Tumour but not stromal expression of β3 integrin is essential, and is required early, for spontaneous dissemination of bone-metastatic breast cancer.

Although many preclinical studies have implicated β3 integrin receptors (αvβ3 and αIIbβ3) in cancer progression, β3 inhibitors have shown only modest efficacy in patients with advanced solid tumours. The limited efficacy of β3 inhibitors in patients could arise from our incomplete understanding of the precise function of β3 integrin and, consequently, inappropriate clinical application. Data from animal studies are conflicting and indicate heterogeneity with respect to the relative contributions of β3-expressing tumour and stromal cell populations in different cancers. Here we aimed to clarify the function and relative contributions to metastasis of tumour versus stromal β3 integrin in clinically relevant models of spontaneous breast cancer metastasis, with particular emphasis on bone metastasis. We show that stable down-regulation of tumour β3 integrin dramatically impairs spontaneous (but not experimental) metastasis to bone and lung without affecting primary tumour growth in the mammary gland. Unexpectedly, and in contrast to subcutaneous tumours, orthotopic tumour vascularity, growth and spontaneous metastasis were not altered in mice null for β3 integrin. Tumour β3 integrin promoted migration, protease expression and trans-endothelial migration in vitro and increased vascular dissemination in vivo, but was not necessary for bone colonization in experimental metastasis assays. We conclude that tumour, rather than stromal, β3 expression is essential and is required early for efficient spontaneous breast cancer metastasis to bone and soft tissues. Accordingly, differential gene expression analysis in cohorts of breast cancer patients showed a strong association between high β3 expression, early metastasis and shorter disease-free survival in patients with oestrogen receptor-negative tumours. We propose that β3 inhibitors may be more efficacious if used in a neoadjuvant setting, rather than after metastases are established. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Of great love and immense hate: the ambivalence of the other in a local/global school

In recent times, and in times of insurgent globalisation, modern notions of identity and with them, conceptions of essential and primordially defined difference seem to have fallen apart. Identity is understood as post-modern, a ‘moveable feast’ of ever-in-process, negotiated differences. The examination of the material and conceptual terms and conditions that position these logics otherwise suggests that these arguments remain tied within conceptions of ourselves made through the ambivalent conceptions of others. In this paper, I trace these paradoxical relations as they are represented in a particular local Melbourne school at each end of a decade and at a time of increasing demographic change and global transformation. Teachers and parents understood and defined their identities and the identities of others in ways that were increasingly fragmented, changing and complex. Beneath these changing patterns, they continued to define others as different and as not us in ways that were ambivalent and extreme. These negotiations took place differently in recent years as the definitions of essential notions of identity changed and became more complex to define. Nevertheless, they continued as ambivalent stories of otherness that transversed the tortuous spectrum between orientalism and nativism speculated upon in post-colonial writings.

A review of terrestrial bird atlases of the world and their application

We reviewed 272 bird atlases (standardised surveys intended to document the distribution of birds) from around the world. Atlases we located were conducted in 50 countries from six continents with most (82.4%) from Europe and North America. Atlases were mostly run by ornithological societies (67.1%), had amassed at least 27.9 million records of birds over an area roughly 31.4% of the land area of the Earth, and had involved at least 108 000 contributors. They had a modal data collection period of 4 years (some ran over several decades) and varied greatly in scale, covering local areas to entire continents (21 km² – 10 390 000 km²); atlases that covered larger areas involved more observers and generated more records. Most atlases (88.3%) were constrained to particular seasons, and most of these focussed on the main local breeding period (81.0%). Spatial sampling units ranged from 0.02 km² (2 ha) to 3092 km² and temporal units of sampling varied from 20 minutes to several years. Little information is available on the application of data generated by atlases. We focussed on five major atlases for which information was available. We located 97 scientific publications drawing on data from these five major atlases; papers most frequently focussed on bird distribution (26.8%), ecology (20.6%) and land-use planning (17.5%). Atlas books were cited often, 7–31 times per year. Provision of data to third parties from two major atlases (one from Australia and one from Britain and Ireland) was frequent and remarkably similar. Data were requested mostly for environmental impact studies (almost half of all requests), conservation policy and planning (~20%), research (~20%) and other mapping (~13%). Despite the uses we describe, atlas data seem under-utilised.

Cloud-linked and campus-linked students’ perceptions of collaborative learning and design based learning in engineering

The aim of this paper is to analyse and present cloud- link as well as campus-linked students’ perceptions of collaborative learning and design based learning in engineering. Project oriented design based learning (PODBL) is a learning and teaching approach, where students learn through design activities while being driven by project(s). PODBL enhances cloud-linked and campus-linked students’ ability to acquire career essential skills that fulfill future industry needs. A paper-based survey is used to recognise a cohort of students' experience of collaborative learning and design based learning in engineering. The paper-based survey was given to 30 students from an engineering discipline. The quantitative analysis of the survey results shows that more than 50% of the students view collaborative learning to have a large benefit in design-based learning.

Lateral positioning for critically ill adult patients

BACKGROUND: Critically ill patients require regular body position changes to minimize the adverse effects of bed rest, inactivity and immobilization. However, uncertainty surrounds the effectiveness of lateral positioning for improving pulmonary gas exchange, aiding drainage of tracheobronchial secretions and preventing morbidity. In addition, it is unclear whether the perceived risk levied by respiratory and haemodynamic instability upon turning critically ill patients outweighs the respiratory benefits of side-to-side rotation. Thus, lack of certainty may contribute to variation in positioning practice and equivocal patient outcomes. OBJECTIVES: To evaluate effects of the lateral position compared with other body positions on patient outcomes (mortality, morbidity and clinical adverse events) in critically ill adult patients. (Clinical adverse events include hypoxaemia, hypotension, low oxygen delivery and global indicators of impaired tissue oxygenation.) We examined single use of the lateral position (i.e. on the right or left side) and repeat use of the lateral position (i.e. lateral positioning) within a positioning schedule. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1950 to 23 May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to 23 May 2015), the Allied and Complementary Medicine Database (AMED) (1984 to 23 May 2015), Latin American Caribbean Health Sciences Literature (LILACS) (1901 to 23 May 2015), Web of Science (1945 to 23 May 2015), Index to Theses in Great Britain and Ireland (1950 to 23 May 2015), Trove (2009 to 23 May 2015; previously Australasian Digital Theses Program (1997 to December 2008)) and Proquest Dissertations and Theses (2009 to 23 May 2015; previously Proquest Digital Dissertations (1980 to 23 May 2015)). We handsearched the reference lists of potentially relevant reports and two nursing journals. SELECTION CRITERIA: We included randomized and quasi-randomized trials examining effects of lateral positioning in critically ill adults. We included manual or automated turns but limited eligibility to studies that included duration of body position of 10 minutes or longer. We examined each lateral position versus at least one comparator (opposite lateral position and/or another body position) for single therapy effects, and the lateral positioning schedule (repeated lateral turning) versus other positioning schedules for repetitive therapy effects. DATA COLLECTION AND ANALYSIS: We pre-specified methods to be used for data collection, risk of bias assessment and analysis. Two independent review authors carried out each stage of selection and data extraction and settled differences in opinion by consensus, or by third party adjudication when disagreements remained unresolved. We planned analysis of pair-wise comparisons under composite time intervals with the aim of considering recommendations based on meta-analyses of studies with low risk of bias. MAIN RESULTS: We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. AUTHORS' CONCLUSIONS: Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients.