Cortical processing of human gut sensation: an evoked potential study

The rectum has a unique physiological role as a sensory organ and differs in its afferent innervation from other gut organs that do not normally mediate conscious sensation. We compared the central processing of human esophageal, duodenal, and rectal sensation using cortical evoked potentials (CEP) in 10 healthy volunteers (age range 21-34 yr). Esophageal and duodenal CEP had similar morphology in all subjects, whereas rectal CEP had two different but reproducible morphologies. The rectal CEP latency to the first component P1 (69 ms) was shorter than both duodenal (123 ms; P = 0.008) and esophageal CEP latencies (106 ms; P = 0.004). The duodenal CEP amplitude of the P1-N1 component (5.0 µV) was smaller than that of the corresponding esophageal component (5.7 µV; P = 0.04) but similar to that of the corresponding rectal component (6.5 µV; P = 0.25). This suggests that rectal sensation is either mediated by faster-conducting afferent pathways or that there is a difference in the orientation or volume of cortical neurons representing the different gut organs. In conclusion, the physiological and anatomic differences between gut organs are reflected in differences in the characteristics of their afferent pathways and cortical processing.

Contrast- and illumination-invariant object recognition from active sensation

It has been suggested that the deleterious effect of contrast reversal on visual recognition is unique to faces, not objects. Here we show from priming, supervised category learning, and generalization that there is no such thing as general invariance of recognition of non-face objects against contrast reversal and, likewise, changes in direction of illumination. However, when recognition varies with rendering conditions, invariance may be restored, and effects of continuous learning may be reduced, by providing prior object knowledge from active sensation. Our findings suggest that the degree of contrast invariance achieved reflects functional characteristics of object representations learned in a task-dependent fashion.

Understanding the psychosocial factors influencing the risky behaviour of young drivers

Young people aged 17–24 years are at high risk of being killed in road crashes around the world. Road safety interventions consider some influences upon young driver behaviour; for example, imposing passenger restrictions on young novice drivers indirectly minimises the potential negative social influences of peers as passengers. To change young driver risky behaviour, the multitude of psychosocial influences upon its initiation and maintenance must be identified. A study questionnaire was developed to investigate the relationships between risky driving and Akers’ social learning theory, social identity theory, and thrill seeking variables. The questionnaire was completed by 165 participants (105 women,60 men) residing in south-east Queensland, Australia. The sociodemographic variables of age, gender, and exposure explained 19% of the variance in self-reported risky driving behaviour, whilst Akers’ social learning variables explained an additional 42%. Thrill seeking and social identity variables did not explain any significant additional variance. Significant predictors of risky driving included imitation of the driving behaviours of, and anticipated rewards and punishments administered by, parents and peers. Road safety policy that directly considers and incorporates these factors in their design, implementation, and enforcement of young driver road safety interventions should prove more efficacious than current approaches.

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

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.

The consequences of substance use among gay and bisexual men : a consensual qualitative research analysis

- Background Substance use is common among gay/bisexual men and is associated with significant health risks (e.g. HIV transmission). The consequences of substance use, across the range of substances commonly used, have received little attention. The purpose of this study is to map participant’s beliefs about the effects of substance use to inform prevention, health promotion and clinical interventions. - Methods Participants were interviewed about experiences regarding their substance use and recruited through medical and sexual health clinics. Data were collected though a consumer panel and individual interviews. Responses regarding perceived consequences of substance use were coded using Consensual Qualitative Research (CQR) methodology. - Results Most participants reported lifetime use of alcohol, cannabis, stimulants and amyl nitrite, and recent alcohol and cannabis use. A wide range of themes were identified regarding participant’s thoughts, emotions and behaviours (including sexual behaviours) secondary to substance use, including: cognitive functioning, mood, social interaction, physical effects, sexual activity, sexual risk-taking, perception of sexual experience, arousal, sensation, relaxation, disinhibition, energy/activity level and numbing. Analyses indicated several consequences were consistent across substance types (e.g. cognitive impairment, enhanced mood), whereas others were highly specific to a given substance (e.g. heightened arousal post amyl nitrite use). - Conclusions Prevention and interventions need to consider the variety of effects of substance use in tailoring effective education programs to reduce harms. A diversity of consequences appear to have direct and indirect impacts on decision-making, sexual activity and risk-taking. Findings lend support for the role of specific beliefs (e.g. expectancies) related to substance use on risk-related cognitions, emotions and behaviours.

Image acquisition and manipulation protocols for CT-PET fusion to improve the accuracy of gross tumour volume localisation for 3D conformal radiotherapy for lung cancer

Aims: To develop clinical protocols for acquiring PET images, performing CT-PET registration and tumour volume definition based on the PET image data, for radiotherapy for lung cancer patients and then to test these protocols with respect to levels of accuracy and reproducibility. Method: A phantom-based quality assurance study of the processes associated with using registered CT and PET scans for tumour volume definition was conducted to: (1) investigate image acquisition and manipulation techniques for registering and contouring CT and PET images in a radiotherapy treatment planning system, and (2) determine technology-based errors in the registration and contouring processes. The outcomes of the phantom image based quality assurance study were used to determine clinical protocols. Protocols were developed for (1) acquiring patient PET image data for incorporation into the 3DCRT process, particularly for ensuring that the patient is positioned in their treatment position; (2) CT-PET image registration techniques and (3) GTV definition using the PET image data. The developed clinical protocols were tested using retrospective clinical trials to assess levels of inter-user variability which may be attributed to the use of these protocols. A Siemens Somatom Open Sensation 20 slice CT scanner and a Philips Allegro stand-alone PET scanner were used to acquire the images for this research. The Philips Pinnacle3 treatment planning system was used to perform the image registration and contouring of the CT and PET images. Results: Both the attenuation-corrected and transmission images obtained from standard whole-body PET staging clinical scanning protocols were acquired and imported into the treatment planning system for the phantom-based quality assurance study. Protocols for manipulating the PET images in the treatment planning system, particularly for quantifying uptake in volumes of interest and window levels for accurate geometric visualisation were determined. The automatic registration algorithms were found to have sub-voxel levels of accuracy, with transmission scan-based CT-PET registration more accurate than emission scan-based registration of the phantom images. Respiration induced image artifacts were not found to influence registration accuracy while inadequate pre-registration over-lap of the CT and PET images was found to result in large registration errors. A threshold value based on a percentage of the maximum uptake within a volume of interest was found to accurately contour the different features of the phantom despite the lower spatial resolution of the PET images. Appropriate selection of the threshold value is dependant on target-to-background ratios and the presence of respiratory motion. The results from the phantom-based study were used to design, implement and test clinical CT-PET fusion protocols. The patient PET image acquisition protocols enabled patients to be successfully identified and positioned in their radiotherapy treatment position during the acquisition of their whole-body PET staging scan. While automatic registration techniques were found to reduce inter-user variation compared to manual techniques, there was no significant difference in the registration outcomes for transmission or emission scan-based registration of the patient images, using the protocol. Tumour volumes contoured on registered patient CT-PET images using the tested threshold values and viewing windows determined from the phantom study, demonstrated less inter-user variation for the primary tumour volume contours than those contoured using only the patient’s planning CT scans. Conclusions: The developed clinical protocols allow a patient’s whole-body PET staging scan to be incorporated, manipulated and quantified in the treatment planning process to improve the accuracy of gross tumour volume localisation in 3D conformal radiotherapy for lung cancer. Image registration protocols which factor in potential software-based errors combined with adequate user training are recommended to increase the accuracy and reproducibility of registration outcomes. A semi-automated adaptive threshold contouring technique incorporating a PET windowing protocol, accurately defines the geometric edge of a tumour volume using PET image data from a stand alone PET scanner, including 4D target volumes.

Examining psychosocial influences on speeding in Australian and Chinese contexts : a social learning approach

Speeding remains a significant contributing factor to road trauma internationally, despite increasingly sophisticated speed management strategies being adopted around the world. Increases in travel speed are associated with increases in crash risk and crash severity. As speed choice is a voluntary behaviour, driver perceptions are important to our understanding of speeding and, importantly, to designing effective behavioural countermeasures. The four studies conducted in this program of research represent a comprehensive approach to examining psychosocial influences on driving speeds in two countries that are at very different levels of road safety development: Australia and China. Akers’ social learning theory (SLT) was selected as the theoretical framework underpinning this research and guided the development of key research hypotheses. This theory was chosen because of its ability to encompass psychological, sociological, and criminological perspectives in understanding behaviour, each of which has relevance to speeding. A mixed-method design was used to explore the personal, social, and legal influences on speeding among car drivers in Queensland (Australia) and Beijing (China). Study 1 was a qualitative exploration, via focus group interviews, of speeding among 67 car drivers recruited from south east Queensland. Participants were assigned to groups based on their age and gender, and additionally, according to whether they self-identified as speeding excessively or rarely. This study aimed to elicit information about how drivers conceptualise speeding as well as the social and legal influences on driving speeds. The findings revealed a wide variety of reasons and circumstances that appear to be used as personal justifications for exceeding speed limits. Driver perceptions of speeding as personally and socially acceptable, as well as safe and necessary were common. Perceptions of an absence of danger associated with faster driving speeds were evident, particularly with respect to driving alone. An important distinction between the speed-based groups related to the attention given to the driving task. Rare speeders expressed strong beliefs about the need to be mindful of safety (self and others) while excessive speeders referred to the driving task as automatic, an absent-minded endeavour, and to speeding as a necessity in order to remain alert and reduce boredom. For many drivers in this study, compliance with speed limits was expressed as discretionary rather than mandatory. Social factors, such as peer and parental influence were widely discussed in Study 1 and perceptions of widespread community acceptance of speeding were noted. In some instances, the perception that ‘everybody speeds’ appeared to act as one rationale for the need to raise speed limits. Self-presentation, or wanting to project a positive image of self was noted, particularly with respect to concealing speeding infringements from others to protect one’s image as a trustworthy and safe driver. The influence of legal factors was also evident. Legal sanctions do not appear to influence all drivers to the same extent. For instance, fear of apprehension appeared to play a role in reducing speeding for many, although previous experiences of detection and legal sanctions seemed to have had limited influence on reducing speeding among some drivers. Disregard for sanctions (e.g., driving while suspended), fraudulent demerit point use, and other strategies to avoid detection and punishment were widely and openly discussed. In Study 2, 833 drivers were recruited from roadside service stations in metropolitan and regional locations in Queensland. A quantitative research strategy assessed the relative contribution of personal, social, and legal factors to recent and future self-reported speeding (i.e., frequency of speeding and intentions to speed in the future). Multivariate analyses examining a range of factors drawn from SLT revealed that factors including self-identity (i.e., identifying as someone who speeds), favourable definitions (attitudes) towards speeding, personal experiences of avoiding detection and punishment for speeding, and perceptions of family and friends as accepting of speeding were all significantly associated with greater self-reported speeding. Study 3 was an exploratory, qualitative investigation of psychosocial factors associated with speeding among 35 Chinese drivers who were recruited from the membership of a motoring organisation and a university in Beijing. Six focus groups were conducted to explore similar issues to those examined in Study 1. The findings of Study 3 revealed many similarities with respect to the themes that arose in Australia. For example, there were similarities regarding personal justifications for speeding, such as the perception that posted limits are unreasonably low, the belief that individual drivers are able to determine safe travel speeds according to personal comfort with driving fast, and the belief that drivers possess adequate skills to control a vehicle at high speed. Strategies to avoid detection and punishment were also noted, though they appeared more widespread in China and also appeared, in some cases, to involve the use of a third party, a topic that was not reported by Australian drivers. Additionally, higher perceived enforcement tolerance thresholds were discussed by Chinese participants. Overall, the findings indicated perceptions of a high degree of community acceptance of speeding and a perceived lack of risk associated with speeds that were well above posted speed limits. Study 4 extended the exploratory research phase in China with a quantitative investigation involving 299 car drivers recruited from car washes in Beijing. Results revealed a relatively inexperienced sample with less than 5 years driving experience, on average. One third of participants perceived that the certainty of penalties when apprehended was low and a similar proportion of Chinese participants reported having previously avoided legal penalties when apprehended for speeding. Approximately half of the sample reported that legal penalties for speeding were ‘minimally to not at all’ severe. Multivariate analyses revealed that past experiences of avoiding detection and punishment for speeding, as well as favourable attitudes towards speeding, and perceptions of strong community acceptance of speeding were most strongly associated with greater self-reported speeding in the Chinese sample. Overall, the results of this research make several important theoretical contributions to the road safety literature. Akers’ social learning theory was found to be robust across cultural contexts with respect to speeding; similar amounts of variance were explained in self-reported speeding in the quantitative studies conducted in Australia and China. Historically, SLT was devised as a theory of deviance and posits that deviance and conformity are learned in the same way, with the balance of influence stemming from the ways in which behaviour is rewarded and punished (Akers, 1998). This perspective suggests that those who speed and those who do not are influenced by the same mechanisms. The inclusion of drivers from both ends of the ‘speeding spectrum’ in Study 1 provided an opportunity to examine the wider utility of SLT across the full range of the behaviour. One may question the use of a theory of deviance to investigate speeding, a behaviour that could, arguably, be described as socially acceptable and prevalent. However, SLT seemed particularly relevant to investigating speeding because of its inclusion of association, imitation, and reinforcement variables which reflect the breadth of factors already found to be potentially influential on driving speeds. In addition, driving is a learned behaviour requiring observation, guidance, and practice. Thus, the reinforcement and imitation concepts are particularly relevant to this behaviour. Finally, current speed management practices are largely enforcement-based and rely on the principles of behavioural reinforcement captured within the reinforcement component of SLT. Thus, the application of SLT to a behaviour such as speeding offers promise in advancing our understanding of the factors that influence speeding, as well as extending our knowledge of the application of SLT. Moreover, SLT could act as a valuable theoretical framework with which to examine other illegal driving behaviours that may not necessarily be seen as deviant by the community (e.g., mobile phone use while driving). This research also made unique contributions to advancing our understanding of the key components and the overall structure of Akers’ social learning theory. The broader SLT literature is lacking in terms of a thorough structural understanding of the component parts of the theory. For instance, debate exists regarding the relevance of, and necessity for including broader social influences in the model as captured by differential association. In the current research, two alternative SLT models were specified and tested in order to better understand the nature and extent of the influence of differential association on behaviour. Importantly, the results indicated that differential association was able to make a unique contribution to explaining self-reported speeding, thereby negating the call to exclude it from the model. The results also demonstrated that imitation was a discrete theoretical concept that should also be retained in the model. The results suggest a need to further explore and specify mechanisms of social influence in the SLT model. In addition, a novel approach was used to operationalise SLT variables by including concepts drawn from contemporary social psychological and deterrence-based research to enhance and extend the way that SLT variables have traditionally been examined. Differential reinforcement was conceptualised according to behavioural reinforcement principles (i.e., positive and negative reinforcement and punishment) and incorporated concepts of affective beliefs, anticipated regret, and deterrence-related concepts. Although implicit in descriptions of SLT, little research has, to date, made use of the broad range of reinforcement principles to understand the factors that encourage or inhibit behaviour. This approach has particular significance to road user behaviours in general because of the deterrence-based nature of many road safety countermeasures. The concept of self-identity was also included in the model and was found to be consistent with the definitions component of SLT. A final theoretical contribution was the specification and testing of a full measurement model prior to model testing using structural equation modelling. This process is recommended in order to reduce measurement error by providing an examination of the psychometric properties of the data prior to full model testing. Despite calls for such work for a number of decades, the current work appears to be the only example of a full measurement model of SLT. There were also a number of important practical implications that emerged from this program of research. Firstly, perceptions regarding speed enforcement tolerance thresholds were highlighted as a salient influence on driving speeds in both countries. The issue of enforcement tolerance levels generated considerable discussion among drivers in both countries, with Australian drivers reporting lower perceived tolerance levels than Chinese drivers. It was clear that many drivers used the concept of an enforcement tolerance in determining their driving speed, primarily with the desire to drive faster than the posted speed limit, yet remaining within a speed range that would preclude apprehension by police. The quantitative results from Studies 2 and 4 added support to these qualitative findings. Together, the findings supported previous research and suggested that a travel speed may not be seen as illegal until that speed reaches a level over the prescribed enforcement tolerance threshold. In other words, the enforcement tolerance appears to act as a ‘de facto’ speed limit, replacing the posted limit in the minds of some drivers. The findings from the two studies conducted in China (Studies 2 and 4) further highlighted the link between perceived enforcement tolerances and a ‘de facto’ speed limit. Drivers openly discussed driving at speeds that were well above posted speed limits and some participants noted their preference for driving at speeds close to ‘50% above’ the posted limit. This preference appeared to be shaped by the perception that the same penalty would be imposed if apprehended, irrespective of what speed they travelling (at least up to 50% above the limit). Further research is required to determine whether the perceptions of Chinese drivers are mainly influenced by the Law of the People’s Republic of China or by operational practices. Together, the findings from both studies in China indicate that there may be scope to refine enforcement tolerance levels, as has happened in other jurisdictions internationally over time, in order to reduce speeding. Any attempts to do so would likely be assisted by the provision of information about the legitimacy and purpose of speed limits as well as risk factors associated with speeding because these issues were raised by Chinese participants in the qualitative research phase. Another important practical implication of this research for speed management in China is the way in which penalties are determined. Chinese drivers described perceptions of unfairness and a lack of transparency in the enforcement system because they were unsure of the penalty that they would receive if apprehended. Steps to enhance the perceived certainty and consistency of the system to promote a more equitable approach to detection and punishment would appear to be welcomed by the general driving public and would be more consistent with the intended theoretical (deterrence) basis that underpins the current speed enforcement approach. The use of mandatory, fixed penalties may assist in this regard. In many countries, speeding attracts penalties that are dependent on the severity of the offence. In China, there may be safety benefits gained from the introduction of a similar graduated scale of speeding penalties and fixed penalties might also help to address the issue of uncertainty about penalties and related perceptions of unfairness. Such advancements would be in keeping with the principles of best practice for speed management as identified by the World Health Organisation. Another practical implication relating to legal penalties, and applicable to both cultural contexts, relates to the issues of detection and punishment avoidance. These two concepts appeared to strongly influence speeding in the current samples. In Australia, detection avoidance strategies reported by participants generally involved activities that are not illegal (e.g., site learning and remaining watchful for police vehicles). The results from China were similar, although a greater range of strategies were reported. The most common strategy reported in both countries for avoiding detection when speeding was site learning, or familiarisation with speed camera locations. However, a range of illegal practices were also described by Chinese drivers (e.g., tampering with or removing vehicle registration plates so as to render the vehicle unidentifiable on camera and use of in-vehicle radar detectors). With regard to avoiding punishment when apprehended, a range of strategies were reported by drivers from both countries, although a greater range of strategies were reported by Chinese drivers. As the results of the current research indicated that detection avoidance was strongly associated with greater self-reported speeding in both samples, efforts to reduce avoidance opportunities are strongly recommended. The practice of randomly scheduling speed camera locations, as is current practice in Queensland, offers one way to minimise site learning. The findings of this research indicated that this practice should continue. However, they also indicated that additional strategies are needed to reduce opportunities to evade detection. The use of point-to-point speed detection (also known as sectio

The candidate : a novella and examination of Australian Gothic crime fiction

Australia is a land without haunted castles or subterranean corridors, without ancient graveyards or decaying monasteries, a land whose climate is rarely gloomy. Yet, the literary landscape is splattered with shades of the Gothic genre. This Gothic heritage is especially evident within elements of nineteenth century Australian sensation fiction. Australian crime fiction in the twentieth century, in keeping with this lineage, repeatedly employs elements of the Gothic, adapting and appropriating these conventions for literary effect. I believe that a ‘mélange’ of historical Gothic crime traditions could produce an exciting new mode of Gothic crime writing in the Australian context. As such, I have written a contemporary literary experiment in a Gothic crime ‘hybrid’ style: this novella forms my creative practice. The accompanying exegesis is a critical study of a selection of Australian literary works that exhibit the characteristics of both Gothic and crime genres. Through an analysis of these creative works, this study argues that the interlacing of Gothic traditions with crime writing conventions has been a noteworthy practice in Australian fiction during both the nineteenth and twentieth centuries and these literary tropes are interwoven in the writing of ‘The Candidate’, a Gothic crime novella.

Predicting effects of monotony on driver’s vigilance

Monotony has been identified as a contributing factor to road crashes. Drivers’ ability to react to unpredictable events deteriorates when exposed to highly predictable and uneventful driving tasks, such as driving on Australian rural roads, many of which are monotonous by nature. Highway design in particular attempts to reduce the driver’s task to a merely lane-keeping one. Such a task provides little stimulation and is monotonous, thus affecting the driver’s attention which is no longer directed towards the road. Inattention contributes to crashes, especially for professional drivers. Monotony has been studied mainly from the endogenous perspective (for instance through sleep deprivation) without taking into account the influence of the task itself (repetitiveness) or the surrounding environment. The aim and novelty of this thesis is to develop a methodology (mathematical framework) able to predict driver lapses of vigilance under monotonous environments in real time, using endogenous and exogenous data collected from the driver, the vehicle and the environment. Existing approaches have tended to neglect the specificity of task monotony, leaving the question of the existence of a “monotonous state” unanswered. Furthermore the issue of detecting vigilance decrement before it occurs (predictions) has not been investigated in the literature, let alone in real time. A multidisciplinary approach is necessary to explain how vigilance evolves in monotonous conditions. Such an approach needs to draw on psychology, physiology, road safety, computer science and mathematics. The systemic approach proposed in this study is unique with its predictive dimension and allows us to define, in real time, the impacts of monotony on the driver’s ability to drive. Such methodology is based on mathematical models integrating data available in vehicles to the vigilance state of the driver during a monotonous driving task in various environments. The model integrates different data measuring driver’s endogenous and exogenous factors (related to the driver, the vehicle and the surrounding environment). Electroencephalography (EEG) is used to measure driver vigilance since it has been shown to be the most reliable and real time methodology to assess vigilance level. There are a variety of mathematical models suitable to provide a framework for predictions however, to find the most accurate model, a collection of mathematical models were trained in this thesis and the most reliable was found. The methodology developed in this research is first applied to a theoretically sound measure of sustained attention called Sustained Attention Response to Task (SART) as adapted by Michael (2010), Michael and Meuter (2006, 2007). This experiment induced impairments due to monotony during a vigilance task. Analyses performed in this thesis confirm and extend findings from Michael (2010) that monotony leads to an important vigilance impairment independent of fatigue. This thesis is also the first to show that monotony changes the dynamics of vigilance evolution and tends to create a “monotonous state” characterised by reduced vigilance. Personality traits such as being a low sensation seeker can mitigate this vigilance decrement. It is also evident that lapses in vigilance can be predicted accurately with Bayesian modelling and Neural Networks. This framework was then applied to the driving task by designing a simulated monotonous driving task. The design of such task requires multidisciplinary knowledge and involved psychologist Rebecca Michael. Monotony was varied through both the road design and the road environment variables. This experiment demonstrated that road monotony can lead to driving impairment. Particularly monotonous road scenery was shown to have the most impact compared to monotonous road design. Next, this study identified a variety of surrogate measures that are correlated with vigilance levels obtained from the EEG. Such vigilance states can be predicted with these surrogate measures. This means that vigilance decrement can be detected in a car without the use of an EEG device. Amongst the different mathematical models tested in this thesis, only Neural Networks predicted the vigilance levels accurately. The results of both these experiments provide valuable information about the methodology to predict vigilance decrement. Such an issue is quite complex and requires modelling that can adapt to highly inter-individual differences. Only Neural Networks proved accurate in both studies, suggesting that these models are the most likely to be accurate when used on real roads or for further research on vigilance modelling. This research provides a better understanding of the driving task under monotonous conditions. Results demonstrate that mathematical modelling can be used to determine the driver’s vigilance state when driving using surrogate measures identified during this study. This research has opened up avenues for future research and could result in the development of an in-vehicle device predicting driver vigilance decrement. Such a device could contribute to a reduction in crashes and therefore improve road safety.

Imagination

Imagination is a capacity of internal visualization, concept creation and manipulation not directly dependent upon sensation. Imagination is associated with a range of phenomena: mental imagery, fancy, inventiveness, insight, counterfactual reasoning, pretence, simulation and conceivability.

Increased Langerhan cell density and corneal nerve damage in diabetic patients : role of immune mechanisms in human diabetic neuropathy

Aim/hypothesis Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients. Methods 128 diabetic patients aged 58±1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS—4.7±0.28) and 26 control subjects aged 53±3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM). Results The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P=0.001. Furthermore, LC density (no/mm2) was significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58), P=0.001 and there was a significant correlation with age (r=0.162, P=0.047) and severity of neuropathy (r=−0.202, P=0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r=0.414, P=0.000). Corneal nerve fibre density (P<0.001), branch density (P<0.001) and length (P<0.001) were significantly decreased whilst tortuosity (P<0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy. Conclusion Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Predictors of future falls in Parkinson disease

Background: Falls are a major health and injury problem for people with Parkinson disease (PD). Despite the severe consequences of falls, a major unresolved issue is the identification of factors that predict the risk of falls in individual patients with PD. The primary aim of this study was to prospectively determine an optimal combination of functional and disease-specific tests to predict falls in individuals with PD. ----- ----- Methods: A total of 101 people with early-stage PD undertook a battery of neurologic and functional tests in their optimally medicated state. The tests included Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk; the latter assessment includes physiologic tests of visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway. Falls were recorded prospectively over 6 months. ----- ----- Results: Forty-eight percent of participants reported a fall and 24% more than 1 fall. In the multivariate model, a combination of the Unified Parkinson's Disease Rating Scale (UPDRS) total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction produced the best sensitivity (78%) and specificity (84%) for predicting falls. From the UPDRS items, only the rapid alternating task category was an independent predictor of falls. Reduced peripheral sensation and knee extension strength in fallers contributed to increased postural instability. ----- ----- Conclusions: Falls are a significant problem in optimally medicated early-stage PD. A combination of both disease-specific and balance- and mobility-related measures can accurately predict falls in individuals with PD.

Postural balance under normal and altered sensory conditions in normal-weight and overweight children

Background Little or no research has been done in the overweight child on the relative contribution of multisensory information to maintain postural stability. Therefore, the purpose of this study was to investigate postural balance control under normal and experimentally altered sensory conditions in normal-weight versus overweight children. Methods Sixty children were stratified into a younger (7–9 yr) and an older age group (10–12 yr). Participants were also classified as normal-weight (n = 22) or overweight (n = 38), according to the international BMI cut-off points for children. Postural stability was assessed during quiet bilateral stance in four sensory conditions (eyes open or closed, normal or reduced plantar sensation), using a Kistler force plate to quantify COP dynamics. Coefficients of variation were calculated as well to describe intra-individual variability. Findings Removal of vision resulted in systematically higher amounts of postural sway, but no significant BMI group differences were demonstrated across sensory conditions. However, under normal conditions lower plantar cutaneous sensation was associated with higher COP velocities and maximal excursion of the COP in the medial-lateral direction for the overweight group. Regardless of condition, higher variability was shown in the overweight children within the 7–9 yr old subgroup for postural sway velocity, and more specifically medial–lateral velocity. Interpretation In spite of these subtle differences, results did not establish any clear underlying sensory organization impairments that may affect standing balance performance in overweight children compared to normal-weight peers. Consequently, it is believed that other factors account for overweight children's functional balance deficiencies.