An analytical tool that quantifies cellular morphology changes from three-dimensional fluorescence images

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology(1) even in complex tissue sections(2). Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells(3), however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.

What do emergency physicians think of law?

What do emergency physicians think of law? Do they know the law? What role does it have in the practice of emergency medicine? Emergency physicians in New South Wales, Victoria and Queensland are being asked about these issues in a study by the Queensland University of Technology, Brisbane, Australia, titled ‘Withholding and withdrawing life-sustaining treatment from adults who lack capacity: The role of law in medical practice’. The study aims to examine the role that law plays in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity.

Should law have a role in end-of-life care?

What do physicians think of law? Do they know the law? What role does it have in the provision of end-of-life care? Physicians in New South Wales, Victoria and Queensland are being asked about these issues in a study by the Queensland University of Technology entitled ‘Withholding and withdrawing life-sustaining treatment from adults who lack capacity: The role of law in medical practice’. This research aims to examine the role that law plays in decisions to withhold or withdraw life-sustaining treatment from adults who lack capacity.

Facilitating first year students’ engagement with planning education : utilising student affinity for technology to increase cohort cohesion and decrease attrition

First year students overwhelmingly indicate that a strong interest in a field of study prompts them to enrol in university (McInnis et al 2000), yet over a quarter indicate that they have seriously considered dropping out of studies during their first year, with boredom most frequently cited by those domestic students who do depart before graduation (Coates and Ransom 2011). While it may be comforting to write off such withdrawals to the presumed apathy of youth, student “disquiet (in) their first year on campus may be a result of courses and institutions that do not match their needs and objectives, rather than any uncertainty or lack of purpose on their part” (James et al 1999). Voting with their mouse clicks, The current research investigate two conceptualized types of student participation in online discussion forums to increase understanding of student affinity for technology and its potential for fostering social network development amongst first year students.

Integration of medical images to the teaching of systematic pathology : an evaluation of relevance

A sound knowledge of pathological disease processes is required for professional practice within health professions. The project described in this paper reviewed the resources currently available for the delivery of systematic pathology tutorials. Additional complementary resources were developed and the inclusion of these additional learning resources in practical tutorial sessions was evaluated for their impact on student learning. Student evaluation of the learning resources was undertaken across one semester with two different cohorts of health profession students using questionnaires and focus group discussion. Both cohorts reported an enhancement to their understanding of pathological disease processes through the use of the additional resources. Results indicate student perception of the value of the resources correlates with staff perception and is independent of prior experiences.

On governing collaborative Information Technology (IT) : a relational perspective

Organizations today invest in collaborative IT to engage in collaborative alliances to sustain or improve their competitive positions. Effective use of this collaborative IT in an alliance requires a deeper understanding of their governance structures. This effort is to ensure the sustainability of these alliances. Through the relational view of the firm, we suggest relational lateral IT-steering committees, relational IT operational committees, and relational IT performance management systems as IT governance structures for collaborative alliances. We then incorporate these structures, develop a model for approaches to governing collaborative IT, and evaluate the effectiveness for such governance structures in the IT-dependent alliances. We suggest that IT governance efforts of an alliance should contribute to their collaborative rent. We also suggest that the collaborative rent of an alliance would relate to the business value of its alliance partners. Field survey data containing 192 responses indicates a positive influence of the suggested IT governance efforts of the alliance on the collaborative rent of the alliance. The results also suggest a positive impact of the collaborative rent of the alliance on the business value of the alliance partners.

Pervasive technology and public transport : opportunities beyond telematics

The advancements of technology in the field of public transport have been considerable. Information Technology (IT) has made the dissemination of information effortless, contributing to reduced perceived waiting time, increased sense of security, and value for money. Nevertheless, and in light of the ever more obvious widespread presence of powerful mobile devices, it seems that the use of technology may be geared towards supplementary services other than telematics. Looking at it from a passenger’s perspective, this article provides an overview of what IT-based services are currently offered in public transport and what is their assessed impact. We finalise by putting forward possible directions that future services might follow, and stress out the necessity to come up with frameworks that enable for the impact assessment on service quality and customer satisfaction.

Culture, technology and the city

The 21st century has been described as the “century of cities”. By 2030, 70 per cent of the world’s population will live in cities, with the most rapid urbanization occurring in the developing world. This paper will draw up geographer Ed Soja’s concept of the “spatial turn” in social theory to consider how the culture of cities can act as a catalyst to innovation and the development of new technologies. In doing so, the paper will develop a three-layered approach to culture as: the arts; the way of life of people and communities; and the embedded structure underpinning socio-economic relations. It will also consider technology at a three-layered element, including devices, practices and ‘logics’ of technology, or what the Greeks termed techne. The paper will consider recent approaches to urban cultural policy, including cluster development and creative cities, and suggest some alternatives, noting that a problem with current approaches is that they focus excessively upon production (clusters) or consumption (creative cities). It will also consider the development of digital creative industries such as games, and the strategies of different cities to develop an innovation culture.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Depression: an emotional obstacle to seeking medical advice for infertility

Objective: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. Design: Longitudinal cohort study.Setting Population based.Patient(s) Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936).Intervention(s) None.Main Outcome Measure(s) Infertility, not seeking medical advice. Result(s): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. Conclusion(s): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility.

Agreement between self-reported use of in vitro fertilization or ovulation induction, and medical insurance claims in Australian women aged 28–36 years

STUDY QUESTION: What is the self-reported use of in vitro fertilization (IVF) and ovulation induction (OI) in comparison with insurance claims by Australian women aged 28–36 years? SUMMARY ANSWER: The self-reported use of IVF is quite likely to be valid; however, the use of OI is less well reported. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Population-based research often relies on the self-reported use of IVF and OI because access to medical records can be difficult and the data need to include sufficient personal identifying information for linkage to other data sources. There have been few attempts to explore the reliability of the self-reported use of IVF and OI using the linkage to medical insurance claims for either treatment. STUDY DESIGN: This prospective, population-based, longitudinal study included the cohort of women born during 1973–1978 and participating in the Australian Longitudinal Study on Women's Health (ALSWH) (n = 14247). From 1996 to 2009, participants were surveyed up to five times. PARTICIPANTS AND SETTING: Participants self-reported their use of IVF or OI in two mailed surveys when aged 28–33 and 31–36 years (n = 7280), respectively. This study links self-report survey responses and claims for treatment or medication from the universal national health insurance scheme (i.e. Medicare Australia). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between self-reports and claims data were undertaken for all women consenting to the linkage (n = 3375). The self-reported use of IVF was compared with claims for OI for IVF (Kappa, K = 0.83), oocyte collection (K = 0.82), sperm preparation (K = 0.83), intracytoplasmic sperm injection (K = 0.40), fresh embryo transfers (K = 0.82), frozen embryo transfers (K = 0.64) and OI for IVF medication (K = 0.17). The self-reported use of OI was compared with ovulation monitoring (K = 0.52) and OI medication (K = 0.71). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: There is a possibility of selection bias due to the inclusion criteria for participants in this study: (1) completion of the last two surveys in a series of five and (2) consent to the linkage of their responses with Medicare data. GENERALIZABILITY TO OTHER POPULATIONS: The results are relevant to questionnaire-based research studies with infertile women in developed countries. STUDY FUNDING/COMPETING INTEREST(S): ALSWH is funded by the Australian Government Department of Health and Ageing. This research is funded by a National Health and Medical Research Council Centre of Research Excellence grant.

Enabling access to research data in developing countries : designing a policy and practice framework for Malaysia’s Public Research Universities

Members of the World Trade Organisation (WTO) are obliged to implement the Agreement on Trade-related Intellectual Property Rights 1994 (TRIPS) which establishes minimum standards for the protection and enforcement of intellectual property rights. Almost two decades after TRIPS was adopted at the conclusion of the Uruguay Round of trade negotiations, it is widely accepted that intellectual property systems in developing and least-developed countries must be consistent with, and serve, their development needs and objectives. In adopting the Development Agenda in 2007, the World Intellectual Property Organisation (WIPO) emphasised the importance to developing and least-developed countries of being able to obtain access to knowledge and technology and to participate in collaborations and exchanges with research and scientific institutions in other countries. Access to knowledge, information and technology is crucial if creativity and innovation is to be fostered in developing and least-developed countries. It is particularly important that developing and least-developed countries give effect to their TRIPS obligations by implementing intellectual property systems and adopting intellectual property management practices that enable them to benefit from knowledge flows and support their engagement in international research and science collaborations. However, developing and least-developed countries did not participate in the deliberations leading to the adoption in 2004 by Organisation for Economic Co-operation and Development (OECD) member countries of the Ministerial Declaration on Access to Research Data from Public Funding, nor have they formulated policies on access to publicly funded research outputs such as those developed by the National Institutes of Health in the United States, the United Kingdom Research Councils or the Australian National Health and Medical Research Council. These issues are considered from the viewpoint of Malaysia, a developing country whose economy has grown strongly in recent years. Lacking an established policy covering access to the outputs of publicly funded research, data sharing and licensing practices continue to be fragmented. Obtaining access to research data requires arrangements to be negotiated with individual data owners and custodians. Given the potential for restrictions on access to impact negatively on scientific progress and development in Malaysia, measures are required to ensure that access to knowledge and research results is facilitated. This paper proposes a policy framework for Malaysia‘s public research universities that recognises intellectual property rights while enabling the open access to research data that is essential for innovation and development. It also considers how intellectual property rights in research data can be managed in order to give effect to the policy‘s open access objectives.

Fertility and infertility : studies in reproductive epidemiology in Australia

Worldwide, there are few large-scale epidemiological studies on infertility. In Australia, population-based research on infertility is limited to a few small-scale studies. Therefore, the prevalence of infertility and unmet need for specialist medical advice and treatment cannot be estimated reliably. Women who have used assisted reproductive technologies (ART) are recorded in treatment registries. However, there are many infertile women who are excluded from these clinical populations because they neither seek advice nor use treatment. The thesis was based on a biopsychosocial model of health and used the methods of reproductive epidemiology to address the lack of national data on the prevalence of infertility in Australia. Firstly, numbers of births and pregnancy losses were investigated in two generations of women participating in the Australian Longitudinal Study on Women’s Health (ALSWH). The ALSWH is a broad-ranging, longitudinal examination of biological, psychological and social factors that impact on women’s health and wellbeing. Women from three age cohorts were randomly sampled from the population using the universal public health insurance (i.e., Medicare) database and ALSWH participants were representative of the female population. However, the studies in the thesis only involved data from two cohorts. The younger cohort were born in 1973-78 and completed up to four mailed surveys between 1996 (when they were aged 18-23 years, n=14247) and 2006 (28-33 years, n=9145). The mid-aged cohort were born in 1946-51 and completed four mailed surveys between 1996 (when they were aged 45-50 years n=13715) and 2004 (53-58 years, n=10905). Compared to other studies that focus on outcomes of single pregnancies, these studies included all pregnancy outcomes by developing comprehensive reproductive histories for each woman. Pregnancy outcomes included birth, miscarriage, stillbirth, termination and ectopic pregnancy. Women in the youngest cohort (born in 1973-78) were only just reaching their peak childbearing years and many (44%) had yet to report their first pregnancy outcome. Women from the mid-aged cohort (born 1946-51) had completed their reproductive lives and 92% were able to report on their lifetime pregnancy outcomes. Pregnancy losses, especially miscarriage, were common for both generations of women. Secondly, the prevalence of infertility, seeking medical advice and using treatment was identified for these two generations of women. For the older generation, the lifetime prevalence of infertility and demand for treatment was investigated in the context of the specialist medical services which became available circa 1980. By this time, however, most of these older women had already been pregnant and completed their families. For women who experienced infertility (11%), their options for advice and treatment were limited and less than half (42%) had used any treatment. More recently for the younger generation of women, who were aged 28-33 years in 2006, specialist advice and treatment were extensively available. Among women who had tried to conceive or had been pregnant (n=5936), 17% had experienced infertility and the majority (72%) were able to access medical advice. However, after seeking advice only half of these infertile women had used treatment with fertility hormones or in vitro fertilisation (IVF). Overall for infertile women aged up to 33 years, only one-third had used these treatments. Thirdly, the barriers to accessing medical advice and using treatment for infertility were identified for women aged less than 34 years. Among a community sample of infertile women aged 28-33 years (ALSWH participants), self-reported depression was found to be a barrier to accessing medical advice. The characteristics of these infertile women in the community who had (n=121) or had not (n=110) used treatment were compared to infertile women aged 27-33 years (n=59) attending four fertility clinics. Compared to infertile women in the community, living in major cities and having private health insurance were associated with early use of treatment for infertility at specialist clinics by women aged <34 years. In contrast to most clinical studies of IVF, the final study reported in the thesis took into account repeated IVF cycles and the impact of women’s individual histories on IVF outcomes. Among 121 infertile women (aged 27-46 years) who had 286 IVF cycles, older age and prolonged use of the oral contraceptive pill were associated with fewer eggs collected. Further, women in particular occupations had lower proportions of eggs fertilised normally than women in other occupational groups. These studies form the first large-scale epidemiological examination of infertility in Australia. The finding that two-thirds of women with infertility had not used treatment indicates that there is an unmet need for specialist treatment in women aged less than 34 years. However, barriers to accessing treatment prevent women using ART at a younger age when there is a higher chance of pregnancy.

Mastering medical terminology : Australia and New Zealand

Mastering Medical Terminology: Australia and New Zealand is medical terminology book of relevance to an audience in Australia and New Zealand. Australian terminology, perspectives, examples and spelling have been included and Australian pronunciation specified. The textbook is accompanied by a self-help workbook, an online workbook and a Smartphone app. Throughout Mastering Medical Terminology, review of medical terminology as it is used in clinical practice is highlighted. Features of the textbook, workbook and electronic product include: • Simple, non-technical explanations of medical terms • Workbook format with ample spaces to write answers • Explanations of clinical procedures, laboratory tests and abbreviations used in Australian clinical practice, as they apply to each body system and speciality area • Pronunciation of terms and spaces to write meanings of terms • Practical applications sections • Exercises that test understanding of terminology as students work through the text chapter by chapter • Review activities that pull together terminology to help students study • Comprehensive glossary and appendices for reference • Links to other useful references, such as websites and textbooks.

Evaluation of the cost-effectiveness of strategies claiming to reduce the risk of surgical site infections following primary total hip arthroplasty

Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.