Project which is currently underway and due for completion in May 2009. The Australian Nursing Informatics Competencies will be presented at the conference.

Latent variable models in statistical genetics

Understanding the complexities that are involved in the genetics of multifactorial diseases is still a monumental task. In addition to environmental factors that can influence the risk of disease, there is also a number of other complicating factors. Genetic variants associated with age of disease onset may be different from those variants associated with overall risk of disease, and variants may be located in positions that are not consistent with the traditional protein coding genetic paradigm. Latent Variable Models are well suited for the analysis of genetic data. A latent variable is one that we do not directly observe, but which is believed to exist or is included for computational or analytic convenience in a model. This thesis presents a mixture of methodological developments utilising latent variables, and results from case studies in genetic epidemiology and comparative genomics. Epidemiological studies have identified a number of environmental risk factors for appendicitis, but the disease aetiology of this oft thought useless vestige remains largely a mystery. The effects of smoking on other gastrointestinal disorders are well documented, and in light of this, the thesis investigates the association between smoking and appendicitis through the use of latent variables. By utilising data from a large Australian twin study questionnaire as both cohort and case-control, evidence is found for the association between tobacco smoking and appendicitis. Twin and family studies have also found evidence for the role of heredity in the risk of appendicitis. Results from previous studies are extended here to estimate the heritability of age-at-onset and account for the eect of smoking. This thesis presents a novel approach for performing a genome-wide variance components linkage analysis on transformed residuals from a Cox regression. This method finds evidence for a dierent subset of genes responsible for variation in age at onset than those associated with overall risk of appendicitis. Motivated by increasing evidence of functional activity in regions of the genome once thought of as evolutionary graveyards, this thesis develops a generalisation to the Bayesian multiple changepoint model on aligned DNA sequences for more than two species. This sensitive technique is applied to evaluating the distributions of evolutionary rates, with the finding that they are much more complex than previously apparent. We show strong evidence for at least 9 well-resolved evolutionary rate classes in an alignment of four Drosophila species and at least 7 classes in an alignment of four mammals, including human. A pattern of enrichment and depletion of genic regions in the profiled segments suggests they are functionally significant, and most likely consist of various functional classes. Furthermore, a method of incorporating alignment characteristics representative of function such as GC content and type of mutation into the segmentation model is developed within this thesis. Evidence of fine-structured segmental variation is presented.

A psychometric comparison of the Toronto Alexithymia Scale (TAS-20) and the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample

Alexithymia is characterised by deficits in emotional insight and self reflection, that impact on the efficacy of psychological treatments. Given the high prevalence of alexithymia in Alcohol Use Disorders, valid assessment tools are critical. The majority of research on the relationship between alexithymia and alcohol-dependence has employed the self-administered Toronto Alexithymia Scale (TAS-20). The Observer Alexithymia Scale (OAS) has also been recommended. The aim of the present study was to assess the validity and reliability of the OAS and the TAS-20 in an alcohol-dependent sample. Two hundred and ten alcohol-dependent participants in an outpatient Cognitive Behavioral Treatment program were administered the TAS-20 at assessment and upon treatment completion at 12 weeks. Clinical psychologists provided observer assessment data for a subsample of 159 patients. The findings confirmed acceptable internal consistency, test-retest reliability and scale homogeneity for both the OAS and TAS-20, except for the low internal consistency of the TAS-20 EOT scale. The TAS-20 was more strongly associated with alcohol problems than the OAS.

Effects of age on peripheral ocular aberrations

On-axis monochromatic higher-order aberrations increase with age. Few studies have been made of peripheral refraction along the horizontal meridian of older eyes, and none of their off-axis higher-order aberrations. We measured wave aberrations over the central 42°x32° visual field for a 5mm pupil in 10 young and 7 older emmetropes. Patterns of peripheral refraction were similar in the two groups. Coma increased linearly with field angle at a significantly higher rate in older than in young emmetropes (−0.018±0.007 versus −0.006±0.002 µm/deg). Spherical aberration was almost constant over the measured field in both age groups and mean values across the field were significantly higher in older than in young emmetropes (+0.08±0.05 versus +0.02±0.04 µm). Total root-mean-square and higher-order aberrations increased more rapidly with field angle in the older emmetropes. However, the limits to monochromatic peripheral retinal image quality are largely determined by the second-order aberrations, which do not change markedly with age, and under normal conditions the relative importance of the increased higher-order aberrations in older eyes is lessened by the reduction in pupil diameter with age. Therefore it is unlikely that peripheral visual performance deficits observed in normal older individuals are primarily attributable to the increased impact of higher-order aberration.

A Helicopter named Dolly : behavioural cloning for autonomous helicopter control

This paper considers the pros and cons of using Behavioural cloning for the development of low-level helicopter automation modules. Over the course of this project several Behavioural cloning approaches have been investigated. The results of the most effective Behavioural cloning approach are then compared to PID modules designed for the same aircraft. The comparison takes into consideration development time, reliability, and control performance. It has been found that Behavioural cloning techniques employing local approximators and a wide state-space coverage during training can produce stabilising control modules in less time than tuning PID controllers. However, performance and reliabity deficits have been found to exist with the Behavioural Cloning, attributable largely to the time variant nature of the dynamics due to the operating environment, and the pilot actions being poor for teaching. The final conclusion drawn here is that tuning PID modules remains superior to behavioural cloning for low-level helicopter automation.

A preliminary investigation of the role of the Phenylalynine: Tyrosine Ratio in children with early and continuously treated phenylketonuria : toward identification of “safe” levels

Children with early and continuously treated phenylketonuria (ECT-PKU) remain at risk of developing executive function (EF) deficits. There is some evidence that a high phenylalanine to tyrosine ratio (phe:tyr) is more strongly associated with impaired EF development than high phenylalanine alone. This study examined EF in a sample of 11 adolescents against concurrent and historical levels of phenylalanine, phe:tyr, and tyrosine. Lifetime measures of phe:tyr were more strongly associated with EF than phenylalanine-only measures. Children with a lifetime phe:tyr less than 6 demonstrated normal EF, whereas children who had a lifetime phe:tyr above 6, on average, demonstrated clinically impaired EF.

The domestic kitchen : the weak link in the food chain : is convenience leading to apathy?

To investigate the meaning and understanding of domestic food preparation within the lived experience of the household's main food preparer this ethnographic study used a combination of qualitative and quantitative methodologies. Data were collected from three sources: the literature; an in-store survey of251 food shoppers chosen at random while shopping during both peak and off peak shopping periods at metropolitan supermarkets; and semi-structured interviews with the principal food shopper and food preparer of 15 different Brisbane households. Male and female respondents representing a cross section of socio-economic groupings, ranged in age from 19-79 years and were all from English speaking backgrounds. Changes in paid labour force participation, income and education have increased the value of the respondents' time, instigating massive changes in the way they shop, cook and eat. Much of their food preparation has moved from the domestic kitchen into the kitchens of other food establishments. For both sexes, the dominant motivating force behind these changes is a combination of the their self perceived lack of culinary skill; lack of enjoyment of cooking and lack of motivation to cook. The females in paid employment emphasise all factors, particularly the latter two, significantly more than the non-employed females. All factors are of increasing importance for individuals aged less than 35 years and conversely, of significantly diminished importance to older respondents. Overall, it is the respondents aged less than 25 years who indicate the lowest cooking frequency and/or least cooking ability. Inherent in this latter group is an indifference to the art/practice of preparing food. Increasingly, all respondents want to do less cooking and/or get the cooking over with as quickly as possible. Convenience is a powerful lure by which to spend less time in the kitchen. As well, there is an apparent willingness to pay a premium for convenience. Because children today are increasingly unlikely to be taught to cook, addressing the food skills deficit and encouraging individuals to cook for themselves are significant issues confronting health educators. These issues are suggested as appropriate subjects of future research.

The role of social skills and school connectedness in preadolescent depressive symptoms

In the current study, we tested whether school connectedness mediates more distal deficits in social skills in influencing depressive symptoms in a sample of 127 sixth- and seventh-grade students. Results demonstrated that school connectedness and social skills accounted for 44% and 26% of variance in depressive symptoms respectively and 49% in a combined model. Although the full mediation model hypothesis was not supported, follow-up analyses revealed that school connectedness partially mediated the link between social skills and preadolescent depressive symptoms. Thus, school connectedness appears to play as strong a role in depressive symptoms in this younger preadolescent age group.