Due to a policy of no release, oil sands process-affected water (OSPW) produced by the surface-mining oil sands industry in North Eastern Alberta, Canada, is stored on-site in tailings ponds. There is concern regarding the toxic effects of OSPW on aquatic organisms. Knowledge of the chemical composition and toxicity of OSPW is limited. Research is necessary for potential remediation and release of OSPW back into the environment. Due to the large volume and persistency of OSPW, active efforts are necessary for the remediation of OSPW before release and habitat reclamation. Currently, ozonation is considered one possible method for remediation of OSPW by reducing the concentrations of dissolved organic compounds, including naphthenic acids (NAs), which are considered among the primary toxic constituents. However, further work is needed to evaluate the effectiveness of ozonation in reducing the toxicity of OSPW and to ensure that ozonation does not increase the toxicity of OSPW. The overall objective of this work was to determine the toxic effects of OSPW on endocrine disruption and embryo development, using both in vitro and in vivo models, and the effectiveness of ozone treatment for reducing the toxicity of OSPW. In the first study, untreated and ozone-treated OSPW were examined for effects on sex steroid production using the H295R cell line steroidogenesis Assay. The results indicate that exposure to untreated OSPW can significantly decrease synthesis of testosterone (T) and increase synthesis of 17β-estradiol (E2) by 0.55±0.06 and 2.0±0.13-fold, respectively, compared to that of control groups (ρ < 0.05). These effects were due to increased aromatase enzyme activity and decreased E2 metabolism. The results also suggest that ozonation is an effective treatment to reduce concentrations of NAs in OSPW without altering steroidogenesis. In the second study, the T47D-kbluc (estrogen responsive) and MDA-kb2 (androgen responsive) cell assays were used to determine whether OSPW might act as either agonists or antagonists of the estrogen receptor (ER) or androgen receptor (AR), respectively. The estrogenic responses to untreated OSPW were significantly greater by 2.6±0.22-fold compared to control group (ρ < 0.05). Exposure to untreated OSPW produced significant antiandrogenic response in the presence of 0.01, 0.05 and 0.1 nM T by 16±6.5%, 47±7.6% and 75±9.7%, respectively, of that of the corresponding concentrations of T alone (ρ < 0.05). The results suggest that compounds in the dissolved organic fraction of OSPW have estrogenic and anti-androgenic properties, acting as ER agonists and/or AR antagonists. Ozonation of the OSPW partially mitigated the antiandrogenicity but had no effect on the estrogenicity of OSPW. In the third study, the endocrine-disrupting effects of OSPW and ozone-treated OSPW were determined by quantifying relative changes in the abundances of transcripts of genes along the brain-gonad-liver (BGL) axis in male and female fathead minnows (Pimephales promelas). The results indicate that OSPW has endocrine-disrupting effects at all levels of BGL axis and these effects of impaired expression of genes along the BGL axis are sex specific. For example, exposure to OSPW resulted in significantly greater abundances of transcripts of vtg (Vitellogenin), chg-l (Choriogenin L) and chg-h (Choriogenin H minor) by 4.9±1.2, 5.4±1.5 and 3.4±0.78-fold, respectively, compared to those of control groups (ρ < 0.05) in livers from male fathead minnow. However, in livers from female fathead minnows, exposure to OSPW resulted in significantly lesser abundances of transcripts of vtg, chg-l and chg-h by 0.002±0.0011, 0.022±0.007 and 0.036±0.024-fold, respectively, compared to those of control fish (ρ < 0.05). Ozonation of OSPW attenuated the effects on abundances of transcripts of some genes, and the attenuation was more prominent in males than in females. However, impact of ozonation on endocrine-disrupting effects of OSPW was less evident than in the in vitro studies described in Chapter 2 and 3. The results also provide a mechanistic basis for the endocrine-disrupting effects of OSPW from other studies, including impaired reproduction of fathead minnows exposed to OSPW. In the final study the effects of untreated, ozone-treated, and activated charcoal-treated OSPW (OSPW, O3-OSPW, and AC-OSPW) on the survival, growth, and development of embryos of fathead minnows were determined. Compared to the control group, which had an embryo survival rate of 98±2.1%, survival was significantly less when exposed to OSPW (44±7.1%; ρ < 0.05). Eggs exposed to untreated OSPW exhibited a significantly greater rate of premature hatching, and embryos exhibited more frequent spontaneous movements. Incidences of hemorrhage (50±3.4%), pericardial edema (56±7.1%), and malformation of the spine (38±5.4%) were significantly greater in embryos exposed to OSPW compared to control group (ρ < 0.05). Significantly greater concentrations of ROS (1.7±0.11-fold), and greater abundances of transcripts cyp3a, gst, sod, casp9, and apopen (2.4±0.34, 2.2±0.26, 3.1±0.74, 3.3±0.57 and 2.4±0.25-fold, respectively) compared to control groups (ρ < 0.05), indicated that exposure to OSPW caused oxidative stress, which can result in damage to mitochondria and promote activation of caspase enzymes and apoptotic cell death. Removal of dissolved organic constituents in OSPW by ozone treatment, or by activated charcoal, significantly attenuated all of the adverse effects associated with untreated OSPW. The results suggest that the organic fraction of OSPW can negatively impact the development of fathead minnow embryos through oxidative stress and apoptosis, and that ozonation attenuates this developmental toxicity. Overall, the findings from the research described in this thesis provide novel and important insights into the toxicity and mechanisms of the toxicity of OSPW with respect to endocrine disruption and development of embryos of fish. In addition, the research provides compelling evidence that ozonation might be an effective method for accelerating the remediation of OSPW. The results of the research might help regulators develop effective strategies for reclamation, remediation and potential release of OSPW back to the environment.

Fluoxetine (FLX), the active ingredient of Prozac™, is a member of the selective serotonin reuptake inhibitor (SSRI) class of anti-depressant drugs and is present in aquatic environments worldwide. Previous studies reported that FLX is an endocrine disruptor in fish, bioconcentrating in tissues including the brain. Evidence implicates that serotonin influences the activity of the hypothalamo-pituitary-interrenal (HPI) stress axis, thus exposure to FLX may disrupt the teleost stress response. This study examined in vitro cortisol production in rainbow trout (Oncorhynchus mykiss) head kidney/interrenal cells exposed to FLX and 14C-pregnenolone metabolism in head kidney microsome preparations of FLX-exposed trout. Results indicated that cells exposed in vitro to increasing concentrations of FLX had lower cortisol production and cell viability (versus control) and microsomes isolated from trout exposed to 54 μg/L FLX had higher pregnenolone metabolism versus those of control and low FLX-exposed (0.54 μg/L) trout.

SAMMANFATTNING Syftet med studien var att undersöka patienters inställning till att dela rum med patienter av motsatt kön och ålder. Metoden som användes var en deskriptiv tvärsnittsstudie med kvantitativ ansats som utfördes på två akutkirurgiska avdelningar. Det var 33 inneliggande patienter som deltog i studien. En studiespecifik enkät delades ut med tio frågor och två frågor om kön och ålder. Frågorna rörde olika synpunkter om hur det är att dela rum med andra patienter och om hur det är att dela rum med patienter med motsatt kön och ålder. Enkäten innehöll även en öppen fråga där deltagarna kunde lämna övriga synpunkter. Materialet analyserades med beskrivande statistik. För att jämföra skillnaden mellan män och kvinnor användes Mann Whitney U test och för att jämföra skillnader mellan de olika åldersgrupperna användes Kruskall Wallis. Resultatet visade att kvinnor ansåg att det var något obekvämare att dela rum med motsatt kön än vad det var för männen. Kvinnorna ville också i större utsträckning få information om detta innan man blev tilldelad en sal och plats. Den yngsta åldersgruppen 18-30 år upplevde sig mest besvärad av störd nattsömn jämfört med de två äldre grupperna. Slutsatsen var att kvinnor tyckte att det var mer obekvämt att dela rum med personer av motsatt kön. De yngsta deltagarna ansåg att det var mest besvärande att dela rum med andra och då med tanke på störd nattsömn. Det som skapade mest oro på patientsalen var när medpatienterna inte visade hänsyn eller om det var medicinskt oroliga. / ABSTRACT The aim of this study was to investigate the patient´s views on their expirience and preference of sharing a patient room with other patients of the opposite sex en age. The metod was a deskriptive cross-sectional study with a quantitavie analyxix. A survey was conducted at two surgical departments. The sample consisted of 33 inpatients. The investigation included questions of gender and age in order to compare differances between men and women and between age groups. The differences between sexes were analysed using Mann Whitney U test and the Kruskall Wallis test was used to determine differances between age groups. The results showed that women felt it somewhat inconvenient to share a room with the opposite sex than men did. The women would also like to receive information about this before the were assigned a room and place. the youngest age group of 18-30 years was the most troubled by disturbed sleep compared with the two older groups. The conclusion was that women found it more uncomfortable to share a room with people of the opposite sex. Among age groups the youngest participants experienced that it was most embarrassing to share a room with others and especially when considering distrubed sleep. What created the most concern was when the other patients did not show respect or if they were medically worried.

In vivo real-time data of ultrasound and microbubble assisted blood-brain barrier disruption is centrally based on low-resolution magnetic resonance images. Additional information can be gained using online microscopic monitoring. This study presents the first ever in vivo two-photon microscopy, four-dimensional data sets of ultrasound and microbubble assisted blood-brain barrier disruption. It characterized the threshold pressures and mechanical index needed to disrupt the vasculature with 800 kHz ultrasound, and found three different leakage constants from the compromised vasculature. Furthermore, using numerical models, an ultrasound array was designed and optimized to perform specifically with our two-photon microscope. It was fabricated, fully characterized, and its performance met both the required pressure field profile and the pressure values needed for our in vivo two-photon microscopy experiments. This array is an important step in microscopically characterizing ultrasound and microbubble assisted blood-brain barrier disruption.

In vivo real-time data of ultrasound and microbubble assisted blood-brain barrier disruption is centrally based on low-resolution magnetic resonance images. Additional information can be gained using online microscopic monitoring. This study presents the first ever in vivo two-photon microscopy, four-dimensional data sets of ultrasound and microbubble assisted blood-brain barrier disruption. It characterized the threshold pressures and mechanical index needed to disrupt the vasculature with 800 kHz ultrasound, and found three different leakage constants from the compromised vasculature. Furthermore, using numerical models, an ultrasound array was designed and optimized to perform specifically with our two-photon microscope. It was fabricated, fully characterized, and its performance met both the required pressure field profile and the pressure values needed for our in vivo two-photon microscopy experiments. This array is an important step in microscopically characterizing ultrasound and microbubble assisted blood-brain barrier disruption.

The overall objective of the research conducted and described in this thesis was to develop an environmentally relevant bioassay to assess the effects of complex effluents on a sentinel fish species. A short-term fathead minnow (FHM) reproductive bioassay was utilized to assess the effects of industrial effluents on multiple levels of biological organization (sub-organismal to population endpoints). The FHM bioassay was tested in both lab and on-site investigations using an artificial stream system. The incorporation of trophic-transfer into the bioassay was also developed to quantify the importance of contaminated food as a source of exposure. This work was conducted in two key phases. Phase I focused on testing and developing the FHM bioassay, in the lab and on-site with pulp mill effluent (PME), to firstly document response patterns and, secondly, to conduct an investigation of cause study. Phase II focused on developing the trophic-transfer system to document responses to metal mine effluent (MME) in the lab and on-site in an artificial stream system. Development of the trophic-transfer system was also conducted during this phase to compare responses to standard water-only exposures. <p>In Phase I, exposure to PME in both the lab and field studies resulted in disruptions in egg production and spawning events. By focusing on identifying response patterns I was able to determine that the effects observed were indicative of an estrogenic response. I was also able to identify a process stream that was the potential cause of responses observed after exposure to final effluent. Isolation of this process stream will assist the mill in developing approaches for future mitigation. The results from this research will also provide additional data for the environmental effects monitoring (EEM) program for pulp and paper and investigation of cause studies on a national basis. <p> In Phase II, in both the field and laboratory investigations, significant decreases in reproductive output (egg production and spawning events) were observed in the water-only system exposures. Significant decreases in hatching success and increases in deformities were observed in the trophic-transfer system only, suggesting that the combination of both food and water was important in assessing the effects on the F1 generation. Overall, the responses in the trophic-transfer system were not comparable between the lab and field studies. In the lab study, significant decreases in reproductive output occurred, compared to the field study where significant increases in egg production and spawning events occurred. In addition, the effects on the F1 generation in the field study were not as severe as those observed in the lab investigation. It was concluded that the presence of reference water and the environment within the trophic-transfer system were responsible for this reduction in toxicity. <p> Phases I and II of this research have made significant contributions to artificial stream development within Canada for the assessment of industrial effluents and their effects on aquatic biota. The results from these studies have also demonstrated that environmentally relevant testing is essential if we are to accurately assess effects on aquatic biota. Future development and application of this bioassay should be towards developing a standardized approach for not only assessing the effects of industrial effluents in a comparative manner, but also in investigation of cause studies.

Fluoxetine (FLX), the active ingredient of Prozac™, is a member of the selective serotonin reuptake inhibitor (SSRI) class of anti-depressant drugs and is present in aquatic environments worldwide. Previous studies reported that FLX is an endocrine disruptor in fish, bioconcentrating in tissues including the brain. Evidence implicates that serotonin influences the activity of the hypothalamo-pituitary-interrenal (HPI) stress axis, thus exposure to FLX may disrupt the teleost stress response. This study examined in vitro cortisol production in rainbow trout (Oncorhynchus mykiss) head kidney/interrenal cells exposed to FLX and 14C-pregnenolone metabolism in head kidney microsome preparations of FLX-exposed trout. Results indicated that cells exposed in vitro to increasing concentrations of FLX had lower cortisol production and cell viability (versus control) and microsomes isolated from trout exposed to 54 μg/L FLX had higher pregnenolone metabolism versus those of control and low FLX-exposed (0.54 μg/L) trout.

The purpose of this study is to examine the disruption risk resolution process in supply chains; specifically, to assess how risk attributes impact the approach firms select to resolve risks and the associated final outcomes. We propose that high magnitude risks are positively associated with mutually beneficial problem resolution; on the other hand, low likelihood risks have the opposite effect, they are negatively associated with mutually beneficial resolution. Our conceptual contribution lies in our articulation of the mechanisms though which risk magnitude and risk likelihood impact mutual problem resolution. We posit that high magnitude risks and low likelihood (uncommon) risks mobilize the social network of actors, triggering vigilant monitoring for risks, communication among actors and across firm boundaries, and resource sharing and coordination which facilitate collaborative problem solving and mutual resolutions. These mobilization mechanisms help supply chain partners to overcome the challenges of complexity and allow for information and resource flows among actors and between firms. Our statistical analysis demonstrates that the impact of risk attributes on mutual problem solutions is fully mediated by timely problem identification and collaborative problem solving.

This paper grapples with the differences between genuine and ordinary democracy within the political thought of Jacques Rancière, Sheldon Wolin, and Hannah Arendt. Each discusses the problems of ordinary democracy and offer solutions in terms of what I call genuine democracy. Ordinary democracy is the established norm of liberal democracy celebrated as the stable and a desired “end” of political action. It is what happens when politics as usual becomes the norm and shuts the people from the halls of power. Genuine politics exist within the structure ordinary democracy and seeks to achieve the continuous re-establishment of democratic processes while in the process speeding up and disrupting “politics as usual”.

The overall objective of the research conducted and described in this thesis was to develop an environmentally relevant bioassay to assess the effects of complex effluents on a sentinel fish species. A short-term fathead minnow (FHM) reproductive bioassay was utilized to assess the effects of industrial effluents on multiple levels of biological organization (sub-organismal to population endpoints). The FHM bioassay was tested in both lab and on-site investigations using an artificial stream system. The incorporation of trophic-transfer into the bioassay was also developed to quantify the importance of contaminated food as a source of exposure. This work was conducted in two key phases. Phase I focused on testing and developing the FHM bioassay, in the lab and on-site with pulp mill effluent (PME), to firstly document response patterns and, secondly, to conduct an investigation of cause study. Phase II focused on developing the trophic-transfer system to document responses to metal mine effluent (MME) in the lab and on-site in an artificial stream system. Development of the trophic-transfer system was also conducted during this phase to compare responses to standard water-only exposures. <p>In Phase I, exposure to PME in both the lab and field studies resulted in disruptions in egg production and spawning events. By focusing on identifying response patterns I was able to determine that the effects observed were indicative of an estrogenic response. I was also able to identify a process stream that was the potential cause of responses observed after exposure to final effluent. Isolation of this process stream will assist the mill in developing approaches for future mitigation. The results from this research will also provide additional data for the environmental effects monitoring (EEM) program for pulp and paper and investigation of cause studies on a national basis. <p> In Phase II, in both the field and laboratory investigations, significant decreases in reproductive output (egg production and spawning events) were observed in the water-only system exposures. Significant decreases in hatching success and increases in deformities were observed in the trophic-transfer system only, suggesting that the combination of both food and water was important in assessing the effects on the F1 generation. Overall, the responses in the trophic-transfer system were not comparable between the lab and field studies. In the lab study, significant decreases in reproductive output occurred, compared to the field study where significant increases in egg production and spawning events occurred. In addition, the effects on the F1 generation in the field study were not as severe as those observed in the lab investigation. It was concluded that the presence of reference water and the environment within the trophic-transfer system were responsible for this reduction in toxicity. <p> Phases I and II of this research have made significant contributions to artificial stream development within Canada for the assessment of industrial effluents and their effects on aquatic biota. The results from these studies have also demonstrated that environmentally relevant testing is essential if we are to accurately assess effects on aquatic biota. Future development and application of this bioassay should be towards developing a standardized approach for not only assessing the effects of industrial effluents in a comparative manner, but also in investigation of cause studies.