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.

Wide-field assessment of the human corneal subbasal nerve plexus in diabetic neuropathy using a novel mapping technique

To develop a rapid optimized technique of wide-field imaging of the human corneal subbasal nerve plexus. A dynamic fixation target was developed and, coupled with semiautomated tiling software, a rapid method of capturing and montaging multiple corneal confocal microscopy images was created. To illustrate the utility of this technique, wide-field maps of the subbasal nerve plexus were produced in 2 participants with diabetes, 1 with and 1 without neuropathy. The technique produced montages of the central 3 mm of the subbasal corneal nerve plexus. The maps seem to show a general reduction in the number of nerve fibers and branches in the diabetic participant with neuropathy compared with the individual without neuropathy. This novel technique will allow more routine and widespread use of subbasal nerve plexus mapping in clinical and research situations. The significant reduction in the time to image the corneal subbasal nerve plexus should expedite studies of larger groups of diabetic patients and those with other conditions affecting nerve fibers. The inferior whorl and the surrounding areas may show the greatest loss of nerve fibers in individuals with diabetic neuropathy, but this should be further investigated in a larger cohort.

Optimal image sample size for corneal nerve morphometry

Purpose Arbitrary numbers of corneal confocal microscopy images have been used for analysis of corneal subbasal nerve parameters under the implicit assumption that these are a representative sample of the central corneal nerve plexus. The purpose of this study is to present a technique for quantifying the number of random central corneal images required to achieve an acceptable level of accuracy in the measurement of corneal nerve fiber length and branch density. Methods Every possible combination of 2 to 16 images (where 16 was deemed the true mean) of the central corneal subbasal nerve plexus, not overlapping by more than 20%, were assessed for nerve fiber length and branch density in 20 subjects with type 2 diabetes and varying degrees of functional nerve deficit. Mean ratios were calculated to allow comparisons between and within subjects. Results In assessing nerve branch density, eight randomly chosen images not overlapping by more than 20% produced an average that was within 30% of the true mean 95% of the time. A similar sampling strategy of five images was 13% within the true mean 80% of the time for corneal nerve fiber length. Conclusions The “sample combination analysis” presented here can be used to determine the sample size required for a desired level of accuracy of quantification of corneal subbasal nerve parameters. This technique may have applications in other biological sampling studies.

Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy

Aims:  To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with Type 2 diabetes, particularly in those who are at higher risk of foot ulceration. Methods:  Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with Type 2 diabetes and 24 healthy controls) using the 0–10 neuropathy disability score. Participants were stratified into four neuropathy groups: none (0–2), mild (3–5), moderate (6–8), and severe (9–10). A neuropathy disability score ≥ 6 was used to define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness. Results:  Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability scores ≥ 6 in the inferior quadrant (P < 0.005). Age, duration of disease and retinopathy levels did not significantly influence retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements from the group with diabetes and no neuropathy (P > 0.24 for global and all sectors). Conclusions:  Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.

Malnutrition and poor food intake are associated with prolonged hospital stay, frequent readmissions, and greater in-hospital mortality: Results from the Nutrition Care Day Survey 2010

Background & aims The Australasian Nutrition Care Day Survey (ANCDS) ascertained if malnutrition and poor food intake are independent risk factors for health-related outcomes in Australian and New Zealand hospital patients. Methods Phase 1 recorded nutritional status (Subjective Global Assessment) and 24-h food intake (0, 25, 50, 75, 100% intake). Outcomes data (Phase 2) were collected 90-days post-Phase 1 and included length of hospital stay (LOS), readmissions and in-hospital mortality. Results Of 3122 participants (47% females, 65 ± 18 years) from 56 hospitals, 32% were malnourished and 23% consumed ≤ 25% of the offered food. Malnourished patients had greater median LOS (15 days vs. 10 days, p < 0.0001) and readmissions rates (36% vs. 30%, p = 0.001). Median LOS for patients consuming ≤ 25% of the food was higher than those consuming ≤ 50% (13 vs. 11 days, p < 0.0001). The odds of 90-day in-hospital mortality were twice greater for malnourished patients (CI: 1.09–3.34, p = 0.023) and those consuming ≤ 25% of the offered food (CI: 1.13–3.51, p = 0.017), respectively. Conclusion The ANCDS establishes that malnutrition and poor food intake are independently associated with in-hospital mortality in the Australian and New Zealand acute care setting.

The status of the Greater Flamingo in the Galapagos

The paper covers census work carried out in 1976-77 on the Greater Flamingoes on all the islands in the Galapagos Archipelago, Ecuador South America. The work was supported by funding from the World Wildlife Fund.

Steps toward the validation of the Trendelenburg Test : the effect of experimentally reduced hip abductor muscle function on frontal plane mechanics

Objective: To investigate the validity of the Trendelenburg test (TT) using an ultrasound-guided nerve block (UNB) of the superior gluteal nerve and determine whether the reduction in hip abductor muscle (HABD) strength would result in the theorized mechanical compensatory strategies measured during the TT. Design: Quasi-experimental. Setting: Hospital. Participants: Convenience sample of 9 healthy men. Only participants with no current or previous injury to the lumbar spine, pelvis, or lower extremities, and no previous surgeries were included. Interventions: Ultrasound-guided nerve block. Main Outcome Measures: Hip abductor muscle strength (percent body weight [%BW]), contralateral pelvic drop (cPD), change in contralateral pelvic drop (Delta cPD), ipsilateral hip adduction, and ipsilateral trunk sway (TRUNK) measured in degrees. Results: The median age and weight of the participants were 31 years (interquartile range [IQR], 22-32 years) and 73 kg (IQR, 67-81 kg), respectively. An average 52% reduction of HABD strength (z = 2.36, P = 0.02) resulted after the UNB. No differences were found in cPD or Delta cPD (z = 0.01, P = 0.99, z = 20.67, P = 0.49, respectively). Individual changes in biomechanics showed no consistency between participants and nonsystematic changes across the group. One participant demonstrated the mechanical compensations described by Trendelenburg. Conclusions: The TT should not be used as a screening measure for HABD strength in populations demonstrating strength greater than 30% BW but should be reserved for use with populations with marked HABD weakness. Clinical Relevance: This study presents data regarding a critical level of HABD strength required to support the pelvis during the TT.

Steps towards the validation of the Trendelenburg test : The effect of experimentally reduced hip abductor muscle function on frontal plane mechanics

Introduction: The Trendelenburg Test (TT) is used to assess the functional strength of the hip abductor muscles (HABD), their ability to control frontal plane motion of the pelvis, and the ability of the lumbopelvic complex to transfer load into single leg stance. Rationale: Although a standard method to perform the test has been described for use within clinical populations, no study has directly investigated Trendelenburg’s hypotheses. Purpose: To investigate the validity of the TT using an ultrasound guided nerve block (UNB) of the superior gluteal nerve and determine whether the reduction in HABD strength would result in the theorized mechanical compensatory strategies measured during the TT. Methods: Quasi-experimental design using a convenience sample of nine healthy males. Only subjects with no current or previous injury to the lumbar spine, pelvis, or lower extremities, and no previous surgeries were included. Force dynamometry was used to evaluation HABD strength (%BW). 2D mechanics were used to evaluate contralateral pelvic drop (cMPD), change in contralateral pelvic drop (∆cMPD), ipsilateral hip adduction (iHADD) and ipsilateral trunk sway (TRUNK) measured in degrees (°). All measures were collected prior to and following a UNB on the superior gluteal nerve performed by an interventional radiologist. Results: Subjects’ age was median 31yrs (IQR:22-32yrs); and weight was median 73kg (IQR:67-81kg). An average 52% reduction of HABD strength (z=2.36,p=0.02) resulted following the UNB. No differences were found in cMPD or ∆cMPD (z=0.01,p= 0.99, z=-0.67,p=0.49). Individual changes in biomechanics show no consistency between subjects and non-systematic changes across the group. One subject demonstrated the mechanical compensations described by Trendelenburg. Discussion: The TT should not be used as screening measure for HABD strength in populations demonstrating strength greater than 30%BW but reserved for use with populations with marked HABD weakness. Importance: This study presents data regarding a critical level of HABD strength required to support the pelvis during the TT.

Review : "English language education across Greater China" by A. Feng

I have formally learned English from Year Four till the completion of my undergraduate study in China. Because of this personal history, I was keen to review this book and revisit English education in China. The list of contributors to the book includes Anwei Feng (editor) and his colleagues, who play an insider role in English language practice, research, and policy-making in ‘Greater China’. ‘Greater China’ according to Feng, can be defined as geographically close, demographically Chinese-dominated, and culturally, economically, and socio-politically interrelated countries and territories where Chinese is either the mother tongue or used as an official language.

Moderate sleep restriction in treated older male OSA participants: Greater impairment during monotonous driving compared with controls

Objectives To examine the effects on monotonous driving of normal sleep versus one night of sleep restriction in continuous positive airway pressure (CPAP) treated obstructive sleep apnoea (OSA) patients compared with age matched healthy controls. Methods Nineteen CPAP treated compliant male OSA patients (OSA-treated patients (OPs)), aged 50–75 years, and 20 healthy age-matched controls underwent both a normal night’s sleep and sleep restriction to 5 h (OPs remained on CPAP) in a counterbalanced design. All participants completed a 2 h afternoon monotonous drive in a realistic car simulator. Driving was monitored for sleepiness-related minor and major lane deviations, with ‘safe’ driving time being total time driven prior to first major lane deviation. EEGs were recorded continuously, and subjective sleepiness ratings were taken at regular intervals throughout the drive. Results After a normal night’s sleep, OPs and controls did not differ in terms of driving performance or in their ability to assess the levels of their own sleepiness, with both groups driving ‘safely’ for approximately 90 min. However, after sleep restriction, OPs had a significantly shorter (65 min) safe driving time and had to apply more compensatory effort to maintain their alertness compared with controls. They also underestimated the enhanced sleepiness. Nevertheless, apart from this caveat, there were generally close associations between subjective sleepiness, likelihood of a major lane deviation and EEG changes indicative of sleepiness. Conclusions With a normal night’s sleep, effectively treated older men with OSA drive as safely as healthy men of the same age. However, after restricted sleep, driving impairment is worse than that of controls. This suggests that, although successful CPAP treatment can alleviate potential detrimental effects of OSA on monotonous driving following normal sleep, these patients remain more vulnerable to sleep restriction.

Does sustainable housing construction provide the home owner with a greater investment return?

Over the past 20 years there has been a considerable push at all three tiers of Government and private industry in Australia to improve the energy efficiency and sustainability levels of residential housing. A number of these initiatives have been voluntary, such as solar power and solar heating rebates, with other mandatory measures being incorporated into building standards and codes. Although the importance of energy efficiency and sustainable materials have been widely conveyed both at the academic and public level, it does not always reflect in the residential house purchase decision by typical house buyers, including residential property investors. This paper will analyse a range of housing markets in Brisbane to determine the investment performance of those markets over the past 3 years to determine any significant differences between new residential suburbs and older residential suburbs where houses have not been constructed to the current energy efficiency and sustainability guidelines. The range of suburbs to be analysed will focus on middle to lower high value suburbs, with a particular focus on residential housing in Master Planned Communities to determine if socio-economic factors and development size and scope have an impact of the purchase and investment performance of sustainable houses in comparison to older housing stock. The paper confirms that the residential property market shows a higher capital return for residential property built under stricter sustainability guidelines than similar located and type of property built prior to the BCA 2004 and older style project type homes erected prior to 2000.