A method of extracting switching loss from a high efficiency MOSFET based half bridge converter

The measurement of losses in high efficiency / high power converters is difficult. Measuring the losses directly from the difference between the input and output power results in large errors. Calorimetric methods are usually used to bypass this issue but introduce different problems, such as, long measurement times, limited power loss measurement range and/or large set up cost. In this paper the total losses of a converter are measured directly and switching losses are exacted. The measurements can be taken with only three multimeters and a current probe and a standard bench power supply. After acquiring two or three power loss versus output current sweeps, a series of curve fitting processes are applied and the switching losses extracted.

Sessional Academic Success : A distributed framework for academic support and development

With approximately half of Australian university teaching now performed by sessional academics, there has been growing recognition of the contribution they make to student learning. At the same time, sector-wide research and institutional audits continue to raise concerns about academic development, quality assurance, recognition and belonging. In response, universities have increasingly begun to offer academic development programs for sessional academics. However, such programs may be centrally delivered, generic in nature, and contained within the moment of delivery, while the Faculty contexts and cultures that sessional academics work within are diverse, and the need for support unfolds in ad-hoc and often unpredictable ways. In this paper we present the Sessional Academic Success (SAS) program–a new framework that complements and extends the central academic development program for sessional academic staff at Queensland University of Technology. This program recognises that experienced sessional academics have much to contribute to the advancement of learning and teaching, and harnesses their expertise to provide school-based academic development opportunities, peer-to-peer support, and locally contextualized community building. We describe the program’s implementation and explain how Sessional Academic Success Advisors (SASAs) are employed, trained and supported to provide advice and mentorship and, through a co-design methodology, to develop local development opportunities and communities of teaching practice within their schools. Besides anticipated benefits to new sessional academics in terms of timely and contextual support and improved sense of belonging, we explain how SAS provides a pathway for building leadership capacity and academic advancement for experienced sessional academics. We take a collaborative, dialogic and reflective practice approach to this paper, interlacing insights from the Associate Director, Academic: Sessional Development who designed the program, and two Sessional Academic Success Advisors who have piloted it within their schools.

Ross River virus arthritis

“Epidemics” of a benign disease causing polyarthralgia and rash were first described in Australia in 1927.63 Following the recovery of the causative agent and the advent of serologic tests able to diagnose Ross River virus infection, epidemic polyarthritis has been recognized as endemic in Australia and has occurred as epidemics in numerous Pacific nations. Approximately 4000 cases of epidemic polyarthritis are reported in Australia each year, with a peak of 7800 cases in 1996. Some confusion has been generated recently by use of the term Ross River fever to describe clinical Ross River virus infections because fever does not develop in more than half of those with clinical disease.59 Additional confusion has been generated by efforts to describe any polyarthritis caused by an Australian arbovirus as epidemic polyarthritis. The term epidemic polyarthritis should be used to describe only clinical disease caused by Ross River virus.

Invading edge vs. inner (edvin) patterns of vascularization : an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis. Copyright (C) 2000 John Wiley and Sons, Ltd.

Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent

Introduction: Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence. The caspase 8 inhibitor FLIP is an anti-apoptotic protein over-expressed in several cancer types including MPM. The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM. Methods: The mechanism of SAHA-induced apoptosis was assessed in 7 MPM cell lines and in a multicellular spheroid model. SiRNA and overexpression approaches were used, and cell death was assessed by flow cytometry, Western blotting and clonogenic assays. Results: RNAi-mediated FLIP silencing resulted in caspase 8-dependent apoptosis in MPM cell line models. SAHA potently down-regulated FLIP protein expression in all 7 MPM cell lines and in a multicellular spheroid model of MPM. In 6/7 MPM cell lines, SAHA treatment resulted in significant levels of apoptosis induction. Moreover, this apoptosis was caspase 8-dependent in all six sensitive cell lines. SAHA-induced apoptosis was also inhibited by stable FLIP overexpression. In contrast, down-regulation of HR23B, a candidate predictive biomarker for HDAC inhibitors, significantly inhibited SAHA-induced apoptosis in only 1/6 SAHA-sensitive MPM cell lines. Analysis of MPM patient samples demonstrated significant inter-patient variations in FLIP and caspase 8 expressions. In addition, SAHA enhanced cisplatin-induced apoptosis in a FLIP-dependent manner. Conclusions: These results indicate that FLIP is a major target for SAHA in MPM and identifies FLIP, caspase 8 and associated signalling molecules as candidate biomarkers for SAHA in this disease. © 2011 Elsevier Ltd. All rights reserved.

Emergency Health Services (EHS) : demand and service delivery models. monograph 3 : patients’ reasons and perceptions

Executive Summary Emergency health is a critical component of Australia’s health system and emergency departments (EDs) are increasingly congested from growing demand and blocked access to inpatient beds. The Emergency Health Services Queensland (EHSQ) study aims to identify the factors driving increased demand for emergency health and to evaluate strategies which may safely reduce the future demand growth. This monograph addresses the perspectives of users of both ambulance services and EDs. The research reported here aimed to identify the perspectives of users of emergency health services, both ambulance services and public hospital Emergency Departments and to identify the factors that they took into consideration when exercising their choice of location for acute health care. A cross-sectional survey design was used involving a survey of patients or their carers presenting to the EDs of a stratified sample of eight hospitals. A specific purpose questionnaire was developed based on a novel theoretical model which had been derived from analysis of the literature (Monograph 1). Two survey versions were developed: one for adult patients (self-complete); and one for children (to be completed by parents/guardians). The questionnaires measured perceptions of social support, health status, illness severity, self-efficacy; beliefs and attitudes towards ED and ambulance services; reasons for using these services, and actions taken prior to the service request. The survey was conducted at a stratified sample of eight hospitals representing major cities (four), inner regional (two) and outer regional and remote (two). Due to practical limitations, data were collected for ambulance and ED users within hospital EDs, while patients were waiting for or under treatment. A sample size quota was determined for each ED based on their 2009/10 presentation volumes. The data collection was conducted by four members of the research team and a group of eight interviewers between March and May 2011 (corresponding to autumn season). Of the total of 1608 patients in all eight emergency departments the interviewers were able to approach 1361 (85%) patients and seek their consent to participate in the study. In total, 911 valid surveys were available for analysis (response rate= 67%). These studies demonstrate that patients elected to attend hospital EDs in a considered fashion after weighing up alternatives and there is no evidence of deliberate or ill-informed misuse. • Patients attending ED have high levels of social support and self-efficacy that speak to the considered and purposeful nature of the exercise of choice. • About one third of patients have new conditions while two thirds have chronic illnesses • More than half the attendees (53.1%) had consulted a healthcare professional prior to making the decision. • The decision to seek urgent care at an ED was mostly constructed around the patient’s perception of the urgency and severity of their illness, reinforced by a strong perception that the hospital ED was the correct location for them (better specialised staff, better care for my condition, other options not as suitable). • 33% of the respondent held private hospital insurance but nevertheless attended a public hospital ED. Similarly patients exercised considered and rational judgements in their choice to seek help from the ambulance service. • The decision to call for ambulance assistance was based on a strong perception about the severity of the illness (too severe to use other means of transport) and that other options were not considered appropriate. • The decision also appeared influenced by a perception that the ambulance provided appropriate access to the ED which was considered most appropriate for their particular condition (too severe to go elsewhere, all facilities in one spot, better specialised and better care). • In 43.8% of cases a health care professional advised use of the ambulance. • Only a small number of people perceived that ambulance should be freely available regardless of severity or appropriateness. These findings confirm a growing understanding that the choice of professional emergency health care services is not made lightly but rather made by reasonable people exercising a judgement which is influenced by public awareness of the risks of acute health and which is most often informed by health professionals. It is also made on the basis of a rational weighing up of alternatives and a deliberate and considered choice to seek assistance from a service which the patient perceived was most appropriate to their needs at that time. These findings add weight to dispensing with public perceptions that ED and ambulance congestion is a result of inappropriate choice by patients. The challenge for health services is to better understand the patient’s needs and to design and validate services that meet those needs. The failure of our health system to do so should not be grounds for blaming the patient, claiming inappropriate patient choices.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Procaspase 8 overexpression in non-small-cell lung cancer promotes apoptosis induced by FLIP silencing

We found that procaspase 8 was overexpressed in non-small-cell lung cancers (NSCLCs) compared with matched normal tissues. The caspase 8 inhibitor FLICE-inhibitory protein (FLIP) was also overexpressed in the majority of NSCLCs. Silencing FLIP induced caspase 8 activation and apoptosis in NSCLC cell lines, but not in normal lung cell lines. Apoptosis induced by FLIP silencing was mediated by the TRAIL death receptors DR4 and DR5, but was not dependent on ligation of the receptors by TRAIL. Furthermore, the apoptosis induced by FLIP silencing was dependent on the overexpression of procaspase 8 in NSCLC cells. Moreover, in NSCLC cells, but not in normal cells, FLIP silencing induced co-localization of DR5 and ceramide, and disruption of this co-localization abrogated apoptosis. FLIP silencing supra-additively increased TRAIL-induced apoptosis of NSCLC cells; however, normal lung cells were resistant to TRAIL, even when FLIP was silenced. Importantly, FLIP silencing sensitized NSCLC cells but not normal cells to chemotherapy in vitro, and silencing FLIP in vivo retarded NSCLC xenograft growth and enhanced the anti-tumour effects of cisplatin. Collectively, our results suggest that due to frequent procaspase 8 overexpression, NSCLCs may be particularly sensitive to FLIP-targeted therapies.

DRB2 is required for microRNA biogenesis in Arabidopsis thaliana

Background The Arabidopsis thaliana (Arabidopsis) DOUBLE-STRANDED RNA BINDING (DRB) protein family consists of five members, DRB1 to DRB5. The biogenesis of two developmentally important small RNA (sRNA) species, the microRNAs (miRNAs) and trans-acting small interfering RNAs (tasiRNAs) by DICER-LIKE (DCL) endonucleases requires the assistance of DRB1 and DRB4 respectively. The importance of miRNA-directed target gene expression in plant development is exemplified by the phenotypic consequence of loss of DRB1 activity (drb1 plants). Principal Findings Here we report that the developmental phenotype of the drb235 triple mutant plant is the result of deregulated miRNA biogenesis in the shoot apical meristem (SAM) region. The expression of DRB2, DRB3 and DRB5 in wild-type seedlings is restricted to the SAM region. Small RNA sequencing of the corresponding tissue of drb235 plants revealed altered miRNA accumulation. Approximately half of the miRNAs detected remained at levels equivalent to those of wild-type plants. However, the accumulation of the remaining miRNAs was either elevated or reduced in the triple mutant. Examination of different single and multiple drb mutants revealed a clear association between the loss of DRB2 activity and altered accumulation for both the elevated and reduced miRNA classes. Furthermore, we show that the constitutive over-expression of DRB2 outside of its wild-type expression domain can compensate for the loss of DRB1 activity in drb1 plants. Conclusions/Significance Our results suggest that in the SAM region, DRB2 is both antagonistic and synergistic to the role of DRB1 in miRNA biogenesis, adding an additional layer of gene regulatory complexity in this developmentally important tissue.

Prognostic and therapeutic relevance of FLIP and procaspase-8 overexpression in non-small cell lung cancer

Non-small cell lung carcinoma remains by far the leading cause of cancer-related deaths worldwide. Overexpression of FLIP, which blocks the extrinsic apoptotic pathway by inhibiting caspase-8 activation, has been identified in various cancers. We investigated FLIP and procaspase-8 expression in NSCLC and the effect of HDAC inhibitors on FLIP expression, activation of caspase-8 and drug resistance in NSCLC and normal lung cell line models. Immunohistochemical analysis of cytoplasmic and nuclear FLIP and procaspase-8 protein expression was carried out using a novel digital pathology approach. Both FLIP and procaspase-8 were found to be significantly overexpressed in tumours, and importantly, high cytoplasmic expression of FLIP significantly correlated with shorter overall survival. Treatment with HDAC inhibitors targeting HDAC1-3 downregulated FLIP expression predominantly via post-transcriptional mechanisms, and this resulted in death receptor- and caspase-8-dependent apoptosis in NSCLC cells, but not normal lung cells. In addition, HDAC inhibitors synergized with TRAIL and cisplatin in NSCLC cells in a FLIP- and caspase-8-dependent manner. Thus, FLIP and procaspase-8 are overexpressed in NSCLC, and high cytoplasmic FLIP expression is indicative of poor prognosis. Targeting high FLIP expression using HDAC1-3 selective inhibitors such as entinostat to exploit high procaspase-8 expression in NSCLC has promising therapeutic potential, particularly when used in combination with TRAIL receptor-targeted agents.

The Nagle Royal Commission 25 years on : gaining perspective on two and a half decades of NSW prison reform

This article attempts an audit of changes in the NSW penal system over the last nearly 30 years. Taking the 1978 Nagle Royal Commission findings and analysis as the starting point a comparison is made between the Nagle era and the contemporary scene across a range of practices including imprisonment rates, violence, drug use, deaths in custody, prison conditions, prisoners rights, legal regulation, and others. It is suggested that developments since Nagle are mixed and cannot be attributed to a single logic or force. Major changes include a doubling of imprisonment rates, significant increases in Indigenous and women's imprisonment rates, the apparent ending of institutionalised bashings and the centrality of drug use to imprisonment and to the culture, health and security practices which characterise the current prison experience. The article may constitute a useful starting point for broader attempts to relate current penal practices to far wider changes in the conditions of life under late modernity.

Exploring pedestrian accessibility and walkability : insight from public place observations in inner-urban higher density Brisbane, Australia

As planners work to create more sustainable and liveable urban environments, a priority is to transition away from prioritising the automobile and towards enhancing the pedestrian experience. Thus, this research explores the experience of pedestrian accessibility in inner-urban higher-density Brisbane in Australia, drawing on findings from semi-structured in-depth interviews with 24 residents and over 100 hours of public place observations in three case-study neighbourhoods. The interviews took place in residents homes and explored their experience of higher density living and their neighbourhood, whilst observations were recorded through a combination of methods including photographs, sketch maps, recordings and field journals. Observation locations included retail and commercial space, roads, parkland and open space, with multiple observations at each location. A thematic analysis identified common themes in both interviews and the observations, with this paper focusing on residents’ lived experience in urban built environments. This analysis revealed that pedestrian accessibility is linked to access to local amenities and direct routes, aesthetics, sense of community, ownership of space and safety. In particular, observations revealed how pedestrian accessibility and route-taking works with, against or in spite of the design features of urban environments, as well as the importance of the social use of the built environment. Residents spoke about although walking quick and preferred for local amenities, the decision to walk was moderated by factors such as time of day and perceived safety. Measures to ensure and improve the pedestrian accessibility of urban areas needs to take into account the propensity for people to prefer and improvise direct routes (often to the detriment of traffic safety considerations), the importance of ongoing maintenance and upgrading of walking infrastructure and the importance of aesthetically pleasing and safe walking environments. By combining interviews and observations, this research highlights the current dominance of the automobile culture in Brisbane and the layers of meaning, experiences and complexity hidden within the pedestrian experience.

Reasons for non-urgent presentations to the emergency department in Saudi Arabia

Background The majority of patients who attend emergency departments (EDs) in Saudi Arabia have non-urgent problems, resulting in overcrowding, excessive waiting times and delayed care for more acutely ill patients. The purpose of this research was to examine the reasons for non-urgent visits to a Saudi ED and factors associated with patient perceptions of urgency. Methods We administered a survey to 350 consecutively presenting Canadian Triage and Acuity Scale (CTAS) IV or V adult patients at a large tertiary ED in Riyadh region, Saudi Arabia, during 25 days of data collection in March 2013. Results Over half of the sample usually visited the ED to access healthcare. The most common reasons for attending the ED were not having a regular healthcare provider (63%), being able to receive care on the same day (62%), and the convenience of and access to medical care 24/7 (62%). Approximately two-thirds of CTAS V patients and one-third of CTAS IV patients believed their condition was more urgent than their triage nurse rating. Conclusion Multiple factors influence non-urgent visits to the ED in the Saudi context including insufficient community awareness of the role of the ED and perceived lack of access to primary healthcare services.

Equal access to the opportunities available? Equity and diversity laws and policies in Australia

Australia has been populated for more than 40,000 years with Indigenous Australians joined by European settlers only 230 years ago. The first settlers consisted of convicts from more than 28 countries and members of the British army who arrived in 1788 to establish a British penal colony. Mass migration in the nineteenth century with one and a half million immigrants from Europe, principally from the United Kingdom and Ireland (Haines and Shlomowitz, 1992), established the continent as an Anglo society in the Pacific. In the twentieth century immigrants came from many European countries and in the latter decades from many parts of Asia and the Middle East (Collins, 1991, pp.10-13). In the 21st century Australia has an ethnically and culturally diverse population. The original Indigenous population of Australia accounts for approximately 460,000 or 2.5 per cent of the total population (ABS, 2006a). Estimates are that around 4.5m. persons in the population (close to 20 per cent), were born outside Australia with the majority of these arriving from Europe, principally the United Kingdom, and New Zealand (ABS, 2006b). Like many other countries, Australia has a legacy of discrimination and inequality in employment. Propelled by racist ideologies and the male breadwinner ideology, Indigenous Australians, and non-European immigrants, and women were barred from certain jobs and paid less for their work than any white male counterpart. These conditions were legally sanctioned through the industrial relations system and other laws in the nineteenth and first half of the twentieth century. Since the 1960s a dramatic change has occurred in social policy and national legislation and Australia today has an extensive array of laws which forbid employment discrimination on race, ethnicity, gender and many other characteristics, and other approaches which promote proactive organizational plans and actions to achieve equity in employment. This chapter outlines these developments.