Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Stability analysis based on birfurcation theory of the DSTATCOM operating in current control mode

This paper presents the stability analysis for a distribution static compensator (DSTATCOM) that operates in current control mode based on bifurcation theory. Bifurcations delimit the operating zones of nonlinear circuits and, hence, the capability to compute these bifurcations is of important interest for practical design. A control design for the DSTATCOM is proposed. Along with this control, a suitable mathematical representation of the DSTATCOM is proposed to carry out the bifurcation analysis efficiently. The stability regions in the Thevenin equivalent plane are computed for different power factors at the point of common coupling. In addition, the stability regions in the control gain space, as well as the contour lines for different Floquet multipliers are computed. It is demonstrated through bifurcation analysis that the loss of stability in the DSTATCOM is due to the emergence of a Neimark bifurcation. The observations are verified through simulation studies.

Development of accident modification factors on intersection crash maneuvers

In order to estimate the safety impact of roadway interventions engineers need to collect, analyze, and interpret the results of carefully implemented data collection efforts. The intent of these studies is to develop Accident Modification Factors (AMF's), which are used to predict the safety impact of various road safety features at other locations or in upon future enhancements. Models are typically estimated to estimate AMF's for total crashes, but can and should be estimated for crash outcomes as well. This paper first describes data collected with the intent estimate AMF's for rural intersections in the state of Georgia within the United Sates. Modeling results of crash prediction models for the crash outcomes: angle, head-on, rear-end, sideswipe (same direction and opposite direction) and pedestrian-involved crashes are then presented and discussed. The analysis reveals that factors such as the Annual Average Daily Traffic (AADT), the presence of turning lanes, and the number of driveways have a positive association with each type of crash, while the median width and the presence of lighting are negatively associated with crashes. The model covariates are related to crash outcome in different ways, suggesting that crash outcomes are associated with different pre-crash conditions.

Safety-restraint use rate as function of law enforcement and other factors : preliminary analysis

Persistent use of safety restraints prevents deaths and reduces the severity and number of injuries resulting from motor vehicle crashes. However, safety-restraint use rates in the United States have been below those of other nations with safety-restraint enforcement laws. With a better understanding of the relationship between safety-restraint law enforcement and safety-restraint use, programs can be implemented to decrease the number of deaths and injuries resulting from motor vehicle crashes. Does safety-restraint use increase as enforcement increases? Do motorists increase their safety-restraint use in response to the general presence of law enforcement or to targeted law enforcement efforts? Does a relationship between enforcement and restraint use exist at the countywide level? A logistic regression model was estimated by using county-level safety-restraint use data and traffic citation statistics collected in 13 counties within the state of Florida in 1997. The model results suggest that safety-restraint use is positively correlated with enforcement intensity, is negatively correlated with safety-restraint enforcement coverage (in lanemiles of enforcement coverage), and is greater in urban than rural areas. The quantification of these relationships may assist Florida and other law enforcement agencies in raising safety-restraint use rates by allocating limited funds more efficiently either by allocating additional time for enforcement activities of the existing force or by increasing enforcement staff. In addition, the research supports a commonsense notion that enforcement activities do result in behavioral response.

Conducting statistical tests of hypotheses : five common misconceptions found in transportation research

Most statistical methods use hypothesis testing. Analysis of variance, regression, discrete choice models, contingency tables, and other analysis methods commonly used in transportation research share hypothesis testing as the means of making inferences about the population of interest. Despite the fact that hypothesis testing has been a cornerstone of empirical research for many years, various aspects of hypothesis tests commonly are incorrectly applied, misinterpreted, and ignored—by novices and expert researchers alike. On initial glance, hypothesis testing appears straightforward: develop the null and alternative hypotheses, compute the test statistic to compare to a standard distribution, estimate the probability of rejecting the null hypothesis, and then make claims about the importance of the finding. This is an oversimplification of the process of hypothesis testing. Hypothesis testing as applied in empirical research is examined here. The reader is assumed to have a basic knowledge of the role of hypothesis testing in various statistical methods. Through the use of an example, the mechanics of hypothesis testing is first reviewed. Then, five precautions surrounding the use and interpretation of hypothesis tests are developed; examples of each are provided to demonstrate how errors are made, and solutions are identified so similar errors can be avoided. Remedies are provided for common errors, and conclusions are drawn on how to use the results of this paper to improve the conduct of empirical research in transportation.

Single nucleotide polymorphism (SNP) - genotyping of Community Acquired Methicillin-Resistant Staphylococcus aureus, including the subtyping of PVL toxin producers using Real-Time PCR

Staphylococcus aureus is a common pathogen that causes a variety of infections including soft tissue infections, impetigo, septicemia toxic shock and scalded skin syndrome. Traditionally, Methicillin-Resistant Staphylococcus aureus (MRSA) was considered a Hospital-Acquired (HA) infection. It is now recognised that the frequency of infections with MRSA is increasing in the community, and that these infections are not originating from hospital environments. A 2007 report by the Centers for Disease Control and Prevention (CDC) stated that Staphylococcus aureus is the most important cause of serious and fatal infections in the USA. Community-Acquired MRSA (CA-MRSA) are genetically diverse and distinct, meaning they are able to be identified and tracked by way of genotyping. Genotyping of MRSA using Single nucleotide polymorphisms (SNPs) is a rapid and robust method for monitoring MRSA, specifically ST93 (Queensland Clone) dissemination in the community. It has been shown that a large proportion of CA-MRSA infections in Queensland and New South Wales are caused by ST93. The rationale for this project was that SNP analysis of MLST genes is a rapid and cost-effective method for genotyping and monitoring MRSA dissemination in the community. In this study, 16 different sequence types (ST) were identified with 41% of isolates identified as ST93 making it the predominate clone. Males and Females were infected equally with an average patient age of 45yrs. Phenotypically, all of the ST93 had an identical antimicrobial resistance pattern. They were resistant to the β-lactams – Penicillin, Flu(di)cloxacillin and Cephalothin but sensitive to all other antibiotics tested. Virulence factors play an important role in allowing S. aureus to cause disease by way of colonising, replication and damage to the host. One virulence factor of particular interest is the toxin Panton-Valentine leukocidin (PVL), which is composed of two separate proteins encoded by two adjacent genes. PVL positive CA-MRSA are shown to cause recurrent, chronic or severe skin and soft tissue infections. As a result, it is important that PVL positive CA-MRSA is genotyped and tracked. Especially now that CA-MRSA infections are more prevalent than HA-MRSA infections and are now deemed endemic in Australia. 98% of all isolates in this study tested positive for the PVL toxin gene. This study showed that PVL is present in many different community based ST, not just ST93, which were all PVL positive. With this toxin becoming entrenched in CA-MRSA, genotyping would provide more accurate data and a way of tracking the dissemination. PVL gene can be sub-typed using an allele-specific Real-Time PCR (RT-PCR) followed by High resolution meltanalysis. This allows the identification of PVL subtypes within the CA-MRSA population and allow the tracking of these clones in the community.

Work-related driving safety in light vehicle fleets : a review of past research and the development of an intervention framework

This paper presents a critical review of past research in the work-related driving field in light vehicle fleets (e.g., vehicles < 4.5 tonnes) and an intervention framework that provides future direction for practitioners and researchers. Although work-related driving crashes have become the most common cause of death, injury, and absence from work in Australia and overseas, very limited research has progressed in establishing effective strategies to improve safety outcomes. In particular, the majority of past research has been data-driven, and therefore, limited attention has been given to theoretical development in establishing the behavioural mechanism underlying driving behaviour. As such, this paper argues that to move forward in the field of work-related driving safety, practitioners and researchers need to gain a better understanding of the individual and organisational factors influencing safety through adopting relevant theoretical frameworks, which in turn will inform the development of specifically targeted theory-driven interventions. This paper presents an intervention framework that is based on relevant theoretical frameworks and sound methodological design, incorporating interventions that can be directed at the appropriate level, individual and driving target group.

What factors are associated with cyclists getting injured? Correlates of cyclist injuries in Queensland

Pedal cyclists are over-represented in traffic crash injuries in Australia. This study examined correlates of cycling injuries in a sample of Queensland cyclists. Members of Bicycle Queensland (n=1976) were asked about cycling injuries as part of an online survey. They also reported demographic characteristics, reasons for cycling, years of cycling as an adult, and cycling frequency. Multivariate logistic regression modelling was used to examine the association between these variables and experiencing cycling injuries last year (yes/no). Thirty-one percent of respondents (n=617) reported at least one cycling injury. Respondents had greater likelihood of injury if they cycled more frequently, had cycled <5 years, or cycled for recreation or competition. These findings suggest that injuries are mostly likely to occur among less experienced cyclists, those cycling the most, and those cycling for sport and recreation. Injury prevention interventions should include cycle skills training along with fostering safer cycling environments.

Evaluation of risk factors leading to cost overrun in delivery of highway construction projects

Accurate owner budget estimates are critical to the initial decision-to-build process for highway construction projects. However, transportation projects have historically experienced significant construction cost overruns from the time the decision to build has been taken by the owner. This paper addresses the problem of why highway projects overrun their predicted costs. It identifies the owner risk variables that contribute to significant cost overrun and then uses factor analysis, expert elicitation, and the nominal group technique to establish groups of importance ranked owner risks. Stepwise multivariate regression analysis is also used to investigate any correlation of the percentage of cost overrun with risks, together with attributes such as highway project type, indexed cost, geographics location, and project delivery method. The research results indicate a correlation between the reciprocal of project budgets size and percentage cost overrun. This can be useful for owners in determining more realistic decision-to-build highway budget estimates by taking into account the economies of scale associated with larger projects.

Deriving grassland management factors for a carbon accounting method developed by the intergovernmental panel on climate change

Grassland management affects soil organic carbon (SOC) storage and can be used to mitigate greenhouse gas emissions. However, for a country to assess emission reductions due to grassland management, there must be an inventory method for estimating the change in SOC storage. The Intergovernmental Panel on Climate Change (IPCC) has developed a simple carbon accounting approach for this purpose, and here we derive new grassland management factors that represent the effect of changing management on carbon storage for this method. Our literature search identified 49 studies dealing with effects of management practices that either degraded or improved conditions relative to nominally managed grasslands. On average, degradation reduced SOC storage to 95% +/- 0.06 and 97% +/- 0.05 of carbon stored under nominal conditions in temperate and tropical regions, respectively. In contrast, improving grasslands with a single management activity enhanced SOC storage by 14% 0.06 and 17% +/- 0.05 in temperate and tropical regions, respectively, and with an additional improvement(s), storage increased by another 11% +/- 0.04. We applied the newly derived factor coefficients to analyze C sequestration potential for managed grasslands in the U.S., and found that over a 20-year period changing management could sequester from 5 to 142 Tg C yr(-1) or 0.1 to 0.9 Mg C ha(-1) yr(-1), depending on the level of change. This analysis provides revised factor coefficients for the IPCC method that can be used to estimate impacts of management; it also provides a methodological framework for countries to derive factor coefficients specific to conditions in their region.

Environmental factors controlling soil respiration in three semiarid ecosystems

Previous research suggests that soil organic C pools may be a feature of semiarid regions that are particularly sensitive to climatic changes. We instituted an 18-mo experiment along an elevation gradient in northern Arizona to evaluate the influence of temperature, moisture, and soil C pool size on soil respiration. Soils, from underneath different free canopy types and interspaces of three semiarid ecosystems, were moved upslope and/or downslope to modify soil climate. Soils moved downslope experienced increased temperature and decreased precipitation, resulting in decreased soil moisture and soil respiration las much as 23 acid 20%, respectively). Soils moved upslope to more mesic, cooler sites had greater soil water content and increased rates of soil respiration las much as 40%), despite decreased temperature. Soil respiration rates normalized for total C were not significantly different within any of the three incubation sites, indicating that under identical climatic conditions, soil respiration is directly related to soil C pool size for the incubated soils. Normalized soil respiration rates between sites differed significantly for all soil types and were always greater for soils incubated under more mesic, but cooler, conditions. Total soil C did not change significantly during the experiment, but estimates suggest that significant portions of the rapidly cycling C pool were lost. While long-term decreases in aboveground and belowground detrital inputs may ultimately be greater than decreased soil respiration, the initial response to increased temperature and decreased precipitation in these systems is a decrease in annual soil C efflux.

An empirical test of causal relationships of factors affecting ICT adoption for building project management : an Indian SME case study

Purpose - Building project management (BPM) requires effective coordination and collaboration between multiple project team organisations which can be achieved by real time information flow between all participants. In the present scenario, this can be achieved by the use of information communication technologies (ICT). The purpose of this paper is to present part of a research project conducted to study the causal relationships between factors affecting ICT adoption for BPM by small and medium enterprises. Design/methodology/approach - This paper discusses structural equation modelling (SEM) analysis conducted to test the causal relationships between quantitative factors. Data for quantitative analysis were gathered through a questionnaire survey conducted in the Indian construction industry. Findings - SEM analysis results help in demonstrating that an increased and matured use of ICT for general administration within the organisation would lead to: an improved ICT infrastructure within the organisation; development of electronic databases; and a staff that is confident of using information technology (IT) tools. In such a scenario, staff would use advanced software and IT technologies for project management (PM) processes and that would lead to an increased adoption of ICT for PM processes. But, for general administration also, ICT adoption would be enhanced if the organisation is interacting more with geographically separated agencies and senior management perceives that significant benefits would accrue by adoption of ICT. All the factors are inter-related and their effect cannot be maximized in isolation. Originality/value - The results provide direction to building project managements for strategically adopting the effective use of ICT within their organisations and for BPM general.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

Background: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. ---------- Methods: Australian women (n = 287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy- Breast questionnaire were used to assess self-reported UBF and QoL, respectively. ---------- Results: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between sixand 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least twofold (p < 0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p < 0.05). ---------- Conclusions: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.