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Incidence of endocrine disruption in wild fish species has been documented globally and is well characterised in the UK, where the occurrence of intersex in roach (Rutilus rutilus) is widespread. Although this has been associated with concentrations of steroid oestrogens, research indicates that anti-androgenic chemicals may also play a role in inducing these effects. Anti-androgenic activity is commonly detected in wastewater treatment works effluents and some receiving waters, but the chemicals responsible remain largely uncharacterised. This thesis aimed to identify environmental anti-androgens in UK and South Australian catchments and to produce environmentally relevant exposures to assess their potential impacts on sexual disruption in fish, alone and in combination with steroid oestrogens. By using hydrological modelling techniques, pharmaceuticals with an anti-androgenic mode of action were predicted to occur in the ng/L concentration range in UK and South Australian wastewater treatment works effluents and river catchments. This work included analysis of future trends in environmental concentrations of the pharmaceuticals and the steroid oestrogens in these catchments. Modest increases in concentrations by 2050 were predicted in the absence of mitigation, which could increase in the risk posed to fish health by the steroid oestrogens in the future. The effects of the predicted concentrations of two pharmaceuticals, bicalutamide and cyproterone acetate, were then assessed in fathead minnows (Pimephales promelas) and Japanese medaka (Oryzias latipes) based on the UK modelling for the present day. These concentrations did not contribute to endpoints characteristic of sexual disruption, alone or in combination with steroid oestrogens. However, the results did support an environmental role for the steroid oestrogens in intersex induction. Concurrently, effect directed analysis identified some highly potent anti-androgens, such as triclosan and pyrene, in wastewater treatment works effluents from the UK. However, they are likely to make a minor contribution to overall anti-androgenic activity due to their low concentrations. Consequently, more work is required to identify the causes of this activity in the environment and its implications for wild fish health.

The extensive use of pharmaceuticals and their poor removal by wastewater treatment plants has led to the emergence of pharmaceutical compounds as global aquatic contaminants. Progestins, the synthetic analogues to progesterone (P4), are receiving increasing attention as contaminants and have been shown to impair reproduction in fish and amphibians at low ng L-1 concentrations. Certain progestins have androgenic properties and are several orders of magnitude more potent in terms of reproductive impairment in fish than non-androgenic progestins. To characterize the androgenic effects of progestins in fish, adult three-spined sticklebacks (Gasterosteus aculeatus) and zebrafish (Danio rerio) larvae were exposed to progestins via the ambient water. In female sticklebacks, the androgenic progestins levonorgestrel (LNG) and norethindrone (NET) induced production of the androgenic biomarker protein spiggin and reduced production of the egg yolk protein vitellogenin. Comparison with well-known environmental androgens showed that LNG and NET, with regard to spiggin induction and vitellogenin induction, are among the most potent environmental androgens known. In male sticklebacks, LNG inhibited the post-breeding regression of secondary sex characters and spiggin production, as well as the resumption of spermatogenesis, functionally inhibiting the natural transition from breeding into non-breeding condition. Exposure of zebrafish larvae to LNG caused all fish to develop into males, whose sexual development was also significantly accelerated. P4 had no effect on the sex ratio, while slightly accelerating sexual development at high concentrations. Suppression of vitellogenesis in females, disruption of the male reproductive cycle, male-biased sex ratios and precious male puberty could all entail severe fitness costs and severely affect fish populations. Most of the effects of androgenic progestins in this thesis occurred at levels within the range of reported environmental levels, and may therefore occur in progestin-contaminated waters. In conclusion, the present results establish LNG and NET as highly potent androgenic pollutants of environmental concern, and provide strong support to the contention that the reproductive impairment in fish caused by progestins is chiefly mediated by their androgenic properties.

This work describes the design, development and testing of a portable charge-coupled device detector system to be used for the simultaneous collection of X-ray diffraction and X-ray fluorescence data from powdered samples. The detector was designed for both terrestrial and extra-terrestrial applications that require in-situ analysis of samples, where access to a laboratory instrument is restricted. The detector system incorporates 4 e2v technologies CCD30-11 devices, employing multi-phase pinned technology for low noise operation. Geometrical calculations and thermal studies concerning the design of the detector are presented, with particular emphasis on motivations for the chosen geometry. Initial characterisation and calibration of the detector was performed in a laboratory environment using a purpose built test facility. The test facility included a high brightness X-ray micro-source from Bede Scientific Instruments, coupled with an XOS polycapillary collimating optic, which was used to deliver a focused beam of low divergent X-rays to the sample. The design of the test facility is discussed and the spectra and flux produced by the X-ray micro-source are investigated. The operational performance of the detector is highlighted and the use of the instrument in different applications is described, namely the planetary sciences and pharmaceuticals sector. Finally, based on the knowledge gained from initial testing of the instrument, improvements to the detector design are outlined, which greatly enhance the combined X-ray diffraction/X-ray fluorescence performance of the instrument.

This thesis provides an overview of case studies investigating the behaviour of freshwater crayfish, including social and reproductive interactions, decision making, and channels for recognition or processing of environmental stimuli. We described relationships between the environment and the organism and relationships among conspecifics and heterospecifics. These aspects are important, given that every decision and interaction has consequences for crayfish survival and reproduction, i.e. individual and even species success. For ethological studies in aquatic ecosystems, crustaceans, and especially crayfish, represent practical model organisms. Crayfish are advantageous over other invertebrates given their high level of social interaction in both the field and the laboratory. They exhibit unique eco- ethological behaviour in variety of feeding habits, activity cycles, habitat selection, and resource utilization at the level of species, sex, and age. Similar to vertebrates, crayfish demonstrate unique behaviours throughout their life. Subsequently, pollution impacts on native crayfish stock can result in ecosystem instability. The different reproductive strategies of females and males demonstrate that females rely on some familiarity of sexual partners as a reliable guarantee for successful mating. Crayfish females are choosier than males because of their higher energy costs for reproduction (oogenesis, incubation, parental care). While male reproduction prioritises securing their genetic information by searching for as many mates as possible. Crayfish mate preferences was analysed by facing the choosing crayfish with two equal sized mature counterparts from the same or different origin. Our conclusions could be applied in conservation research, captive breeding, and recovery programs as well as in aquaculture. The success of biological invaders has been described as the outcome from intra- and interspecific interactions. The marbled crayfish, known as parthenogenetic species with high adaptability, fast growth, early maturation, and high fecundity, established dominant status in more cases by interspecific combat victories. Fight intensity and aggressiveness decreased after dominance was established in particular pairs. Marbled crayfish seem to have an ability to conserve energy by increasing activity only at times of danger. Based on known species-specific abilities, the marbled crayfish is capable of outcompeting aggressive species, such as the red swamp crayfish. This parthenogenetic species poses a substantial threat to native ecosystems and biodiversity of aquatic environments, since it can establish not only in crayfish free habitats, but is also capable of outcompeting resident species. Recently, dilute concentrations of contaminants such as pharmaceuticals, daily-care products and pesticides have been reported to indirectly affect aquatic organisms. We found that selected pharmaceuticals can alter the behavioural patterns of crayfish, event at the very low concentration. The risks associated with surface water pollutants stresses the importance of research investigating their ecological impacts and their different/specific mechanisms of action. Prolonged exposure to the low concentrations of two pesticides exhibited changes in crayfish behavioural patterns. Various alterations in locomotion were observed after treatment in pesticide-free water. In the wild, decreased movement and activity can be a challenge for crayfish survival because of predation, even foraging to compensate for energy loss could be very difficult for less active individuals. This study suggests that crayfish behaviour assessment is a practical approach not only for investigating basic biology, or intra- and inter-specific interactions, but also for assessing the risks associated with micro-pollutants.

Raphael is leading a hedonistic life when he has a traumatic realization that the world is indifferent about who lives and who dies, and Raphael is no exception. This is a story, written by Raphael, about seeking to reconcile the fleeting world he and everyone else has been subjected to.

Thomas Pogge proposes the Health Impact Fund (HIF) as a realistic, feasible reform to the pharmaceutical patent regime that would incentivize pharmaceutical research and reward innovation for medicines based on their impact on the global burden of disease. Pogge advances a human rights-based argument to show that the HIF is a morally required addition to the current pharmaceutical patent regime. One objection to his human rights argument comes from a libertarian appeal to property rights. Pogge’s response to the libertarian leads to the counterintuitive conclusion that libertarianism is incompatible with any system of intellectual property rights. This paper will show how Pogge fails to distinguish between what I call status quo and revisionist libertarian positions on intellectual property. Making this distinction, I maintain, would strengthen the human rights argument and allow Pogge to avoid the counterintuitive conclusion of his response to the libertarian.

The central objective of this study is to examine the factors that have influenced the evolution of the drug patenting regulatory framework in Canada from 1965 to 2005. The principal focus is on the extent to which in formulating that regulatory framework the Canadian federal government has been influenced by domestic and international interests and forces. In examining the domestic interests and forces attention is devoted to the financial interests of the two sectoral associations representing the patented and generic drug manufacturers and the economic and political interests of the governing and opposition parties. In examining the international interests and forces the focus is both on the emergence of international institutions and agreements and on the interests of various countries and drug companies located therein which wanted to ensure that Canadas regulatory framework would not have an adverse effect on them. This study reveals that there was three relatively distinct phases in the evolution of Canadas drug patenting regulatory framework and that each was influenced primarily by different sets of factors. The first phase which lasted from 1965 to 1991 was influenced entirely by domestic interests and forces produced by a highly charged political debate over reduced patent protection and drug price restrictions on the one hand, and increased patent protection and economic development on the other. The second phase, which lasted from 1992 to 2001, consisted largely of international forces. This included the emergence of new international institutions and agreements such as the World Trade Organization and the North American Free Trade Agreement, which created new intellectual property obligations for Canada and provided for even longer periods of patent protection than what had already existed. The third phase which began 2002 and continues to the present day, consists of a combination of domestic and international forces which attempt to reconcile domestic issues such as price restriction and economic development with international issues such as allowing Third World countries an opportunity to import drugs at reasonable prices. The Government of Canadas response to all of these pressures has predominantly reflected the objectives of patented drug manufacturers.