Corneal sensitivity is related to established measures of diabetic peripheral neuropathy

Purpose:  The objective was to investigate the association between corneal sensitivity and established measures of diabetic peripheral neuropathy (DPN). Methods:  Corneal sensitivity was measured in 93 individuals with diabetes, 146 diabetic individuals without neuropathy and 61 control individuals without diabetes or neuropathy using a non-contact corneal aesthesiometer at the baseline visit of a five-year longitudinal natural history study of DPN. The correlation between corneal sensitivity and established measures of neuropathy was estimated and multi-dimensional scaling was used to represent similarities and dissimilarities between variables. Results:  The corneal sensitivity threshold was significantly correlated with a majority of established measures of DPN. Correlation coefficients ranged from -0.32 to 0.26. Using multi-dimensional scaling, non-contact corneal aesthesiometry was closer to the neuropathy disability score, diabetic neuropathy symptom score and Neuropad and most dissimilar to electrophysiological parameters and quantitative sensory testing. Conclusion:  Corneal sensitivity, although not strongly related, is associated with other functional measures of DPN and might provide a useful adjunct in identifying functional loss of small nerve fibre integrity.

Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

The impact of fatigue caused by sprint running on the median power frequency of the hamstring muscle group

Hamstring strain injuries (HSI) are the predominant non-contact injury in many sports. Intermittent running has been shown to result in preferential reductions in eccentric hamstring strength, which increase the risk of sustaining a HSI. The eccentric specific nature of this decline in hamstring function implicates central mechanisms, as peripheral fatigue mechanisms tend to impact upon both concentric and eccentric contractions modes. However, neural function of the hamstrings, such as the median power frequency (MPF) of the surface electromyography signal has yet to be examined in the fatigued hamstring following intermittent sprint running. AIM: To determine the impact of fatigue induced by intermittent sprinting on the MPF of the medial and lateral hamstring muscles. METHODS: Fifteen recreationally active males completed 18 × 20m overground sprints. Maximal strength (concentric and eccentric knee flexor and concentric knee extensor) was determined isokinetically at the velocities of ±180.s-1 and ±60.s- while hamstring muscle activation was assessed using surface electromyography, before and 15 minutes after the running protocol. RESULTS: Overground intermittent running caused a significant reduction in eccentric knee flexor strength (27.2 Nm; 95% CI = 11.2 to 43.3; p=0.0001) but not concentric strength (9.3 Nm; 95% CI = -6.7 to 25.3; P=0.6361). Following the overground running, MPF of the lateral hamstrings showed a significant decline eccentrically (0.86; 95% CI = 0.59 to 1.54; P=0.038) and concentrically (0.76; 95%CI = 0.66 to 0.83; P=0.039). Similar declines in MPF were also noted in the medial hamstrings eccentrically (1.54; 95% CI = 0.59 to 7.9; P=0.005) and concentrically (1.18; 95% CI = 0.44 to 6.8; P=0.040). CONCLUSION: Whilst sprint running induced fatigue led to a eccentric specific reduction in knee flexor torque, MPF was suppressed across both contraction modes. This would indicate that factors associated with the decline in MPF do not appear to explain the contraction mode-specific loss of strength after intermittent sprints. This would implicate other central mechanisms, such as declines in voluntary activation, in explaining the eccentric specific decline in strength seen following sprint running.

Malnutrition in a sample of community-dwelling people with Parkinson’s disease

Objective: Malnutrition results in poor health outcomes, and people with Parkinson’s disease may be more at risk of malnutrition. However, the prevalence of malnutrition in Parkinson’s disease is not yet well defined. The aim of this study is to provide an estimate of the extent of malnutrition in community-dwelling people with Parkinson’s disease. Methods: This is a cross-sectional study of people with Parkinson’s disease residing within a 2 hour driving radius of Brisbane, Australia. The Subjective Global Assessment (SGA) and scored Patient Generated Subjective Global Assessment (PG-SGA) were used to assess nutritional status. Body weight, standing or knee height, mid-arm circumference and waist circumference were measured. Results: Nineteen (15%) of the participants were moderately malnourished (SGA-B). The median PG-SGA score of the SGA-B group was 8 (4 – 15), significantly higher than the SGA-A group, U=1860.5,p<.05. The symptoms most influencing intake were loss of appetite, constipation, early satiety and problems swallowing. Conclusions: As with other populations, malnutrition remains under-recognised and undiagnosed in people with Parkinson’s disease. Regular screening of nutritional status in people with Parkinson’s disease by health professionals with whom they have regular contact should occur to identify those who may benefit from further nutrition assessment and intervention.

The Multidimensional Loss Scale : validating a cross cultural instrument for measuring loss in Burmese refugees

The Multidimensional Loss Scale: Initial Development and Psychometric Evaluation The Multidimensional Loss Scale (MLS) represents the first instrument designed specifically to measure loss in refugee populations. Researchers developed initial items of the Multidimensional Loss Scale to assess Experience of Loss Events and Loss Distress in a culturally sensitive manner across multiple domains (social, material, intra-personal and cultural). A sample of 70 recently settled Burmese adult refugees completed a battery of questionnaires, including new scale items. Analyses explored the scale’s factor structure, internal consistency, convergent validity and divergent validity. Principal Axis Factoring supported a five-factor model: Loss of Symbolic Self, Loss of Interdependence, Loss of Home, Interpersonal Loss, and Loss of Intrapersonal Integrity. Chronbach’s Alphas indicated satisfactory internal consistency for Experience of Loss Events (.85) and Loss Distress (.92). Convergent and divergent validity of Loss Distress were supported by moderate correlations with interpersonal grief and trauma symptoms and weak correlations with depression and anxiety. The new scale was well received by people from refugee backgrounds and shows promise for application in future research and practice

Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles

Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic approaches. As there is also an increasing body of evidence suggesting that successful lasting tissue reconstruction requires an implant that mimics natural tissue organization, it is imperative that depth-dependent characteristics of equine osteochondral tissue are known, to assess to what extent they resemble those in humans. Therefore, osteochondral cores (4-8 mm) were obtained from the medial and lateral femoral condyles of equine and human donors. Cores were processed for histology and for biochemical quantification of DNA, glycosaminoglycan (GAG) and collagen content. Equine and human osteochondral tissues possess similar geometrical (thickness) and organizational (GAG, collagen and DNA distribution with depth) features. These comparable trends further underscore the validity of the equine model for the evaluation of regenerative approaches for articular cartilage.

Non-invasive identification of proteoglycans and chondrocyte differentiation state by Raman microspectroscopy

Proteoglycans (PGs) are crucial extracellular matrix (ECM) components that are present in all tissues and organs. Pathological remodeling of these macromolecules can lead to severe diseases such as osteoarthritis or rheumatoid arthritis. To date, PG-associated ECM alterations are routinely diagnosed by invasive analytical methods. Here, we employed Raman microspectroscopy, a laser-based, marker-free and non-destructive technique that allows the generation of spectra with peaks originating from molecular vibrations within a sample, to identify specific Raman bands that can be assigned to PGs within human and porcine cartilage samples and chondrocytes. Based on the non-invasively acquired Raman spectra, we further revealed that a prolonged in vitro culture leads to phenotypic alterations of chondrocytes, resulting in a decreased PG synthesis rate and loss of lipid contents. Our results are the first to demonstrate the applicability of Raman microspectroscopy as an analytical and potential diagnostic tool for non-invasive cell and tissue state monitoring of cartilage in biomedical research. ((c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

A critical appraisal of responses to Maori offending

This article critically analyses the role that criminological theory and specific policy formulations of culture play in the New Zealand state’s response to the over-representation of Māori in the criminal justice system. Part one provides an overview of the changing criminological explanations of, and responses to, Māori offending in New Zealand from the 1980s onwards and how these understandings extended colonialist approaches to Māori and crime into the neo-colonial context. In particular, we chart the shift in policy development from theorising Māori offending as attributable to loss of cultural identity to a focus on socio-economic and institutional antecedents and, finally, through the risk factors, assessment, and criminogenic needs approaches that have gained prominence in the current policy context. In part two, the focus moves to the strategies employed by members of the academy to elevate their own epistemological constructions of Māori social reality within the policy development process. In particular, the critique scrutinises recent attempts to portray Indigenous responses to social harm as “unscientific” and, in part, responsible for the continuing over-representation of Māori in New Zealand’s criminal justice system. The purpose of this analysis is to focus the critical, criminological gaze firmly on the activities of policy makers and administrative criminologists, to examine how their policies and approaches impact on Māori as an Indigenous people.

At times of crisis, Twitter shines brightest

By any measure, 2011 was a year marked by disasters. In Australia, it began with major flooding which saw vast portions of the state of Queensland, including Brisbane and surrounding areas, under water. A significant earthquake caused massive destruction and serious loss of life in Christchurch, New Zealand. And a 9.0 quake off the Sendai coast caused an unprecedented tsunami in Japan and led to the Fukushima meltdown. All this before the end of March; later months would see a range of human-made crises from the Arab Spring to the London riots.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Full compensation no longer sacrosanct : reflections on the past and future economic loss ‘cap’ for high income earners

The civil liability provisions relating to the assessment of damages for past and future economic loss have abrogated the common law principle of full compensation by imposing restrictions on the damages award, most commonly by a “three times average weekly earnings” cap. This consideration of the impact of those provisions is informed by a case study of the Supreme Court of Victoria Court of Appeal decision, Tuohey v Freemasons Hospital (Tuohey) , which addressed the construction and arithmetic operation of the Victorian cap for high income earners. While conclusions as to operation of the cap outside of Victoria can be drawn from Tuohey, a number of issues await judicial determination. These issues, which include the impact of the damages caps on the calculation of damages for economic loss in the circumstances of fluctuating income; vicissitudes; contributory negligence; claims per quod servitum amisit; and claims by dependants, are identified and potential resolutions discussed.

Quantitative assessment of fault tolerant precision timing for electricity substations

Advanced substation applications, such as synchrophasors and IEC 61850-9-2 sampled value process buses, depend upon highly accurate synchronizing signals for correct operation. The IEEE 1588 Precision Timing Protocol (PTP) is the recommended means of providing precise timing for future substations. This paper presents a quantitative assessment of PTP reliability using Fault Tree Analysis. Two network topologies are proposed that use grandmaster clocks with dual network connections and take advantage of the Best Master Clock Algorithm (BMCA) from IEEE 1588. The cross-connected grandmaster topology doubles reliability, and the addition of a shared third grandmaster gives a nine-fold improvement over duplicated grandmasters. The performance of BMCA mediated handover of the grandmaster role during contingencies in the timing system was evaluated experimentally. The 1 µs performance requirement of sampled values and synchrophasors are met, even during network or GPS antenna outages. Slave clocks are shown to synchronize to the backup grandmaster in response to degraded performance or loss of the main grandmaster. Slave disturbances are less than 350 ns provided the grandmaster reference clocks are not offset from one another. A clear understanding of PTP reliability and the factors that affect availability will encourage the adoption of PTP for substation time synchronization.

Application of clustering technique to generating capacity state model for reliability evaluation

Capacity probability models of generating units are commonly used in many power system reliability studies, at hierarchical level one (HLI). Analytical modelling of a generating system with many units or generating units with many derated states in a system, can result in an extensive number of states in the capacity model. Limitations on available memory and computational time of present computer facilities can pose difficulties for assessment of such systems in many studies. A cluster procedure using the nearest centroid sorting method was used for IEEE-RTS load model. The application proved to be very effective in producing a highly similar model with substantially fewer states. This paper presents an extended application of the clustering method to include capacity probability representation. A series of sensitivity studies are illustrated using IEEE-RTS generating system and load models. The loss of load and energy expectations (LOLE, LOEE), are used as indicators to evaluate the application

Identification of copper species present in Cu-ZSM-5 catalysts for NOx reduction

The structure of Cu-ZSM-5 catalysts that show activity for direct NO decomposition and selective catalytic reduction of NOx by hydrocarbons has been investigated by a multitude of modern surface analysis and spectroscopy techniques including X-ray photoelectron spectroscopy, thermogravimetric analysis, and in situ Fourier transform infrared spectroscopy. A series of four catalysts were prepared by exchange of Na-ZSM-5 with dilute copper acetate, and the copper loading was controlled by variation of the solution pH. Underexchanged catalysts contained isolated Cu2+OH-(H2O) species and as the copper loading was increased Cu2+ ions incorporated into the zeolite lattice appeared. The sites at which the latter two copper species were located were fundamentally different. The Cu2+OH-(H2O) moieties were bound to two lattice oxygen ions and associated with one aluminum framework species. In contrast, the Cu2+ ions were probably bound to four lattice oxygen ions and associated with two framework aluminum ions. Once the Cu-ZSM-5 samples attained high levels of exchange, the development of [Cu(μ-OH)2Cu]n2+OH-(H2O) species along with a small concentration of Cu(OH)2 was observed. On activation in helium to 500°C the Cu2+OH-(H2O) species transformed into Cu2+O- and Cu+ moieties, whereas the Cu2+ ions were apparently unaffected by this treatment (apart from the loss of ligated water molecules). Calcination of the precursors resulted in the formation of Cu2+O2- and a one-dimensional CuO species. Temperature-programmed desorption studies revealed that oxygen was removed from the latter two species at 407 and 575°C, respectively. © 1999 Academic Press.

Abundance of Natural Riparian Forests and Tree Plantations in the Amudarya Delta of Uzbekistan and their impact on emissions of soil-borne greenhouse gases

Through a forest inventory in parts of the Amudarya river delta, Central Asia, we assessed the impact of ongoing forest degradation on the emissions of greenhouse gases (GHG) from soils. Interpretation of aerial photographs from 2001, combined with data on forest inventory in 1990 and field survey in 2003 provided comprehensive information about the extent and changes of the natural tugai riparian forests and tree plantations in the delta. The findings show an average annual deforestation rate of almost 1.3% and an even higher rate of land use change from tugai forests to land with only sparse tree cover. These annual rates of deforestation and forest degradation are higher than the global annual forest loss. By 2003, the tugai forest area had drastically decreased to about 60% compared to an inventory in 1990. Significant differences in soil GHG emissions between forest and agricultural land use underscore the impact of the ongoing land use change on the emission of soil-borne GHGs. The conversion of tugai forests into irrigated croplands will release 2.5 t CO2 equivalents per hectare per year due to elevated emissions of N2O and CH4. This demonstrates that the ongoing transformation of tugai forests into agricultural land-use systems did not only lead to a loss of biodiversity and of a unique ecosystem, but substantially impacts the biosphere-atmosphere exchange of GHG and soil C and N turnover processes.