An analysis of a specific application of anaerobic wastewater treatment at a pulp and board mill, Stora Enso Skoghall, was carried out. A literature study was done and effluent wastewater from CTMP pulp production was analyzed. The analysis consisted of a broad constituent analysis and an anaerobic treatment trial. Results from these test where used to calculate the treatment effectiveness and resulting energy potential at the mill. The literature study and constituent analysis showed that toxicity of the water to be treated, due to wood extractives and sulphur content, was of concern. Detoxification chemicals targeting these constituents where used in the anaerobic treatment trial. The trial consisted of a two chamber upflow reactor and aerobic post treatment. The result of the trial is that the water of concern has about 50% anaerobically degradable content. A full scale implementation of anaerobic wastewater treatment would result in a methane production of 3,76 to 7,76 GWh/yr. An application of anaerobic wastewater treatment will also result in electricity savings, in aerated pond, and increase the capacity margin on current sludge handling techniques.

<p>The liver is a primary target for toxicants and/or their metabolites. Selected fish species now serve as model organisms for laboratory investigations of toxic responses in the liver. One such model is the Japanese medaka (<italic>Oryzias latipes</italic>), a small freshwater teleost with a robust history of usage in liver and biliary toxicity studies. The structural components of the medaka hepatobiliary system have been well-described by recent studies in two- and three-dimensional contexts, but efforts to characterize the molecular mechanisms underlying critical medaka liver functions during normalcy remain sparse. This dearth of information makes it difficult to definitively characterize toxic responses in this model organism. A crucial transcription factor underlying proper hepatobiliary function in both mammalian and non-mammalian species is the farnesoid X receptor alpha (FXR&alpha;), a member of the nuclear receptor superfamily that plays a key role in bile acid homeostasis. This dissertation describes the function of medaka fxr&alpha; during both normalcy and toxicity.</p><p>To achieve this overall objective, <italic>in vitro</italic> techniques were first employed to study the function of medaka <italic>fxr&alpha;</italic>. Two isoforms of <italic>fxr&alpha;</italic> that differ in the AF1 domain, Fxr&alpha;1 and Fxr&alpha;2, were isolated from liver cDNA and are the result of alternative splicing of one gene locus. Fxr&alpha;2 responded significantly to C24 bile acids and the synthetic FXR&alpha; agonist GW4064. On the other hand, Fxr&alpha;1, despite having an identical ligand-binding domain to that of Fxr&alpha;2, showed no response to any agonists tested by transient transactivation assays. Furthermore, Fxr&alpha;2 interacted with nuclear receptor coactivators PGC-1&alpha; and SRC-1 in mammalian two-hybrid assays while Fxr&alpha;1 did not. These findings point to a significant importance of the AF1 domain to overall receptor structure and function. </p><p>Following <italic>in vitro</italic> functional characterization, <italic>in vivo</italic> experiments using medaka larvae were performed to determine <italic>fxr&alpha;'s</italic> function during normalcy. Quantitative, real-time PCR data demonstrated that Fxr&alpha;1 is highly expressed in adult liver, while Fxr&alpha;2 is expressed predominantly in gut. Fxr&alpha;1's expression was higher than Fxr&alpha;2 in embryos and larvae at all developmental timepoints tested. In vivo exposures of medaka hatchlings to GW4064 at various doses significantly altered expression of defined FXR&alpha; targets, including: bile salt export protein (BSEP), small heterodimer partner (SHP), and cytochrome P450 7A1 (CYP7A1). Surprisingly, numerous sublethal hepatic alterations to hepatocytes and bile preductular epithelial cells (BPDECs) were observed following exposure to GW4064; alterations included: lipid accumulation, glycogen depletion, mitochondrial swelling and rupture of mitochondrial membranes, disruption of endoplasmic reticulum, and apoptosis. Significant lipid accumulation, as revealed by oil red O whole mount staining of larvae, was also noted at lower doses of GW4064. These findings were the first observations of sublethal hepatotoxicity of GW4064; to date, no studies in the mammalian literature reported alterations following its administration.</p><p>Because of studies in the mammalian literature that demonstrated alleviation of cholestatic injury induced via the classic hepatotoxicant &alpha;-naphthylisothiocyanate (ANIT) by GW4064, it was originally hypothesized that a similar finding would be observed in medaka coexposed to these compounds. However, because of GW4064's ability to induce sublethal hepatic alterations in medaka, it was anticipated that its coadministration with ANIT would result in enhanced toxicity rather than alleviation as described in rodent models. However, despite the sublethal alterations induced by 1 uM GW4064, alleviation of toxicity following exposure to 15 uM ANIT was observed. Surprisingly, reduction of GW4064's toxicity was also observed in larvae exposed to both compounds. These investigations of <italic>fxr&alpha;</italic> function are an important and essential component in furthering our understanding of hepatobiliary toxicity in small aquarium fish models of human liver disease. These collective findings have created molecular underpinnings necessary for understanding medaka hepatobiliary function during normalcy and toxicity.</p> / Dissertation

<p>Reactive oxygen species (ROS) are produced endogenously in all aerobes and are induced by environmental stressors. ROS oxidize and disable essential cellular components such as DNA, proteins, and lipid membranes. Exposure to metals, polycyclic aromatic hydrocarbons (PAHs), and some pesticides can induce oxidative stress in marine invertebrates. All aerobic organisms have a network of antioxidants and enzymes to quench ROS and prevent oxidative damage. This dissertation examines antioxidant and oxidative stress biomarkers in endemic molluscs and crabs from two natural extreme environments: deep-sea hydrothermal vents in the Lau and North Fiji Basin, and cold seeps in the Gulf of Mexico. In addition, the acute toxicity and sub-lethal effects of four insecticides and an herbicide are examined in the estuarine blue crab, <italics>Callinectes sapidus</italics>. Blue crabs are North Carolina's most important fishery species and are frequently found in agricultural drainage ditches, an example of an anthropogenic extreme environment. </p> <p>Total glutathione, catalase, superoxide dismutase, and lipid peroxidation levels were of the same respective order of magnitude in the two vent gastropods, <italics>Alviniconcha</italics> sp. and <italics>Ifremeria nautilei</italics>, and vent mussel, <italics>Bathymodiolus brevior</italics>. These biomarkers activities were similar to those from previous reports on Mid-Atlantic Ridge mussels, except for ~100-fold higher lipid peroxidation levels among Lau molluscs. Principal component analysis (PCA) of mollusc tissue-specific biomarker levels grouped individuals by species rather than by site. </p> <p>Biomarker levels in the seep mussels <italics>Bathymodiolus childressi, B. brooksi</italics>, and <italics>B. heckerae</italics> were similar across species except for elevated foot and gill cytosolic SOD in mussels from MC-640 compared to those from AC-645. PCA of seep mussel biomarker levels differentiated by species with <italics>B. childressi</italics> isolated from <italics>B. brooksi</italics> and <italics>B. heckerae</italics>. The addition of <italics>B. brevior</italics> biomarker data to the PCA showed them grouping around <italics>B. brooksi</italics> and <italics>B. heckerae</italics>. <italics>Bathymodiolus childressi</italics> is ancestral to the other species and contains only methanotrophic endosymbionts. Whether symbionts play a role in alleviating possible toxic conditions remains unknown.</p> <p>Pesticides were acutely toxic to blue crabs in the order of Lambda-cyhalothrin > imidacloprid &#8776; aldicarb > acephate &#8776; Roundup® (glyphosate). Megalopae were almost always more sensitive to pesticides than early stage juveniles. Commercial formations of pesticides generally showed similar toxicity to active ingredients alone. Exposure to LC₂₀ levels of acephate, aldicarb, imidacloprid and Roundup significantly increased the frequency of juvenile mortality after molting. There was no significant change in total glutathione or lipid peroxidation of exposed megalopae. Lambda-cyhalothrin-, imidacloprid-, and aldicarb-based products have the potential to cause acute toxicity and molting-related mortality in shallow creeks and ditches.</p> / Dissertation

Ferrite process (denoted by FP) has been used for treating the waste-liquid containing heavy metal for many years. Related researches have shown that this method could catch the heavy metal regulated by environmental law into the structure of spinel, and sludge from FP also conformed the standards of toxicity characteristic leaching procedure in EPA of Taiwan. On comparing with neutral precipitation of conventional method, spinel¡¦s sludge produced in FP had an ease separation of solid-liquid and no need of solidification in further treatment. These spinel, belonged to the magnetic material, could be used for applications such as brick of blinder guide, magnetic symbol, absorber of electric wave and adsorbent. Therefore, this method has a great potential for treating the waste containing heavy metal in laboratory. This study was to investigate the optima conditions in removal of heavy metal in waste liquid in laboratory by using the FP of conventional, two and three stage. All experiments, including one ion and ten ions heavy metal mixed in a solution, were conducted in a batch- type reactor for total concentration of 2000 mg/L heavy metals. The major parameters included temperature, ferric ion dosage, aeration intensity and pH. The performance of treatment in FP was judging by that the concentration of all heavy metals in filtered solution and the heavy metal containing in sediment sludge should be below the regulations of effluent standards and TCLP standards. In conventional one stage of FP experiments performed at constant temperature and pH, the residual concentration of heavy metals in filtered solution was below the effluent standards except of Cd and of Hg; in results of TCLP showed that higher dissolvion of Cd, Cu and Pb leached from sediment and the rest ions of heavy metal passed the regulations. Thus, we conducted individually for Cd, Cu and Pb to find the optimal conditions. The optimal pH of 7 and temperature above 70 ¢J for Cd and Pb and the optimal pH of 10 and temperature above 80 ¢J for Cu were obtained. They were be used for combination of process in various stage to achieve the goal of treatment performance. After the combination of two and three stage reactions, three stage reactions in series was the only selection in removal of ten heavy metals performed by FP. As a result, the sequences were in the following: (1) 70¢J, pH=9 (2) 90¢J, pH=9 (3) 80¢J, pH =10 , and the reaction period was 40 min for each stage.

Aquacultural production of hybrid striped bass (HSB) Morone chrysops × M. saxatilis is highly vulnerable to losses from bacterial pathogens such as Streptococcus iniae. Therefore, research was conducted to evaluate various dietary factors that may enhance immunocompetence and disease resistance of HSB. In the first experiment, purified and practical diets were supplemented with &#946;-glucan and selenium in a factorial arrangement and fed to juvenile HSB for 6 wk followed by a S. iniae challenge. Weight gain (WG) and feed efficiency (FE) were higher for fish fed either practical diets or purified diets supplemented with selenium, but not those supplemented with &#946;-glucan. Survival after disease challenge for fish fed the selenium-supplemented practical and purified diets was 75% and 35%, respectively. Because selenium supplementation also improved WG and FE, and because selenium and vitamin E have complementary biochemical functions, a second experiment evaluated potential interactions by feeding purified diets with or without vitamin E or sodium selenite (Na2SeO3), singularly or in combination, for 12 wk. Dietary selenium significantly affected whole-body selenium concentration but there was no effect of dietary selenium, vitamin E or their interaction on WG, FE, survival or blood neutrophil oxidative radical production. Three additional 12-wk experiments were conducted to establish selenium essentiality, toxicity, tissue deposition, dietary requirements, bioavailability and nonspecific immune responses using purified diets with a basal selenium level of 0.11 mg/kg. In one experiment, diets had selenium concentrations of 1.19, 2.00, 5.17 and 21.23 mg/kg from Na2SeO3. Another experiment had selenium concentrations of 0.90, 1.26 and 2.55 mg/kg from seleno-DL-methionine. The third trial utilized selenium from Na2SeO3, seleno-DL-methionine and selenium yeast at approximately 0.15, 0.30 and 0.60 mg/kg diet. No overt selenium deficiency signs were observed in any of the three latter experiments, but based on selenium retention values, a minimum dietary requirement of approximately 0.1 mg/kg was estimated. Selenium toxicity was observed in fish fed the diet containing more than 20 mg/kg. Bioavailability of selenium sources was ranked as seleno-DL-methionine > selenium yeast > Na2SeO3.

Physicians are familiar with organophosphates (OPs) as a classic, though obscure, cause of cholinergic poisoning. Many opportunities for human exposure existsixty million pounds of OPs are applied as insecticides to sixty million acres of U.S. land each year, and, until recently, over one-fifth of Americans used these chemicals in their homes. Most physicians, however, still know little about the dangers that these pesticides pose to the developing nervous system. By the late 1980s, toxicologists increasingly recognized that toxicants such as lead and mercury, even at doses well-below the level required to cause symptomatic poisoning, could induce subtle, yet permanent, neurological deficits if the exposure occurred during critical periods of brain development. In the early 1990s, scientists and regulators began to realize that developmental neurotoxicity (DNT), as this phenomenon was called, could also result from OPs. In 1996 Congress passed the Food Quality Protection Act (FQPA), marking a major turning point in the regulation of hazardous chemicals. Prior to the FQPA, the Environmental Protection Agency (EPA) based its calculations of pesticide risk on adults and largely neglected the increased susceptibility of infants and children. The new law took a precautionary stance, protecting the vulnerable neural and physical development of the fetus and child with the inclusion of a 10-X safety factor, and shifting the burden of proof from health advocates to the pesticide manufacturers. The ensuing ten-year battle between health groups, pesticide manufacturers, and the EPA over the laws enforcement now provides an instructive lesson into the complex scientific, political, and economic world of environmental health, and serves as a relatively successful example of effective policy improving public health.

Derzeit ist es gängige Praxis, die Chemotherapie entsprechend der Körperoberfläche des Patienten zu dosieren. Diese Praxis ist jedoch nicht ideal, da es Patienten gibt, die starke Nebenwirkungen haben und andere, die kaum Nebenwirkungen aufweisen. Damit intelligentere Dosierungsschemata entwickelt werden können und prophylaktische Maßnahmen zum Verhindern von Therapienebenwirkungen besser geplant werden können, ist die Kenntnis der Faktoren erforderlich, welche die Nebenwirkungen verursachen. Die hämatologischen Nebenwirkungen der Chemotherapie sind dabei am stärksten ausgeprägt und führen oft zu Dosiserosionen, Zeitverschiebungen zwischen den Chemotherapiezyklen oder sogar zu einem Abbruch der Therapie. Das hat wiederum negative Auswirkungen auf den Therapieerfolg. In dieser Arbeit wurden daher Prognosemodelle für chemotherapieinduzierte hämatologische Nebenwirkungen aufgebaut. Die Daten von 1399 Patienten mit aggressivem Non-Hodgkin-Lymphom und einem breiten Altersspektrum von 18-75 Jahren aus der NHL-B1/B2-Studie (Pfreundschuh et al. 2004a und b) gingen in die Analyse ein. Es wurden für die jüngeren (<= 60 Jahre) und die älteren Patienten (> 60 Jahre) multivariate Proportionale Odds Regressionsmodelle für die drei hämatopoetischen Linien der Leukozytopenie, Thrombozytopenie und Anämie gerechnet und an zwei unabhängigen Datensätzen, auch unter Rituximab-haltigen Chemotherapieschemata, validiert. Die hier entwickelten Modelle konnten ein breites Heterogenitätsspektrum für die hämatologischen Nebenwirkungen erklären. Bemerkenswert ist, dass einige der Faktoren für hämatologische Nebenwirkungen gleichzeitig auch Faktoren des Internationalen Prognostischen Index für das Therapieergebnis sind. Die im ersten Chemotherapiezyklus beobachtete Nebenwirkung war der stärkste prognostische Faktor. Mit einigen der Modelle konnte die kumulative Nebenwirkung über die Chemotherapiezyklen hinweg gezeigt werden. Die Demonstration des Zusammenhangs zwischen den für Leukozytopenie ermittelten Risikogruppen und den klinisch relevanten Größen Infektion, Antibiotikagabe, Hospitalisierungstage und therapieassoziierte Todesfälle ist ein sehr wichtiges Ergebnis der Arbeit. Es wurde eine Internetseite (www.toxcalculator.com) entwickelt, welche den Ärzten die Möglichkeit bietet, die bei dem Patienten vorliegenden Prognosefaktoren einzugeben und dann die Modellvorhersagen für die zu erwartenden hämatologischen Nebenwirkungen zu erhalten. Die Ergebnisse der Arbeit wurden in der hochrangigen Zeitschrift ‚Annals of Oncology‘ publiziert (Ziepert et al. 2008).

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xiii, 133 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 110-125).

The purpose of this thesis is to determine the factors that contributed to the decline of Florida apple snail ( Pomacea paludosa) populations in the A.R.M. Loxahatchee National Wildlife Refuge with the goal of devising management recommendations to the Refuge regarding population management strategies. The factors examined that could have potentially contributed to population decline include the use of copper-based herbicides, insecticide application, the occurrence of drought, the use of other herbicides, the occurrence of fire, and non-avian predation. Annual Narrative documents produced by Refuge managers and staff members, dated from 1951 to 2007, were used to collect historical data for these factors. The quality of data reporting within the Annual Narratives was also examined. To support data on droughts documented in the Annual Narratives, surface water and rainfall data were obtained and analyzed. The methodology includes the use of conceptual ecological models and historical ecology to determine whether or not the factors examined produced an ecological effect capable of affecting the Refuge population of apple snails. Evidence from the Annual Narratives suggests that the use of copper-based herbicides, the occurrence of drought, and predation by alligators were responsible for the decline of the apple snail on the Refuge. A lack of consistently reported data regarding apple snail densities makes it difficult to determine the degree to which each factor had an effect on the apple snails or to determine if any spatio-temporal relationship existed between the Florida apple snail and Everglade snail kite ( Rostrhamus sociabilis plumbeus) based on copper-based herbicide use. The overall quality of the Annual Narratives improved throughout the study period and eventually focused heavily on investigative studies. Several management recommendations were suggested to improve Florida apple snail populations on the Refuge. First, in order to monitor the health and trends of the apple snail population, a monitoring network needs to be established with results maintained in a geodatabase. Both apple snail density and egg cluster counts need to be made following an established sampling method. Second, in an attempt to sustain higher apple snail densities, stocking of the interior should be attempted. Finall, in the event that adjacent farmlands are to be restored, soil samples need to be analyzed to determine if concentrations are high enough that desorption of copper from the flooded agricultural soils could pose a serious threat to the Refuge by reintroducing toxic levels of copper.

published_or_final_version / Environmental Management / Master / Master of Science in Environmental Management