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.

Flower animals

The coral reefs around the world may be likened to canaries down the mineshaft of global warming. These sensitive plant-like animals have evolved for life in tropical seas. Their needs are quite specific – not too cold, not too hot. A rise of as little as one degree Celsius is enough to cause some bleaching of these colourful jewels of the sea. Many climate models indicate we can expect sea temperature increases of between two and six degrees Celsius. Research - such as that detailed in a 2004 report by the University of Queensland’s Centre for Marine Studies – indicates that by the year 2050 most of the worlds major reef systems will be dead. Many of us have heard this kind of information, but it remains difficult to comprehend. It’s almost impossible to imagine the death of the Great Barrier Reef. Some six to nine thousand years old and visible from space, it is the world’s largest structure created by living organisms. Yet whilst it is hard to believe, this gentle, sensitive giant is at grave risk because it cannot adapt quickly enough to the changes in the environment. This cluster of fluffy felt brain coral sculptures are connected in real time to temperature data collected by monitoring stations within the Great Barrier Reef, that form part of the Australian Institute of Marine Science’s Great Barrier Reed Ocean Observing System. These corals display illumination patterns showing changes in sea temperature at Heron Reef, one of the 2,900 reefs that comprise the Great Barrier Reef. Their spectrum of colour ranges from cool hues, through warm tones to bright white when temperatures exceed those that tropical corals are able to tolerate over sustained periods. The Flower Animals also blush in colour and make sound when people come within close proximity. In a reef, fishes and other creatures generate significant amounts of sound. These cacophonies are considered an indicator of reef health, and are used by reef fish to determine where they can best live and forage.

Contemporary take on deconstructed Medea : a review

THEATRE: The New Dead: Medea Material. By Heiner Muller. Stella Electrika in association with La Boite Theatre Company, Brisbane, November 19. THERE has been a lot of intensity in independent theatre in Brisbane during the past year, as companies, production houses and producers have begun building new programs and platforms to support an expansion of pathways within the local theatre ecology. Audiences have been exposed to works signalling the diversity of what Brisbane theatre makers want to see on stage, from productions of new local and international pieces to new devised works, and the results of residencies and development programs. La Boite Theatre Company closes its inaugural indie season with a work that places it at the contemporary, experimental end of the spectrum. The New Dead: Medea Material is emerging director Kat Henry's interpretation of Heiner Muller's 1981 text Despoiled Shore Medea Material Landscape with Argonauts. Start of sidebar. Skip to end of sidebar. End of sidebar. Return to start of sidebar. Muller is known for his radical adaptations of historical dramas, from the Greeks to Shakespeare, and for deconstructed texts in which the characters - in this case, Medea - violently reject the familial, cultural and political roles society has laid out for them. Muller's combination of deconstructed characters, disconnected poetic language and constant references to aspects of popular culture and the Cold War politics he sought to abjure make his texts challenging to realise. The poetry entices but the density, together with the increasing distance of the Cold War politics in the texts, leaves contemporary directors with clear decisions to make about how to adapt these open texts. In The New Dead: Medea Material, Henry works with some interesting imagery and conceptual territory. Lucinda Shaw as Medea, Guy Webster as Jason and Kimie Tsukakoshi as King Creon's daughter Glauce, the woman for whom Jason forsakes his wife Medea, each reference different aspects of contemporary culture. Medea is a bitter, drunken, satin-gowned diva with bite; Jason - first seen lounging in front of the television with a beer in an image reminiscent of Sarah Kane's in-yer-face characterisation of Hippolytus in Phaedra's Love - has something of the rock star about him; and Glauce is a roller-skating, karaoke-singing, pole-dancing young temptress. The production is given a contemporary tone, dominated by Medea's twisted love and loss, rather than by any commentary on her circumstances. Its strength is the aesthetic Henry creates, supported by live electro-pop music, a band stage that stands as a metaphor for Jason's sea voyage, and multimedia that inserts images of the story unfolding beyond these characters' speeches as sorts of subconscious flashes. While Tsukakoshi is engaging throughout, there are moments when Shaw and Webster's performances - particularly in the songs - are diminished by a lack of clarity. The result is a piece that, while slightly lacking in its realisation at times, undoubtedly flags Henry's facility as an emerging director and what she wants to bring to the Brisbane theatre scene.

Towards improvement of autonomous glider navigation accuracy through the use of regional ocean models

Autonomous underwater gliders are robust and widely-used ocean sampling platforms that are characterized by their endurance, and are one of the best approaches to gather subsurface data at the appropriate spatial resolution to advance our knowledge of the ocean environment. Gliders generally do not employ sophisticated sensors for underwater localization, but instead dead-reckon between set waypoints. Thus, these vehicles are subject to large positional errors between prescribed and actual surfacing locations. Here, we investigate the implementation of a large-scale, regional ocean model into the trajectory design for autonomous gliders to improve their navigational accuracy. We compute the dead-reckoning error for our Slocum gliders, and compare this to the average positional error recorded from multiple deployments conducted over the past year. We then compare trajectory plans computed on-board the vehicle during recent deployments to our prediction-based trajectory plans for 140 surfacing occurrences.

Death by Drowning : Gary Bryson's Turtle [A Review]

Accused of being autobiographical, as many debut novels often are, Turtle, upon first reading and further prying, does read as a story wrenched out of Gary Bryson’s own life. In a recent interview with Mandy Sayer, however, he was quick to deny all sorts of archetypal allegations. “Any resemblance to turtles living or dead”, Bryson explained, “is entirely coincidental”. Regardless of the many parallels that align author with protagonist—both were born and raised in a grey-skied Glasgow, both grew up in self-described dysfunctional families, and both returned to the colourless city to attend their mothers’ funerals—the narrative combines bruising black comedy with moments of magic realism. The result is an unlikely but often surprising concoction of twists and turns, each of which mixes the fallibility of memory with the slippery nature of truth. This playfulness between the material world and its metaphorical counterpart raises questions, not only about the curse that poisons its characters, but about the ethical implications of blurring fact and fiction...

Diesel engine condition monitoring and simulated diesel knock

This paper discusses diesel engine condition monitoring (CM) using acoustic emissions (AE)as well as some of the commonly encountered diesel engine problems. Also discussed are some of the underlying combustion related faults and the methods used in past studies to simulate diesel engine faults. The initial test involved an experimental simulation of two common combustion related diesel engine faults, namely diesel knock and misfire. These simulated faults represent the first step towards a comprehensive investigation and analysis into the characteristics of acoustic emission signals arising from combustion related diesel engine faults. Data corresponding to different engine running conditions was captured using in-cylinder pressure, vibration and acoustic emission transducers along with both crank angle encoder and top-dead centre (TDC) signals. Using these signals, it was possible to characterise the effect of different combustion conditions and hence, various diesel engine in-cylinder pressure profiles.

Adam Smith's dinner

In 1961, the East German government erected what they claimed was an anti-capitalist barricade. In 1989, this barricade was dismantled by those whom it was supposed to keep apart: the forces it was intended to contain had overwhelmed it. In the aftermath, the victims of Stalinist oppression and the planned economy opted for radical change. Some might have hoped that they would intellectually march resolutely westwards towards the forms of social democracy that had proven so successful in their nearest neighbours – Scandinavia, Germany and Austria – and stop when they had reached a point on the political spectrum with which they felt comfortable, and which worked for them. Unfortunately, they went to the opposite end of political economy. That choice was celebrated by those theorists who wanted our own countries to move in the same direction. Eastern Europe suffered a decline of 50% in its GDP. Much earlier in 1653, Peter Stuyvesant had erected an earth and wooden wall to protect the westernmost settlement of a great commercial nation from those they imagined to be barbarians. In 1699 Stuyvesant’s barrier was dismantled by the British, who replaced it with a street named after the wall. So it came to be that one of the most inconsequential walls in history became one of history’s most famous streets. I am not sure if the Dutch had left some tulip bulbs on either side of the wall, perhaps as a reminder of capitalism’s first bubble, and an inspiration to later bubbles. However, many of the victims of the latest burst bubble are pretty keen to tear down that Wall.1 As in 1989, they want to take action against the guardians of the system that failed them. And the more they suffer, the more likely it is that they will demand radical change, and the more likely that the resulting change will go too far – as seems to have been the case in Eastern Europe after the terminal crisis of communism, and in the majority of democracies that fell in the dozen years following the Great Crash. The current reaction is so strong that some are even wondering what role there will be for markets. I was invited to address a conference in the EU Parliament last November on the topic ‘Capitalism: Quo Vadis?’, where I apologized to the international audience that the topic was posed in a dead European language because the answer to this question is not going to be determined by the west alone. The problems we have been addressing emerged in the west and have affected the rest. However, the answers will not come, solely from the west, and may even come primarily from the south and the east.

Experimentally induced diesel engine injector faults and some preliminary acoustic emission signal observations

Diesel engine fuel injector faults can lead to reduced power, increased fuel consumption and greater exhaust emission levels and if left unchecked, can eventually lead to premature engine failure. This paper provides an overview of the Diesel, or compression ignition combustion process, and of the two basic fuel injector nozzle designs used in Diesel engines, namely, the pintle-type and hole-type nozzles. Also described are some common faults associated with these two types of fuel injector nozzles and the techniques previously used to experimentally simulate these faults. This paper also presents a recent experimental campaign undertaken using two different diesel engines whereby various fuel injector nozzle faults were induced into the engines. The first series of tests was undertaken using a turbo-charged 5.9 litre; Cummins Diesel engine whist the second series of tests was undertaken using a naturally aspirated 4 cylinder, 2.216 litre, Perkins Diesel engine. Data corresponding to different injector fault conditions was captured using in-cylinder pressure, and acoustic emission transducers along with both crank-angle encoder and top-dead centre reference signals. Using averaged in-cylinder pressure signals, it was possible to qualify the severity of the faults whilst averaged acoustic emission signals were in turn, used as the basis for wavelets decomposition. Initial observations from this signal decomposition are also presented and discussed.

Mapping resilience : A framework for changing cities

Urban centres base their resilience on the ability to evolve and adapt as needed throughout their life. Although constantly developing, changing and subsuming nature for its needs, the current age of environmental awareness requires that cities progress in a more conscious and considered way. While they have become the dominant form of human habitation, there now exists a need to integrate 'green' solutions into urban centres to address social, physical and environmental wellbeing. The means of implementing the vast array of possible solutions without negative impacts is not clear; cities are complex systems, layering meaning, history and cultural memory ‐ they are a manifestation of shared cultural values, and as such, they do not allow a tabula rasa approach of 'blanket' solutions. All around us, cities are continuing to develop and change, and although their form is varied ‐ sprawling cities with density and sustainability problems; or collapsing cities with 'dead' centres and dilapidated districts – a common issue is the resilience of the local identity. The strength or resilience of cities lies in the elements which have become fixed points in the urban structure, giving character and identity to a shared urban experience. These elements need to be identified and either maintained or revitalised. Similarly, the identification of urban elements which can most viably be modified without compromising character and identity of place, will assist in making concrete contributions to increasing both the sustainability and experience of cities, making them more resilient. Through an examination of case studies, this paper suggests a framework to inform urban renewal assessing the widespread elements which generate an urban identity, beyond the traditional approach of heritage conservation for cultural or tourist purposes. The rapid contemporary alteration of urban structures requires an innovative methodology which satisfies on one side the need of new sustainable performances and, on the other, the resilience of the local character.

A simulation study of unified GPS and roadside ranging technologies for vehicle positioning

The future vehicle navigation for safety applications requires seamless positioning at the accuracy of sub-meter or better. However, standalone Global Positioning System (GPS) or Differential GPS (DGPS) suffer from solution outages while being used in restricted areas such as high-rise urban areas and tunnels due to the blockages of satellite signals. Smoothed DGPS can provide sub-meter positioning accuracy, but not the seamless requirement. A disadvantage of the traditional navigation aids such as Dead Reckoning and Inertial Measurement Unit onboard vehicles are either not accurate enough due to error accumulation or too expensive to be acceptable by the mass market vehicle users. One of the alternative technologies is to use the wireless infrastructure installed in roadside to locate vehicles in regions where the Global Navigation Satellite Systems (GNSS) signals are not available (for example: inside tunnels, urban canyons and large indoor car parks). The examples of roadside infrastructure which can be potentially used for positioning purposes could include Wireless Local Area Network (WLAN)/Wireless Personal Area Network (WPAN) based positioning systems, Ultra-wide band (UWB) based positioning systems, Dedicated Short Range Communication (DSRC) devices, Locata’s positioning technology, and accurate road surface height information over selected road segments such as tunnels. This research reviews and compares the possible wireless technologies that could possibly be installed along roadside for positioning purposes. Models and algorithms of integrating different positioning technologies are also presented. Various simulation schemes are designed to examine the performance benefits of united GNSS and roadside infrastructure for vehicle positioning. The results from these experimental studies have shown a number of useful findings. It is clear that in the open road environment where sufficient satellite signals can be obtained, the roadside wireless measurements contribute very little to the improvement of positioning accuracy at the sub-meter level, especially in the dual constellation cases. In the restricted outdoor environments where only a few GPS satellites, such as those with 45 elevations, can be received, the roadside distance measurements can help improve both positioning accuracy and availability to the sub-meter level. When the vehicle is travelling in tunnels with known heights of tunnel surfaces and roadside distance measurements, the sub-meter horizontal positioning accuracy is also achievable. Overall, simulation results have demonstrated that roadside infrastructure indeed has the potential to provide sub-meter vehicle position solutions for certain road safety applications if the properly deployed roadside measurements are obtainable.

Diesel knock combustion and its detection using acoustic emission

This paper presents an experimental investigation into the detection of excessive Diesel knock using acoustic emission signals. Three different dual-fuel Diesel engine operating regimes were induced into a compression ignition (Diesel) engine operating on both straight Diesel fuel and two different mixtures of fumigated ethanol and Diesel. The experimentally induced engine operating regimes were; normal, or Diesel only operation, acceptable dual-fuel operation and dual-fuel operation with excessive Diesel knock. During the excessive Diesel knock operating regime, high rates of ethanol substitution induced potentially damaging levels of Diesel knock. Acoustic emission data was captured along with cylinder pressure, crank-angle encoder, and top-dead centre signals for the different engine operating regimes. Using these signals, it was found that acoustic emission signals clearly distinguished between the two acceptable operating regimes and the operating regime experiencing excessive Diesel knock. It was also found that acoustic emission sensor position is critical. The acoustic emission sensor positioned on the block of the engine clearly related information concerning the level of Diesel knock occurring in the engine whist the sensor positioned on the head of the engine gave no indication concerning Diesel knock severity levels.

Diesel engine problems, acoustic emission signals and simulated misfire faults

This paper discusses commonly encountered diesel engine problems and the underlying combustion related faults. Also discussed are the methods used in previous studies to simulate diesel engine faults and the initial results of an experimental simulation of a common combustion related diesel engine fault, namely diesel engine misfire. This experimental fault simulation represents the first step towards a comprehensive investigation and analysis into the characteristics of acoustic emission signals arising from combustion related diesel engine faults. Data corresponding to different engine running conditions was captured using in-cylinder pressure, vibration and acoustic emission transducers along with both crank-angle encoder and top-dead centre signals. Using these signals, it was possible to characterise the diesel engine in-cylinder pressure profiles and the effect of different combustion conditions on both vibration and acoustic emission signals.

Corneal nerve structure and function as markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterisation and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression and assess new therapies. This thesis evaluates novel corneal methods of assessing diabetic neuropathy. Over the past several years two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy (CCM) allows quantification of corneal nerve parameters and non-contact corneal aesthesiometry (NCCA), the presumed functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and with automatic analysis paradigms developed, are suitable for clinical settings. Each has advantages and disadvantages over established techniques for assessing diabetic neuropathy. New information is presented regarding measurement bias of CCM images, and a unique sampling paradigm and associated accuracy determination method of combinations is described. A novel high-speed corneal nerve mapping procedure has been developed and application of this procedure in individuals with neuropathy has revealed regions of sub-basal nerve plexus that dictate further evaluation, as they appear to show earlier signs of damage than the central region of the cornea that has to date been examined. The discriminative capacity of corneal sensitivity measured by NCCA is revealed to have reasonable potential as a marker of diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Building community resilience – learning from the 2011 floods in Southeast Queensland, Australia

The year 2010 was the wettest year on record for Queensland, Australia and the wettest year since 1974 for Southeast Queensland. The extremely heavy rain in early January 2011 fell on the catchments of heavily saturated Brisbane and Stanley Rivers systems resulting in significant runoff which rapidly produced a widespread and devastating flood event. The area of inundation was equivalent to the total land area of France and Germany combined. Over 200,000 people were affected leaving 35 people dead and 9 missing. The damage bill was estimated at over $1B and cost to the economy at over $10B with over 30,000 homes and 6,000 business flooded and 86 towns and regional centres affected. The need to disburse disaster funding in a prompt manner to the affected population was paramount to facilitate individuals getting their lives back to some normality. However, the payout of insurance claims has proved to be a major area of community anger. The ongoing impasse in payment of insurance compensation is attributed to the nature and number of claims, confusing definition of flooding and the lack or accuracy of information needed to determine individually the properties affected and legitimacy of claims. Information was not readily available at the micro-level including, extent and type of inundation, flood heights at property level and cause of damage. Events during the aftermath highlighted widespread community misconceptions concerning the technical factors associated with the flood event and the impact of such on access to legitimate compensation and assistance. Individual and community wide concerns and frustration, anger and depression, have arisen resulting from delays in the timely settlement of insurance claims. Lessons learnt during the aftermath are presented in the context of their importance as a basis for inculcating communities impacted by the flood event with resilience for the future.