Longitudinal assessment of corneal subbasal nerve morphology as a potential measure of diabetic peripheral neuropathy

This thesis represents a significant step forward in developing a validated measure for diabetic peripheral neuropathy – a debilitating and prevalent complication of diabetes. The candidate investigated corneal nerve structure in healthy people as well as in type 1 diabetic individuals in a 4-year longitudinal study. The outcomes of stability of the corneal small nerve fibre in healthy people and evidence of significant decline in diabetic individuals with peripheral neuropathy over time provide justification for the ongoing efforts to establish corneal nerve structure as an objective and appropriate adjunct to conventional measures of peripheral neuropathy.

Putting an "end" to the motor cortex representations of action words

Language processing is an example of implicit learning of multiple statistical cues that provide probabilistic information regarding word structure and use. Much of the current debate about language embodiment is devoted to how action words are represented in the brain, with motor cortex activity evoked by these words assumed to selectively reflect conceptual content and/or its simulation. We investigated whether motor cortex activity evoked by manual action words (e.g., caress) might reflect sensitivity to probabilistic orthographic-phonological cues to grammatical category embedded within individual words. We first review neuroimaging data demonstrating that nonwords evoke activity much more reliably than action words along the entire motor strip, encompassing regions proposed to be action category specific. Using fMRI, we found that disyllabic words denoting manual actions evoked increased motor cortex activity compared with non-body-part-related words (e.g., canyon), activity which overlaps that evoked by observing and executing hand movements. This result is typically interpreted in support of language embodiment. Crucially, we also found that disyllabic nonwords containing endings with probabilistic cues predictive of verb status (e.g., -eve) evoked increased activity compared with nonwords with endings predictive of noun status (e.g., -age) in the identical motor area. Thus, motor cortex responses to action words cannot be assumed to selectively reflect conceptual content and/or its simulation. Our results clearly demonstrate motor cortex activity reflects implicit processing of ortho-phonological statistical regularities that help to distinguish a word's grammatical class.

Motor response suppression and the prepotent tendency to respond: A parametric fMRI study

In the present study we utilised functional magnetic resonance imaging (fMRI) to examine cerebral activation during performance of a classic motor task in which response suppression load was parametrically varied. Linear increases in activity were observed in a distributed network of regions across both cerebral hemispheres, although with more extensive involvement of the right prefrontal cortex. Activated regions included prefrontal, parietal and occipitotemporal cortices. Decreasing activation was similarly observed in a distributed network of regions. These response forms are discussed in terms of an increasing requirement for visual cue discrimination and suppression/selection of motor responses, and a decreasing probability of the occurrence of non-target stimuli and attenuation of a prepotent tendency to respond. The results support recent proposals for a dominant role for the right-hemisphere in performance of motor response suppression tasks that emphasise the importance of the right prefrontal cortex.

L-dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults.Weexamined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

No specific role for the manual motor system in processing the meanings of words related to the hand

The present study explored whether semantic and motor systems are functionally interwoven via the use of a dual-task paradigm. According to embodied language accounts that propose an automatic and necessary involvement of the motor system in conceptual processing, concurrent processing of hand-related information should interfere more with hand movements than processing of unrelated body-part (i.e., foot, mouth) information. Across three experiments, 100 right-handed participants performed left- or right-hand tapping movements while repeatedly reading action words related to different body-parts, or different body-part names, in both aloud and silent conditions. Concurrent reading of single words related to specific body-parts, or the same words embedded in sentences differing in syntactic and phonological complexity (to manipulate context-relevant processing), and reading while viewing videos of the actions and body-parts described by the target words (to elicit visuomotor associations) all interfered with right-hand but not left-hand tapping rate. However, this motor interference was not affected differentially by hand-related stimuli. Thus, the results provide no support for proposals that body-part specific resources in cortical motor systems are shared between overt manual movements and meaning-related processing of words related to the hand.

General motor vehicle drivers' knowledge and practices regarding drink driving in Yinchuan and Guangzhou, China

Objective: Drink driving contributes to significant levels of injury and economic loss in China but is not well researched. This study examined knowledge, drink-driving practices, and alcohol misuse problems among general drivers in Yinchuan. The objectives were to gain a better understanding of drink driving in Yinchuan, identify areas that need to be addressed, and compare the results with a similar study in Guangzhou. Methods: This was a cross-sectional study with a survey designed to collect information on participants’ demographic characteristics and their knowledge and practices in relation to drinking and driving. The survey was composed of questions on knowledge and practices in relation to drink driving and was administered to a convenience sample of 406 drivers. Alcohol misuse problems were assessed by using the Alcohol Use Disorders Identification Test (AUDIT). Results: Males accounted for the main proportion of drivers sampled from the general population (“general drivers”). A majority of general drivers in both cities knew that drunk driving had become a criminal offense in 2011; however, knowledge of 2 legal blood alcohol concentration (BAC) limits was quite low. Fewer drivers in Yinchuan (22.6%) than in Guangzhou (27.9) reported having been stopped by police conducting breath alcohol testing at least once in the last 12 months. The mean AUDIT score in Yinchuan (M = 8.2) was higher than that in Guangzhou (M = 7.4), and the proportion of Yinchuan drivers with medium or higher alcohol misuse problems (31.2%) was correspondingly higher than in Guangzhou (23.1%). In Yinchuan, males had a significantly higher AUDIT score than females (t = 3.454, P < .001), similar to Guangzhou. Multiple regression analyses were conducted on potential predictors of the AUDIT score (age, gender, monthly income, education level, years licensed, and age started drinking). There were significant individual contributions of gender (beta = 0.173, P = .09) and age at which drinking started (beta = 0.141, P = .033), but the overall model for Yinchuan was not significant, unlike Guangzhou. Conclusions: The results show that there are shortfalls in knowledge of the legislation and how to comply with it and deficiencies in police enforcement. In addition, there was evidence of drink driving and drink riding at high levels in both cities. Recommendations are made to address these issues.

An alternative approach to describing agility in sports through establishment of a relationship between velocity and radius of curvature

Agility is an essential part of many athletic activities. Currently, agility drill duration is the sole criterion used for evaluation of agility performance. The relationship between drill duration and factors such as acceleration, deceleration and change of direction, however, has not been fully explored. This paper provides a mathematical description of the relationship between velocity and radius of curvatures in an agility drill through implementation of a power law (PL). Two groups of skilled and unskilled participants performed a cyclic forward/backward shuttle agility test. Kinematic data was recorded using motion capture system at a sampling rate of 200 Hz. The logarithmic relationship between tangential velocity and radius of curvature of participant trajectories in both groups was established using the PL. The slope of the regression line was found to be 0.26 and 0.36, for the skilled and unskilled groups, respectively. The magnitudes of regression line slope for both groups were approximately 0.3 which is close to the expected 1/3 value. Results are an indication of how the PL could be implemented in an agility drill thus opening the way for establishment of a more representative measure of agility performance instead of drill duration.

Do motor vehicle crashes arise from single or multiple unique risk processes? An inquiry into crash causes and modelling

Crashes at any particular transport network location consist of a chain of events arising from a multitude of potential causes and/or contributing factors whose nature is likely to reflect geometric characteristics of the road, spatial effects of the surrounding environment, and human behavioural factors. It is postulated that these potential contributing factors do not arise from the same underlying risk process, and thus should be explicitly modelled and understood. The state of the practice in road safety network management applies a safety performance function that represents a single risk process to explain crash variability across network sites. This study aims to elucidate the importance of differentiating among various underlying risk processes contributing to the observed crash count at any particular network location. To demonstrate the principle of this theoretical and corresponding methodological approach, the study explores engineering (e.g. segment length, speed limit) and unobserved spatial factors (e.g. climatic factors, presence of schools) as two explicit sources of crash contributing factors. A Bayesian Latent Class (BLC) analysis is used to explore these two sources and to incorporate prior information about their contribution to crash occurrence. The methodology is applied to the state controlled roads in Queensland, Australia and the results are compared with the traditional Negative Binomial (NB) model. A comparison of goodness of fit measures indicates that the model with a double risk process outperforms the single risk process NB model, and thus indicating the need for further research to capture all the three crash generation processes into the SPFs.

Association between glaucoma and at–fault motor vehicle collision involvement among older drivers

Objective To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found. Design A retrospective population-based study Participants A sample of 2,000 licensed drivers aged 70 years and older who reside in north central Alabama. Methods At-fault MVC involvement for five years prior to enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RR) and 95% confidence intervals (CI). Main Outcomes Measures At-fault MVC involvement for five years prior to enrollment. Results Drivers with glaucoma (n = 206) had a 1.65 (95% confidence interval [CI] 1.20-2.28, p = 0.002) times higher MVC rate compared to those without glaucoma after adjusting for age, gender and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR = 2.11, 95% CI 1.09-4.09, p = 0.027), whereas no significant association was found among those with impaired visual acuity and contrast sensitivity. When the visual field was sub-divided into six regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (RR = 3.16, p = 0.001) compared to other regions. However, no significant association was found in deficits in the right side or along the horizontal or vertical meridian. Conclusions A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma appears to have an independent association with at-fault MVC involvement, whereas visual acuity and contrast sensitivity impairments do not.

In vivo velocity vector imaging and time-resolved strain rate measurements in the wall of blood vessels using MRI

In this paper, we present a new approach for velocity vector imaging and time-resolved measurements of strain rates in the wall of human arteries using MRI and we prove its feasibility on two examples: in vitro on a phantom and in vivo on the carotid artery of a human subject. Results point out the promising potential of this approach for investigating the mechanics of arterial tissues in vivo.

Normative values for corneal nerve morphology assessed using corneal confocal microscopy: A multinational normative data set

OBJECTIVE Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm(2) per year for men, P < 0.01, and -0.161 no./mm(2) per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm(2) per year for men, P = 0.26, and -0.050 no./mm(2) per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm(2) per year, P = 0.07) and women (-0.060 mm/mm(2) per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

Electrical conduction in plasma polymerized thin films of γ-terpinene

Plasma polymerized c-terpinene (pp2GT) thin films are fabricated using RF plasma polymerization. MIM structures are fabricated and using the capacitive structures dielectric properties of the material is studied. The dielectric constant values are found to be in good agreement with those determined from ellipsometric data. At a frequency of 100 kHz, the dielectric constant varies with RF deposition power, from 3.69 (10 W) to 3.24 (75 W). The current density–voltage (J2V) characteristics of pp–GT thin films are investigated as a function of RF deposition power at room temperature to determine the resistivity and DC conduction mechanism of the films. At higher applied voltage region, Schottky conduction is the dominant DC conduction mechanism. The capacitance and the loss tangent are found to be frequency dependent. The conductivity of the pp2GT thin films is found to decrease from 1.39 3 10212 S/cm (10 W) to 1.02 3 10213 S/cm (75 W) and attributed to the change in the chemical composition and structure of the polymer. The breakdown field for pp–GT thin films increases from 1.48 MV/cm (10 W) to 2 MV/cm (75 W). A single broad relaxation peak is observed indicating the contribution of multiple relaxations to the dielectric response for temperature dependent J2V. The distribution of these relaxation times is determined through regularization methods. VC 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42318.

‘Lemon Laws’: an inquiry into consumer protections and remedies for buyers of new motor vehicles

1. Under the Terms of Reference for the Committee’s Inquiry, ‘lemons’ are defined as ‘new motor vehicles with numerous, severe defects that re-occur despite multiple repair attempts or where defects have caused a new motor vehicle to be out of service for a prolonged period of time’. Consumers are currently protected in relation to lemon purchases by the Australian Consumer Law (ACL) located in Schedule 2 of the Competition and Consumer Act 2010 (Cth) (CCA). The ACL applies as a law of Queensland pursuant to the Fair Trading Act 1989 (Qld). The voluntary recall and consumer guarantees law took effect on 1 January 2011. 2. In 2006, the Government of Victoria made a commitment to introduce a lemon law into the provisions of the then Fair Trading Act 1999 (Vic). The public consultation process on the proposal to introduce a lemon law for motor vehicle purchases in Victoria was conducted by Ms Janice Munt MP, with the assistance of Consumer Affairs Victoria (CAV). CAV released an Issues Paper to canvas with industry and the community options for the development and introduction of a motor vehicle lemon law.(Consumer Affairs Victoria, Introducing Victorian motor vehicle lemon laws, Issues Paper, (September, 2007). 3. A CAV report prepared by Janice Munt MP was released in July, 2008 (Consumer Affairs Victoria, Motor Cars: A report on the motor vehicle lemon law consultations (July 2008) (Victorian Lemon Law Report). However, the Victorian proposal was overtaken by events leading to the adoption of a uniform consumer protection law in all Australian jurisdictions, the ACL. 4. The structure of this submission is to consider first the three different bases upon which consumers can obtain relief for economic loss arising from defects in motor vehicles. The second part of the submission considers the difficulties encountered by consumers in litigating motor vehicle disputes in the courts and tribunals. The third part of the submission examines the approach taken in other jurisdictions to resolving motor vehicle disputes. The final part of the submission considers a number of possible reforms that could be made to the existing law and its enforcement to reduce consumer detriment arising from the purchase of ‘lemon’ motor vehicles. 5. There are three principal bases upon which a consumer can obtain redress for defects in new motor vehicles under the ACL. The first is where the manufacturer admits liability and initiates the voluntary recall procedure provided for in s 128 of the ACL. Under this basis the manufacturer generally repairs or replaces the part subject to the recall free of charge. The second basis is where the manufacturer or dealer denies liability and the consumer is initiates proceedings in the court or tribunal seeking a statutory remedy under the ACL, the nature of which will depend on whether the failure to comply with the consumer guarantee was major or not. The third basis upon which a consumer can obtain redress is pursuant to public enforcement by the ACCC. Each basis will be considered in this part. What all three bases have in common is the need to conduct an investigation to identify the nature of the defect and how it arose.

Risk factors associated with corneal nerve alteration in type 1 diabetes in the absence of neuropathy: A longitudinal in vivo corneal confocal microscopy study

Purpose The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over four years using in vivo corneal confocal microscopy (IVCM) in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. Methods A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning IVCM, ocular screening, and health and metabolic assessment at baseline and the examinations continued for four subsequent annual visits. At each annual visit, eight central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL). Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters. Results A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure or BMI. However, CNFD was negatively associated with HbA1c (β=-0.76, P<0.01) and age (β=-0.13, P<0.01) and positively related to high density lipids (HDL) (β=2.01, P=0.03). Higher HbA1c (β=-1.58, P=0.04) and age (β=-0.23, P<0.01) also negatively impacted CNBD. CNFL was only affected by higher age (β=-0.06, P<0.01). Conclusions Glycemic control, HDL and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage as well as the capability of IVCM for monitoring subclinical alterations in the corneal SNP in diabetes.