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.

Frequency response function based structural damage detection using artificial neural networks

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, few attempts have been made to explore the structure damage with frequency response functions (FRFs). This paper illustrates the damage identification and condition assessment of a beam structure using a new frequency response functions (FRFs) based damage index and Artificial Neural Networks (ANNs). In practice, usage of all available FRF data as an input to artificial neural networks makes the training and convergence impossible. Therefore one of the data reduction techniques Principal Component Analysis (PCA) is introduced in the algorithm. In the proposed procedure, a large set of FRFs are divided into sub-sets in order to find the damage indices for different frequency points of different damage scenarios. The basic idea of this method is to establish features of damaged structure using FRFs from different measurement points of different sub-sets of intact structure. Then using these features, damage indices of different damage cases of the structure are identified after reconstructing of available FRF data using PCA. The obtained damage indices corresponding to different damage locations and severities are introduced as input variable to developed artificial neural networks. Finally, the effectiveness of the proposed method is illustrated and validated by using the finite element modal of a beam structure. The illustrated results show that the PCA based damage index is suitable and effective for structural damage detection and condition assessment of building structures.

The use of semantic priming as a paradigm for the detection of faking on self-report psychological tests

It is recognised that individuals do not always respond honestly when completing psychological tests. One of the foremost issues for research in this area is the inability to detect individuals attempting to fake. While a number of strategies have been identified in faking, a commonality of these strategies is the latent role of long term memory. Seven studies were conducted in order to examine whether it is possible to detect the activation of faking related cognitions using a lexical decision task. Study 1 found that engagement with experiential processing styles predicted the ability to fake successfully, confirming the role of associative processing styles in faking. After identifying appropriate stimuli for the lexical decision task (Studies 2A and 2B), Studies 3 to 5 examined whether a cognitive state of faking could be primed and subsequently identified, using a lexical decision task. Throughout the course of these studies, the experimental methodology was increasingly refined in an attempt to successfully identify the relevant priming mechanisms. The results were consistent and robust throughout the three priming studies: faking good on a personality test primed positive faking related words in the lexical decision tasks. Faking bad, however, did not result in reliable priming of negative faking related cognitions. To more completely address potential issues with the stimuli and the possible role of affective priming, two additional studies were conducted. Studies 6A and 6B revealed that negative faking related words were more arousing than positive faking related words, and that positive faking related words were more abstract than negative faking related words and neutral words. Study 7 examined whether the priming effects evident in the lexical decision tasks occurred as a result of an unintentional mood induction while faking the psychological tests. Results were equivocal in this regard. This program of research aligned the fields of psychological assessment and cognition to inform the preliminary development and validation of a new tool to detect faking. Consequently, an implicit technique to identify attempts to fake good on a psychological test has been identified, using long established and robust cognitive theories in a novel and innovative way. This approach represents a new paradigm for the detection of individuals responding strategically to psychological testing. With continuing development and validation, this technique may have immense utility in the field of psychological assessment.

An exploration of young students' ability to generalise function tasks

The Early Years Generalising Project involves Australian students, Years 1-4 (age 5-9), and explores how the students grasp and express generalisations. This paper focuses on the data collected from clinical interviews with Year 3 and 4 cohorts in an investigative study focusing on the identifications, prediction and justification of function rules. It reports on students' attempts to generalise from function machine contexts, describing the various ways students express generalisation and highlighting the different levels of justification given by students. Finally, we conjecture that there are a set of stages in the expression and justification of generalisations that assist students to reach generality within tasks.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia. CITATION: O'Donoghue FJ; Wellard RM; Rochford PD; Dawson A; Barnes M; Ruehland WR; Jackson ML; Howard ME; Pierce RJ; Jackson GD. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

Section moment capacity tests of LiteSteel Beams

The LiteSteel Beam (LSB) is a new cold-formed hollow flange channel section developed by OneSteel Australian Tube Mills using their patented dual electric resistance welding and automated continuous roll-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. In addition to this unique geometry, the LSB sections also have unique characteristics relating to their stress-strain curves, residual stresses, initial geometric imperfections and hollow flanges that are not encountered in conventional hot-rolled and cold-formed steel channel sections. An experimental study including 20 section moment capacity tests was therefore conducted to investigate the behaviour and strength of LSB flexural members. The presence of inelastic reserve bending capacity in these beams was investigated in detail although the current design rules generally limit the section moment capacities of cold-formed steel members to their first yield moments. The ultimate moment capacities from the tests were compared with the section moment capacities predicted by the current cold-formed and hot-rolled steel design standards. It was found that compact and non-compact LSB sections have greater moment capacities than their first yield moments. The current cold-formed steel design standards were found to be conservative in predicting the section moment capacities of compact and non-compact LSB sections while the hot-rolled steel design standards were able to better predict them. This paper has shown that suitable modifications are needed to the current design rules to allow the inclusion of available inelastic bending capacities of LSBs in design.

Genetic evidence for the vital function of osterix in cementogenesis

To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of OSX and the formation of cellular cementum. We then generated 3.6 Col 1-OSX transgenic mice, which displayed accelerated cementum formation vs. WT controls. Importantly, the conditional deletion of OSX in the mesenchymal cells with two different Cre systems (the 2.3 kb Col 1 and an inducible CAG-CreER) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the OSX gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered SEM and resin-cast SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support 1) the mesenchymal origin of cellular cementum (from PDL progenitor cells); 2) the vital role of OSX in controlling the formation of cellular cementum; and 3) the limited remodeling of cellular cementum in adult mice.

Assessment of function and clinical utility of alcohol and other drug web sites : an observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed.

Time limitations in NAPLAN numeracy tests

The article discusses evidence that time prevented many students from showing what they could do in the 2010 Year 7 and 9 NAPLAN numeracy tests. In addition to analysing the available data, the article discusses some NAPLAN numeracy questions that contribute to this problem. It is suggested that schools should investigate whether time limitation is a problem for their own students. The article discusses the implications of these findings for teachers preparing students for NAPLAN tests and for the developers of the tests.

Non-compositional concepts and quantum tests

Compositionality is a frequently made assumption in linguistics, and yet many human subjects reveal highly non-compositional word associations when confronted with novel concept combinations. This article will show how a non-compositional account of concept combinations can be supplied by modelling them as interacting quantum systems.

Tests and Models of Non-compositional Concepts

The question of under what conditions conceptual representation is compositional remains debatable within cognitive science. This paper proposes a well developed mathematical apparatus for a probabilistic representation of concepts, drawing upon methods developed in quantum theory to propose a formal test that can determine whether a specific conceptual combination is compositional, or not. This test examines a joint probability distribution modeling the combination, asking whether or not it is factorizable. Empirical studies indicate that some combinations should be considered non-compositionally.

A new tip area function for instrumented nanoindentation at extremely small contact depths

The accuracy of measurement of mechanical properties of a material using instrumented nanoindentation at extremely small penetration depths heavily relies on the determination of the contact area of the indenter. Our experiments have demonstrated that the conventional area function could lead to a significant error when the contact depth was below 40. nm, due to the singularity in the first derivation of the function in this region and thus, the resultant unreasonable sharp peak on the function curve. In this paper, we proposed a new area function that was used to calculate the contact area for the indentations where the contact depths varied from 10 to 40. nm. The experimental results have shown that the new area function has produced better results than the conventional function. © 2011 Elsevier B.V.

Regulation of proteasome structure and function

Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.