Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.

Molecular characterisation of environmental enterococci derived from water samples and assessment of associated public health hazards

Enterococci are versatile Gram-positive bacteria that can survive under extreme conditions. Most enterococci are non-virulent and found in the gastrointestinal tract of humans and animals. Other strains are opportunistic pathogens that contribute to a large number of nosocomial infections globally. Epidemiological studies demonstrated a direct relationship between the density of enterococci in surface waters and the risk of swimmer-associated gastroenteritis. The distribution of infectious enterococcal strains from the hospital environment or other sources to environmental water bodies through sewage discharge or other means, could increase the prevalence of these strains in the human population. Environmental water quality studies may benefit from focusing on a subset of Enterococcus spp. that are consistently associated with sources of faecal pollution such as domestic sewage, rather than testing for the entire genus. E. faecalis and E. faecium are potentially good focal species for such studies, as they have been consistently identified as the dominant Enterococcus spp. in human faeces and sewage. On the other hand enterococcal infections are predominantly caused by E. faecalis and E. faecium. The characterisation of E. faecalis and E. faecium is important in studying their population structures, particularly in environmental samples. In developing and implementing rapid, robust molecular genotyping techniques, it is possible to more accurately establish the relationship between human and environmental enterococci. Of particular importance, is to determine the distribution of high risk enterococcal clonal complexes, such as E. faecium clonal complex 17 and E. faecalis clonal complexes 2 and 9 in recreational waters. These clonal complexes are recognized as particularly pathogenic enterococcal genotypes that cause severe disease in humans globally. The Pimpama-Coomera watershed is located in South East Queensland, Australia and was investigated in this study mainly because it is used intensively for agriculture and recreational purposes and has a strong anthropogenic impact. The primary aim of this study was to develop novel, universally applicable, robust, rapid and cost effective genotyping methods which are likely to yield more definitive results for the routine monitoring of E. faecalis and E. faecium, particularly in environmental water sources. To fullfill this aim, new genotyping methods were developed based on the interrogation of highly informative single nucleotide polymorphisms (SNPs) located in housekeeping genes of both E. faecalis and E. faecium. SNP genotyping was successfully applied in field investigations of the Coomera watershed, South-East Queensland, Australia. E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles respectively. This study showed the high longitudinal diversity of E. faecalis and E. faecium over a period of two years, and both human-related and human-specific SNP profiles were identified. Furthermore, 4.25% of E. faecium strains isolated from water was found to correspond to the important clonal complex-17 (CC17). Strains that belong to CC17 cause the majority of hospital outbreaks and clinical infections globally. Of the six sampling sites of the Coomera River, Paradise Point had the highest number of human-related and human-specific E. faecalis and E. faecium SNP profiles. The secondary aim of this study was to determine the antibiotic-resistance profiles and virulence traits associated with environmental E. faecalis and E. faecium isolates compared to human pathogenic E. faecalis and E. faecium isolates. This was performed to predict the potential health risks associated with coming into contact with these strains in the Coomera watershed. In general, clinical isolates were found to be more resistant to all the antibiotics tested compared to water isolates and they harbored more virulence traits. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). However, tetracycline, gentamicin, ciprofloxacin and ampicillin resistance was observed in water isolates. The virulence gene esp was the most prevalent virulence determinant observed in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium), and this gene has been described as a human-specific marker used for microbial source tracking (MST). The presence of esp in water isolates (16.36% of E. faecalis and 19.14% of E. faecium) could be indicative of human faecal contamination in these waterways. Finally, in order to compare overall gene expression between environmental and clinical strains of E. faecalis, a comparative gene hybridization study was performed. The results of this investigation clearly demonstrated the up-regulation of genes associated with pathogenicity in E. faecalis isolated from water. The expression study was performed at physiological temperatures relative to ambient temperatures. The up-regulation of virulence genes demonstrates that environmental strains of E. faecalis can pose an increased health risk which can lead to serious disease, particularly if these strains belong to the virulent CC17 group. The genotyping techniques developed in this study not only provide a rapid, robust and highly discriminatory tool to characterize E. faecalis and E. faecium, but also enables the efficient identification of virulent enterococci that are distributed in environmental water sources.

As trajetorias de carreiras tradicionais estao dando passegem as proteanas? Um estudo com gereentes no setor public Australiano com foco em diferencas quanto ao genero ( Have traditional career paths given way to protean ones?: Evidence from senior managers in the Australian public sector)

Purpose – This mixed-method study aims to determine the extent to which the career paths of senior managers conform with the traditional versus protean elements described in the careers literature and whether these paths vary by gender. Design/methodology/approach – A total of 15 senior managers (seven women and eight men) in a large public sector agency in Australia were interviewed about their career trajectories to date. Data were coded according to four major areas which characterise and distinguish between traditional and protean careers: development, orientation of the employee, definition of success, and organisational environment. A total of 81 managers (34 women and 47 men) from the same organisation were also surveyed. Variables of interest were those that could be triangulated with qualitative data such as the availability of career opportunities. Findings – Results suggest that, contrary to much existing literature which proposes that all careers have been fundamentally altered, the traditional career which relies on length of service, geographic mobility and a steady climb up the corporate ladder, is still the dominant model in some organisations. However, the trend towards protean careers is evident and is more pronounced for women than for men. Research limitations/implications – The specific nature of the organisation (large, male-dominated, public sector) may limit the generalisability of results. Practical implications – The framework used to explore career paths according to traditional/ protean elements in this study may assist human resource practitioners to develop appropriate strategies which maximise the professional development of employees. Originality/value – The results of this research challenge the universality of change in the nature of careers, particularly in public sector environments.

Between a rock and a hard place : what do public sector leaders learn from the past as they lead into the future

The purpose of this paper is to bring leadership context into sharper focus and to suggest there are strong constraints on public leaders’ discretion to lead in ways consistent with NPM or NPL. Much of the existing public leadership research focuses on the individual leader and tends to give little attention to the influence of context. This lack of focus on leader context adversely affects our ability to build public leadership capacity. We draw on prior research to establish that (1) there are strong contextual constraints on public leaders’ capacity to lead in ways consistent with NPL, (2) public leaders are subject to contradictory messages and for the most part these contradictions are unacknowledged and unresolved, the impact of which is confusion and informal power-politics, (3) the task of leader transition from traditional leadership to new public leadership is very much underestimated and requires a new way to think about leadership development. On the basis of this analysis, we argue that public leaders find themselves between a rock and a hard place.

Negative change and job outcomes : the impact of subjective fit in public sector health care organization

There is an ongoing level of organizational-wide change (such as empowerment and downsizing) occurring within the Australian health care sector. However, there is a paucity of empirical evidence on how public and nonprofit sector nurses cope with these organizational-wide change initiatives and their consequences on individual and work outcomes. This will be the primary aim of the current paper. To this end, a path model is developed base on an integration of existing theoretical perspectives on occupational stress, change management, and person-organizational fit. Data were collected from 252 public and not-for-profit sector nurses. The path analysis suggests that public and nonprofit nurses experience positive and negative change initiatives. Negative change initiatives resulted in an increase in the level of administrative-related stressors. Nurses with more congruent values report less experience with administrative stressors. As nurses experienced more administrative stressors, they tend to report more job dissatisfaction. Nurses whose values were more congruent during organizational change reported higher level of psychological wellbeing. Nurses who were had higher level of psychological wellbeing were found to have higher job satisfaction, which subsequently led to a higher level of organizational commitment.

Strategizing public sector human resource management : the implications of working network

Networks have come to the fore as a means by which government can achieve its strategic objectives, particularly when addressing complex or “wicked” issues. Such joined-up arrangements differ in their operations from other forms of organizing as they require collaborative effort to deliver the collaborative advantage. Strategic Human Resource Management is concerned with the matching of human resource practices to the strategic direction of organizations. It is argued that the strategic direction of government has been towards network involvement and that, as a result, a reconfiguration of Human Resource Management practices is needed to support this new direction. Drawing on eight network case studies findings are presented in relation to the roles government is expected to play in networks and conclusions are drawn about what types of human resource management practices would best support those roles. Implications for Strategic Human Resource Management are posited.

Their space, my space, our space? Report of the 2009 Redland City Council Youth and Public Space Survey

This report analyses data collected through the Redland City Council’s Young People and Public Space Survey of 2148 high school students aged 12-19. The survey conducted in 2009 explored their sense of safety and experiences in public spaces across the City, and views on what Council could do to improve these. It is apparent they base their assessment of a space as ‘public’ on their ‘use’ of a space alone or with friends, and where strangers may be present, rather than on a type of ownership of a space (public/ private). The findings of the survey are summarised according to the themes of safety, community attitudes towards young people being in public spaces, young people and authorities, young people’s views of what is needed, and understanding different young people’s experiences of public space.

Public Fundraising Charities in Queensland

A financial study is presented of charities registered under the Queensland Collections Act. These charities are required to register under that Act as they seek donations from the public. The study collected financial information from the audited annual financial statements lodged in 1989 and 1992. The charities were classified into industry classes according to Australian Standard Industry Classification. Data is presented on charity's numerical growth, growth of assets and receipts, lodging of first returns under the Act and defaults in lodging returns. A series of exploratory case studies of greater financial detail are presented to establish possible reasons for the aggregated trends established in the first part of the study. The study concludes by raising three issues, the methodological implications posed by the research, substantive issues about the behaviour of nonprofit organisations and issues for the focus of future research.

Sentencing and public confidence : results from a national Australian survey on public opinions towards sentencing

This paper examines the critical issue of public confidence in sentencing, and presents findings from Phase I of an Australia-wide sentencing and public confidence project. Phase I comprised a nationally representative telephone survey of 6005 participants. The majority of respondents expressed high levels of punitiveness and were dissatisfied with sentences imposed by the courts. Despite this, many were strongly supportive of the use of alternatives to imprisonment for a range of offences. These nuanced views raise questions regarding the efficacy of gauging public opinion using opinion poll style questions; indeed the expected outcome from this first phase of the four phase sentencing and public confidence project. The following phases of this project, reported on elsewhere, examined the effects of various interventions on the robustness and nature of these views initially expressed in a standard ‘top of the head’ opinion poll.

Barriers and facilitators to public bicycle scheme use : a qualitative approach

The purpose of this study was to explore barriers and facilitators to using CityCycle, a public bicycle share scheme in Brisbane, Australia. Focus groups were conducted with participants belonging to one of three categories. Group one consisted of infrequent and noncyclists (no bicycle riding over the past month), group two were regular bicycle riders (ridden a bicycle at least once in the past month) and group three was composed of CityCycle members. A thematic analytic method was used to analyse the data. Three main themes were found: Accessibility/spontaneity, safety and weather/topography. The lengthy sign-up process was thought to stifle the spontaneity typically thought to attract people to public bike share. Mandatory helmet legislation was thought to reduce spontaneous use. Safety was a major concern for all groups and this included a perceived lack of suitable bicycle infrastructure, as well as regular riders describing a negative attitude of some car drivers. Interestingly, CityCycle riders unanimously perceived car driver attitudes to improve when on CityCycle bicycles relative to riding on personal bicycles. Conclusions: In order to increase the popularity of the CityCycle scheme, the results of this study suggest that a more accessible, spontaneous sign-up process is required, 24/7 opening hours, and greater incentives to sign up new members and casual users, as seeing people using CityCycle appears critical to further take up.

Content sharing on public screens: experiences through iterating social and spatial contexts

This paper describes the design and study of public urban screen applications aiming to facilitate urban dwellers to control content shown on public urban screens. Two types of content sharing are presented: aggregating existing social media content about particular locations for sharing, and sharing online videos with collocated people at a public urban screen. The paper describes an exploratory study, an observational study, as well as an interpretational study in regards to application usage and user experience. Sharing content on public urban screens can pique the curiosity of users towards collocated people and the application itself resulting in raised awareness of collocated people.

Nonprofit organisations and public policy : exploring the research role of the Brotherhood of St Laurence

This paper begins to explore the role of the Brotherhood of St Laurence as a nonprofit welfare organisation and its influence on public policy in Australia. The Brotherhood's impact on Australian social policy has been evident through a range of actions: the production of research on relevant social issues; the preparation of submissions and position papers and involvement in consultations with governments on social policy; and the personal influence of many of the charismatic (mostly) men who have led the organisation throughout its history. This paper highlights the Brotherhood’s research aspect and speculates upon the impact of its considerable research contribution. The Brotherhood has been involved in service delivery through a range of often innovative programs throughout its history, but the organisation's involvement in research and advocacy has rendered it unique in comparison to any other nonprofit welfare organisation in Australia. This paper finds that different kinds of research can be utilised in different ways; by studying the output of the Brotherhood it will explore and highlight how knowledge utilisation takes place. [Introduction]

Kaleidoscopes and contradictions : the legitimacy of social media for public relations

If the current discourses of progress are to be believed, the new or social media promise a kaleidoscope of opportunity for connecting and informing citizens. This is by allegedly revitalizing the fading legitimacy and practice of institutions and providing an agent for social interaction. However, as social media adoption has increased, it has revealed a wealth of contradictions both of its own making and reproduction of past action. This has created a crisis for traditional media as well as for public relations. For example, social media such as WikiLeaks have bypassed official channels about government information. In other cases, social media such as Facebook and Twitter informed BBC coverage of the Rio Olympics. Although old media are unlikely to go away, social media have had an impact with several large familybased media companies collapsing or being reintegrated into the new paradigm. To use Walter Lippman’s analogy of the phantom public, the social media contradictorily serve to both disparate the phantom in part and reinforce it...