870 resultados para K32 - Environmental, Health, and Safety Law


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As defined by the European Union, “ ’Nanomaterial’ (NM) means a natural, incidental or manufactured material containing particles, in an unbound state or as an aggregate or agglomerate, where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1 nm-100 nm ” (2011/696/UE). Given their peculiar physico-chemical features, nanostructured materials are largely used in many industrial fields (e.g. cosmetics, electronics, agriculture, biomedical) and their applications have astonishingly increased in the last fifteen years. Nanostructured materials are endowed with very large specific surface area that, besides making them very useful in many industrial processes, renders them very reactive towards the biological systems and, hence, potentially endowed with significant hazard for human health. For these reasons, in recent years, many studies have been focused on the identification of toxic properties of nanostructured materials, investigating, in particular, the mechanisms behind their toxic effects as well as their determinants of toxicity. This thesis investigates two types of nanostructured TiO2 materials, TiO2 nanoparticles (NP), which are yearly produced in tonnage quantities, and TiO2 nanofibres (NF), a relatively novel nanomaterial. Moreover, several preparations of MultiWalled Carbon Nanotubes (MWCNT), another nanomaterial widely present in many products, are also investigated.- Although many in vitro and in vivo studies have characterized the toxic properties of these materials, the identification of their determinants of toxicity is still incomplete. The aim of this thesis is to identify the structural determinants of toxicity, using several in vitro models. Specific fields of investigation have been a) the role of shape and the aspect ratio in the determination of biological effects of TiO2 nanofibres of different length; b) the synergistic effect of LPS and TiO2 NP on the expression of inflammatory markers and the role played therein by TLR-4; c) the role of functionalization and agglomeration in the biological effects of MWCNT. As far as biological effects elicited by TiO2 NF are concerned, the first part of the thesis demonstrates that long TiO2 nanofibres caused frustrated phagocytosis, cytotoxicity, hemolysis, oxidative stress and epithelial barrier perturbation. All these effects were mitigated by fibre shortening through ball-milling. However, short TiO2 NF exhibited enhanced ability to activate acute pro-inflammatory effects in macrophages, an effect dependent on phagocytosis. Therefore, aspect ratio reduction mitigated toxic effects, while enhanced macrophage activation, likely rendering the NF more prone to phagocytosis. These results suggest that, under in vivo conditions, short NF will be associated with acute inflammatory reaction, but will undergo a relatively rapid clearance, while long NF, although associated with a relatively smaller acute activation of innate immunity cells, are not expected to be removed efficiently and, therefore, may be associated to chronic inflammatory responses. As far as the relationship between the effects of TiO2 NP and LPS, investigated in the second part of the thesis, are concerned, TiO2 NP markedly enhanced macrophage activation by LPS through a TLR-4-dependent intracellular pathway. The adsorption of LPS onto the surface of TiO2 NP led to the formation of a specific bio-corona, suggesting that, when bound to TiO2 NP, LPS exerts a much more powerful pro-inflammatory effect. These data suggest that the inflammatory changes observed upon exposure to TiO2 NP may be due, at least in part, to their capability to bind LPS and, possibly, other TLR agonists, thus enhancing their biological activities. Finally, the last part of the thesis demonstrates that surface functionalization of MWCNT with amino or carboxylic groups mitigates the toxic effects of MWCNT in terms of macrophage activation and capability to perturb epithelial barriers. Interestingly, surface chemistry (in particular surface charge) influenced the protein adsorption onto the MWCNT surface, allowing to the formation of different protein coronae and the tendency to form agglomerates of different size. In particular functionalization a) changed the amount and the type of proteins adsorbed to MWCNT and b) enhanced the tendency of MWCNT to form large agglomerates. These data suggest that the different biological behavior of functionalized and pristine MWCNT may be due, at least in part, to the different tendency to form large agglomerates, which is significantly influenced by their different capability to interact with proteins contained in biological fluids. All together, these data demonstrate that the interaction between physico-chemical properties of nanostructured materials and the environment (cells + biological fluids) in which these materials are present is of pivotal importance for the understanding of the biological effects of NM. In particular, bio-persistence and the capability to elicit an effective inflammatory response are attributable to the interaction between NM and macrophages. However, the interaction NM-cells is heavily influenced by the formation at the nano-bio interface of specific bio-coronae that confer a novel biological identity to the nanostructured materials, setting the basis for their specific biological activities.

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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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Patient and public involvement has been at the heart of UK health policy for more than two decades. This commitment to putting patients at the heart of the British National Health Service (NHS) has become a central principle helping to ensure equity, patient safety and effectiveness in the health system. The recent Health and Social Care Act 2012 is the most significant reform of the NHS since its foundation in 1948. More radically, this legislation undermines the principle of patient and public involvement, public accountability and returns the power for prioritisation of health services to an unaccountable medical elite. This legislation marks a sea-change in the approach to patient and public involvement in the UK and signals a shift in the commitment of the UK government to patient-centred care. © 2013 John Wiley & Sons Ltd.

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The ambitious and comprehensive Transatlantic Trade and Investment Partnership Agreement (TTIP/TAFTA) agreement between the European Union and United States is now being negotiated and may have far-reaching consequences for health services. The agreement extends to government procurement, investment, and further regulatory cooperation. In this article, we focus on the United Kingdom National Health Service and how these negotiations can limit policy space to change policies and to regulate in relation to health services, pharmaceuticals, medical devices, and health industries. The negotiation of TTIP/TAFTA has the potential to "harmonize" more corporate-friendly regulation, resulting in higher costs and loss of policy space, an example of "trade creep" that potentially compromises health equity, public health, and safety concerns across the Atlantic.

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OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals.

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OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. METHODS: A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. RESULTS: Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95 % CI 3.69-14.26], followed by abatacept OR 3.7 [95 % CI 2.17-6.06], tocilizumab OR 3.69 [95 % CI 1.87-6.62] and infliximab-biosimilar OR 3.47 [95 % CI 0.85-9.7]. For ACR50 response, certolizumab pegol showed the highest OR compared to placebo OR 8.46 [3.74-16.82], followed by tocilizumab OR 5.57 [95 % CI 2.77-10.09], and infliximab-biosimilar OR 4.06 [95 % CI 1.01-11.54]. Regarding the occurrence of serious adverse events, the results show no statistically significant difference between infliximab-biosimilar and placebo, OR 1.87 [95 % CI 0.74-3.84]. No significant difference regarding efficacy and safety was found between infliximab-biosimilar and the other biological treatments. CONCLUSION: This is the first indirect meta-analysis in RA that compares the efficacy and safety of biosimilar-infliximab to the other biologicals indicated in RA. We found no significant difference between infliximab-biosimilar and other biological agents in terms of clinical efficacy and safety.