Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Diurnal variation of corneal shape and thickness

Purpose: To investigate associations between the diurnal variation in a range of corneal parameters, including anterior and posterior corneal topography, and regional corneal thickness. ----- Methods: Fifteen subjects had their corneas measured using a rotating Scheimpflug camera (Pentacam) every 3-7 hours over a 24-hour period. Anterior and posterior corneal axial curvature, pachymetry and anterior chamber depth were analysed. The best fitting corneal sphero-cylinder from the axial curvature, and the average corneal thickness for a series of different corneal regions were calculated. Intraocular pressure and axial length were also measured at each measurement session. Repeated measures ANOVA were used to investigate diurnal change in these parameters. Analysis of covariance was used to examine associations between the measured ocular parameters. ----- Results: Significant diurnal variation was found to occur in both the anterior and posterior corneal curvature and in the regional corneal thickness. Flattening of the anterior corneal best sphere was observed at the early morning measurement (p < 0.0001). The posterior cornea also underwent a significant steepening (p < 0.0001) and change in astigmatism 90/180° at this time. A significant swelling of the cornea (p < 0.0001) was also found to occur immediately after waking. Highly significant associations were found between the diurnal variation in corneal thickness and the changes in corneal curvature. ----- Conclusions: Significant diurnal variation occurs in the regional thickness and the shape of the anterior and posterior cornea. The largest changes in the cornea were typically evident upon waking. The observed non-uniform regional corneal thickness changes resulted in a steepening of the posterior cornea, and a flattening of the anterior cornea to occur at this time.

Making the processes of designing explicit within an information technology environment

In this paper, technology is described as involving processes whereby resources are utilised to satisfy human needs or to take advantage of opportunities, to develop practical solutions to problems. This study, set within one type of technology context, information technology, investigated how, through a one semester undergraduate university course, elements of technological processes were made explicit to students. While it was acknowledged in the development and implementation of this course that students needed to learn technical skills, technological skills and knowledge, including design, were seen as vital also, to enable students to think about information technology from a perspective that was not confined and limited to `technology as hardware and software'. This paper describes how the course, set within a three year program of study, was aimed at helping students to develop their thinking and their knowledge about design processes in an explicit way. An interpretive research approach was used and data sources included a repertory grid `survey'; student interviews; video recordings of classroom interactions, audio recordings of lectures, observations of classroom interactions made by researchers; and artefacts which included students' journals and portfolios. The development of students' knowledge about design practices is discussed and reflections upon student knowledge development in conjunction with their learning experiences are made. Implications for ensuring explicitness of design practice within information technology contexts are presented, and the need to identify what constitutes design knowledge is argued.

Ultrasonic measurement of fine head movements in a standard ophthalmic headrest

We aimed to investigate the naturally occurring horizontal plane movements of a head stabilized in a standard ophthalmic headrest and to analyze their magnitude, velocity, spectral characteristics, and correlation to the cardio pulmonary system. Two custom-made air-coupled highly accurate (±2 μm)ultrasound transducers were used to measure the displacements of the head in different horizontal directions with a sampling frequency of 100 Hz. Synchronously to the head movements, an electrocardiogram (ECG) signal was recorded. Three healthy subjects participated in the study. Frequency analysis of the recorded head movements and their velocities was carried out, and functions of coherence between the two displacements and the ECG signal were calculated. Frequency of respiration and the heartbeat were clearly visible in all recorded head movements. The amplitude of head displacements was typically in the range of ±100 μm. The first harmonic of the heartbeat (in the range of 2–3 Hz), rather than its principal frequency, was found to be the dominant frequency of both head movements and their velocities. Coherence analysis showed high interdependence between the considered signals for frequencies of up to 20 Hz. These findings may contribute to the design of better ophthalmic headrests and should help other studies in the decision making of whether to use a heavy headrest or a bite bar.

Mathematical modelling of muscle recruitment and function in the lumbar spine

Low back pain is an increasing problem in industrialised countries and although it is a major socio-economic problem in terms of medical costs and lost productivity, relatively little is known about the processes underlying the development of the condition. This is in part due to the complex interactions between bone, muscle, nerves and other soft tissues of the spine, and the fact that direct observation and/or measurement of the human spine is not possible using non-invasive techniques. Biomechanical models have been used extensively to estimate the forces and moments experienced by the spine. These models provide a means of estimating the internal parameters which can not be measured directly. However, application of most of the models currently available is restricted to tasks resembling those for which the model was designed due to the simplified representation of the anatomy. The aim of this research was to develop a biomechanical model to investigate the changes in forces and moments which are induced by muscle injury. In order to accurately simulate muscle injuries a detailed quasi-static three dimensional model representing the anatomy of the lumbar spine was developed. This model includes the nine major force generating muscles of the region (erector spinae, comprising the longissimus thoracis and iliocostalis lumborum; multifidus; quadratus lumborum; latissimus dorsi; transverse abdominis; internal oblique and external oblique), as well as the thoracolumbar fascia through which the transverse abdominis and parts of the internal oblique and latissimus dorsi muscles attach to the spine. The muscles included in the model have been represented using 170 muscle fascicles each having their own force generating characteristics and lines of action. Particular attention has been paid to ensuring the muscle lines of action are anatomically realistic, particularly for muscles which have broad attachments (e.g. internal and external obliques), muscles which attach to the spine via the thoracolumbar fascia (e.g. transverse abdominis), and muscles whose paths are altered by bony constraints such as the rib cage (e.g. iliocostalis lumborum pars thoracis and parts of the longissimus thoracis pars thoracis). In this endeavour, a separate sub-model which accounts for the shape of the torso by modelling it as a series of ellipses has been developed to model the lines of action of the oblique muscles. Likewise, a separate sub-model of the thoracolumbar fascia has also been developed which accounts for the middle and posterior layers of the fascia, and ensures that the line of action of the posterior layer is related to the size and shape of the erector spinae muscle. Published muscle activation data are used to enable the model to predict the maximum forces and moments that may be generated by the muscles. These predictions are validated against published experimental studies reporting maximum isometric moments for a variety of exertions. The model performs well for fiexion, extension and lateral bend exertions, but underpredicts the axial twist moments that may be developed. This discrepancy is most likely the result of differences between the experimental methodology and the modelled task. The application of the model is illustrated using examples of muscle injuries created by surgical procedures. The three examples used represent a posterior surgical approach to the spine, an anterior approach to the spine and uni-lateral total hip replacement surgery. Although the three examples simulate different muscle injuries, all demonstrate the production of significant asymmetrical moments and/or reduced joint compression following surgical intervention. This result has implications for patient rehabilitation and the potential for further injury to the spine. The development and application of the model has highlighted a number of areas where current knowledge is deficient. These include muscle activation levels for tasks in postures other than upright standing, changes in spinal kinematics following surgical procedures such as spinal fusion or fixation, and a general lack of understanding of how the body adjusts to muscle injuries with respect to muscle activation patterns and levels, rate of recovery from temporary injuries and compensatory actions by other muscles. Thus the comprehensive and innovative anatomical model which has been developed not only provides a tool to predict the forces and moments experienced by the intervertebral joints of the spine, but also highlights areas where further clinical research is required.

ePortfolios and preservice teachers : governing at a distance through non-human actors

This chapter seeks to develop an analysis of the contemporary use of the ePortfolio (Electronic Portfolio) in education practices. Unlike other explorations of this new technology which are deterministic in their approach, the authors seek to reveal the techniques and practices of government which underpin the implementation of the e-portfolio. By interrogating a specific case study example from a large Australian university’s preservice teacher program, the authors find that the e-portfolio is represented as eLearning technology but serves to govern students via autonomization and self responsibilization. Using policy data and other key documents, they are able to reveal the e-portfolio as a delegated authority in the governance of preservice teachers. However, despite this ongoing trend, they suggest that like other practices of government, the e-portfolio will eventually fail. This however the authors conclude opens up space for critical thought and engagement which is not afforded presently.

Effect of optical aberrations on the colour appearance of small lights

Purpose: Small red lights (one minute of arc or less) change colour appearance with positive defocus. We investigated the influence of longitudinal chromatic aberration and monochromatic aberrations on the colour appearance of small narrow band lights. Methods: Seven cyclopleged, trichromatic observers viewed a small light (one minute of arc, λmax = 510, 532, 550, 589, 620, 628 nm, approximately 19 per cent Weber contrast) centred within a black annulus (4.5 minutes of arc) and surrounded by a uniform white field (2,170 cd/m2). Pupil size was four millimetres. An optical trombone varied focus. Longitudinal chromatic aberration was controlled with a two component Powell achromatising lens that neutralises the eye’s chromatic aberration; a doublet that doubles and a triplet that reverses the eye’s chromatic aberration. Astigmatism and higher order monochromatic aberrations were corrected using adaptive optics. Results: Observers reported a change in appearance of the small red light (628 nm) without the Powell lens at +0.49 ± 0.21 D defocus and with the doublet at +0.62 ± 0.16 D. Appearance did not alter with the Powell lens, and five of seven observers reported the phenomenon with the triplet for negative defocus (-0.80 ± 0.47 D). Correction of aberrations did not significantly affect the magnitude at which the appearance of the red light changed (+0.44 ± 0.18 D without correction; +0.46 ± 0.16 D with correction). The change in colour appearance with defocus extended to other wavelengths (λmax = 510 to 620 nm), with directions of effects being reversed for short wavelengths relative to long wavelengths. Conclusions: Longitudinal chromatic aberrations but not monochromatic aberrations are involved in changing the appearance of small lights with defocus.

A new definition for today’s Chinese independent cinema

Different terminologies have been used to characterize the Chinese independent cinema in the 1990s. These definitions focus on the experimental practices outside the official production system and independent of official ideology. The film industry has had distinctive development since the entry of WTO in 2001. Private investors have played essential role in cinematic economy; strict censorship has been obviously relaxed; the film industry is being divided into two opposing extremes. Thus, it is necessary to give a new definition of the Chinese independent cinema. The definition of independent cinema in today China I suggest in the light of American independence is that any film that has not been financed, produced and distributed by majors is independent. At least four corporations are majors in the Chinese film industry. They are China Film Group Corporation, Huayi Brothers Corporation, PolyBona Film Distribution Corporation and Shanghai Film Group Corporation. Except the four majors, all the other film production or distribution companies are independents.

The role of the teacher

This chapter introduces principles of methodology in TESOL, and provides an overview of issues learners of a second language may have

A prospective study of personality features predictive of early adolescent alcohol misuse

Personality factors implicated in alcohol misuse have been extensively investigated in adult populations. Fewer studies have clarified the robustness of personality dimensions in predicting early onset alcohol misuse in adolescence. The aim of this study was to examine the predictive utility of two prominent models of personality (Cloninger, 1987; Eysenck & Eysenck, 1975) in emergent alcohol misuse in adolescence. One hundred and 92 secondary school students (mean age = 13.8 years, SD = 0.5) were administered measures of personality (Revised Junior Eysenck Personality Questionnaire – abbreviated; Temperament scale of Junior Temperament and Character Inventory) and drinking behavior (quantity and frequency of consumption, Alcohol Use Disorders Identification Test) at Time 1. At 12-month follow-up, 170 students (88.5%) were retained. Hierarchical multiple regressions revealed the dimensions of psychoticism, extraversion, and Novelty-Seeking to be the most powerful predictors of future alcohol misuse in adolescents. Results provide support for the etiological relevance of these dimensions in the development of early onset alcohol misuse. Findings can be used to develop early intervention programs that target personality risk factors for alcohol misuse in high-risk youth.