Corneal sensitivity and slit scanning in vivo confocal microscopy of the subbasal nerve plexus of the normal central and peripheral human cornea

Purpose: To determine the subbasal nerve density and tortuosity at 5 corneal locations and to investigate whether these microstructural observations correlate with corneal sensitivity. Method: Sixty eyes of 60 normal human subjects were recruited into 1 of 3 age groups, group 1: aged ,35 years, group 2: aged 35–50 years, and group 3: aged .50 years. All eyes were examined using slit-lamp biomicroscopy, noncontact corneal esthesiometry, and slit scanning in vivo confocal microscopy. Results: The mean subbasal nerve density and the mean corneal sensitivity were greatest centrally (14,731 6 6056 mm/mm2 and 0.38 6 0.21 millibars, respectively) and lowest in the nasal mid periphery (7850 6 4947 mm/mm2 and 0.49 6 0.25 millibars, respectively). The mean subbasal nerve tortuosity coefficient was greatest in the temporal mid periphery (27.3 6 6.4) and lowest in the superior mid periphery (19.3 6 14.1). There was no significant difference in mean total subbasal nerve density between age groups. However, corneal sensation (P = 0.001) and subbasal nerve tortuosity (P = 0.004) demonstrated significant differences between age groups. Subbasal nerve density only showed significant correlations with corneal sensitivity threshold in the temporal cornea and with subbasal nerve tortuosity in the inferior and nasal cornea. However, these correlations were weak. Conclusions: This study quantitatively analyzes living human corneal nerve structure and an aspect of nerve function. There is no strong correlation between subbasal nerve density and corneal sensation. This study provides useful baseline data for the normal living human cornea at central and mid-peripheral locations

Human cortical processing of colour and pattern

Investigated human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that the authors specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. The authors did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. 10 right-handed male volunteers aged 18–35 yrs were recruited. The authors found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions.

Art the big winner at the Oscars

Are the Academy Awards heading towards an identity crisis? This year's Academy Awards have been characterised by a major disconnect between the most popular films at the box office and socially important films deemed the 'best pictures' by the Academy. Will the popularity of a film always remain inferior to whether or not it tackles serious social issues? Can popularity in its own right ever become indicative of a film's worth? Or should the awards retain their artistic integrity and suffer declining audiences and any criticisms they receive to maintain the respect they garner within the film industry? Whatever the answers may be, the winner of this year's Academy Awards was art over commerce, but this may not always be the case.

Are combination forecasts of S&P 500 volatility statistically superior?

Forecasting volatility has received a great deal of research attention, with the relative performances of econometric model based and option implied volatility forecasts often being considered. While many studies find that implied volatility is the pre-ferred approach, a number of issues remain unresolved, including the relative merit of combining forecasts and whether the relative performances of various forecasts are statistically different. By utilising recent econometric advances, this paper considers whether combination forecasts of S&P 500 volatility are statistically superior to a wide range of model based forecasts and implied volatility. It is found that a combination of model based forecasts is the dominant approach, indicating that the implied volatility cannot simply be viewed as a combination of various model based forecasts. Therefore, while often viewed as a superior volatility forecast, the implied volatility is in fact an inferior forecast of S&P 500 volatility relative to model-based forecasts.

The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model

Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features.

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.

The mechanical response of the ovine lumbar anulus fibrosus to uniaxial, biaxial and shear loads

Analytical and computational models of the intervertebral disc (IVD) are commonly employed to enhance understanding of the biomechanics of the human spine and spinal motion segments. The accuracy of these models in predicting physiological behaviour of the spine is intrinsically reliant on the accuracy of the material constitutive representations employed to represent the spinal tissues. There is a paucity of detailed mechanical data describing the material response of the reinforced­ground matrix in the anulus fibrosus of the IVD. In the present study, the ‘reinforced­ground matrix’ was defined as the matrix with the collagen fibres embedded but not actively bearing axial load, thus incorporating the contribution of the fibre-fibre and fibre-matrix interactions. To determine mechanical parameters for the anulus ground matrix, mechanical tests were carried out on specimens of ovine anulus, under unconfined uniaxial compression, simple shear and biaxial compression. Test specimens of ovine anulus fibrosus were obtained with an adjacent layer of vertebral bone/cartilage on the superior and inferior specimen surface. Specimen geometry was such that there were no continuous collagen fibres coupling the two endplates. Samples were subdivided according to disc region - anterior, lateral and posterior - to determine the regional inhomogeneity in the anulus mechanical response. Specimens were loaded at a strain rate sufficient to avoid fluid outflow from the tissue and typical stress-strain responses under the initial load application and under repeated loading were determined for each of the three loading types. The response of the anulus tissue to the initial and repeated load cycles was significantly different for all load types, except biaxial compression in the anterior anulus. Since the maximum applied strain exceeded the damage strain for the tissue, experimental results for repeated loading reflected the mechanical ability of the tissue to carry load, subsequent to the initiation of damage. To our knowledge, this is the first study to provide experimental data describing the response of the ‘reinforced­ground matrix’ to biaxial compression. Additionally, it is novel in defining a study objective to determine the regionally inhomogeneous response of the ‘reinforced­ground matrix’ under an extensive range of loading conditions suitable for mechanical characterisation of the tissue. The results presented facilitate the development of more detailed and comprehensive constitutive descriptions for the large strain nonlinear elastic or hyperelastic response of the anulus ground matrix.

The effect of dialect mismatch on likelihood-maximising speech enhancement for noise-robust speech recognition

Traditional speech enhancement methods optimise signal-level criteria such as signal-to-noise ratio, but these approaches are sub-optimal for noise-robust speech recognition. Likelihood-maximising (LIMA) frameworks are an alternative that optimise parameters of enhancement algorithms based on state sequences generated for utterances with known transcriptions. Previous reports of LIMA frameworks have shown significant promise for improving speech recognition accuracies under additive background noise for a range of speech enhancement techniques. In this paper we discuss the drawbacks of the LIMA approach when multiple layers of acoustic mismatch are present – namely background noise and speaker accent. Experimentation using LIMA-based Mel-filterbank noise subtraction on American and Australian English in-car speech databases supports this discussion, demonstrating that inferior speech recognition performance occurs when a second layer of mismatch is seen during evaluation.

Tissue engineered prefabricated vascularized flaps

BACKGROUND.: Microvascular free tissue transfer has become increasingly popular in the reconstruction of head and neck defects, but it also has its disadvantages. Tissue engineering allows the generation of neo-tissue for implantation, but these tissues are often avascular. We propose to combine tissue-engineering techniques together with flap prefabrication techniques to generate a prefabricated vascularized soft tissue flap. METHODS: Human dermal fibroblasts (HDFs) labeled with fluorescein diacetate were static seeded onto polylactic-co-glycolic acid-collagen (PLGA-c) mesh. Controls were plain PLGA-c mesh. The femoral artery and vein of the nude rat was ligated and used as a vascular carrier for the constructs. After 4 weeks of implantation, the constructs were assessed by gross morphology, routine histology, Masson trichrome, and cell viability determined by green fluorescence. RESULTS: All the constructs maintained their initial shape and dimensions. Angiogenesis was evident in all the constructs with neo-capillary formation within the PLGA-c mesh seen. HDFs proliferated and filled the interyarn spaces of the PLGA-c mesh, while unseeded PLGA-c mesh remained relatively acellular. Cell tracer study indicated that the seeded HDFs remained viable and closely associated to remaining PLGA-c fibers. Collagen formation was more abundant in the constructs seeded with HDFs. CONCLUSIONS: PLGA-c, enveloped by a cell sheet composed of fibroblasts, can serve as a suitable scaffold for generation of a soft tissue flap. A ligated arteriovenous pedicle can serve as a vascular carrier for the generation of a tissue engineered vascularized flap.

Peripheral ocular aberrations in mild and moderate keratoconus

Purpose: To investigate the influence of keratoconus on peripheral ocular aberrations. Methods: Aberrations of 7 mild and 5 moderate keratoconics were determined over a 42°horizontal x 32° vertical visual field with a modified COAS-HD aberrometer. Control data were obtained from an emmetropic group. Results: Most aberrations in keratoconics showed field dependence predominately along the vertical meridian. Mean spherical equivalent M, oblique astigmatism J45 and regular astigmatism J180 refraction components and total root mean square aberrations (excluding defocus) had high magnitudes in the inferior visual field. The rates of change of aberrations were higher in moderate than in mild keratoconics. Coma was the dominant peripheral higher-order aberration in both emmetropes and keratoconics; for the latter it had high magnitudes in the centre and periphery of the visual field. Conclusion: Greater rates of change of aberrations across the visual field occurred for the keratoconic groups than for the emmetropic control group. Moderate keratoconics had more rapid changes in, and higher magnitudes of aberrations across the visual field than mild keratoconics. The dominant higher-order aberration for the keratoconics across the visual field was vertical coma.

Functional status, postural stability and falls among older adults with glaucoma

Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.

Identification of factors contributing to recurrence of venous leg ulcers

Background and Significance Venous leg ulcers are a significant cause of chronic ill-health for 1–3% of those aged over 60 years, increasing in incidence with age. The condition is difficult and costly to heal, consuming 1–2.5% of total health budgets in developed countries and up to 50% of community nursing time. Unfortunately after healing, there is a recurrence rate of 60 to 70%, frequently within the first 12 months after heaing. Although some risk factors associated with higher recurrence rates have been identified (e.g. prolonged ulcer duration, deep vein thrombosis), in general there is limited evidence on treatments to effectively prevent recurrence. Patients are generally advised to undertake activities which aim to improve the impaired venous return (e.g. compression therapy, leg elevation, exercise). However, only compression therapy has some evidence to support its effectiveness in prevention and problems with adherence to this strategy are well documented. Aim The aim of this research was to identify factors associated with recurrence by determining relationships between recurrence and demographic factors, health, physical activity, psychosocial factors and self-care activities to prevent recurrence. Methods Two studies were undertaken: a retrospective study of participants diagnosed with a venous leg ulcer which healed 12 to 36 months prior to the study (n=122); and a prospective longitudinal study of participants recruited as their ulcer healed and data collected for 12 months following healing (n=80). Data were collected from medical records on demographics, medical history and ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer history, compression and other self-care activities. Follow-up data for the prospective study were collected every three months for 12 months after healing. For the retrospective study, a logistic regression model determined the independent influences of variables on recurrence. For the prospective study, median time to recurrence was calculated using the Kaplan-Meier method and a Cox proportional-hazards regression model was used to adjust for potential confounders and determine effects of preventive strategies and psychosocial factors on recurrence. Results In total, 68% of participants in the retrospective study and 44% of participants in the prospective study suffered a recurrence. After mutual adjustment for all variables in multivariable regression models, leg elevation, compression therapy, self efficacy and physical activity were found to be consistently related to recurrence in both studies. In the retrospective study, leg elevation, wearing Class 2 or 3 compression hosiery, the level of physical activity, cardiac disease and self efficacy scores remained significantly associated (p<0.05) with recurrence. The model was significant (p <0.001); with a R2 equivalent of 0.62. Examination of relationships between psychosocial factors and adherence to wearing compression hosiery found wearing compression hosiery was significantly positively associated with participants’ knowledge of the cause of their condition (p=0.002), higher self-efficacy scores (p=0.026) and lower depression scores (p=0.009). Analysis of data from the prospective study found there were 35 recurrences (44%) in the 12 months following healing and median time to recurrence was 27 weeks. After adjustment for potential confounders, a Cox proportional hazards regression model found that at least an hour/day of leg elevation, six or more days/week in Class 2 (20–25mmHg) or 3 (30–40mmHg) compression hosiery, higher social support scale scores and higher General Self-Efficacy scores remained significantly associated (p<0.05) with a lower risk of recurrence, while male gender and a history of DVT remained significant risk factors for recurrence. Overall the model was significant (p <0.001); with an R2 equivalent 0.72. Conclusions The high rates of recurrence found in the studies highlight the urgent need for further information in this area to support development of effective strategies for prevention. Overall, results indicate leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence. In addition, optimal management of depression and strategies to improve patient knowledge and self-efficacy may positively influence adherence to compression therapy. This research provides important information for development of strategies to prevent recurrence of venous leg ulcers, with the potential to improve health and decrease health care costs in this population.

The 3D model of l(IT)eracy and the English curriculum

The field of literacy studies has always been challenged by the changing technologies that humans have used to express, represent and communicate their feelings, ideas, understandings and knowledge. However, while the written word has remained central to literacy processes over a long period, it is generally accepted that there have been significant changes to what constitutes ‘literate’ practice. In particular, the status of the printed word has been challenged by the increasing dominance of the image, along with the multimodal meaning-making systems facilitated by digital media. For example, Gunther Kress and other members of the New London Group have argued that the second half of the twentieth century saw a significant cultural shift from the linguistic to the visual as the dominant semiotic mode. This in turn, they suggest, was accompanied by a cultural shift ‘from page to screen’ as a dominant space of representation (e.g. Cope & Kalantzis, 2000; Kress, 2003; New London Group, 1996). In a similar vein, Bill Green has noted that we have witnessed a shift from the regime of the print apparatus to a regime of the digital electronic apparatus (Lankshear, Snyder and Green, 2000). For these reasons, the field of literacy education has been challenged to find new ways to conceptualise what is meant by ‘literacy’ in the twenty first century and to rethink the conditions under which children might best be taught to be fully literate so that they can operate with agency in today’s world.

Instability prolongs the chondral phase during bone healing in sheep

In this sheep study, we investigated the influence of fixation stability on the temporal and spatial distribution of tissues in the fracture callus. As the initial mechanical conditions have been cited as being especially important for the healing outcome, it was hypothesized that differences in the path of healing would be seen as early as the initial phase of healing. ----- ----- Sixty-four sheep underwent a mid-shaft tibial osteotomy that was treated with either a rigid or a semi-rigid external fixator. Animals were sacrificed at 2, 3, 6 and 9 weeks postoperatively and the fracture calluses were analyzed using radiological, biomechanical and histological techniques. Statistical comparison between the groups was performed using the Mann–Whitney U test for unpaired non-parametric data. ----- ----- In the callus of the tibia treated with semi-rigid fixation, remnants of the fracture haematoma remained present for longer, although new periosteal bone formation during early healing was similar in both groups. The mechanical competence of the healing callus at 6 weeks was inferior compared to tibiae treated with rigid fixation. Semi-rigid fixation resulted in a larger cartilage component of the callus, which persisted longer. Remodeling processes were initiated earlier in the rigid group, while new bone formation continued throughout the entire investigated period in the semi-rigid group. ----- ----- In this study, evidence is provided that less rigid fixation increased the time required for healing. The process of intramembranous ossification appeared during the initial stages of healing to be independent of mechanical stability. However, the delay in healing was related to a prolonged chondral phase.