Effects of Concurrent Phenathrene and Mycobacterium marinum Exposure in the Zebrafish (Danio rerio)

As a way to gain better understanding of how aquatic organisms respond within their natural environment, this dissertation set up a series of controlled laboratory experiments to investigate the effects of chemical and biological stressors on the zebrafish (Danio rerio). I performed a series of studies in which animals were simultaneously exposed to the toxicant phenanthrene, and infected with the bacterium Mycobacterium marinum. Unexpectedly, we found that at a high dose of phenanthrene (284 mug L-1) results in an antagonistic relationship between stressors with dually challenged fish having significantly higher survivorship than those exposed solely to phenanthrene. Dually challenged fish also had reduced phenanthrene metabolism, suggesting higher mortality in phenanthrene only exposed fish may be due to increased toxicity from phenanthrene metabolites. We postulated metabolic reduction was due to inflammatory cytokines suppressing metabolism. However, in latter experiments using a more environmentally relevant dose of phenanthrene (157 mug L-1), dually challenged fish had significantly higher mortalities than all other treatments, and there was no disruption in phenanthrene metabolism. Our second study clearly showed an additive effect: the summation of mortalities for each stressor individually is approximate to what is observed in dually challenged fish. My third experiment was designed to better elucidate the effects of dose and exposure order on stressor interaction. I used a matrix of dose and order such that two phenanthrene doses were used (157 mug L -1 and 86 mug L-1), with a staggered order of exposure. Significantly higher mortalities in dually challenged fish for the high dose of phenanthrene versus the low dose, regardless of exposure order, demonstrated phenanthrene concentration, not exposure order is a significant factor. This study also showed activation of the cytochrome P450 pathway by phenanthrene. These studies highlight the exceptionally complex interactions between multiple stressors and how minor alterations in experimental design can produce dramatic changes in stressor interaction. I have concluded that toxicant dose plays a significant role in this interaction causing an antagonistic interaction at high concentrations; however, at lower doses an additive effect is seen. Additionally, I have shown the importance of phenanthrene metabolites in toxicity. Finally I have clearly demonstrated that phenanthrene can induce the cytochrome P450 pathway. In addition to dual-stressor experiments, I conducted a comparative study between two Mycobacterium spp.: M marinum and M. pseudoshottsii. The goal of this study was to find a bacterium to model disease recrudescence. Despite the close relationship between these two species, we observed dramatically different virulence and pathology. M. marium infected fish had \u3c10% survivorship over a 4-week exposure; however M. pseudoshottsii infected fish had ∼98% survivorship. Additionally, M. marinum infected fish displayed a classic granulomatous inflammation with bacilli sequestered within, or in immediate proximity to, well formed granulomas. In contrast, M. pseudoshottsii infected fish displayed little granuloma formation, instead having large area of diffuse inflammation and cellular necrosis. M. pseudoshottsii were seen disseminated both extra and intra-cellularly throughout areas of inflammation, a phenomenon not seen with M. marinum. I postulate that these differences are due to a unique mycolactone toxin secreted by M. pseudoshottsii. M. ulcerans is the only other Mycobacterium spp. to produce a mycolactone toxin, and produces pathologies similar to what we observe here for M. pseudoshottsii

Missing Nonvoters and Misweighted Samples:Explaining the 2015 Great British Polling Miss

Preelection polls for the 2015 UK General Election missed the final result by a considerable margin: underestimating the Conservative Party and overestimating Labour. Analyzing evidence for five theories of why the polls missed using British Election Study (BES) data, we find limited evidence for systematic vote intention misreporting, late swing, systematically different preferences among “don’t knows,” or differential turnout of parties’ supporters. By comparing the BES face-to-face probability sample and BES Internet panel, we show that the online survey’s polling error is primarily caused by undersampling nonvoters, then weighting respondents to represent the general population. Consequently, demographic groups with a low probability of voting are overweighted within the voter subsample. Finally, we show that this mechanism is likely partially responsible for the polls overestimating the Liberal Democrats in 2010, illustrating that this is a long-standing problem

The Locke Exception: What Trinity Lutheran Means for the Future of State Blaine Amendments

At its core, this Article is about whether states have the discretion to discriminate against religious organizations by excluding them from generally available secular government aid programs. In the wake of the Supreme Court’s 2004 decision in Locke v. Davey, the federal courts have developed conflicting interpretations of whether the Court’s holding in Locke permits states to exclude religious organizations from generally available secular aid programs. However, the Court’s 2017 decision in Trinity Lutheran v. Comer has cast doubt on the ability of states to exclude religious organizations from such programs and seemingly restricts the Court’s prior decision in Locke to a narrow reading. Reconciling both holdings is difficult, but Locke seemingly provides an exception from Trinity Lutheran’s general rule that prohibits the withholding of aid on the basis of the recipient’s religious character. This Article seeks to reconcile those two holdings and, in the process, posits that the Supreme Court’s current “play in the joints” framework is problematic primarily because it rests on a series of mistakes about the nature and purpose of the Religion Clauses. As a result, the Court’s framework bestows upon the states a large amount of discretion in how to draw the line between discrimination and non-discrimination. Ultimately, foreclosing a state’s discretion to unconstitutionally target religious organizations for exclusion from generally applicable secular aid requires rebuilding a theoretical framework from a proper understanding of the relationship between the Establishment and Free Exercise Clauses as well as acknowledging the importance of substantive neutrality

Going veggie:Identifying and overcoming the social and psychological barriers to veganism

We conceptualize the journey to ethical veganism in the stages of the transtheoretical model of change, from precontemplation through contemplation, preparation, action, and maintenance. At each stage, we explore the psychological barriers to progressing towards veganism, discuss how they manifest, and explore ways to overcome them. It is hoped that this paper can be used as a guide for animal advocates to identify the stage an individual is at, and understand and overcome the social and psychological barriers they may face to progressing. We argue that, while many people are ignorant of the cruel practices entailed in animal farming, many deliberately avoid thinking about the issue, are unable to appreciate the scale of the issue, and simply tend to favour the status quo. When engaging with the issue of farm animal suffering, meat-eaters are largely driven by cognitive dissonance, which manifests as motivated reasoning aimed at protecting one's image of oneself and one's society. This is facilitated by confirmation bias and complicit media which cater to the preferred views of their meat-eating audience. Even once convinced of veganism, habit and willpower present further barriers to acting on those beliefs. This is all in the context of a speciesist and carnistic culture where meat consumption is normal, farming is noble, and vegans are 'others'. We locate and elucidate each of these biases within the stages of the transtheoretical model and discuss the implications of this model for animal advocates and for further research.</p

Electoral Shocks

This book offers a novel perspective on British elections, focusing on the importance of increasing electoral volatility in British elections, and the role of electoral shocks in the context of increasing volatility. It demonstrates how shocks have contributed to the level of electoral volatility, and also which parties have benefited from the ensuing volatility. It follows in the tradition of British Election Study books, providing a comprehensive account of specific election outcomes—the General Elections of 2015 and 2017—and a more general approach to understanding electoral change.We examine five electoral shocks that affected the elections of 2015 and 2017: the rise in EU immigration after 2004, particularly from Eastern Europe; the Global Financial Crisis prior to 2010; the coalition government of the Conservatives and the Liberal Democrats between 2010 and 2015; the Scottish Independence Referendum in 2014; and the European Union Referendum in 2016.Our focus on electoral shocks offers an overarching explanation for the volatility in British elections, alongside the long-term trends that have led us to this point. It offers a way to understand the rise and fall of the UK Independence Party (UKIP), Labour’s disappointing 2015 performance and its later unexpected gains, the collapse in support for the Liberal Democrats, the dramatic gains of the Scottish National Party (SNP) in 2015, and the continuing period of tumultuous politics that has followed the EU Referendum and the General Election of 2017. It provides a new way of understanding electoral choice in Britain, and beyond, and a better understanding of the outcomes of recent elections