eHealth-as-a-Service (eHaaS) : the industrialisation of health informatics, a practical approach

With the introduction of the Personally Controlled Health Record (PCEHR), the Australian public is being asked to accept greater responsibility for their healthcare. Although well designed, constructed and intentioned, policy and privacy concerns have resulted in an eHealth model that may impact future health information sharing requirements. Thus an opportunity to transform the beleaguered Australian PCEHR into a sustainable on-demand technology consumption model for patient safety must be explored further. Moreover, the current clerical focus of healthcare practitioners must be renegotiated to establish a shared knowledge creation landscape of action for safer patient interventions. To achieve this potential however requires a platform that will facilitate efficient and trusted unification of all health information available in real-time across the continuum of care. As a conceptual paper, the goal of the authors is to deliver insights into the antecedents of usage influencing superior patient outcomes within an eHealth-as-a-Service framework. To achieve this, the paper attempts to distil key concepts and identify common themes drawn from a preliminary literature review of eHealth and cloud computing concepts, specifically cloud service orchestration to establish a conceptual framework and a research agenda. Initial findings support the authors’ view that an eHealth-as-a-Service (eHaaS) construct will serve as a disruptive paradigm shift in the aggregation and transformation of health information for use as real-world knowledge in patient care scenarios. Moreover, the strategic value of extending the community Health Record Bank (HRB) model lies in the ability to automatically draw on a multitude of relevant data repositories and sources to create a single source of practice based evidence and to engage market forces to create financial sustainability.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

The unequal distribution of road trauma in China : understanding risk factors to improve public health

The World Health Organization identifies road trauma as a major public health issue in every country; most notably among low-to-middle income countries. More than 90% of all road fatalities occur in these countries, although they have only 48% of all registered vehicles [1]. Unprecedented focus has been placed on reducing the global road trauma burden through the United Nations Decade of Action for Road Safety (2011-2020). China is rapidly transitioning from a nation of bicycle riders and pedestrians to one where car ownership and use is increasing. This transition presents important public health, mobility, and safety challenges. Rapid motorisation has resulted in an increased road trauma burden, shouldered disproportionately among the population. Vulnerable road users (bicyclists, pedestrians, and motorcyclists) are of particular concern, representing 70% of all road-related fatalities [1]. Furthermore, those at greatest risk of sustaining a crash-related disability are: male, older, less educated, and earning a lower income [2] and residing in urban areas [3], with higher fatality rates in north-western poorer provinces [3]. Speeding is a key factor in road crashes in China [1, 4] and is one of two risk factors targeted in the Bloomberg Philanthropies-funded Global Road Safety Program operating in two Chinese cities over five year [5] to which the first author has provided expert advice. However, little evidence exists to help understand the factors underpinning speeding behaviour. Previous research conducted by the authors in Beijing and Hangzhou explored personal, social, and legal factors relating to speeding to assist in better understanding the motivations for non-compliance with speed limits. Qualitative and quantitative research findings indicated that speeding is relatively common, including self-reported travel speeds of greater than 30 km/hour above posted speed limits [6], and that the road safety laws and enforcement practices may, in some circumstances, contribute to this [7]. Normative factors were also evident; the role of friends, family members and driving instructors were influential. Additionally, using social networks to attempt to avoid detection and penalty was reported, thereby potentially reinforcing community perceptions that speeding is acceptable [8, 9]. The authors established strong collaborative links with the Chinese Academy of Sciences and Zhejiang Police College to conduct this research. The first author has worked in both institutions for extended time periods and recognises that research must include an understanding of culturally-relevant issues if road safety is to improve in China. Future collaborations to assist in enhancing our understanding of such issues are welcomed. References [1] World Health Organization. (2009). Global status report on road safety: Time for action; Geneva. [2] Chen, H., Du, W., & Li, N. (2013). The socioeconomic inequality in traffic-related disability among Chinese adults: the application of concentration index. Accident Analysis & Prevention, 55(101-106). [3] Wang, S. Y., Li, Y. H., Chi, G. B., Xiao, S. Y., Ozanne-Smith, J., Stevenson, M., & Phillips, M. (2008). Injury-related fatalities in China: an under-recognised public-health problem. The Lancet (British edition), 372(9651), 1765-1773. [4] He, J., King, M. J., Watson, B., Rakotonirainy, A., & Fleiter, J. J. (2013). Speed enforcement in China: National, provincial and city initiatives and their success. Accident Analysis & Prevention, 50, 282-288. [5] Bhalla, K., Li, Q., Duan, L., Wang, Y., Bishai, D., & Hyder, A. A. (2013). The prevalence of speeding and drink driving in two cities in China: a mid project evaluation of ongoing road safety interventions. Injury, 44, 49-56. doi:10.1016/S0020-1383(13)70213-4. [6] Fleiter, J. J., Watson, B., & Lennon, A. (2013). Awareness of risky behaviour among Chinese drivers. Peer-reviewed paper presented at 23rd Canadian Multidisciplinary Road Safety Conference, Montréal, Québec. [7] Fleiter, J. J., Watson, B., Lennon, A., King, M. J., & Shi, K. (2009). Speeding in Australia and China: A comparison of the influence of legal sanctions and enforcement practices on car drivers. Peer-reviewd paper presented at Australasian Road Safety Research Policing Education Conference, Sydney. [8] Fleiter, J. J., Watson, B., Lennon, A., King, M. J., & Shi, K. (2011). Social influences on drivers in China. Journal of the Australasian College of Road Safety, 22(2), 29-36. [9] Fleiter, J. J., Watson, B., Guan, M. Q., Ding, J. Y., & Xu, C. (2013). Characteristics of Chinese Drivers Attending a Mandatory Training Course Following Licence Suspension. Peer-reviewed paper presented at Road Safety on Four Continents, Beijing, China.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Reframe QUT's evaluation framework : a case study of planning, policy and positioning leading to educational best practice

Every university in Australia has a set of policies that guide the institution in its educational practices, however, the policies are often developed in isolation to each other. Now imagine a space where policies are evidence-based, refined annually, cohesively interrelated, and meet stakeholders’ needs. Is this happenstance or the result of good planning? Culturally, Queensland University of Technology (QUT) is a risk-averse institution that takes pride in its financial solvency and is always keen to know “how are we going?” With a twenty-year history of annual reporting that assures the quality of course performance through multiple lines of evidence, QUT’s Learning and Teaching Unit went one step further and strategically aligned a suite of policies that take into consideration the needs of their stakeholders, collaborate with other areas across the institution and use multiple lines of evidence to inform curriculum decision-making. In QUT’s experience, strategic planning can lead to policy that is designed to meet stakeholders’ needs, not manage them; where decision-making is supported by evidence, not rhetoric; where all feedback is incorporated, not ignored; and where policies are cohesively interrelated, not isolated. While many may call this ‘policy nirvana’, QUT has positioned itself to demonstrate good educational practice through Reframe, its evaluation framework. In this case, best practice was achieved through the application of a theory of change and a design-led logic model that allows for transition to other institutions with different cultural specificity. The evaluation approach follows Seldin’s (2003) notion to offer depth and breadth to the evaluation framework along with Berk’s (2005) concept of multiple lines of evidence. In summary, this paper offers university executives, academics, planning and quality staff an opportunity to understand the critical steps that lead to strategic planning and design of evidence-based educational policy that positions a university for best practice in learning and teaching.

Optimal allocation of conservation effort among subpopulations of a threatened species: How important is patch quality?

Money is often a limiting factor in conservation, and attempting to conserve endangered species can be costly. Consequently, a framework for optimizing fiscally constrained conservation decisions for a single species is needed. In this paper we find the optimal budget allocation among isolated subpopulations of a threatened species to minimize local extinction probability. We solve the problem using stochastic dynamic programming, derive a useful and simple alternative guideline for allocating funds, and test its performance using forward simulation. The model considers subpopulations that persist in habitat patches of differing quality, which in our model is reflected in different relationships between money invested and extinction risk. We discover that, in most cases, subpopulations that are less efficient to manage should receive more money than those that are more efficient to manage, due to higher investment needed to reduce extinction risk. Our simple investment guideline performs almost as well as the exact optimal strategy. We illustrate our approach with a case study of the management of the Sumatran tiger, Panthera tigris sumatrae, in Kerinci Seblat National Park (KSNP), Indonesia. We find that different budgets should be allocated to the separate tiger subpopulations in KSNP. The subpopulation that is not at risk of extinction does not require any management investment. Based on the combination of risks of extinction and habitat quality, the optimal allocation for these particular tiger subpopulations is an unusual case: subpopulations that occur in higher-quality habitat (more efficient to manage) should receive more funds than the remaining subpopulation that is in lower-quality habitat. Because the yearly budget allocated to the KSNP for tiger conservation is small, to guarantee the persistence of all the subpopulations that are currently under threat we need to prioritize those that are easier to save. When allocating resources among subpopulations of a threatened species, the combined effects of differences in habitat quality, cost of action, and current subpopulation probability of extinction need to be integrated. We provide a useful guideline for allocating resources among isolated subpopulations of any threatened species. © 2010 by the Ecological Society of America.

An investigation of the effect of some stable nitroxide antioxidants in prostate cancer cells

The risk of prostate cancer and disease progression may potentially be increased by oxidative stress. This project examined the stability of nitroxide antioxidants and their effects on cell growth, survival and gene regulation in prostate cancer cells. The novel nitroxide, CTMIO, synthesised here at QUT, was found to have minimal toxicity and modulated the expression of a subset of oxidative stress and antioxidant-related genes distinct from those regulated by a related derivative. This study has provided a step forward in our understanding of the mechanism of action of nitroxides within cells.

One-year clinical outcomes of a two-step surgical management for keratoconus-topography-guided photorefractive keratectomy/cross-linking after intrastromal corneal ring implantation

PURPOSE - To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen cross-linking (CXL) after intrastromal corneal ring (ISCR) implantation in patients with keratoconus. METHODS - Thirty-three patients (41 eyes) aged between 19 and 45 years were included in this prospective study. All patients underwent a femtosecond laser-enabled (Intralase FS; Abbott Medical Optics, Inc.) placement of intracorneal ring segments (Kerarings; Mediphacos, Brazil). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings remained stable for 6 months. Same-day PRK and CXL was subsequently performed in all patients. RESULTS - After 12 months of completion of the procedure, mean UDVA in log of minimal angle of resolution was significantly improved (0.74±0.54-0.10±0.16); CDVA did not improve significantly but 85% of eyes maintained or gained multiple lines of CDVA; mean refraction spherical equivalent improved (from -3.03±1.98 to -0.04±0.99 D), all keratometry readings were significantly reduced, from preoperative values, but coma did not vary significantly from preoperative values. Central corneal thickness and corneal thickness at the thinnest point were significantly (P<0.0001) reduced from 519.76±29.33 and 501.87±31.50 preoperatively to 464.71±36.79 and 436.55±47.42 postoperatively, respectively. Safety and efficacy indices were 0.97 and 0.88, respectively. From 6 months up until more than 1 year of follow-up, further significant improvement was observed only for UDVA (P<0.0001). CONCLUSIONS - Same-day combined TG-PRK and CXL after ISCR implantation is a safe and effective option for improving visual acuity and visual function, and it halts the progression of the keratoconus. The improvements recorded after 6 months of follow-up were maintained or improved upon 1 year after the procedure.

Looking back to look forwards: Expanding the sociology of education

As we write these lines, sociology celebrates 50 years of the French publication of the book ‘The Inheritors’, written by Bourdieu and Passeron in 1964. This ‘classic’ was followed by a series of works in the sociology of education (mainly published in England, France and the United States) devoted to the inequalities inherent within disparate projects revolving around school democratisation . From the 1960s to the mid-1970s, if the paradigms of educational sociologists do not all inscribe to that of critical sociology , several common factors are involved in researchers’ overarching lines of enquiry: the development of statistical data on schools, conferences and publication of reports on education (see Coleman, 1966 in the United States; Plowden, 1967 in the United Kingdom), and the structuration of school policies around democratisation underlying theories of human capital and the dependence of the school vis-à-vis the labour market, and the stratification and socio-economic organisation of societies.

B-adrenoceptor determinants of contractility in the human heart: The role of phosphodiesterase enzymes

This thesis investigated how enzymes called phosphodiesterases control changes in contractility mediated by noradrenaline and adrenaline through activation of β1- and β2-adrenoceptors in live human heart tissue from patients with advanced heart failure undergoing transplantation. The study compared patients who had been administered β-blocker medicines metoprolol or carvedilol or no β-blocker treatment. This work helped to further elucidate the complex roles of target receptors and enzymes that are integral to the progression of heart failure, to compare the mechanisms of action of β-blockers currently used to manage heart failure and to identify new drug targets for heart failure treatment.

Mechanisms of cisplatin resistance: DNA repair and cellular implications

Cisplatin (cis-diamminedichloroplatinum (II)), is a platinum based chemotherapeutic employed in the clinic to treat patients with lung, ovarian, colorectal or head and neck cancers. Cisplatin acts to induce tumor cell death via multiple mechanisms. The best characterized mode of action is through irreversible DNA cross-links which activate DNA damage signals leading to cell death via the intrinsic mitochondrial apoptosis pathway. However, the primary issue with cisplatin is that while patients initially respond favorably, sustained cisplatin therapy often yields chemoresistance resulting in therapeutic failure. In this chapter, we review the DNA damage and repair pathways that contribute to cisplatin resistance. We also examine the cellular implications of cisplatin resistance that may lead to selection of subpopulations of cells within a tumor. In better understanding the mechanisms conferring cisplatin resistance, novel targets may be identified to restore drug sensitivity.

The role of DNA repair pathways in cisplatin resistant lung cancer

Platinum chemotherapeutic agents such as cisplatin are currently used in the treatment of various malignancies such as lung cancer. However, their efficacy is significantly hindered by the development of resistance during treatment. While a number of factors have been reported that contribute to the onset of this resistance phenotype, alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating this phenomenon. The mode of action of cisplatin has been linked to its ability to crosslink purine bases on the DNA, thereby interfering with DNA repair mechanisms and inducing DNA damage. Following DNA damage, cells respond by activating a DNA-damage response that either leads to repair of the lesion by the cell thereby promoting resistance to the drug, or cell death via activation of the apoptotic response. Therefore, DNA repair is a vital target to improving cancer therapy and reduce the resistance of tumour cells to DNA damaging agents currently used in the treatment of cancer patients. To date, despite the numerous findings that differential expression of components of the various DNA repair pathways correlate with response to cisplatin, translation of such findings in the clinical setting are still warranted. The identification of alterations in specific proteins and pathways that contribute to these unique DNA repair pathways in cisplatin resistant cancer cells may potentially lead to a renewed interest in the development of rational novel therapies for cisplatin resistant cancers, in particular, lung cancer.

Biomarkers of exercise-induced myocardial stress in relation to inflammatory and oxidative stress

Increased concentrations of biomarkers reflecting myocardial stress such as cardiac troponin I and T and brain natriuretic peptide (BNP) have been observed following strenuous, long-lasting endurance exercise. The pathophysiological mechanisms are still not fully elucidated and the interpretations of increased post-exercise concentrations range from (i) evidence for exercise-induced myocardial damage to (ii) non-relevant spurious troponin elevations, presumably caused by assay imprecision or heterophilic antibodies. Several lines of evidence suggest that inflammatory processes or oxidative stress could be involved in the rise of NT-proBNP and Troponin observed in critically ill patients with sepsis or burn injury. We tested the hypothesis that inflammatory or oxidative stress is also responsible for exercise-induced cardiomyocyte strain in a large cohort of triathletes following an Ironman triathlon. However, the post-race increase in cardiac troponin T and NT-proBNP was not associated with several markers of exercise-induced inflammation, oxidative stress or antioxidant vitamins. Therefore, we clearly need more studies with other inflammatory markers and different designs to elucidate the scientific background for increases in myocardial stress markers following strenuous endurance events.

Democratic and participatory citizenship: Youth action for sustainability in Australia

Purpose – The purpose of this paper is to provide a critical analysis of recent examples of action competence among young people engaged in democratic participatory action in sustainability programs in Australia. It explores examples of priorities identified for citizen action, the forms this action takes and the ways that democratic participation can achieve positive outcomes for future sustainability. It suggests multiple ways for developing action competence that provides further opportunities for authentic and engaging citizen action for youth connected to school- and community-based learning, in new and powerful ways. Design/methodology/approach – This conceptual paper examines international literature on the theory of “action competence,” its significance for education for sustainability (EfS) and the ways it can inform education for young people’s democratic participatory citizenship and civic engagement. It analyses examples of the development of action competency among young people in Australia, including the problems and priorities identified for citizen action, the forms this action takes and how it can achieve positive outcomes for sustainability. Following this analysis, the paper suggests multiple ways for developing action competence in EfS in schools and communities in new and powerful ways. Findings – Developing EfS to increase democratic and participatory action among young citizens is now widely regarded as an urgent education priority. There are growing exemplars of school and community organizations’ involvement in developing EfS learning and teaching to increase participatory citizenship. Young people are being empowered to develop a greater sense of agency through involvement in programs that develop action competence with a focus on sustainability in and out of school. New forms of participation include student action teams and peer collaboration among youth who are marshaling social media and direction action to achieve change. Originality/value – It contributes to the literature on multiple ways for developing action competence in EfS.

Action word meaning representations in cytoarchitectonically defined primary and premotor cortices

Recent models of language comprehension have assumed a tight coupling between the semantic representations of action words and cortical motor areas. We combined functional MRI with cytoarchitectonically defined probabilistic maps of left hemisphere primary and premotor cortices to analyse responses of functionally delineated execution- and observation-related regions during comprehension of action word meanings associated with specific effectors (e.g., punch, bite or stomp) and processing of items with various levels of lexical information (non body part-related meanings, nonwords, and visual character strings). The comprehension of effector specific action word meanings did not elicit preferential activity corresponding to the somatotopic organisation of effectors in either primary or premotor cortex. However, generic action word meanings did show increased BOLD signal responses compared to all other classes of lexical stimuli in the pre-SMA. As expected, the majority of the BOLD responses elicited by the lexical stimuli were in association cortex adjacent to the motor areas. We contrast our results with those of previous studies reporting significant effects for only 1 or 2 effectors outside cytoarchitectonically defined motor regions and discuss the importance of controlling for potentially confounding lexical variables such as imageability. We conclude that there is no strong evidence for a somatotopic organisation of action word meaning representations and argue the pre-SMA might have a role in maintaining abstract representations of action words as instructional cues.