Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1-integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1-integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

Literature review : use of respite by carers of people with dementia

Respite care is a cornerstone service for the home management of people with dementia. It is used by carers to mitigate the stress related to the demands of caring by allowing time for them to rest and do things for themselves, thus maintaining the caring relationship at home and perhaps forestalling long-term placement in a residential aged care facility. Despite numerous anecdotal reports in support of respite care, its uptake by carers of people with dementia remains relatively low. The aim of this paper was to examine the factors that constitute the use of respite by carers of people with dementia by reviewing quantitative and qualitative research predominantly from the years 1990 to 2012. Seventysix international studies of different types of respite care were included for this review and their methods were critically appraised. The key topics identified were in relation to information access, the barriers to carers realising need for and seeking respite, satisfaction with respite services including the outcomes for carers and people with dementia, the characteristics of an effective respite service and the role of health workers in providing appropriate respite care. Finally, limitations with considering the literature as a whole were highlighted and recommendations made for future research.

Designing mobile systems for social navigation in urban public places

This thesis presents social requirements and design considerations from a study evaluating interactive approaches to social navigation and user-generated information sharing in urban environments using mobile devices. It investigates innovative ways to leverage mobile information and communication technology in order to provide a social navigation platform for residents and visitors in and for public urban places. Through a design case study this work presents CityFlocks, a mobile information system that offers an easy way for information-seeking new residents or visitors to access tacit knowledge from local people about their new community. It is intended to enable visitors and new residents in a city to tap into the knowledge and experiences of local residents in order to gather information about their new environment. Its design specifically aims to lower existing barriers of access and facilitate social navigation in urban places. In various user tests it evaluates two general user interaction alternatives – direct and indirect social navigation – and analyses which interaction method works better for people using a mobile device to socially navigate urban environments. The outcomes are relevant for the user interaction design of future mobile information systems that leverage the social navigation approach.

New approaches to making the microenvironment of the female reproductive tract hostile to HIV

The studies presented in this review explore three distinct areas with potential for inhibiting HIV infection in women. Based on emerging information from the physiology, endocrinology and immunology of the female reproductive tract (FRT), we propose unique 'works in progress' for protecting women from HIV. Various aspects of FRT immunity are suppressed by estradiol during the menstrual cycle, making women more susceptible to HIV infection. By engineering commensal Lactobacillus to secrete the anti-HIV molecule Elafin as estradiol levels increase, women could be protected from HIV infection. Selective estrogen response modifiers enhance barrier integrity and enhance secretion of protective anti-HIV molecules. Finally, understanding the interactions and regulation of FRT endogenous antimicrobials, proteases, antiproteases, etc., all of which are under hormonal control, will open new avenues to therapeutic manipulation of the FRT mucosal microenvironment. By seeking new alternatives to preventing HIV infection in women, we may finally disrupt the HIV pandemic.

Sensorimotor and postural control factors associated with driving safety in a community-dwelling older driver population

Background. To establish whether sensorimotor function and balance are associated with on-road driving performance in older adults. Methods. The performance of 270 community-living adults aged 70–88 years recruited via the electoral roll was measured on a battery of peripheral sensation, strength, flexibility, reaction time, and balance tests and on a standardized measure of on-road driving performance. Results. Forty-seven participants (17.4%) were classified as unsafe based on their driving assessment. Unsafe driving was associated with reduced peripheral sensation, lower limb weakness, reduced neck range of motion, slow reaction time, and poor balance in univariate analyses. Multivariate logistic regression analysis identified poor vibration sensitivity, reduced quadriceps strength, and increased sway on a foam surface with eyes closed as significant and independent risk factors for unsafe driving. These variables classified participants into safe and unsafe drivers with a sensitivity of 74% and specificity of 70%. Conclusions. A number of sensorimotor and balance measures were associated with driver safety and the multivariate model comprising measures of sensation, strength, and balance was highly predictive of unsafe driving in this sample. These findings highlight important determinants of driver safety and may assist in developing efficacious driver safety strategies for older drivers.

The effect of three different (-135°C) whole body cryotherapy exposure durations on elite rugby league players

Background: Whole body cryotherapy (WBC) is the therapeutic application of extreme cold air for a short duration. Minimal evidence is available for determining optimal exposure time. Purpose: To explore whether the length of WBC exposure induces differential changes in inflammatory markers, tissue oxygenation, skin and core temperature, thermal sensation and comfort. Method: This study was a randomised cross over design with participants acting as their own control. Fourteen male professional first team super league rugby players were exposed to 1, 2, and 3 minutes of WBC at -135°C. Testing took place the day after a competitive league fixture, each exposure separated by seven days. Results: No significant changes were found in the inflammatory cytokine interleukin six. Significant reductions (p<0.05) in deoxyhaemoglobin for gastrocnemius and vastus lateralis were found. In vastus lateralis significant reductions (p<0.05) in oxyhaemoglobin and tissue oxygenation index (p<0.05) were demonstrated. Significant reductions (p<0.05) in skin temperature were recorded. No significant changes were recorded in core temperature. Significant reductions (p<0.05) in thermal sensation and comfort were recorded. Conclusion: Three brief exposures to WBC separated by 1 week are not sufficient to induce physiological changes in IL-6 or core temperature. There are however significant changes in tissue oxyhaemoglobin, deoxyhaemoglobin, tissue oxygenation index, skin temperature and thermal sensation. We conclude that a 2 minute WBC exposure was the optimum exposure length at temperatures of -135°C and could be applied as the basis for future studies.

Forrest v ASIC : a ‘perfect storm’

The policy objectives of the continuous disclosure regime augmented by the misleading or deceptive conduct provisions in the Corporations Act are to enhance the integrity and efficiency of Australian capital markets by ensuring equality of opportunity for all investors through public access to accurate and material company information to enable them to make well-informed investment decisions. This article argues that there were failures by the regulators in the performance of their roles to protect the interests of investors in Forrest v ASIC; FMG v ASIC (2012) 247 CLR 486: ASX failed to enforce timely compliance with the continuous disclosure regime and ensure that the market was properly informed by seeking immediate clarification from FMG as to the agreed fixed price and/or seeking production of a copy of the CREC agreement; and ASIC failed to succeed in the High Court because of the way it pleaded its case. The article also examines the reasoning of the High Court in Forrest v ASIC and whether it might have changed previous understandings of the Campomar test for determining whether representations directed to the public generally are misleading.

How approach and avoidance constructs of personality and trait emotional intelligence predict core human values

In this paper we focus specifically on explaining variation in core human values, and suggest that individual differences in values can be partially explained by personality traits and the perceived ability to manage emotions in the self and others (i.e. trait emotional intelligence). A sample of 209 university students was used to test hypotheses regarding several proposed direct and indirect relationships between personality traits, trait emotional intelligence and values. Consistent with the hypotheses, Harm Avoidance and Novelty Seeking were found to directly predict Hedonism, Conformity, and Stimulation. Harm Avoidance was also found to indirectly predict these values through the mediating effects of key subscales of trait emotional intelligence. Novelty Seeking was not found to be an indirect predictor of values. Results have implications for our understanding of the relationship between personality, trait emotional intelligence and values, and suggest a common basis in terms of approach and avoidance pathways.

Prioritizing process improvement : an example from the Australian financial services sector

Process improvement has become a number one business priority, and more and more project requests are raised in organizations, seeking approval and resources for process-related projects. Realistically, the total of the requested funds exceeds the allocated budget, the number of projects is higher than the available bandwidth, and only some of these (very often only few) can be supported and most never see any light. Relevant resources are scarce, and correct decisions must be made to make sure that those projects that are of best value are implemented. How can decision makers make the right decision on the following: Which project(s) are to be approved and when to commence work on them? Which projects are most aligned with corporate strategy? How can the project’s value to the business be calculated and explained? How can these decisions be made in a fair, justifiable manner that brings the best results to the company and its stakeholders? This chapter describes a business value scoring (BVS) model that was built, tested, and implemented by a leading financial institution in Australia to address these very questions. The chapter discusses the background and motivations for such an initiative and describes the tool in detail. All components and underlying concepts are explained, together with details on its application. This tool has been successfully implemented in the case organization. The chapter provides practical guidelines for organizations that wish to adopt this approach.

Thinking about internal states, a qualitative investigation into metacognitions in women with eating disorders

Background There is a need for qualitative research to help develop case conceptualisations to guide the development of Metacognitive Therapy interventions for Eating Disorders. Method A qualitative study informed by grounded theory methodology was conducted involving open-ended interviews with 27 women aged 18–55 years, who were seeking or receiving treatment for a diagnosed ED. Results The categories identified in this study appeared to be consistent with a metacognitive model including constructs of a Cognitive Attentional Syndrome and metacognitive beliefs. These categories appear to be transdiagnostic, and the interaction between the categories is proposed to explain the maintenance of EDs. Conclusions The transdiagnostic model proposed may be useful to guide the development of future metacognitive therapy interventions for EDs with the hope that this will lead to improved outcomes for individuals with EDs.

Position paper : benchmarking the performance of global and emerging knowledge cities

Knowledge-based development has become a new urban policy approach for the competitive cities of the global knowledge economy era. For those cities seeking a knowledge-based development, benchmarking is an essential prerequisite for informed and strategic vision and policy making to achieve a prosperous development. Nevertheless, benchmarked knowledge-based development performance analysis of global and emerging knowledge cities is an understudied area. This paper aims to contribute to the field by introducing the methodology of a novel performance assessment model—that is the Knowledge-Based Urban Development Assessment Model—and providing lessons from the application of the model in an international knowledge city performance analysis study. The assessment model puts renowned global and emerging knowledge cities—that are Birmingham, Boston, Brisbane, Helsinki, Istanbul, Manchester, Melbourne, San Francisco, Sydney, Toronto, and Vancouver—under the knowledge-based development microscope. The results of the analysis provide internationally benchmarked snapshot of the degree of achievements in various knowledge-based urban development performance areas of the investigated knowledge cities, and reveals insightful lessons on scrutinizing the global perspectives on knowledge-based development of cities.

The National Disability Insurance Scheme Handbook

"The National Disability Insurance Scheme (NDIS) was launched on 1 July 2013. The NDIS Act 2013 is an historic piece of legislation that is the foundation for a national scheme which will deliver meaningful change for people with disabilities across Australia. The NDIS seeks to support the independence and social and economic participation of people with a disability, mainly by funding the provision of reasonable and necessary supports, including early intervention supports. The NDIS establishes three main criteria for access to the scheme - age, residence and disability. The National Disability Insurance Scheme Handbook written by Bill Madden, Janine McIlwraith and Ruanne Brell examines the NDIS from the viewpoint of a person seeking to access the NDIS and those advising or assisting them. The three key criteria are examined, along with the powers of the NDIS Chief Executive Officer and the scope for review of adverse decisions. The important area of interplay between the NDIS and compensation entitlements is carefully scrutinised. This handbook provides scheme users, carers, lawyers and health practitioners with an easy to understand guide to this watershed legal development."--Publisher website

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

The informed manager : exploring absorptive capacity in the non-profit sector

Being across new knowledge is critical to the survival of individual businesses. This study explored the way in which managers of small social services in Queensland identified important new knowledge and brought this into their organisations. New knowledge was found to be highly valued by managers with key resources allocated to knowledge seeking processes particularly in response to regulatory change. Knowledge absorption involved accessing multiple sources, and external professional networks were found to be critical to understanding and integrating new knowledge. The research highlighted the challenges in securing new knowledge and the importance of managers professional links.

Longitudinal assessment of neuropathy in diabetes using novel ophthalmic markers (LANDMark) : baseline findings

Purpose Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results 396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.