The effect of cryotherapy on the vascular regeneration following closed soft tissue trauma

INTRODUCTION Icing (cryotherapy) is being widely used for the treatment of closed soft tissue trauma (CSTT), such as those resulting from sport injuries. It is believed that cryotherapy induces vasoconstriction and through this mechanism reduces inflammation [1]. However, the impact of this technique on the healing of impaired vasculature and muscle injuries following trauma remains controversial. Recent evidence suggests that the muscle regeneration is delayed after cryotherapy [2]. Consequently, we aimed to investigate the effect of cryotherapy on the vascular morphology following CSTT using an experimental model in rats by contrast-enhanced micro-CT imaging. METHODS Fifty four rats were divided into three main groups: control (no injury, n=6), sham (CSTT but no icing treatment, n=24) and icing (CSTT, treated with one session of ice block massaged directly on the injured muscle for 20 minutes, n=24). The CSTT was induced to the left thigh (Biceps Femoris) of anaesthetised rats (Male, Wistar) to create a standardized and reproducible vascular and muscle injury using an impact device [3]. Following trauma, animals were euthanized after 1, 3, 7, and 28 days healing time (n=6 for each time point). For a three-dimensional vascular morphological assessment, the blood vessels of euthanised rats were flushed with heparinised saline and then perfused with a radio-opaque contrast agent (Microfil, MV 122, Flowtech, USA) using an infusion pump. Both hind-limbs were dissected, and then the injured and non-injured limbs were imaged using a micro-CT scanner (µCT 40, Scanco Medical, Switzerland) and total volume of the perfused blood vessels (TVV) was calculated. More detailed morphological parameters such as vessel volume (VV), diameter (VD), spacing (VSp), number (VN) and connectivity (VConn) were quantified through high resolution (6 µm), micro-CT-scanned biopsy samples (diameter: 8mm) taken directly from the region of the injured muscles. The biopsies were then analysed histologically to confirm the results derived from contrast-enhanced micro-CT imaging. RESULTS AND DISCUSSION The TVV was significantly higher in the injured legs compared to the non-injured legs at day 1 and 7 in the sham group and at day 28 in both sham and icing groups. The biopsies from the injured legs of the icing group showed a significant reduction in VV, VN, VD, VConn and an increase in VSp compared to those in the sham and control groups at days 1, 3 and 7, post injury. While the injured legs of the sham group exhibited a decrease in VN and VConn 28 days post trauma, indicating a return to the original values prior to trauma, these parameters had increased in the icing group (Figure 1). Also, at day 1 post injury, VV and VD of the injured legs were significantly higher in the sham group compared to the icing group, which may be attributed to the effect of vasoconstriction induced by icing. Further histomorphological evaluation of day 1 post injury, indicated that although cryotherapy significantly reduced the injury size and influx of inflammatory cells, including macrophages and neutrophils, a delay in vascular and muscle fiber regeneration was found at later time points confirming other reports from the literature [2]. CONCLUSIONS We have demonstrated using micro-CT imaging that the vascular morphology changes after CSTT, and that its recovery is affected by therapeutic modalities such as icing. This may be useful for the development of future clinical monitoring, diagnosis and treatment of CSTT. While icing reduces the swelling after trauma, our results suggest that it may delay the recovery of the vasculature in the injured tissue.

Artemisinin induced dormancy in Plasmodium falciparum : duration, recovery rates and implications in treatment failure

Background Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Methods Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Results Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an ∼10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. Conclusions These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Relation between charge carrier mobility and lifetime in organic photovoltaics

The relationship between charge carrier lifetime and mobility in a bulk heterojunction based organic solar cell, utilizing diketopyrrolopyrole- naphthalene co-polymer and PC71BM in the photoactive blend layer, is investigated using the photoinduced charge extraction by linearly increasing voltage technique. Light intensity, delay time, and temperature dependent experiments are used to quantify the charge carrier mobility and density as well as the temperature dependence of both. From the saturation of photoinduced current at high laser intensities, it is shown that Langevin-type bimolecular recombination is present in the studied system. The charge carrier lifetime, especially in Langevin systems, is discussed to be an ambiguous and unreliable parameter to determine the performance of organic solar cells, because of the dependence of charge carrier lifetime on charge carrier density, mobility, and type of recombination. It is revealed that the relation between charge mobility (μ) and lifetime (τ) is inversely proportional, where the μτ product is independent of temperature. The results indicate that in photovoltaic systems with Langevin type bimolecular recombination, the strategies to increase the charge lifetime might not be beneficial because of an accompanying reduction in charge carrier mobility. Instead, the focus on non-Langevin mechanisms of recombination is crucial, because this allows an increase in the charge extraction rate by improving the carrier lifetime, density, and mobility simultaneously. © 2013 AIP Publishing LLC.

Australian patent enforcement : a proposal for an expert panel opinion

The Australian Government has been concerned “to find ways of making patent enforcement less of an issue” and to make it “cheaper, simpler and quicker to get fair and appropriate resolution for any dispute”. Major problems relating to patent enforcement in Australia have been identified as: the cost of legal proceedings; the lack of patent owners’ financial capacity to fund enforcement proceedings; delay; and uncertainty as to the outcome and lack of knowledge about the processes of enforcement. This paper considers some of the problems associated with patent enforcement in Australia and proposes an approach to patent litigation which is directed at alleviating some of the difficulties which have been identified. Specifically, it proposes a strategy designed to identify the parties’ risks at an early stage of patent litigation proceeding and facilitate an early resolution of the dispute.

Equity in Australian estate litigation

Equitable claims are increasingly arising in Australian estate litigation, particularly in conjunction with family provision applications. Since the leading decision in Bridgewater v Leahy, in addition to undue influence and unconscionable bargain claims, actions based on equitable estoppel, constructive and resulting trusts, breach of fiduciary duty, and breach of legislative duties that mirror equitable obligations are increasingly being brought in contemporary estate litigation. Such litigation often raises challenging issues for claimants, including evidentiary hurdles and allegations of undue delay, especially when claims are made post-mortem in relation to inter vivos dealings with property. Accordingly, solicitors need to ensure that they fully understand the nature and potential application of equitable claims in estate litigation, or face the prospect of incurring liability to clients for professional negligence. This article explores recent trends in Australian estate litigation involving equitable claims.

Factors affecting new project delays in Saudi Arabian manufacturing organisations

Delay in the delivery of manufacturing projects is a major problem in manufacturing industries. This research investigates the factors that influence the lead time of new projects in manufacturing organisations. Employing a questionnaire survey and interview methodologies, this study collected data from five leading manufacturing organisations as well as their suppliers and contractors in Saudi Arabia to examine what, how and why the new project implementation delay occurs. Results show that the main factors contributing to manufacturing delays are related to people and material. On the other hand, social, political and cultural factors were the least significant factors as per the outcome of this study. Views of manufacturers, suppliers and contractors regarding causes of delays have also been analysed.

A national satellite-based land-use regression model for air pollution exposure assessment in Australia

Land-use regression (LUR) is a technique that can improve the accuracy of air pollution exposure assessment in epidemiological studies. Most LUR models are developed for single cities, which places limitations on their applicability to other locations. We sought to develop a model to predict nitrogen dioxide (NO2) concentrations with national coverage of Australia by using satellite observations of tropospheric NO2 columns combined with other predictor variables. We used a generalised estimating equation (GEE) model to predict annual and monthly average ambient NO2 concentrations measured by a national monitoring network from 2006 through 2011. The best annual model explained 81% of spatial variation in NO2 (absolute RMS error=1.4 ppb), while the best monthly model explained 76% (absolute RMS error=1.9 ppb). We applied our models to predict NO2 concentrations at the ~350,000 census mesh blocks across the country (a mesh block is the smallest spatial unit in the Australian census). National population-weighted average concentrations ranged from 7.3 ppb (2006) to 6.3 ppb (2011). We found that a simple approach using tropospheric NO2 column data yielded models with slightly better predictive ability than those produced using a more involved approach that required simulation of surface-to-column ratios. The models were capable of capturing within-urban variability in NO2, and offer the ability to estimate ambient NO2 concentrations at monthly and annual time scales across Australia from 2006–2011. We are making our model predictions freely available for research.

Stop-signal task difficulty and the right inferior frontal gyrus

The stop-signal paradigm is increasingly being used as a probe of response inhibition in basic and clinical neuroimaging research. The critical feature of this task is that a cued response is countermanded by a secondary ‘stop-signal’ stimulus offset from the first by a ‘stop-signal delay’. Here we explored the role of task difficulty in the stop-signal task with the hypothesis that what is critical for successful inhibition is the time available for stopping, that we define as the difference between stop-signal onset and the expected response time (approximated by reaction time from previous trial). We also used functional magnetic resonance imaging (fMRI) to examine how the time available for stopping affects activity in the putative right inferior frontal gyrus and presupplementary motor area (right IFG-preSMA) network that is known to support stopping. While undergoing fMRI scanning, participants performed a stop-signal variant where the time available for stopping was kept approximately constant across participants, which enabled us to compare how the time available for stopping affected stop-signal task difficulty both within and between subjects. Importantly, all behavioural and neuroimaging data were consistent with previous findings. We found that the time available for stopping distinguished successful from unsuccessful inhibition trials, was independent of stop-signal delay, and affected successful inhibition depending upon individual SSRT. We also found that right IFG and adjacent anterior insula were more strongly activated during more difficult stopping. These findings may have critical implications for stop-signal studies that compare different patient or other groups using fixed stop-signal delays.

Choice impulsivity: Definitions, measurement issues, and clinical implications

Background Impulsivity critically relates to many psychiatric disorders. Given the multifaceted construct that impulsivity represents, defining core aspects of impulsivity is vital for the assessment and understanding of clinical conditions. Choice impulsivity (CI), involving the preferential selection of smaller sooner rewards over larger later rewards, represents one important type of impulsivity. Method The International Society for Research on Impulsivity (InSRI) convened to discuss the definition and assessment of CI and provide recommendations regarding measurement across species. Results Commonly used preclinical and clinical CI behavioral tasks are described, and considerations for each task are provided to guide CI task selection. Differences in assessment of CI (self-report, behavioral) and calculating CI indices (e.g., area-under-the-curve, indifference point, steepness of discounting curve) are discussed along with properties of specific behavioral tasks used in preclinical and clinical settings. Conclusions The InSRI group recommends inclusion of measures of CI in human studies examining impulsivity. Animal studies examining impulsivity should also include assessments of CI and these measures should be harmonized in accordance with human studies of the disorders being modeled in the preclinical investigations. The choice of specific CI measures to be included should be based on the goals of the study and existing preclinical and clinical literature using established CI measures.

Supine to standing Cobb angle change in idiopathic scoliosis : the effect of endplate pre-selection

Background Supine imaging modalities provide valuable 3D information on scoliotic anatomy, but the altered spine geometry between the supine and standing positions affects the Cobb angle measurement. Previous studies report a mean 7°-10° Cobb angle increase from supine to standing, but none have reported the effect of endplate pre-selection or whether other parameters affect this Cobb angle difference. Methods Cobb angles from existing coronal radiographs were compared to those on existing low-dose CT scans taken within three months of the reference radiograph for a group of females with adolescent idiopathic scoliosis. Reformatted coronal CT images were used to measure supine Cobb angles with and without endplate pre-selection (end-plates selected from the radiographs) by two observers on three separate occasions. Inter and intra-observer measurement variability were assessed. Multi-linear regression was used to investigate whether there was a relationship between supine to standing Cobb angle change and eight variables: patient age, mass, standing Cobb angle, Risser sign, ligament laxity, Lenke type, fulcrum flexibility and time delay between radiograph and CT scan. Results Fifty-two patients with right thoracic Lenke Type 1 curves and mean age 14.6 years (SD 1.8) were included. The mean Cobb angle on standing radiographs was 51.9° (SD 6.7). The mean Cobb angle on supine CT images without pre-selection of endplates was 41.1° (SD 6.4). The mean Cobb angle on supine CT images with endplate pre-selection was 40.5° (SD 6.6). Pre-selecting vertebral endplates increased the mean Cobb change by 0.6° (SD 2.3, range −9° to 6°). When free to do so, observers chose different levels for the end vertebrae in 39% of cases. Multi-linear regression revealed a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility (p = 0.001), age (p = 0.027) and standing Cobb angle (p < 0.001). The 95% confidence intervals for intra-observer and inter-observer measurement variability were 3.1° and 3.6°, respectively. Conclusions Pre-selecting vertebral endplates causes minor changes to the mean supine to standing Cobb change. There is a statistically significant relationship between supine to standing Cobb change and fulcrum flexibility such that this difference can be considered a potential alternative measure of spinal flexibility.

The defence of hardship to specific performance actions

The decision of Evans v Robcorp Pty Ltd[2014] QSC 26 is of interest as being an instance where the defence of hardship, in this case, financial hardship, was successfully pleaded in defence to a summary application for specific performance of a contract for the sale of land. Equity has always recognised the defence of hardship in response to an action for specific performance which, as an equitable remedy, might be refused in the discretion of the Court (Hewett v Court (1983) 149 CLR 639 at 664). However, whilst the remedy is discretionary, there are certain accepted principles which have guided the courts in their application of this defence to particular facts. It is not a blanket defence to a claim for specific performance where the buyer simply does not have the funds to complete the contract at the time when settlement is called for. Occasionally, a radical change in, say for instance, the health of the defendant between contract and completion, perhaps coupled with a long delay by a seller in calling for completion not being the fault of the buyer might enliven the defence (Patel v Ali [1984]1 Ch 283)

Levels and trends of PBDEs and HBCDs in the global environment : status at the end of 2012

In this paper, we have compiled and reviewed the most recent literature, published from January2010 to December 2012, relating to the human exposure, environmental distribution, behaviour, fate and concentration time trends of polybrominated diphenyl ether (PBDE) and hexabromocyclododecane (HBCD) flame retardants, in order to establish their current trends and priorities for future study. Due to the large volume of literature included, we have provided full detail of the reviewed studies as Electronic Supplementary Information and here summarise the most relevant findings. Decreasing time trends for penta-mix PBDE congeners were seen for soils in northern Europe, sewage sludge in Sweden and the USA, carp from a US river, trout from three of the Great Lakes and in Arctic and UK marine mammals and many birds, but increasing time trends continue in Arctic polar bears and some birds at high trophic levels in northern Europe. This is a result of the time delay inherent in long-range atmospheric transport processes. In general, concentrations of BDE209 (the major component of the deca-mix PBDE product) are continuing to increase. Of major concern is the possible/likely debromination of the large reservoir of BDE209 in soils and sediments worldwide, to yield lower brominated congeners which are both more mobile and more toxic, and we have compiled the most recent evidence for the occurrence of this degradation process. Numerous studies reported here reinforce the importance o f this future concern. Time trends for HBCDs are mixed, with both increases and decreases evident in different matrices and locations and, notably, with increasing occurrence in birds of prey.

Graduated driver licensing : an international review

Graduated driver licensing (GDL) aims to gradually increase the exposure of new drivers to more complex driving situations and typically consists of learner, provisional and open licence phases. The first phase, the learner licence, is designed to allow novice drivers to obtain practical driving experience in lower risk situations. The learner licence can delay licensure, encourage novice drivers to learn under supervision, mandate the number of hours of practice required to progress to the next phase and encourage parental involvement. The second phase, the provisional licence, establishes various driving restrictions and thereby reduces exposure to situations of higher risk, such as driving at night, with passengers or after drinking alcohol. Parental involvement with a GDL system appears essential in helping novices obtain sufficient practice and in enforcing compliance with restrictions once the new driver obtains a provisional licence. Given the significant number of young drivers involved in crashes within Oman, GDL is one countermeasure that may be beneficial in reducing crash risk and involvement for this group.

Performance profiling for predictive train schedules

In this article an alternate sensitivity analysis is proposed for train schedules. It characterises the schedules robustness or lack thereof and provides unique profiles of performance for different sources of delay and for different values of delay. An approach like this is necessary because train schedules are only a prediction of what will actually happen. They can perform poorly with respect to a variety of performance metrics, when deviations and other delays occur, if for instance they can even be implemented, and as originally intended. The information provided by this analytical approach is beneficial because it can be used as part of a proactive scheduling approach to alter a schedule in advance or to identify suitable courses of action for specific “bad behaviour”. Furthermore this information may be used to quantify the cost of delay. The effect of sectional running time (SRT) deviations and additional dwell time in particular were quantified for three railway schedule performance measures. The key features of this approach were demonstrated in a case study.

Old mastheads and new media : newspapers striving to adapt in Australia and South-east Asia

As a key element in their response to new media forcing transformations in mass media and media use, newspapers have deployed various strategies to not only establish online and mobile products, and develop healthy business plans, but to set out to be dominant portals. Their response to change was the subject of an early investigation by one of the present authors (Keshvani 2000). That was part of a set of short studies inquiring into what impact new software applications and digital convergence might have on journalism practice (Tickle and Keshvani 2000), and also looking for demonstrations of the way that innovations, technologies and protocols then under development might produce a “wireless, streamlined electronic news production process (Tickle and Keshvani 2001).” The newspaper study compared the online products of The Age in Melbourne and the Straits Times in Singapore. It provided an audit of the Singapore and Australia Information and Communications Technology (ICT) climate concentrating on the state of development of carrier networks, as a determining factor in the potential strength of the two services with their respective markets. In the outcome, contrary to initial expectations, the early cable roll-out and extensive ‘wiring’ of the city in Singapore had not produced a level of uptake of Internet services as strong as that achieved in Melbourne by more ad hoc and varied strategies. By interpretation, while news websites and online content were at an early stage of development everywhere, and much the same as one another, no determining structural imbalance existed to separate these leading media participants in Australia and South-east Asia. The present research revisits that situation, by again studying the online editions of the two large newspapers in the original study, and one other, The Courier Mail, (recognising the diversification of types of product in this field, by including it as a representative of Newscorp, now a major participant). The inquiry works through the principle of comparison. It is an exercise in qualitative, empirical research that establishes a comparison between the situation in 2000 as described in the earlier work, and the situation in 2014, after a decade of intense development in digital technology affecting the media industries. It is in that sense a follow-up study on the earlier work, although this time giving emphasis to content and style of the actual products as experienced by their users. It compares the online and print editions of each of these three newspapers; then the three mastheads as print and online entities, among themselves; and finally it compares one against the other two, as representing a South-east Asian model and Australian models. This exercise is accompanied by a review of literature on the developments in ICT affecting media production and media organisations, to establish the changed context. The new study of the online editions is conducted as a systematic appraisal of the first level, or principal screens, of the three publications, over the course of six days (10-15.2.14 inclusive). For this, categories for analysis were made, through conducting a preliminary examination of the products over three days in the week before. That process identified significant elements of media production, such as: variegated sourcing of materials; randomness in the presentation of items; differential production values among media platforms considered, whether text, video or stills images; the occasional repurposing and repackaging of top news stories of the day and the presence of standard news values – once again drawn out of the trial ‘bundle’ of journalistic items. Reduced in this way the online artefacts become comparable with the companion print editions from the same days. The categories devised and then used in the appraisal of the online products have been adapted to print, to give the closest match of sets of variables. This device, to study the two sets of publications on like standards -- essentially production values and news values—has enabled the comparisons to be made. This comparing of the online and print editions of each of the three publications was set up as up the first step in the investigation. In recognition of the nature of the artefacts, as ones that carry very diverse information by subject and level of depth, and involve heavy creative investment in the formulation and presentation of the information; the assessment also includes an open section for interpreting and commenting on main points of comparison. This takes the form of a field for text, for the insertion of notes, in the table employed for summarising the features of each product, for each day. When the sets of comparisons as outlined above are noted, the process then becomes interpretative, guided by the notion of change. In the context of changing media technology and publication processes, what substantive alterations have taken place, in the overall effort of news organisations in the print and online fields since 2001; and in their print and online products separately? Have they diverged or continued along similar lines? The remaining task is to begin to make inferences from that. Will the examination of findings enforce the proposition that a review of the earlier study, and a forensic review of new models, does provide evidence of the character and content of change --especially change in journalistic products and practice? Will it permit an authoritative description on of the essentials of such change in products and practice? Will it permit generalisation, and provide a reliable base for discussion of the implications of change, and future prospects? Preliminary observations suggest a more dynamic and diversified product has been developed in Singapore, well themed, obviously sustained by public commitment and habituation to diversified online and mobile media services. The Australian products suggest a concentrated corporate and journalistic effort and deployment of resources, with a strong market focus, but less settled and ordered, and showing signs of limitations imposed by the delay in establishing a uniform, large broadband network. The scope of the study is limited. It is intended to test, and take advantage of the original study as evidentiary material from the early days of newspaper companies’ experimentation with online formats. Both are small studies. The key opportunity for discovery lies in the ‘time capsule’ factor; the availability of well-gathered and processed information on major newspaper company production, at the threshold of a transformational decade of change in their industry. The comparison stands to identify key changes. It should also be useful as a reference for further inquiries of the same kind that might be made, and for monitoring of the situation in regard to newspaper portals on line, into the future.