Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment

Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a 'wound that never heals'. These inflammatory responses elicit signals via NFκB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer-associated fibroblast line compared to normal fibroblasts. Comparison of mouse-specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression.

Study Protocol - Alcohol Management Plans (AMPs) in remote indigenous communities in Queensland: their impacts on injury, violence, health and social indicators and their cost-effectiveness

Background In 2002/03 the Queensland Government responded to high rates of alcohol-related harm in discrete Indigenous communities by implementing alcohol management plans (AMPs), designed to include supply and harm reduction and treatment measures. Tighter alcohol supply and carriage restrictions followed in 2008 following indications of reductions in violence and injury. Despite the plans being in place for over a decade, no comprehensive independent review has assessed to what level the designed aims were achieved and what effect the plans have had on Indigenous community residents and service providers. This study will describe the long-term impacts on important health, economic and social outcomes of Queensland’s AMPs. Methods/Design The project has two main studies, 1) outcome evaluation using de-identified epidemiological data on injury, violence and other health and social indicators for across Queensland, including de-identified databases compiled from relevant routinely-available administrative data sets, and 2) a process evaluation to map the nature, timing and content of intervention components targeting alcohol. Process evaluation will also be used to assess the fidelity with which the designed intervention components have been implemented, their uptake and community responses to them and their perceived impacts on alcohol supply and consumption, injury, violence and community health. Interviews and focus groups with Indigenous residents and service providers will be used. The study will be conducted in all 24 of Queensland’s Indigenous communities affected by alcohol management plans. Discussion This evaluation will report on the impacts of the original aims for AMPs, what impact they have had on Indigenous residents and service providers. A central outcome will be the establishment of relevant databases describing the parameters of the changes seen. This will permit comprehensive and rigorous surveillance systems to be put in place and provided to communities empowering them with the best credible evidence to judge future policy and program requirements for themselves. The project will inform impending alcohol policy and program adjustments in Queensland and other Australian jurisdictions. The project has been approved by the James Cook University Human Research Ethics Committee (approval number H4967 & H5241).

Conceptual framework for understanding the demand for emergency health services

Background & Objectives Emergency health services (EHS) throughout the world are increasingly congested. As more people use EHS, factors such as population growth and aging cannot fully explain this increase. Also, focus on patients’ clinical characteristics ignores the role that attitudinal and perceptual factors and motivations play in directing their decisions and actions. The aim of this study is to review and synthesize an integrated conceptual framework for understanding social psychological factors underpinning demand for EHS. Methodology A comprehensive search and review of empirical and theoretical studies about the utilization of EHS was conducted using major medical, health, social and behavioral sciences databases. Results A small number of studies used a relevant conceptual framework (e.g. Health Services Utilization Model or Health Belief Model) or their components to analyze patients’ decision to use EHS. The studies evidenced that demand was affected by perceived severity of the condition; perceived costs and benefits (e.g. availability, accessibility and affordability of alternative services); experience, preference and knowledge; perceived and actual social support; and demographic characteristics (e.g. age, sex, socioeconomic status, ethnicity, marital and living circumstances, place of residence). Conclusions Conceptual models that are commonly used in areas like social and behavioral sciences have rarely been applied in the EHS utilization field. Understanding patients’ decision-making and associated factors will lay the groundwork for identification of the evidence to inform improved policy responses and the development of demand management strategies. An integrated conceptual framework will be introduced as part of this study.

Wellness programs at firefighter and police workplaces : a systematic review

Objectives This systematic review summarizes the literature on the health effects of wellness programs at police and firefighter workplaces. The review also considers process outcomes and economic evaluations of such programs. Methods A systematic search of articles published from January 1, 2000 through September 1, 2012 in 13 databases was conducted. Data on 7 studies from 9 articles were extracted. An assessment of the methodological quality of the studies was conducted. Results Studies showed acceptable completion rates and high satisfaction with programs, but mixed results for changes in individual outcomes. Conclusion Empirical evidence for effective health and wellness programs in police and firefighter populations is scarce. Better evaluation and documentation of such programs is needed to advance this field of research.

Analysis of albumin-associated peptides and proteins from ovarian cancer patients

Albumin binds low–molecular-weight molecules, including proteins and peptides, which then acquire its longer half-life, thereby protecting the bound species from kidney clearance. We developed an experimental method to isolate albumin in its native state and to then identify [mass spectrometry (MS) sequencing] the corresponding bound low–molecular-weight molecules. We used this method to analyze pooled sera from a human disease study set (high-risk persons without cancer, n= 40; stage I ovarian cancer, n = 30; stage III ovarian cancer, n = 40) to demonstrate the feasibility of this approach as a discovery method. Methods Albumin was isolated by solid-phase affinity capture under native binding and washing conditions. Captured albumin-associated proteins and peptides were separated by gel electrophoresis and subjected to iterative MS sequencing by microcapillary reversed-phase tandem MS. Selected albumin-bound protein fragments were confirmed in human sera by Western blotting and immunocompetition. Results In total, 1208 individual protein sequences were predicted from all 3 pools. The predicted sequences were largely fragments derived from proteins with diverse biological functions. More than one third of these fragments were identified by multiple peptide sequences, and more than one half of the identified species were in vivo cleavage products of parent proteins. An estimated 700 serum peptides or proteins were predicted that had not been reported in previous serum databases. Several proteolytic fragments of larger molecules that may be cancer-related were confirmed immunologically in blood by Western blotting and peptide immunocompetition. BRCA2, a 390-kDa low-abundance nuclear protein linked to cancer susceptibility, was represented in sera as a series of specific fragments bound to albumin. Conclusion Carrier-protein harvesting provides a rich source of candidate peptides and proteins with potential diverse tissue and cellular origins that may reflect important disease-related information.

The impact of nurse practitioner services on cost, quality of care, satisfaction and wait times in the emergency department: A systematic review

Aims To provide the best available evidence to determine the impact of nurse practitioner services on cost, quality of care, satisfaction and waiting times in the emergency department for adult patients. Background The delivery of quality care in the emergency department is one of the most important service indicators in health delivery. Increasing service pressures in the emergency department have resulted in the adoption of service innovation models: the most common and rapidly expanding of these is emergency nurse practitioner services. The rapid uptake of emergency nurse practitioner service in Australia has outpaced the capacity to evaluate this service model in terms of outcomes related to safety and quality of patient care. Previous research is now outdated and not commensurate with the changing domain of delivering emergency care with nurse practitioner services. Data A comprehensive search of four electronic databases from 2006-­‐2013 was conducted to identify research evaluating nurse practitioner service impact in the emergency department. English language articles were sought using MEDLINE, CINAHL, Embase and Cochrane and included two previous systematic reviews completed five and seven years ago. Methods A three step approach was used. Following a comprehensive search, two reviewers assessed identified studies against the inclusion criteria. From the original 1013 studies, 14 papers were retained for critical appraisal on methodological quality by two independent reviewers and data extracted using standardised tools. Results Narrative synthesis was conducted to summarise and report the findings as insufficient data was available for meta-­‐analysis of results. This systematic review has shown that emergency nurse practitioner service has a positive impact on quality of care, patient satisfaction and waiting times. There was insufficient evidence to draw conclusions regarding impact on costs. Conclusion Synthesis of the available research attempts to provide an evidence base for emergency nurse practitioner service to guide healthcare leaders, policy makers and clinicians in reforming emergency department service provision. The findings suggest that further quality research is required for comparative measures of clinical and service effectiveness of emergency nurse practitioner service. In the context of increased health service demand and the need to provide timely and effective care to patients, such measures will assist in delivering quality patient care.

Drosophila 3′ UTRs are more complex than protein-coding sequences

The 3′ UTRs of eukaryotic genes participate in a variety of post-transcriptional (and some transcriptional) regulatory interactions. Some of these interactions are well characterised, but an undetermined number remain to be discovered. While some regulatory sequences in 3′ UTRs may be conserved over long evolutionary time scales, others may have only ephemeral functional significance as regulatory profiles respond to changing selective pressures. Here we propose a sensitive segmentation methodology for investigating patterns of composition and conservation in 3′ UTRs based on comparison of closely related species. We describe encodings of pairwise and three-way alignments integrating information about conservation, GC content and transition/transversion ratios and apply the method to three closely related Drosophila species: D. melanogaster, D. simulans and D. yakuba. Incorporating multiple data types greatly increased the number of segment classes identified compared to similar methods based on conservation or GC content alone. We propose that the number of segments and number of types of segment identified by the method can be used as proxies for functional complexity. Our main finding is that the number of segments and segment classes identified in 3′ UTRs is greater than in the same length of protein-coding sequence, suggesting greater functional complexity in 3′ UTRs. There is thus a need for sustained and extensive efforts by bioinformaticians to delineate functional elements in this important genomic fraction. C code, data and results are available upon request.

Robust numeric set watermarking : numbers don’t lie

Ever since Cox et. al published their paper, “A Secure, Robust Watermark for Multimedia” in 1996 [6], there has been tremendous progress in multimedia watermarking. The same pattern re-emerged with Agrawal and Kiernan publishing their work “Watermarking Relational Databases” in 2001 [1]. However, little attention has been given to primitive data collections with only a handful works of research known to the authors [11, 10]. This is primarily due to the absence of an attribute that differentiates marked items from unmarked item during insertion and detection process. This paper presents a distribution-independent, watermarking model that is secure against secondary-watermarking in addition to conventional attacks such as data addition, deletion and distortion. The low false positives and high capacity provide additional strength to the scheme. These claims are backed by experimental results provided in the paper.

Burden of non-communicable diseases (NCDs) in Nepal and the availability and affordability of NCD medicines

Background: Traditionally communicable diseases were the main causes of burden in developing countries like Nepal. In recent years non-communicable diseases (NCDs), mainly cardiovascular diseases (CVDs), cancer, chronic respiratory diseases and diabetes mellitus, impose a larger disease burden compared to communicable diseases. Most elements of health and medicine policies in Nepal are still focused on communicable diseases. There is limited evidence about NCDs and NCD medicines in Nepal. Aim: To explore the gap between the burden of NCDs and the availability and affordability of NCD medicines in Nepal. Methods: Biomedical databases like Medline, Scopus, Web of Science and other online sources (including Global Burden of Diseases data) were searched for data on the burden of NCDs in term of Disability Adjusted Life Years (DALYs). The Essential Medicines List (EML) of Nepal was compared with World Health Organisation (EML) for inclusion of NCD medicines. Results: In Nepal, NCDs caused nearly 45% of the total 10.5 million DALYs in 2010. CVDs (15.2%), were the leading cause of NCDs burden followed by chronic respiratory diseases (14.7%), cancer (7.3%) and diabetes mellitus (3.2%). One hospital based national survey found that 37% of hospitalised patients had NCDs. Among them, 38% had heart disease followed by COPD (33%) , and diabetes (10%). Most (23 out of 28) non-cancer NCD medicines recommended in WHO-EML were present in Nepal's EML, theoretically indicating good availability. However, it is difficult to say whether they are accessible and affordable due to the lack of adequate data on access and pricing. Conclusion: This study gives some insight into the burden of NCDs. Although NCD medicines are available in Nepal, further research is required to determine whether they are accessible and affordable to the general population.

Designing schools as effective 21st C learning spaces : a review

The Queensland Centre for Social Science Innovation was formed in 2012 to develop collaborations among the Queensland Government and five Queensland universities—The University of Queensland, Griffith University, Queensland University of Technology, James Cook University and Central Queensland University. Three priorities for initial projects were established by the Queensland Government with response by the participating universities. This project addressed the identified priority area: factors affecting educational achievement and investigation of the link between school design, refurbishment and educational outcomes. The proposal for this project indicated that a Review of research literature would be undertaken that linked school and classroom design with educational outcomes for learners in the 21st century. Further, research would be examined for impact of technology on staff and students, as well as learning spaces that addressed the diversity of student learners. Specific investigation of research on effective design to enhance learning outcomes for Aboriginal and Torres Strait Islander students was to be undertaken. The project therefore consists of a Review of research literature to provide an evidence base on the impact of school and classroom on educational outcomes. The original proposal indicated that indicators of successful school and classroom design would be student learning outcomes on a range of variables, with input, the specific architectural design elements. The review was undertaken during the period July 2012 to June 2013. A search was undertaken of journals, databases, and websources to identify relevant material. These were examined for evidence-based statements and design of learning spaces to enhance learning. The Review is comprehensive, and representative of issues raised in research, and conceptualisations and debates informing modern educational design. Initial findings indicated two key findings central to reading this Review. The first key finding is that the predominant focus of modern design of learning space is on process and the engagement of stakeholders. Schools are social institutions and development of a school as a learning space to suit 21st century learning needs necessarily involves the staff, students and other members of the community as key participants. The concept of social aspects of design is threaded throughout the Review. The second key finding is that little research explicitly examined the relationship between the design of learning spaces and educational outcomes. While some research does exist, the most explicitly-focused research uses narrow test-based achievement as the learning outcomes. These are not sympathetic to the overall framings of the research on 21st century learning, future schooling and the needs of the new generation of learners and society.

Assembly and annotation of a non-model gastropod (Nerita melanotragus) transcriptome: a comparison of De novo assemblers

Background The sequencing, de novo assembly and annotation of transcriptome datasets generated with next generation sequencing (NGS) has enabled biologists to answer genomic questions in non-model species with unprecedented ease. Reliable and accurate de novo assembly and annotation of transcriptomes, however, is a critically important step for transcriptome assemblies generated from short read sequences. Typical benchmarks for assembly and annotation reliability have been performed with model species. To address the reliability and accuracy of de novo transcriptome assembly in non-model species, we generated an RNAseq dataset for an intertidal gastropod mollusc species, Nerita melanotragus, and compared the assembly produced by four different de novo transcriptome assemblers; Velvet, Oases, Geneious and Trinity, for a number of quality metrics and redundancy. Results Transcriptome sequencing on the Ion Torrent PGM™ produced 1,883,624 raw reads with a mean length of 133 base pairs (bp). Both the Trinity and Oases de novo assemblers produced the best assemblies based on all quality metrics including fewer contigs, increased N50 and average contig length and contigs of greater length. Overall the BLAST and annotation success of our assemblies was not high with only 15-19% of contigs assigned a putative function. Conclusions We believe that any improvement in annotation success of gastropod species will require more gastropod genome sequences, but in particular an increase in mollusc protein sequences in public databases. Overall, this paper demonstrates that reliable and accurate de novo transcriptome assemblies can be generated from short read sequencers with the right assembly algorithms. Keywords: Nerita melanotragus; De novo assembly; Transcriptome; Heat shock protein; Ion torrent

Climate variability, climate change and land degradation

Effective response by government and individuals to the risk of land degradation requires an understanding of regional climate variations and the impacts of climate and management on condition and productivity of land and vegetation resources. Analysis of past land degradation and climate variability provides some understanding of vulnerability to current and future climate changes and the information needs for more sustainable management. We describe experience in providing climate risk assessment information for managing for the risk of land degradation in north-eastern Australian arid and semi-arid regions used for extensive grazing. However, we note that information based on historical climate variability, which has been relied on in the past, will now also have to factor in the influence of human-induced climate change. Examples illustrate trends in climate for Australia over the past decade and the impacts on indicators of resource condition. The analysis highlights the benefits of insights into past trends and variability in rainfall and other climate variables based on extended historic databases. This understanding in turn supports more reliable regional climate projections and decision support information for governments and land managers to better manage the risk of land degradation now and in the future.

The influence of atmospheric conditions on the leakage current of ceramic insulators on the Colombian Caribbean coast

The contamination of electrical insulators is one of the major contributors to the risk of operation outages in electrical substations, especially in coastal zones with high salinity levels and atmospheric pollution. By using the measurement of leakage-currents, which is one of the main indicators of contamination in insulators, this work seeks to the determine the correlation with climatic variables, such as ambient temperature, relative humidity, solar irradiance, atmospheric pressure, and wind speed and direction. The results obtained provide an input to the behaviour of the leakage current under atmospheric conditions that are particular to the Caribbean coast of Colombia. Spearman’s rank correlation coefficients and principal component analysis are utilised to determine the significant relationships among the different variables under consideration. The necessary information for the study was obtained via historical databases of both atmospheric variables and the leakage current measured in over a period of one year in a 220-kV potential transformer insulator. We identified the influencing factors of temperature, humidity, radiation, wind speed and direction on the magnitude of the leakage current as the most relevant.

Proposing and developing the definition and conceptual framework for healthcare resilience to cope with disasters

Building healthcare resilience is an important step towards creating more resilient communities to better cope with future disasters. To date, however, there appears to be little literature on how the concept of healthcare resilience should be defined and operationalized with a conceptual framework. This article aims to build a comprehensive healthcare disaster management approach guided by the concept of resilience. Methods: Google and major health electronic databases were searched to retrieve critical relevant publications. A total of 61 related publications were included, to provide a comprehensive overview of theories and definitions relevant to disaster resilience. Results and Discussions: Resilience is an inherent and adaptive capacity to cope with future uncertainty, through multiple strategies with all hazards approaches, in an attempt to achieve a positive outcome with linkage and cooperation. Healthcare resilience can be defined as the capability of healthcare organisations to resist, absorb, and respond to the shock of disasters while maintaining the most essential functions, then recover to their original state or adapt to a new state. It can be assessed by criteria, namely: robustness, redundancy, resourcefulness; and a complex of key dimensions, namely: vulnerability and safety, disaster resources and preparedness, continuity of essential health services, recovery and adaptation. Conclusions: This new concept places healthcare organisations’ disaster capabilities, management tasks, activities and disaster outcomes together into a comprehensive whole view, using an integrated approach and establishing achievable goals.

Advance Care Planning in palliative care : a systematic literature review of the contextual factors influencing its uptake 2008-2012

Background: Advance Care Planning is an iterative process of discussion, decision-making and documentation about end-of-life care. Advance Care Planning is highly relevant in palliative care due to intersecting clinical needs. To enhance the implementation of Advance Care Planning, the contextual factors influencing its uptake need to be better understood. Aim: To identify the contextual factors influencing the uptake of Advance Care Planning in palliative care as published between January 2008 and December 2012. Methods: Databases were systematically searched for studies about Advance Care Planning in palliative care published between January 2008 and December 2012. This yielded 27 eligible studies, which were appraised using National Institute of Health and Care Excellence Quality Appraisal Checklists. Iterative thematic synthesis was used to group results. Results: Factors associated with greater uptake included older age, a college degree, a diagnosis of cancer, greater functional impairment, being white, greater understanding of poor prognosis and receiving or working in specialist palliative care. Barriers included having non-malignant diagnoses, having dependent children, being African American, and uncertainty about Advance Care Planning and its legal status. Individuals’ previous illness experiences, preferences and attitudes also influenced their participation. Conclusion: Factors influencing the uptake of Advance Care Planning in palliative care are complex and multifaceted reflecting the diverse and often competing needs of patients, health professionals, legislature and health systems. Large population-based studies of palliative care patients are required to develop the sound theoretical and empirical foundation needed to improve uptake of Advance Care Planning in this setting.