The effect of a high fat meal on postprandial arterial stiffness in men with obesity and type 2 diabetes

Context: Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. Objective: The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). Design and Setting: Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). Results: AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 +/- 1204, 2764 +/- 1102, and 1187 +/- 429% . min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 +/- 68 min) compared with lean subjects (161 +/- 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). Conclusions: Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Determining the detection capabilities of existing real time measurement techniques for different engineered nanoparticles

The application of nanotechnology products has increased significantly in recent years. With their broad range of applications, including electronics, food and agriculture, power and energy, scientific instruments, clothing, cosmetics, buildings, biomedical and health, etc (Catanzariti, 2008), nanomaterials are an indispensible part of human life.

Sensors and imaging for wound healing : a review

Wound healing involves a complex series of biochemical events and has traditionally been managed with 'low tech' dressings and bandages. The concept that diagnostic and theranostic sensors can complement wound management is rapidly growing in popularity as there is tremendous potential to apply this technology to both acute and chronic wounds. Benefits in sensing the wound environment include reduction of hospitalization time, prevention of amputations and better understanding of the processes which impair healing. This review discusses the state-of-the-art in detection of markers associated with wound healing and infection, utilizing devices imbedded within dressings or as point-of-care techniques to allow for continual or rapid wound assessment and monitoring. Approaches include using biological or chemical sensors of wound exudates and volatiles to directly or indirectly detect bacteria, monitor pH, temperature, oxygen and enzymes. Spectroscopic and imaging techniques are also reviewed as advanced wound monitoring techniques. The review concludes with a discussion of the limitations of and future directions for this field.

Visualisation of complex flows using texture-based techniques

Complex flow datasets are often difficult to represent in detail using traditional vector visualisation techniques such as arrow plots and streamlines. This is particularly true when the flow regime changes in time. Texture-based techniques, which are based on the advection of dense textures, are novel techniques for visualising such flows (i.e., complex dynamics and time-dependent). In this paper, we review two popular texture-based techniques and their application to flow datasets sourced from real research projects. The texture-based techniques investigated were Line Integral Convolution (LIC), and Image-Based Flow Visualisation (IBFV). We evaluated these techniques and in this paper report on their visualisation effectiveness (when compared with traditional techniques), their ease of implementation, and their computational overhead.

Post occupancy evaluations relating to discomfort glare : a study of green buildings in Brisbane

Glare indices have yet to be extensively tested in daylit open plan offices, as such there is no effective method to predict discomfort glare within these spaces. This study into discomfort glare in open plan green buildings targeted full-time employees, working under their everyday lighting conditions. Three green buildings in Brisbane were used for data collection, two were Green Star accredited and the other contained innovative daylighting strategies. Data were collected on full-time employees, mostly aged between 30 and 50 years, who broadly reflect the demographics of the wider working population in Australia. It was discovered 36 of the 64 respondents experienced discomfort from both electric and daylight sources at their workspace. The study used a specially tailored post-occupancy evaluation (POE) survey to help assess discomfort glare. Luminance maps extracted from High Dynamic Range (HDR) images were used to capture the luminous environment of the occupants. These were analysed using participant data and the program Evalglare. The physical results indicated no correlation with other developed glare metrics for daylight within these open plan green buildings, including the recently developed Daylight Glare Probability (DGP) Index. The strong influence of vertical illuminance, Ev in the DGP precludes the mostly contrast-based glare from windows observed in this investigation from forming a significant part of this index. Furthermore, critical assessment of the survey techniques used are considered. These will provide insight for further research into discomfort glare in the endeavour to fully develop a suitable glare metric.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Photocatalytic reduction of carbon dioxide to formic acid, formaldehyde, and methanol using dye-sensitized TiO2 film

A bifunctionalized TiO2 film containing a dye-sensitized zone and a catalysis zone is designed for visible-light photocatalytic reduction of CO2 to chemicals continuously. Charge separation can be accomplished with electron transferring to catalysis zone and positive charge transforming to anode. Highly efficient conversion of CO2 to formic acid, formaldehyde, and methanol is achieved through the transferring electrons on conduction bands (CB) of TiO2. Reduction of CO2 and O2 evolution take place in separated solutions on different catalysts. The separated solution carried out in this photo-reactor system can avoid CO2 reduction products being oxidized by anode. The yields of reduction products were enhanced remarkably by external electrical power. This study provides not only a new photocatalytic system but also a potential of renewable energy source via carbon dioxide.

Using the index for inclusion to develop inclusive school communities

This chapter provides an overview of how school communities can work together in processes or review and development to strive towards a more inclusive approach to education. The writers of this chapter have been using a resource called the Index for Inclusion (Booth & Ainscow, 2005, 2011) for a number of years in Australia and in a pilot trail in New Zealand to support education staff in processes of review, with the aim to increase the participation and learning of all students. The resource supports the development of collaborative community processes and defines inclusion as ‘putting values into action’ (Booth & Ainscow, 2011, p.18). The process of review and development for more inclusive and socially just schools supports the development of a school culture, policy and practice where people are valued and treated with respect for their varied knowledge and experiences. In our experience, this resource has been useful to challenge our thinking about education in school communities and in region/districts about inclusive school development. We suggest the Index framework is broad enough to be used in a range of settings and countries. The resource is also useful for pre-service and in-service teacher development to provoke reflection and discussion about inclusion. This chapter provides an overview of the dimensions and framework that inform the Index of Inclusion. We discuss how the Index can be used in school contexts and draw on our own experience to give real examples of how teachers, paraprofessionals, students, principals and parents have experienced the Index when used in their local school communities in Australia and New Zealand. The chapter concludes with some points for discussion to challenge the status quo in schools and to inspire teachers to work towards a more socially just society through making changes at a school level.

An index of best practice performance reporting for Malaysian local authorities

Abstract Purpose – The purpose of this paper is to identify stakeholders’ expectations of information to be conveyed in local authorities’ annual reports and to develop an index of best practice performance reporting. Design/methodology/approach – The paper describes the development of a disclosure index emphasizing the public interest aspect of reporting and the need to provide relevant and meaningful information to stakeholders. The index was crafted from a public accountability perspective and based on the expectations of stakeholders as reconciled and validated by a Delphi panel of experts. Findings – The wide scope of information that was dentified as being important for disclosure by local authorities is consistent with the public accountability paradigm which requires the reporting of comprehensive information (both financial and non financial), about the condition, performance, activities and progress of the entity. Originality/value – The research posits a model of best practice performance reporting for Malaysian, and other, local authorities to meet the need for greater accountability by these entities.

A virtual environment to simulate the experience of psychosis

Psychosis is a mental disorder that affects 1-2% of the population at some point in their lives. One of the main causes of psychosis is the mental illness schizophrenia. Sufferers of this illness often have terrifying symptoms such as hallucinations, delusions, and thought disorder. This project aims to develop a virtual environment to simulate the experience of psychosis, focusing on re-creating auditory and visual hallucinations. A model of a psychiatric ward was created and the psychosis simulation software was written to re-create the auditory and visual hallucinations of one particular patient. The patient was very impressed with the simulation, and commented that it effectively re-created the same emotions that she experienced on a day-to-day basis during her psychotic episodes. It is hoped that this work will result in a useful educational tool about schizophrenia, leading to improved training of clinicians, and fostering improved understanding and empathy toward sufferers of schizophrenia in the community, ultimately improving the quality of life and chances of recovery of patients.

The development of a virtual reality environment to model the experience of schizophrenia

Virtual Reality (VR) techniques are increasingly being used for education about and in the treatment of certain types of mental illness. Research indicates that VR is delivering on its promised potential to provide enhanced training and treatment outcomes through incorporation of this high-end technology. Schizophrenia is a mental disorder affecting 1-2% of the population, and it is estimated 12-16% of hospital beds in Australia are occupied by patients with psychosis. Tragically, there is also an increased risk of suicide associated with this diagnosis. A significant research project being undertaken across the University of Queensland faculties of Health Sciences and EPSA (Engineering, Physical Sciences and Architecture) has constructed a number of virtual environments that reproduce the phenomena experienced by patients who have psychosis. Symptoms of psychosis include delusions, hallucinations and thought disorder. The VR environment will allow behavioral, exposure therapies to be conducted with exactly controlled exposure stimuli and an expected reduction in risk of harm. This paper reports on the current work of the project, previous stages of software development and the final goal to introduce VR to medical consulting rooms.

Non-parametric techniques for fast and robust stereo matching

The mining environment presents a challenging prospect for stereo vision. Our objective is to produce a stereo vision sensor suited to close-range scenes consisting mostly of rocks. This sensor should produce a dense depth map within real-time constraints. Speed and robustness are of foremost importance for this application. This paper compares a number of stereo matching algorithms in terms of robustness and suitability to fast implementation. These include traditional area-based algorithms, and algorithms based on non-parametric transforms, notably the rank and census transforms. Our experimental results show that the rank and census transforms are robust with respect to radiometric distortion and introduce less computational complexity than conventional area-based matching techniques.

Suitability of non-parametric stereo matching algorithms for mining automation

The mining environment, being complex, irregular and time varying, presents a challenging prospect for stereo vision. For this application, speed, reliability, and the ability to produce a dense depth map are of foremost importance. This paper assesses the suitability of a number of matching techniques for use in a stereo vision sensor for close range scenes consisting primarily of rocks. These include traditional area-based matching metrics, and non-parametric transforms, in particular, the rank and census transforms. Experimental results show that the rank and census transforms exhibit a number of clear advantages over area-based matching metrics, including their low computational complexity, and robustness to certain types of distortion.

The application of virtual reality to the understanding and treatment of schizophrenia

Virtual Reality (VR) techniques are increasingly being used in education about and in the treatment of certain types of mental illness. Research indicates VR is delivering on it's promised potential to provide enhanced training and treatment outcomes through incorporation of this high-end technology. Schizophrenia is a mental disorder affecting 1−2% of the population. A significant research project being undertaken at the University of Queensland has constructed virtual environments that reproduce the phenomena experienced by patients who have psychosis. The VR environment will allow behavioral exposure therapies to be conducted with exactly controlled exposure stimuli and an expected reduction in risk of harm. This paper reports on the work of the project, previous stages of software development and current and future educational and clinical applications of the Virtual Environments.