Targeting aurora kinases : a novel approach to curb the growth and chemoresistance of androgen refractory prostate cancer

Aurora Kinase (AK) based therapy targeting AK-A & B is effective against some cancers. We have explored its potential against previously unreported incurable, metastatic androgen depletion independent Prostate Cancer (ADIPC). We used androgen sensitive (AS) and ADI lines derived from Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. The relevance of this model was unequivocally established through focussed array, quantitative PCR and western blotting studies; significantly greater alteration of genes (fold change and number) representing major cancer pathways was shown in ADI cells compared to AS lines. A marked enhancement of in vivo growth of the ADI subline showing the greatest degree of gene modulations [TRAMP C1 (TC1)-T5: TC1-T5] reflected this. In contrast to the parental AS TC1 line, TC1-T5 cells grew with 100% incidence in the prostate, as lung pseudometastases and migrated to the bone and other soft tissues. The potential involvement of AKs in this transition was indicated by the significant upregulation of AK-A/B and their downstream regulators, survivin and phosphorylated-histone H3 in TC1-T5 cells compared to TC1 cells. This led to enhanced sensitivity of TC1-T5 cells to the pan-AK inhibitor, VX680 and to significant reduction in in vivo tumour growth rates when AK-A and/or B were downregulated in TC1-T5 cells. This cell growth inhibition was markedly enhanced when both AKs were downregulated and also led to substantially greater sensitivity of these cells to docetaxel, the only chemotherapeutic with activity against ADI PC. Finally, use of VX680 with docetaxel led to impressive synergies suggesting promise for treating clinical ADI metastatic PC.

Acepromazine pharmacokinetics: A forensic perspective

Acepromazine (ACP) is a useful therapeutic drug, but is a prohibited substance in competition horses. The illicit use of ACP is difficult to detect due to its rapid metabolism, so this study investigated the ACP metabolite 2-(1-hydroxyethyl)promazine sulphoxide (HEPS) as a potential forensic marker. Acepromazine maleate, equivalent to 30 mg of ACP, was given IV to 12 racing-bred geldings. Blood and urine were collected for 7 days post-administration and analysed for ACP and HEPS by liquid chromatography–mass spectrometry (LC–MS). Acepromazine was quantifiable in plasma for up to 3 h with little reaching the urine unmodified. Similar to previous studies, there was wide variation in the distribution and metabolism of ACP. The metabolite HEPS was quantifiable for up to 24 h in plasma and 144 h in urine. The metabolism of ACP to HEPS was fast and erratic, so the early phase of the HEPS emergence could not be modelled directly, but was assumed to be similar to the rate of disappearance of ACP. However, the relationship between peak plasma HEPS and the y-intercept of the kinetic model was strong (P = 0.001, r2 = 0.72), allowing accurate determination of the formation pharmacokinetics of HEPS. Due to its rapid metabolism, testing of forensic samples for the parent drug is redundant with IV administration. The relatively long half-life of HEPS and its stable behaviour beyond the initial phase make it a valuable indicator of ACP use, and by determining the urine-to-plasma concentration ratios for HEPS, the approximate dose of ACP administration may be estimated.

Digital dietetics : practices and attitudes to technology use among Australian dietitians

Recent advancements in the capabilities of information and communication technologies (ICT) offer unique avenues to support the delivery of nutrition care. Despite ICTs being widely available, evidence on the practices and attitudes with regard to ICT use among dietitians is limited. A cross-sectional survey of Dietitians Association of Australia members was administered online in August 2011. All dietitians who responded (n=87) had access to a computer at work. Half reported providing non face-to-face consultations, with the telephone and email the most common modes of delivery. The use of smart phones was prevalent for 49% of practitioners, with 30% recommending nutrition-related applications and/or programs to clients. Benefits to technology use in practice most commonly reported included improvements in access to information/resources, time management, and workflow efficiency. Barriers identified related to cost and access to technology, and lack of suitable programs/applications. Technology was viewed as an important tool in practice among 93% of dietitians surveyed, however only 38% were satisfied with their current level of use. The majority (81%) believed more technology should be integrated within dietetics, while 85% indicated that the development of suitable and practical applications andprograms is necessary for future practice. Technology is regarded as an important tool by Australian dietitians, with an expressed need for theirinclusion to further facilitate nutrition care. Regular and ongoing evaluation of technology use among dietitians is vital to ensure thatapplications and use are evidence based and relevant to consumers in the digital world.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Predictive modelling : parents’ decision making to use online child health information to increase their understanding and/or diagnose or treat their child’s health

Abstract Background The quantum increases in home Internet access and available online health information with limited control over information quality highlight the necessity of exploring decision making processes in accessing and using online information, specifically in relation to children who do not make their health decisions. Objectives To understand the processes explaining parents’ decisions to use online health information for child health care. Methods Parents (N = 391) completed an initial questionnaire assessing the theory of planned behaviour constructs of attitude, subjective norm, and perceived behavioural control, as well as perceived risk, group norm, and additional demographic factors. Two months later, 187 parents completed a follow-up questionnaire assessing their decisions to use online information for their child’s health care, specifically to 1) diagnose and/or treat their child’s suspected medical condition/illness and 2) increase understanding about a diagnosis or treatment recommended by a health professional. Results Hierarchical multiple regression showed that, for both behaviours, attitude, subjective norm, perceived behavioural control, (less) perceived risk, group norm, and (non) medical background were the significant predictors of intention. For parents’ use of online child health information, for both behaviours, intention was the sole significant predictor of behaviour. The findings explain 77% of the variance in parents’ intention to treat/diagnose a child health problem and 74% of the variance in their intentions to increase their understanding about child health concerns. Conclusions Understanding parents’ socio-cognitive processes that guide their use of online information for child health care is important given the increase in Internet usage and the sometimes-questionable quality of health information provided online. Findings highlight parents’ thirst for information; there is an urgent need for health professionals to provide parents with evidence-based child health websites in addition to general population education on how to evaluate the quality of online health information.

Participatory content creation and collective intelligence in Rio de Janeiro's favelas

This proposal combines ethnographic techniques and discourse studies to investigate a collective of people engaged with audiovisual productions who collaborate in Curta Favela’s workshops in Rio de Janeiro’s favelas. ‘Favela’ is often translated simply as ‘slum’ or ‘shantytown’, but these terms connote negative characteristics such as shortage, poverty, and deprivation which end up stigmatizing these low income suburbs. Curta Favela (Favela Shorts) is an independent project in which all participants join to use photography and participatory audiovisual production as tools for social change and to raise consciousness. As cameras are not affordable for favela dwellers, Curta Favela’s volunteers teach favela residents how they can use their mobile phones and compact cameras to take pictures and make movies, and afterwards, how they can edit the data using free editing video software programs and publish it on the Internet. To record audio, they use their mp3 or mobile phones. The main aim of this study is to shed light not only on how this project operates, but also to highlight how collective intelligence can be used as a way of fighting against a lack of basic resources.

The process and patterns of combining the use of traditional Chinese medicine and Western medicine in Taiwanese people with cancer

Objective: The nature of contemporary cancer therapy means that patients are faced with difficult treatment decisions about surgery, chemotherapy and radiotherapy. For some, this process may also involve consideration of therapies that sit outside the biomedical approach to cancer treatment, in our research, traditional Chinese medicine (TCM). Thus, it is important to explore how cancer patients in Taiwan incorporate TCM into their cancer treatment journey. This paper aims to explore of the patterns of combining the use of TCM and Western medicine into cancer treatment journey in Taiwanese people with cancer. Methods: The sampling was purposive and the data collected through in-depth interviews. Data collection occurred over an eleven month. The research was grounded in the premises of symbolic interactionism and adopted the methods of grounded theory. Twenty four participants who were patients receiving cancer treatment were recruited from two health care settings in Taiwan. Results: The study findings suggest that perceptions of health and illness are mediated through ongoing interactions with different forms of therapy. The participants in this study had a clear focus on “process and patterns of using TCM and Western medicine”. Further, ‘different importance in Western medicine and TCM’, ‘taken for granted to use TCM’, ‘each has specialized skills in Western medicine and TCM’ and ‘different symptoms use different approaches (Western medicine or TCM)’ may explicit how the participants in this study see CAM and Western medicine. Conclusions/Implications for practice: The descriptive frame of the study suggests that TCM and Western medicine occupy quite distinct domains in terms of decision making over their use. People used TCM based on interpretations of the present and against a background of an enduring cultural legacy grounded in Chinese philosophical beliefs about health and healthcare. The increasingly popular term of 'integrative medicine' obscures the complex contexts of the patterns of use of both therapeutic modalities. It is this latter point that is worthy of further exploration.

Update on complex nonpharmacological interventions for breathlessness

Purpose of review: The study provides a review of current evidence about the role of complex nonpharmacological strategies in managing the multidimensional components of the breathlessness experience for individuals with life-limiting conditions. Recent findings: Evidence continues to demonstrate the significant impact of breathlessness on patients’ quality of life, day-to-day activity, and physical and psychosocial functioning. Recent evidence also confirms that patients draw on a number of self-initiated actions to cope with breathlessness, although many do not use strategies that are supported by a growing body of evidence from randomized controlled trials. Current literature supports the use of multicomponent, nonpharmacological interventions comprising strategies to improve breathing efficiency and reducing psychological distress to manage breathlessness. However trials of these approaches have mostly been conducted among patients with chronic obstructive pulmonary disease (COPD) or lung cancer, and few studies have investigated the benefits of nonpharmacological for patients in later stages of disease. Further investigation of interventions is required across a broader range of chronic life-limiting conditions. Addressing breathlessness and its co-occurring symptoms (symptom clusters) is also an area for future enquiry. Summary: The experience of breathlessness and strategies adopted by patients to manage the experience highlight the importance of multidimensional approaches to improve outcomes for patients with life-limiting conditions. There is good evidence to support the role of multicomponent, nonpharmacological interventions in reducing breathlessness for patients with COPD and lung cancer, although further studies are required to understand the particular clinical contexts in which such interventions are appropriate.

Generalizing curriculum policy across boarders : crossing boundaries

"This essay is a critique of the scientific and policy rationales for transnational standardization. It analyzes two examples of policy export: early childhood standards in one of North America’s oldest Indigenous communities and the ongoing development of international standards for university teaching. It examines calls for American education to look to Finland, Canada, and Singapore for models of reform and innovation, focusing on the complex historical, cultural, and political settlements at work in these countries. The author addresses two affiliated challenges: first, the possibility of a principled understanding of evidence and policy in cultural and political-economic context, and second, the possibility of a mediative educational science that might guide policy formation." -- EDUCATIONAL RESEARCHER November 2011 vol. 40 no. 8 367-377

A fiber Bragg grating temperature sensor with adjustable sensitivity [一种灵敏度系数可调的光纤光栅温度传感器]

As a novel sensing element, fiber Bragg grating (FBG) is sensitive to both temperature and strain. Basing on this character, high sensitivity FBG temperature sensor can be made. However, as a result of the strain limit of the fiber, the temperature range it can endure is quite narrow. This drawback limits its application and complicates its storage and transport. We design and manufacture a FBG temperature sensor with tunable sensitivity. By tuning its sensitivity, its temperature range is changed, which enlarges its application field, solves the problem of storage and transport, and brighten the future of FBG in temperature measurement. In experiment, by changing the fixing position of the bimetal we tuned the sensitivity of the high sensitivity FBG sensor to different values (-47 pm/℃，-97.7 pm/℃，-153.3 pm/℃).

Confucius Institutes as innovative tools of China's cultural diplomacy

"Chapter 5 by Hartig introduces Confucius Institutes as an innovative tool of China’s cultural diplomacy. It explains the origins and implications of this new approach to promote China’s culture abroad and thus to shape China’s image globally. The chapter draws on case studies of Con- fucius Institutes in Australia and Germany. It shows how China is adapting a Western instrument of cultural diplomacy, namely an organisation like the British Council or Goethe Institute, in an innovative manner to accomplish its goals in the most effective way. In contrast to British Councils or Goethe Institutes, Confucius Institutes are typically set up as joint ventures between Chinese and international partners. By exploring the advantages and disadvantages of this project for both sides, the chapter illustrates how the outside world shapes China and, in turn, China shapes the outside world in the context of cultural exchange and cooperation. It argues that global influences, namely the general negative perception of China in the West, have forced China not only to become active in the field of cultural diplomacy, but furthermore to strive for an innovative way to be successful."

Finding our way to the future : directions for a city of opportunity

This Australian case study of futures methodologies in local government explores the development and implementation of the Logan 2026 City Directions project. As an innovative approach to strategic planning, and forming the city visioning umbrella for the Strategic Planning and Performance Management Framework of Council, Logan 2026 City Directions has facilitated greater engagement with the community and represents an opportunity for Council to explore and build on the organisation's foresight capacity and to enhance internal communications within the organisation. One significant by-product has been ongoing dialogue and actions of the workshop groups in Council seeking to address such issues as climate change.

A bridge over troubling waters : a snapshot of teacher graduates' perceptions of their ongoing professional learning needs

For graduating teachers, the bridging period between formal teacher preparation and joining the profession is a time of high anxiety and great excitement. While this transition influences efficacy, job satisfaction, career length and future teaching quality, it is widely recognized to be inconsistent, poorly planned and resourced and largely unsupported (DEST, 2002; Herrington & Herrington, 2004). In Australia, the transition to teaching remains largely a school-based affair. However, individual schools may not have the resources to support a comprehensive and cohesive transition program. This paper discusses a pilot university program of extended teacher preparation. It reports on the perceived professional learning needs of a group of graduates as they transition to teaching. The key findings indicate that these graduates are seeking ongoing support as they develop confidence in their canonical skills of teaching. We argue that university-based programs are one way of providing professional learning and support for beginning teachers.

An objective measure of reactive behaviour in horses

Several tests have been devised in an attempt to detect behaviour modification due to training, supplements or diet in horses. These tests rely on subjective observations in combination with physiological measures, such as heart rate (HR) and plasma cortisol concentrations, but these measures do not definitively identify behavioural changes. The aim of the present studies was to develop an objective and relevant measure of horse reactivity. In Study 1, HR responses to auditory stimuli, delivered over 6 days, designed to safely startle six geldings confined to individual stalls was studied to determine if peak HR, unconfounded by physical exertion, was a reliable measure of reactivity. Both mean (±SEM) resting HR (39.5 ± 1.9 bpm) and peak HR (82 ± 5.5 bpm) in response to being startled in all horses were found to be consistent over the 6 days. In Study 2, HR, plasma cortisol concentrations and speed of departure from an enclosure (reaction speed (RS)) in response to a single stimulus of six mares were measured when presented daily over 6 days. Peak HR response (133 ± 4 bpm) was consistent over days for all horses, but RS increased (3.02 ± 0.72 m/s on Day 1 increasing to 4.45 ± 0.53 m/s on Day 6; P = 0.005). There was no effect on plasma cortisol, so this variable was not studied further. In Study 3, using the six geldings from Study 1, the RS test was refined and a different startle stimulus was used each day. Again, there was no change in peak HR (97.2 ± 5.8 bpm) or RS (2.9 ± 0.2 m/s on Day 1 versus 3.0 ± 0.7 m/s on Day 6) over time. In the final study, mild sedation using acepromazine maleate (0.04 mg/kg BW i.v.) decreased peak HR in response to a startle stimulus when the horses (n = 8) were confined to a stall (P = 0.006), but not in an outdoor environment when the RS test was performed. However, RS was reduced by the mild sedation (P = 0.02). In conclusion, RS may be used as a practical and objective test to measure both reactivity and changes in reactivity in horses.

Revisiting the concept of the ‘problem young driver’ within the context of the ‘young driver problem’ : Who are they?

For decades there have been two young driver concepts: the ‘young driver problem’ where the driver cohort represents a key problem for road safety; and the ‘problem young driver’ where a sub-sample of drivers represents the greatest road safety problem. Given difficulties associated with identifying and then modifying the behaviour of the latter group, broad countermeasures such as graduated driver licensing (GDL) have generally been relied upon to address the young driver problem. GDL evaluations reveal general road safety benefits for young drivers, yet they continue to be overrepresented in fatality and injury statistics. Therefore it is timely for researchers to revisit the ‘problem young driver’ concept to assess its potential countermeasure implications. This is particularly relevant within the context of broader countermeasures that have been designed to address the ‘young driver problem’. Personal characteristics, behaviours and attitudes of 378 Queensland novice drivers aged 17-25 years were explored during their pre-, Learner and Provisional 1 (intermediate) licence as part of a larger longitudinal project. Self-reported risky driving was measured by the Behaviour of Young Novice Drivers Scale (BYNDS), and five subscale scores were used to cluster the drivers into three groups (high risk n=49, medium risk n=163, low risk n=166). High risk ‘problem young drivers’ were characterised by greater self-reported pre-Licence driving, unsupervised Learner driving, and speeding, driving errors, risky driving exposure, crash involvement, and offence detection during the Provisional period. Medium risk drivers were also characterised by more risky road use than the low risk group. Interestingly problem young drivers appear to have some insight into their high-risk driving, since they report significantly greater intentions to bend road rules in future driving. The results suggest that tailored intervention efforts may need to target problem young drivers within the context of broad countermeasures such as GDL which address the young driver problem in general. Experiences such as crash-involvement could be used to identify these drivers as a pre-intervention screening measure.