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Proteomic and metabolomic blood profiling to detect illegal drug use in food producing animalsKinkead, Ruth Ann January 2016 (has links)
Despite the EU prohibition of anabolic substances administered to food producing animals, reports suggest that the use of growth promoting agents continues, pursued by improved animal health and subsequent financial gains. Current screening methods targeting known compounds are insufficient in discriminating endogenous levels from exogenous applications such as oestradiol. Problems also exist in the detection of corticosteroid misuse through long term, low dose dexamethasone and prednisolone administrations. Efforts have moved towards assessment of the biological response of animals to detect growth promoter exposure and methods employing proteomic'and metabolomic markers are needed. An in vivo animal study consisting of twenty-four male beef cattle randomly assigned to four groups (n=6) for experimental treatment over 40 days was conducted; a control group of untreated bovines, and three groups administered oestradiol, dexamethasone or prednisolone at levels known to reflect growth promoting practice. Plasma was collected from each animal throughout the treatment period and assessed for effect-based monitoring. An untargeted assessment of the plasma proteome utilising two-dimensional gel electrophoresis highlighted 22 proteins showing differential expression in treated cattle. Identification of protein markers via LC-MS/MS elucidated contributions to lipid and vitamin metabolism as well as the immune response. Similarly, untargeted metabolomic analysis was conducted via UHPLC-QTof-MS based on reverse phased separation of plasma under positive electrospray ionisation. Results demonstrated metabolite modifications relative to each treatment group and an OPLS-DA model was generated to predict treated from untreated cohorts based on 99 ions of interest. Further statistical analysis found 24 metabolites significantly altered within treated bovines which were putatively identified as mainly lipid components. Further verification of the biomarkers identified was conducted through targeted assessment of the relative levels in additional sample cohorts. A UHPLC-SRM-MS method was developed to detect eight plasma proteins of interest by quantification of tryptic peptides highlighting the use of vitamin-D binding protein, leucine-rich alpha-2-glycoprotein, retinol-binding protein 4 as novel markers responsive to growth promoter treatment. Additionally blood collected at the slaughterhouse was assessed for protein and metabolite perturbations to reflect authentic screening practice.
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The role of public opinion in the regulation of genomics in the United KingdomGetliffe, Kate Sarah January 2011 (has links)
This thesis analyses the role played by public opinion in the regulation of genomics, and conversely the role that regulation plays in shaping public opinion. It is argued that there has been an over-emphasis on the use of public opinion by regulators, and that this is a rhetorical strategy. There are strong normative drivers behind the regulation of genomics, which include the argument that regulation has the capacity to imbue public confidence in novel technologies and that enhanced deliberation will help to placate public concerns. While not dismissing these arguments, the thesis shows that in practice the interaction between regulation and public opinion is not so clear. It is argued that both regulation per se and the very existence and visible presence of independent regulatory agencies overseeing genomics can help to alleviate public concern. A key finding is that although regulators refer to public opinion, in practice they actually respond to stakeholder opinion. The thesis analyses the classic interpretation of public opinion, survey data, and contrasts it with regulators’ understandings of public opinion and with public opinion data collected by independent regulatory agencies. The regulators interviewed agree that the public opinion data used in the regulatory process is not representative of public opinion. However, public opinion is still used as a way of legitimating policy. It is for this reason that I suggest ‘public opinion’ should, for reasons of transparency, be called ‘public opinion data’. Such a move would reflect its value in the regulatory process, but equally indicate that such data has inherent limitations. The argument is supported by evidence from two case-studies from genomics, both of which are significant areas of scientific and public concern. The first is prenatal testing and preimplantation genetic diagnosis (PGD) and the second is Genetically Modified foods. The thesis questions whether the sui generis features of genomics merit its special regulatory handling and the enhanced role given to public opinion in this area.
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Development of an in vitro model to investigate repeat ocular exposureWilkinson, Peter J. January 2006 (has links)
The Draize eye irritation test has been widely adopted as the "gold standard" to evaluate the potential eye irritation of a wide range of chemicals and formulations, including; pharmaceuticals, cosmetics, and their raw ingredients. The rationale for pursuing the development of human ocular based in vitro alternatives is to provide greater confidence in the prediction of human reactions to mild and moderate chemicals. This is particularly important with the implementation of the EC White Paper, "Strategy for a future chemicals policy" (2001) that is estimated to require the testing of approximately 30,000 'existing' chemicals by 2012. The development of in vitro alternatives for toxicity testing has mainly focused upon tests for quantitative measurement of acute toxicity following a single high-dose exposure. However, the degree of toxicity of any exposure is a function of; the dose which target cells receive, the duration of the exposure and the ability of the exposed cells to recover from the exposure. However, little account is taken of the potential role of long-term effects in modulating the toxic response. This study aims to generate an in vitro model utilizing a human corneal cell line monolayer to investigate the effects chronic exposure to exogenous chemicals has upon toxicity of a subsequent acute challenge. Surfactants are ubiquitous within our daily environment, being significant active components in both household and personal care products, cosmetics and pharmaceuticals. Initially the effects of four representative surfactants (sodium dodecyl sulphate; anionic, tween 20; non-ionic, cocamidopropylbetaine; amphoteric and benzalkonium chloride; cationic) were examined following chronic exposure. Although the measured endpoints (neutral red uptake, resazurin reduction, fluorescein leakage and total protein content) revealed no alterations in J-HCET morphology, barrier function or biochemistry as a consequence of chronic exposure, it was determined that pre-exposure modulated the toxicity of subsequent acute exposures. The observed modulation in toxicity could have significant health implications for personal care products, cosmetics and pharmaceuticals intended for use near or within the eye. However, the mechanism(s) by which the toxicity of subsequent surfactant exposures was modulated remains to be elucidated. Whilst standard surfactants are good indicators of the effects following chronic exposure, there are pharmaceuticals designed for repeat use in the eye that have been associated with long term ocular irritancy, and a discontinuation of use i.e. timolol maleate. J-HCET cultures exposed to BSO in vitro confirm that the toxicity of timolol to the human corneal cells line was enhanced by suppressing the activity of γ-glutamylcysteine synthetase through irreversible inhibition, resulting in a decrease in intracellular glutathione (GSH) levels. In addition, chronic exposures to timolol maleate were also associated with an increase in toxicity of subsequent acute challenges. The long term use of Timolol maleate in the treatment of glaucoma in vivo may result in similar alterations in the intracellular GSH concentrations, resulting in discontinuation of treatment as consequence of ocular irritation through the generation of reactive oxidation species beyond the threshold that depleted intracellular GSH can respond. Since in vitro methods have been, and are being developed as alternatives to animal experiments, the use of bovine serum as a source of growth factors can seem to be contradictory to the purposes of the Three R's concept of Russell and Burch (1959). This study was conducted using culture media that contain animal derived growth supplements and a media where these had been substituted for plant derived materials. Comparisons were made between the effects these two supplements had upon a number of biological factors including morphology, biochemistry, barrier function and the response to exogenous chemicals. No alterations were observed in these parameters as a consequence of using culture medium containing plant derived materials compared to those containing animal derived growth supplements. This study has demonstrated that the development of a reliable and reproducible in vitro assay in keeping with the principles of the Three R's for modeling chronic – repeat ocular irritation is possible. However, the mechanistic relevance of the endpoints chosen and cell layer ultrastructure is considered to be an essential component. The further development of cell based in vitro systems to predict human responses to chronic/repeat ocular irritation is required.
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Discursive intersections of newspapers and policy elites : a case study of genetically modified food in Britain, 1996-2000Howarth, Anita January 2012 (has links)
This thesis explores the under-researched terrain of policy elite-newspaper engagements and in so doing makes a substantive contribution in formulating an original conceptual framework for understanding how the interactional dynamics of the political-media complex work. This framework is then applied to the GM food row in Britain by asking how contestation emerged, was sustained then subsided in the political-media complex. This reconstructs the processes by which the pro-GM government consensus was challenged by newspapers, conflict escalated to fever pitch, threatening policy elite agenda and was finally negotiated through key compromises. Drawing on a theoretical framework that combines participatory politics, the political-media complex and new risks, the thesis conceptualises interactional dynamics as ‘discursive intersections’. These are shifts in claims and counter-claims that emerge during engagement at the interface of different sets of knowledge, cultures and agenda in the political-media complex. However there is an element of unpredictability in discursive intersections that arises from the paradoxical interdependence-independence of the relationship in the political-media complex; the elective and episodic nature of engagement on particular issues; and the variable form this may take with potential for conflict, negotiation or consensus. Historical and wider argumentative contexts are crucial to how and what form engagement takes place but do not define it. Thus, the trajectory of discursive intersections needs to be explored empirically rather than predetermined theoretically. This is done using a hybrid methodology that draws attention to the dialogical, persuasive nature of discursive intersections. The substantive contribution of the research is the formulating of this alternative framework for the analysis of interactional dynamics and its application to the GM food row in Britain. It does this by exploring how – that is the process in which - engagement emerged, escalated into contestation, was negotiated and then subsided. What emerged were the following findings. (1) Parallel, sustained and conflictual systems of argumentation about risk were developed between media and political elites despite elite consensus, abstract debates and short news cycles. (2) Newspaper contestation was constructed around a deeply ambivalent suspended certainty based on claims that there was no evidence of risk or benefit, harm or safety and demands for elite responsiveness to acute public anxiety over this.
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Food safety, perceptions and preferences : empirical studies on risks, responsibility, trust, and consumer choicesErdem, Seda January 2011 (has links)
This thesis addresses various food safety issues and investigates them from an economic perspective within four different, but related, studies. The studies are intended to provide policy-makers and other decision-makers in the industry with valuable information that will help them to implement better mitigation strategies and policies. The studies also present some applications of advancements in choice modelling, and thus contribute to the literature. To address these issues, various surveys were conducted in the UK.The first study investigates different stakeholder groups’ perceptions of responsibility among the stages of the meat chain for ensuring the meat they eat does not cause them to become ill, and how this differed with food types. The means by which this is achieved is novel, as we elicit stakeholders’ relative degrees of responsibility using the Best-Worst Scaling (BWS) technique. BWS is particularly useful because it avoids the necessity of ranking a large set of items, which people have been found to struggle with. The results from this analysis reveal a consistent pattern among respondents of downplaying the extent of their own responsibility. The second study explores people’s perceptions of various food and non-food risks within a framework characterised by the level of control that respondents believe they have over the risks, and the level of worry that the risks prompt. The means by which this is done differs from past risk perception analyses in that it questions people directly regarding their relative assessments of the levels of control and worry over the risks presented. The substantive analysis of the risk perceptions has three main foci concerning the relative assessment of (i) novel vs. more familiar risks, (ii) food vs. non-food risks, (iii) differences in the risk perceptions across farmers and consumers, with a particular orientation on E. coli. The third study investigates consumers’ willingness to pay (WTP) for reductions in the level foodborne health risk achieved by (1) nanotechnology and (2) less controversial manners in the food system. The difference between consumers’ valuations provides an implicit value for nanotechnology. This comparison is achieved via a split sample Discrete Choice Experiment study. Valuations of the risk reductions are derived from conditional, heteroskedastic conditional, mixed, and heteroscedastic mixed logit models. General results show the existence of heterogeneity in British consumers’ preferences and variances, and that the value of nanotechnology differs for different types of consumers. The fourth study investigates consumers’ perceptions of trust in institutions to provide information about nanotechnology and its use in food production and packaging. It is shown how the use of BWS and Latent Class modelling of survey data can provide in-depth information on consumer categories useful for the design of effective public policy, which in turn would allow the development of best practice in risk communication for novel technologies. Results show heterogeneity in British consumers’ preferences. Three distinct consumer segments are identified: Class-1, who trust “government institutions and scientists” most; Class-2, who trust “non-profit organisations and environmental groups” most; and Class-3, who trust “food producers and handlers, and media” most.
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Toward an ecology of addiction : Overeaters Anonymous and Weight Watchers in a culture of consumptionWenger, Melanie S. January 2014 (has links)
There is increasing evidence that aspects of human eating may be 'addictive'. Much of the existing literature examining this focuses on specific foods or individual pathologies of 'addiction'. Qualitative research methods, in particular content analysis, offers a rich opportunity to better understand 'addictive' aspects of human eating through the stories shared by those who have experienced compulsive eating. This research examines two different organizations that use storytelling as a tool for changing eating behaviours. Overeaters Anonymous (OA) and Weight Watchers (WW) began in the United States in the early 1960s as mutual support groups designed to help members with problems of compulsive overeating. This research examines: 1) the ways that OA and WW addressed 'addictions' with food when they were first formed; 2) how each organization has changed over time; and 3) the ways that identities are constructed through the telling of stories within each programme. For this thesis, I used historical analysis, in-person and online participant observation, and content analysis as research methods. I found that while OA and WW once similarly addressed 'addictions' with food, this is no longer the case. WW no longer understands their members as fundamentally different from others in the ways that they eat, and OA now welcomes members with a variety of different compulsive eating behaviours. However, similar themes regarding identity emerged from the OA and WW stories used in this research. OA and WW members describe that they acquire different belief systems regarding health and how to eat in each programme. In comparing these two organizations, how each has changed over time and the shifts in identity described by OA and WW members, this research identifies aspects of everyday living that members of both groups similarly highlight as important factors influencing compulsive eating. Based on these findings, I then assess to what extent a new framework for understanding 'addiction' may be needed, and conclude by suggesting further areas of research that would be suitable for constructing this.
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