969 resultados para Scientific culture


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Safety culture in the construction industry is a growing research area. The unique nature of construction industry works – being project-based, varying in size and focus, and relying on a highly transient subcontractor workforce – means that safety culture initiatives cannot be easily translated from other industries. This paper reports on the first study in a three year collaborative industry and university research project focusing on safety culture practices and development in one of Australia’s largest global construction organisations. The first round of a modified Delphi method is reported, and describes the insights gained from 41 safety leaders’ perceptions and understandings of safety culture within the organisation. In-depth, semi-structured interviews were conducted, and will be followed by a quantitative perception survey with the same sample. Participants included Senior Executives, Corporate Managers, Project Managers, Safety Managers and Site Supervisors. Leaders’ definitions and descriptions of safety culture were primarily action-oriented and some confusion was evident due to the sometimes implicit nature of culture in organisations. Leadership was identified as a key factor for positive safety culture in the organisation, and there was an emphasis on leaders demonstrating commitment to safety, and being visible to the project-based workforce. Barriers to safety culture improvement were also identified, with managers raising diverse issues such as the transient subcontractor workforce and the challenge of maintaining safety as a priority in the absence of safety incidents, under high production pressures. This research is unique in that it derived safety culture descriptions from key stakeholders within the organisation, as opposed to imposing traditional conceptualisations of safety culture that are not customised for the organisation or the construction industry more broadly. This study forms the foundation for integrating safety culture theory and practice in the construction industry, and will be extended upon in future studies within the research program.

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Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.

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These three interventions, given over a three day period in 2010, concern the proposed multifunctional exhibition hall in Gwanju, Korea. The three interventions cover some theoretical and historical issues, but also consider the practical aspects of such a project.

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In this chapter I look at some issues around the transfer of cultural industry policy between two very different national contexts, the UK and Russia. Specifically it draws on a partnership project between Manchester and St. Petersburg financed by the European Union as part of a program to promote economic development through knowledge transfer between Europe and the countries of the former Soviet Union. This specific project attempted to place the cultural industries squarely within the dimension of economic development, and drew on the expertise of Manchester’s Creative Industries Development Service and other partners to effect this policy transfer

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This report was commissioned by the Yorkshire Cultural Observatory and the Yorkshire & Humber Key Cities group. It is not a strategy document but an attempt to give an overview of the current thinking within academia and policy-making about the cultural agenda for regions and regional cities in the UK. In particular it looks at the challenges for Yorkshire cities in the context of the current and potential regional cultural offer. The report is a snapshot of current academic and policy thinking, but it also draws on a series of interviews conducted with policymakers in the five key cities as well as regional agencies. These interviews were limited in number and are not meant to be a comprehensive consultation exercise. Rather they acted to focus some of the issues raised by the literature and policy review and to develop suggestions around priority areas for the region.

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Increasingly scientists are using collections of software tools in their research. These tools are typically used in concert, often necessitating laborious and error-prone manual data reformatting and transfer. We present an intuitive workflow environment to support scientists with their research. The workflow, GPFlow, wraps legacy tools, presenting a high level, interactive web-based front end to scientists. The workflow backend is realized by a commercial grade workflow engine (Windows Workflow Foundation). The workflow model is inspired by spreadsheets and is novel in its support for an intuitive method of interaction enabling experimentation as required by many scientists, e.g. bioinformaticians. We apply GPFlow to two bioinformatics experiments and demonstrate its flexibility and simplicity.

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Background In an attempt to establish some consensus on the proper use and design of experimental animal models in musculoskeletal research, AOVET (the veterinary specialty group of the AO Foundation) in concert with the AO Research Institute (ARI), and the European Academy for the Study of Scientific and Technological Advance, convened a group of musculoskeletal researchers, veterinarians, legal experts, and ethicists to discuss, in a frank and open forum, the use of animals in musculoskeletal research. Methods The group narrowed the field to fracture research. The consensus opinion resulting from this workshop can be summarized as follows: Results & Conclusion Anaesthesia and pain management protocols for research animals should follow standard protocols applied in clinical work for the species involved. This will improve morbidity and mortality outcomes. A database should be established to facilitate selection of anaesthesia and pain management protocols for specific experimental surgical procedures and adopted as an International Standard (IS) according to animal species selected. A list of 10 golden rules and requirements for conduction of animal experiments in musculoskeletal research was drawn up comprising 1) Intelligent study designs to receive appropriate answers; 2) Minimal complication rates (5 to max. 10%); 3) Defined end-points for both welfare and scientific outputs analogous to quality assessment (QA) audit of protocols in GLP studies; 4) Sufficient details for materials and methods applied; 5) Potentially confounding variables (genetic background, seasonal, hormonal, size, histological, and biomechanical differences); 6) Post-operative management with emphasis on analgesia and follow-up examinations; 7) Study protocols to satisfy criteria established for a "justified animal study"; 8) Surgical expertise to conduct surgery on animals; 9) Pilot studies as a critical part of model validation and powering of the definitive study design; 10) Criteria for funding agencies to include requirements related to animal experiments as part of the overall scientific proposal review protocols. Such agencies are also encouraged to seriously consider and adopt the recommendations described here when awarding funds for specific projects. Specific new requirements and mandates related both to improving the welfare and scientific rigour of animal-based research models are urgently needed as part of international harmonization of standards.

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Over the last century, environmental and occupational medicine has played a significant role in the protection and improvement of public health. However, scientific integrity in this field has been increasingly threatened by pressure from some industries and governments. For example, it has been reported that the tobacco industry manipulated eminent scientists to legitimise their industrial positions, irresponsibly distorted risk and deliberately subverted scientific processes, and influenced many organisations in receipt of tobacco funding. Many environmental whistleblowers were sued and encountered numerous personal attacks. In some countries, scientific findings have been suppressed and distorted, and scientific advisory committees manipulated for political purposes by government agencies. How to respond to these threats is an important challenge for environmental and occupational medicine professionals and their societies. The authors recommend that professional organisations adopt a code of ethics that requires openness from public health professionals; that they not undertake research or use data where they do not have freedom to publish their results if these data have public health implications; that they disclose all possible conflicts; that the veracity of their research results should not be compromised; and that their research independence be protected through professional and legal support. The authors furthermore recommend that research funding for public health not be directly from the industry to the researcher. An independent, intermediate funding scheme should be established to ensure that there is no pressure to analyse data and publish results in bad faith. Such a funding system should also provide equal competition for funds and selection of the best proposals according to standard scientific criteria.