Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

Circulating tumor cells: Isolation, expansion, characterization and translation to clinic

Circulating tumor cells (CTCs) are the seeds for cancer metastases development, which is responsible for >90% of cancer-related deaths. Accurate quantification of CTCs in human fluids could be an invaluable tool for understanding cancer prognosis, delivering personalized medicine to prevent metastasis and finding cancer therapy effectiveness. Although CTCs were first discovered more than 200 years ago, until now it has been a nightmare for clinical practitioners to capture and diagnose CTCs in clinical settings. Our society needs rapid, sensitive, and reliable assays to identify the CTCs from blood in order to help save millions of lives. Due to the phenotypic EMT transition, CTCs are undetected for more than one-third of metastatic breast cancer patients in clinics. To tackle the above challenges, the first volume in “Circulating Tumor Cells (CTCs): Detection Methods, Health Impact and Emerging Clinical Challenges discusses recent developments of different technologies, which have the capability to target and elucidate the phenotype heterogenity of CTCS. It contains seven chapters written by world leaders in this area, covering basic science to possible device design which can have beneficial applications in society. This book is unique in its design and content, providing an in-depth analysis to elucidate biological mechanisms of cancer disease progression, CTC detection challenges, possible health effects and the latest research on evolving technologies which have the capability to tackle the above challenges. It describes the broad range of coverage on understanding CTCs biology from early predictors of the metastatic spread of cancer, new promising technology for CTC separation and detection in clinical environment and monitoring therapy efficacy via finding the heterogeneous nature of CTCs. (Imprint: Nova Biomedical)

Should I stay or should I go?: Rural and remote students in first year university stem courses

Research on the achievement of rural and remote students in science and mathematics is located within a context of falling levels of participation in physical science and mathematics courses in Australian schools, and underrepresentation of rural students in higher education. International studies such as the Programme of International Student Assessment (PISA), have reported lower levels of mathematical and scientific literacy in Australian students from rural and remote schools (Thomson et al, 2011). The SiMERR national survey of science, mathematics and ICT education in rural and regional Australia (Lyons et al, 2006) identified factors affecting student achievement in rural and remote schools. Many of the issues faced by rural and remote students in their schools are likely to have implications on their university enrolments in science, technology, engineering and mathematics (STEM) courses. For example, rural and remote students are less likely to attend university in general than their city counterparts and higher university attrition rates have been reported for remote students nationally. This paper examines the responses of a sample of rural/remote Australian first year STEM students at Australian universities to two questions. These related to their intentions to complete the course; and whether -and if so, why- they had ever considered withdrawing from their course. Results indicated that rural students who were still in their course by the end of first year were no more or less likely to consider withdrawing than were their peers from more populous centres. However, almost 20% of the rural cohort had considered withdrawing at some stage in their course, and their explanations provide insights into the reasoning of those who may not persist with their courses at university. These results, in the context of the greater attrition rate of remote students from university, point to the need to identify factors that positively impact on rural and remote students’ interest and achievement in science and mathematics. It also highlights a need for future research into the particular issues remote students may face in deciding whether or not to do science at the two key transition points of senior school and university/TAFE studies, and whether or not to persist in their tertiary studies. This paper is positioned at the intersection of two problems in Australian education. The first is a context of falling levels of participation in physical science and mathematics courses in Australian universities. The second is persistent inequitable access to, and retention in, tertiary education for students from rural and remote areas. Despite considerable research attention to both of these areas over recent years these problems have thus far proved to be intractable. This paper therefore aims to briefly review the relevant Australian literature pertaining to these issues; that is, declining STEM enrolments, and the underrepresentation and retention of rural/remote students in higher education. Given the related problems in these two overlapping domains, we then explore the views of first year rural students enrolled in courses, in relation to their intentions of withdrawing (or not) and the associated reasons for their views.

Switching period randomisation for multilevel converter modulation

The spectral energy associated with the carrier and sidebands of naturally sampled carrier based PWM can be spread by randomising the carrier (switch) half-period Tc = 1/2fc. So long as the switch duty cycle each period still correctly reflects the value of the modulating fundamental waveform as sampled during that switch period, then the fundamental component will remain undistorted. Natural sampling will ensure this occurs. Carrier based PWM can be extended to (m+1) level multilevel converter waveform generation by creating m triangular carriers, each with an equal 2*pi/m phase displacement. Alternatively the carrier disposition strategy calls for m amplitude displaced triangular carriers, each of amplitude 1/m and frequency mfc. Randomising these carrier sub-periods T0> = 1/2mfc is shown to generate (m+ 1) level PWM waveforms where the first (m-1) carrier groups are cancelled, while the remaining carrier and sidebands at multiples of mfc are spectrally spread. Numerous five level simulation and experimentally gathered randomised PWM waveforms are presented, showing the effects of the variation of the degree of randomisation, modulation depth and pulse number.

Combat sports analytics: Boxing punch classification using overhead depth imagery

In competitive combat sporting environments like boxing, the statistics on a boxer's performance, including the amount and type of punches thrown, provide a valuable source of data and feedback which is routinely used for coaching and performance improvement purposes. This paper presents a robust framework for the automatic classification of a boxer's punches. Overhead depth imagery is employed to alleviate challenges associated with occlusions, and robust body-part tracking is developed for the noisy time-of-flight sensors. Punch recognition is addressed through both a multi-class SVM and Random Forest classifiers. A coarse-to-fine hierarchical SVM classifier is presented based on prior knowledge of boxing punches. This framework has been applied to shadow boxing image sequences taken at the Australian Institute of Sport with 8 elite boxers. Results demonstrate the effectiveness of the proposed approach, with the hierarchical SVM classifier yielding a 96% accuracy, signifying its suitability for analysing athletes punches in boxing bouts.

Critical Indigenous Studies: Engagements in First World Locations

With increasing speed, the emerging discipline of critical Indigenous studies is expanding and demarcating its territory from Indigenous studies through the work of a new generation of Indigenous scholars. Critical Indigenous Studies makes an important contribution to this expansion, disrupting the certainty of disciplinary knowledge produced in the twentieth century, when studying Indigenous peoples was primarily the domain of non-Indigenous scholars. Aileen Moreton-Robinson's introductory essay provides a context for the emerging discipline. The volume is organized into three sections: the first includes essays that interrogate the embedded nature of Indigenous studies within academic institutions; the second explores the epistemology of the discipline; and the third section is devoted to understanding the locales of critical inquiry and practice. Each essay places and contemplates critical Indigenous studies within the context of First World nations, which continue to occupy Indigenous lands in the twenty-first century. The contributors include Aboriginal, Metis, Maori, Kanaka Maoli, Filipino-Pohnpeian, and Native American scholars working and writing through a shared legacy born of British and later U.S. imperialism. In these countries, critical Indigenous studies is flourishing and transitioning into a discipline, a knowledge/power domain where distinct work is produced, taught, researched, and disseminated by Indigenous scholars.

A randomised controlled clinical trial of a post-discharge, nurse-led educational intervention to reduce anxiety and enhance self-efficacy in percutaneous coronary intervention (PCI) patients within the first week post-discharge: A pilot study

This research investigated the efficacy of a post-discharge nurse-led clinic, for patients who underwent a cardiovascular interventional procedure in Australia. A randomised controlled clinical trial measured the effects of the clinic on patient confidence to self-manage and minimise psychological distress given the strong link between anxiety, depression and coronary heart disease. Hospitalisation for the procedure is short and stressful, and patients may wait up to 7-64 days for post-discharge review. This study provides preliminary quantitative and qualitative evidence that nurse-led clinics undertaken within the first week post-percutaneous coronary intervention may fill a much-needed gap for patients during a potentially vulnerable period.

'Take away from the dry sixties style marking': Lecturer and student perceptions and experiences of audio feedback

Providing audio feedback to assessment is relatively uncommon in higher education. However, published research suggests that it is preferred over written feedback by students but lecturers were less convinced. The aim of this paper is to examine further these findings in the context of a third year business ethics unit. Data was collected from two sources. The first is a series of in-depth, semi-structured interviews conducted with three lecturers providing audio feeback for the first time in Semester One 2011. The second source of data was drawn from the university student evaluation system. A total of 363 responses were used providing 'before' and 'after' perspectives about the effectiveness of audio feedback versus written feedback. Between 2005 and 2009 the survey data provided information about student attitudes to written assessment feedback (n=261). From 2010 onwards the data relates to audio (mp3) feedback (n=102). The analysis of he interview data indicated that introducing audio feedback should be done with care. The perception of the participating lecturers was mixed, ranging from sceptism to outright enthusiasm, but over time the overall approach became positive. It was found that particular attention needs to be paid to small (but important) technical details, and lecturers need to be convinced of its effectieness, especially that it is not necessarily more time consuming than providing written feedback. For students, the analysis revealed a clear preference for audio feedback. It is concluded that there is cause for concern and reason for optimism. It is a cause for concern because there is a possibility that scepticism on the part of academic staff seems to be based on assumptions about what students prefer and a concern about using the technology. There is reason for optimism because the evidence points towards students preferring audio feedback and as academic staff become more familiar with the technology the scepticism tends to evaporate. While this study is limited in scope, questions are raised about tackling negative staff perceptions of audio feedback that are worthy of further research.

Web-based active learning and frequent feedback: Engaging first-year university students

Web-based technology is particularly well-suited to promoting active student involvement in the processes of learning. All students enrolled in a first-year educational psychology unit were required to complete ten weekly online quizzes, ten weekly student-generated questions and ten weekly student answers to those questions. Results of an online survey of participating students strongly support the viability and perceived benefits of such an instructional approach. Although students reported that the 30 assessments were useful and reasonable, the most common theme to emerge from the professional reflections of participating lecturers was that the marking of questions and answers was unmanageable.

Maternal perception of weight status in first-born Australian toddlers aged 12–16 months – the NOURISH and SAIDI cohorts

Background The preference amongst parents for heavier infants is in contrast to obesity prevention efforts worldwide. Parents are poor at identifying overweight in older children, but few studies have investigated maternal perception of weight status amongst toddlers and none in the Australian setting. Methods Mothers (n = 290) completed a self-administered questionnaire at child age 12–16 months, defining their child's weight status as underweight, normal weight, somewhat overweight or very overweight. Weight-for-length z-score was derived from measured weight and length, and children categorized as underweight, normal weight, at risk overweight or obese (WHO standards). Objective classification was compared with maternal perception of weight status. Mean weight-for-length z-score was compared across categories of maternal perception using one-way ANOVA. Multinomial logistic regression was used to determine child or maternal characteristics associated with inaccurate weight perception. Results Most children (83%) were perceived as normal weight. Twenty nine were described as underweight, although none were. Sixty-six children were at risk of overweight, but 57 of these perceived as normal weight. Of the 14 children who were overweight, only 4 were identified as somewhat overweight by their mother. Compared with mothers who could accurately classify their normal weight child, mothers who were older had higher odds of perceiving their normal weight child as underweight, while mothers with higher body mass index had slightly higher odds of describing their overweight/at risk child as normal weight. Conclusion The leaner but healthy weight toddler was perceived as underweight, while only the heaviest children were recognized as overweight. Mothers unable to accurately identify children at risk are unlikely to act to prevent further excess weight gain. Practitioners can lead a shift in attitudes towards weight in infants and young children, promoting routine growth monitoring and adequate but not rapid weight gain.

Bombs away: Visual thinking and students’ engagement in design studios contexts

In design studio, sketching or visual thinking is part of processes that assist students to achieve final design solutions. At QUT’s First and Third Year industrial design studio classes we engage in a variety of teaching pedagogies from which we identify ‘Concept Bombs’ as instrumental in the development of students’ visual thinking and reflective design process, and also as a vehicle to foster positive student engagement. In First year studios our Concept Bombs’ consist of 20 minute individual design tasks focusing on rapid development of initial concept designs and free-hand sketching. In Third Year studios we adopt a variety of formats and different timing, combining individual and team based tasks. Our experience and surveys tell us that students value intensive studio activities especially when combined with timely assessment and feedback. While conventional longer-duration design projects are essential for allowing students to engage with the full depth and complexity of the design process, short and intensive design activities introduce variety to the learning experience and enhance student engagement. This paper presents a comparative analysis of First and Third Year students’ Concept Bomb sketches to describe the types of design knowledge embedded in them, a discussion of limitations and opportunities of this pedagogical technique, as well as considerations for future development of studio based tasks of this kind as design pedagogies in the midst of current university education trends.

Recent progress on synthesis, multi-scale structure, and properties of Y-Si-O oxides

Yttrium silicates (Y-Si-O oxides), including Y2Si2O7, Y2SiO5, and Y4·67(SiO4)3O apatite, have attracted wide attentions from material scientists and engineers, because of their extensive polymorphisms and important roles as grain boundary phases in improving the high-temperature mechanical/thermal properties of Si3N4and SiC ceramics. Recent interest in these materials has been renewed by their potential applications as high-temperature structural ceramics, oxidation protective coatings, and environmental barrier coatings (EBCs). The salient properties of Y-Si-O oxides are strongly related to their unique chemical bonds and microstructure features. An in-depth understanding on the synthesis - multi-scale structure-property relationships of the Y-Si-O oxides will shine a light on their performance and potential applications. In this review, recent progress of the synthesis, multi-scale structures, and properties of the Y-Si-O oxides are summarised. First, various methods for the synthesis of Y-Si-O ceramics in the forms of powders, bulks, and thin films/coatings are reviewed. Then, the crystal structures, chemical bonds, and atomic microstructures of the polymorphs in the Y-Si-O system are summarised. The third section focuses on the properties of Y-Si-O oxides, involving the mechanical, thermal, dielectric, and tribological properties, their environmental stability, and their structure-property relationships. The outlook for potential applications of Y-Si-O oxides is also highlighted.

Complete genome sequence of a novel zantedeschia mild mosaic virus isolate: The first report from Australia and from Alocasia sp

The complete genome of an Australian isolate of zantedeschia mild mosaic virus (ZaMMV) causing mosaic symptoms on Alocasia sp. (designated ZaMMVAU) was cloned and sequenced. The genome comprises 9942 nucleotides (excluding the poly-A tail) and encodes a polyprotein of 3167 amino acids. The sequence is most closely related to a previously reported ZaMMV isolate from Taiwan (ZaMMV-TW), with 82 and 86 % identity at the nucleotide and amino acid level, respectively. Unlike the amino acid sequence of ZaMMV-TW, however, ZaMMV-AU does not contain a polyglutamine stretch at the N-terminus of the coat-protein-coding region upstream of the DAG motif. This is the first report of ZaMMV from Australia and from Alocasia sp.