907 resultados para System safety


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Thesis (Master's)--University of Washington, 2016-06

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Thesis (Ph.D.)--University of Washington, 2016-06

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Most consumers consider complementary and alternative medicine (CAM) products inherently safe. The growing simultaneous use of CAM products and pharmaceutical drugs by Australian consumers increases the risk of CAM-drug interactions. The Therapeutic Goods Administration (TGA) has a two-tier, risk-based regulatory system for therapeutic goods - CAM products are regulated as low risk products and are assessed for quality and safety; and sponsors of products must hold the evidence for any claim of efficacy made about them. Adverse reactions to CAM products can be classified as intrinsic (innate to the product), or extrinsic (where the risk is not related to the product itself, but results from the failure of good manufacturing practice). Adverse reactions to CAM practices can be classified as risks of commission (which includes removal of medical therapy) and risks of omission (which includes failure to refer when appropriate). While few systematic studies of adverse events with CAM exist, and under-reporting is likely, most CAM products and practices do not appear to present a high risk; their safety needs to be put into the perspective of wider safety issues. A priority for research is to rigorously define the risks associated with both CAM products and practices so that their potential impact on public health can be assessed.

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Background Chaperonin 10 (heat shock protein 10, XToll(TM)) has anti-inflammatory properties related to the inhibition of Toll-like receptor signalling pathways. Our aim was to establish whether chaperonin 10 is safe and effective in the treatment of rheumatoid arthritis. Methods in this randomised, double-blind, multicentre study, 23 patients with moderate to severe active rheumatoid arthritis receiving disease-modifying antirheumatic drugs were randomly allocated to three treatment groups receiving intravenous chaperonin 10 twice weekly for 12 weeks at doses of 5 mg (n=8), 7.5 mg (8), or 10 mg (7). The primary outcomes were change in disease activity score (DAS28) and improvement of core disease measures (American College of Rheumatology response score) from baseline to week 12. All analyses were done by intention to treat. This study is registered with the Australian Clinical Trials Registry, number ACTRNO12606000041550. Findings Primary endpoint measures improved from day 14 in all groups and continued to improve to day 84. By end of study, a 20% improvement of core disease measures was seen in six (86%, 95% Cl 43-100), a 50% improvement in four (57%, 14-86), and a 70% improvement in two (29%, 0-57) patients given the highest dose of chaperonin 10. Clinical remission (as defined by a DAS28

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The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

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This research examines a behavioural based safety (BBS) intervention within a paper mill in the South East of England. Further to this intervention two other mills are examined for the purposes of comparison — one an established BBS programme and the other an improving safety management system through management ownership. BBS programmes have become popular within the UK, but most of the research about their efficacy is carried out by the BBS providers themselves. This thesis aims to evaluate a BBS intervention from a standpoint which is not commercially biased in favour of BBS schemes. The aim of a BBS scheme is to either change personnel behaviours or attitudes, which in turn will positively affect the organisation's safety culture. The research framework involved a qualitative methodology in order to examine the effects of the intervention on the paper mill's safety culture. The techniques used were questionnaires and semi structured interviews, in addition to observation and discussions which were possible because of the author's position as participant observer. The results demonstrated a failure to improve any aspect of the mill's safety culture, which worsened following the BBS intervention. Issues such as trust, morale, communication and support of management showed significant signs of negative workforce response. The paper mill where the safety management system approach was utilised demonstrated a significantly improved safety culture and achieved site ownership from middle managers and supervisors. Research has demonstrated that a solid foundation is required prior to successfully implementing a BBS programme. For a programme to work there must be middle management support in addition to senior management commitment. If a trade union actively distances itself from BBS, it is also unlikely to be effective. This thesis proposes that BBS observation programmes are not suitable for the papermaking industry, particularly when staffing levels are low due to challenging economic conditions. Observers are not available when there are high hazard situations and this suggests that BBS implementation is not the correct intervention for the paper industry.

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This thesis describes a study of the content and applicability of BS8800:1996 Guide to occupational health and safety management systems. The research is presented chronologically, with literature review and content analysis of SMS related guides and standards interwoven with two elements of qualitative empirical work. The first of these was carried out shortly after publication of BS8800 in 1996, a 'before-the-event' investigation of how organisations were intending to approach SMS implementation. The challenges faced by these organisations are reviewed against standard management theory, suggesting that the initial motivation for SMS implementation governs the approach organisations will adopt to guidance such as BS8800. The second phase of empirical work was undertaken in the context of OHSAS 18001, an auditable protocol based on BS8800, which allows organisations to certify their safety management systems. A discussion of the evolution of certifiable safety management system is presented, highlighting the similarities and differences between this, BS8800, SMS and wider management system standards. A case study then reviews the experiences of a catering company that implemented 18001, motivated by the opportunity for certification as a business benefit. The empirical work is used to comment on the guidance provided by BS8800, within its evolved role as guidance organisations may use for implementation of a SMS to be certified according to the specifications of OHSAS 18001. It is suggested that optimal implementation is facilitated by initial status review, continual improvement and the use of annexes, where there are used to make changes to the existing safety management system. This thesis concludes with a discussion of these elements, highlighting pertinent areas within BS8800 where revision or amendment may be appropriate.

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The thesis addresses the economic impacts of construction safety in Greece. The research involved the development of a methodology for determining the overall costs of safety, namely the sum of the costs of accidents and the costs of safety management failures (with or without accident) including image cost. Hitherto, very little work has been published on the cost of accidents in practical case studies. Moreover, to the author’s belief, no research has been published that seeks to determine in real cases the costs of prevention. The methodology developed is new, transparent, and capable of being replicated and adapted to other employment sectors and to other countries. The methodology was applied to three construction projects in Greece to test the safety costing methodology and to offer some preliminary evidence on the business case for safety. The survey work took place between 1999 and 2001 and involved 27 months of costing work on site. The study focuses on the overall costs of safety that apply to the main (principal) contractor. The methodology is supported by 120 discrete cost categories, and systematic criteria for determining which costs are included (counted) in the overall cost of safety. A quality system (in compliance with ISO9000 series) was developed to support the work and ensure accuracy of data gathering. The results of the study offer some support for the business case for safety. Though they offer good support for the economics of safety as they demonstrate need for cost effectiveness. Subject to important caveats, those projects that appeared to manage safety more cost-effectively achieved the lowest overall safety cost. Nevertheless, results are significantly lower than of other published works for two main reasons; first costs due to damages with no potential to injury were not included and second only costs to main constructor were considered. Study’s results are discussed and compared with other publish works.