Class of 2011 Abstract / OBJECTIVES: Five methods for estimating vancomycin pharmacokinetic parameters were studied to determine the accuracy of each method in predicting vancomycin concentration. METHODS Patient vancomycin pharmacokinetic data from a prior study were retrospectively reviewed and used in five methods to calculate vancomycin clearance and volume of distribution in order to determine the accuracy in prediction of the measured value. RESULTS: The coefficients of determination ranged from 0.167 to 0.224, bias ranged from -5.18 to 2.13, and precision ranged from 5.98 to 7.64. The Buelga method had the highest percentage of predictions within 2.5 and 5 mg/L of the measured trough at 42% and 65% respectively, while the Thomson method had the highest percentage of predictions within 50% of the measured trough at 52%. The highest percentage of predictions within 25% of the measured trough were found with both the Thomson and Yasuhara method at 29%. CONCLUSION: There was wide variation in the prediction of vancomycin trough concentrations from the five methods for estimating vancomycin pharmacokinetic parameters. None of the methods provided adequate reliability to recommend discontinuation of therapeutic drug monitoring for vancomycin.

Passive samplers can be used to determine time-integrated patterns of water chemistry at one or many locations throughout a stream network while minimizing cost and sampling time. A passive flux meter (PFM) simultaneously estimates time-averaged water and solute mass fluxes in flowing water. PFMs have been used in groundwater to quantify contaminant flux but have been used only very recently in streams. In this study, PFMs were deployed in the surface and subsurface of headwater stream channels to examine the efficacy of the device to quantify mean concentrations of calcium, aluminum, and sulfur in streams of the Hubbard Brook Experimental Forest in New Hampshire, USA. In general, the PFM estimates of surface and subsurface stream chemistry were more accurate when flow rates were higher and more water passed through the PFM. During the lowest flows, PFMs overpredicted concentrations by 50 to 800%. In estimating calcium concentrations, 5 PFMs were within 10% of grab sample concentrations and 7 PFMs were within 30% of grab sample concentrations out of a total of 35 comparisons. Likewise, for sulfur concentrations, 4 PFMs were within 10% of grab sample concentrations and 7 PFMs were within 30% of grab sample concentrations out of 35 comparisons. Concentrations of aluminum were too low to be quantified above 90% confidence. PFMs calculated a lower cumulative discharge through the surface water PFMs than through the subsurface which may be explained by flow divergence around the sampler. Changes to PFM design and shorter deployment times are proposed to increase the efficacy of the PFM. / Master of Science / Passive sampling of headwater streams has advantages over traditional water sampling in quantifying stream water chemistry over time and space, while minimizing cost and sampling time. A passive flux meter (PFM) is a sampler that estimates local time-averaged discharge of water and time-averaged solute amount in flowing water without the need for constant monitoring, maintenance, or power sources. PFMs have been used in groundwater systems to quantify contaminant concentrations but have only been used very recently in streams or in the sediments below streams. In this study, PFMs were installed in headwater streams and the shallow sediments below the streams to examine the ability of the device to quantify the natural water chemistry. Concentrations of calcium, aluminum, and sulfate were evaluated in streams of the Hubbard Brook watershed in New Hampshire, USA. Concentrations of aluminum were too low to be quantified. In general, the PFM estimates of surface and subsurface stream chemistry were more accurate when flow rates were higher and more water passed through the PFM. During the lowest flows, PFMs overestimated stream concentrations. PFMs installed in small streams measured more total volume through the device than PFMs installed in sediments below the streams. PFM design may have had an impact on these results. Changes to PFM design and shorter deployment times are proposed to increase the efficacy of the PFM

Mean salinity concentrations in the four reservoirs (Moss, Ray Hubbard, Texoma and Possum Kingdom) ranged from 0.2 ppt in Moss Lake to 2.01 ppt in Possum Kingdom Lake. Reservoir sodium and chloride concentrations were hypotonic to hypertonic to plasma levels in all species. Interspecific differences were seen in ionic concentrations within each reservoir. Total osmotic and sodium concentrations in carp, Cyprinus carpio, were correlated to their concentrations in the reservoirs. No such relationship was noted for chloride, potassium and calcium. A laboratory study indicated that fish collection by electroshock did not bias plasma ion concentrations. Exposures to wide variations in ionic concentrations did not appear to induce stress in the species studied.

BACKGROUND:A inverse correlation has been found between changes in ionized calcium concentrations and the addition of albumin in vitro, which may explain adverse cardiovascular effects attributed to exogenous albumin in vivo. The purpose of this investigation was to determine the interaction (if any) between exogenous 25% albumin administration (100 ml given over < 30 min) and calcium concentrations in patients, all but one of whom were in an intensive care unit.RESULTS:There were no significant differences in the ionized calcium concentrations obtained before, at the end and 6 h after the administration of albumin (1.09 +/- 0.23, 1.06 +/- 0.22, 1.06 +/- 0.21 mmol/l, respectively). Similarly, there were no significant differences in the total calcium concentrations between these same time periods (2.03 +/- 0.18, 2.05 +/- 0.20, 2.08 +/- 0.23 mmol/l, respectively).CONCLUSIONS:In patients receiving infusions of 25% albumin, it appears that circulating calcium concentrations are well regulated by homeostatic mechanisms. Albumin infusions had no effect on calcium concentrations, although it is possible that temporary changes of questionable clinical importance may have occurred between measurement periods.

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This thesis consists of one major section with two subsections. The first subsection investigates the activity of Arthrobacter globiformis aspartate transcarbamylase's specific activity with increasing concentrations of the enzyme's substrate. Dihydroorotase (DHOase) activity was also measured with increasing concentrations of the substrate dihydroorotate. The second subsection collected data in order to classify the enzyme, resulting in a classification into the category of class A ATCases with bifunctional ATCase-DHOase complexes. The thesis provides evidence to broaden understanding of the ATCase and DHOase enzymes for members of the family that Arthrobacter belongs to.

Threshold and non-threshold linear models that govern toxicology are challenged by an alternative model, hormesis. It is defined as low-dose stimulation and high-dose inhibition from a stressor. Insecticide-induced hormesis has been studied in a plethora of insect-insecticide models at biochemical, individual and population levels. This research focuses on the effects of sublethal concentrations of insecticides on reproductive responses of green peach aphid, Myzus persicae (Sulzer), at individual and population level besides regulation of stress, dispersal and developmental genes during hormesis. In laboratory studies, irrespective of the duration and route of exposure, sublethal concentrations of imidacloprid induced stimulations in fecundity of M. persicae but the nature of response differed intra- and trans-generationally. Fitness tradeoffs could be rendered due to declined fecundity in successive generations. However, continuous exposure to sublethal concentrations does not compromise overall fitness trans-generationally, considering recovered levels of fecundity as controls in successive generations and the total reproduction after four generations. Greenhouse experiments affirmed uncompromised fitness where reproductive stimulations were noted in aphids exposed to imidacloprid treated potato plants. Up- and down- regulation of stress, dispersal and developmental genes was noted during imidacloprid-induced hormesis in M. persicae that mirrored the reproductive responses in few instances. Global DNA methylation results emphasized the heritability of adapted traits trans-generationally via hypermethylation. Dispersal related genes (OSD, TOL and ANT) that are predominantly expressed in alates (about 2- to 5-fold) were affected in apterous aphids continuously exposed to sublethal concentrations of imidacloprid. No direct relation with the previously noted fecundity was established implying adaptive cellular stress response pathways might be triggered rather than normal regulatory processes due to low-dose imidacloprid exposure. At a biochemical level, a study noted that imidacloprid-induced hormesis concurrently stimulated juvenile hormone III (JH) production and fecundity in M. persicae. Precocene, an anti-JH, at sublethal concentrations induced reproductive stimulations in M. persicae. Gene regulation during precocene-induced hormesis mirrored imidacloprid results for few genes including FPPS, a JH precursor gene, with a higher magnitude of regulation. Considering these stimulatory effects that insecticide-induced hormesis at various biological hierarchies, causes for pest resurgence, hormesis could have ramifications from declines in natural enemy population.

Knowledge of mercury concentrations in fish is essential for human health protection. Mercury is a naturally occurring element that acts as a neurotoxin to humans and other species. The biologically available mercury form, methylmercury (MeHg), bio accumulates from small benthic invertebrates to large pelagic fish, and therefore high end consumers and terminal predators have elevated Hg concentrations. The main pathway of MeHg exposure in humans is by consumption of contaminated fish. In this study total Hg concentrations were measured in 10 Gulf of Mexico pelagic fish species using a DMA 80 analyzer. Total Hg concentrations ranged from 0.004 to 3.55 ppm (wet wt). The highest mean concentration (1.04 ppm, wet wt) recorded in king mackerel (Scomberomorus cavalla) exceeded FDA recommended criteria of 1ppm. Dolphinfish (Coryphaena hippurus) and vermilion snapper (Rhomboplites aurorubens) had lowest mean Hg concentrations (<0.3 ppm). The rest of the species were above the EPA advisory level of 0.3 ppm. Wahoo (Acanthocybium solandri), greater amberjack (Seriola dumerili) and gag grouper (Mysteroperca microlepsis) had high Hg concentrations of approximately 0.7 ppm wet wt. Blackfin tuna (Thunnus atlanticus) and yellowfin tuna (Thunnus albacores) had moderate Hg concentrations (0.39 and 0.36 ppm wet wt respectively). Little tunny (Euthynnus alletteratus) and blacktip shark (Carcharhinus limbatus) had mean concentrations of 0.69 and 0.51 ppm respectively. The relationship between fish length and Hg concentrations was significant for four species.

Avec des recettes de plus d'un milliard de dollars pour l'exercice 2004, l'industrie porcine est le deuxième pilier de la filière bioalimentaire au Québec. Cependant, le développement des entreprises porcines se traduit souvent par des conflits opposant les producteurs agricoles et les riverains à cause de la dispersion des fortes odeurs autour des élevages porcins. En effet, l'élevage porcin pratiqué au Québec est de type intensif, avec des bâtiments pouvant abriter jusqu'à 2995 têtes de porcs. Les déchets solides et/ou liquides générés par ces animaux contiennent des polluants dont les plus nocifs pour la santé humaine sont le sulfure d'hydrogène H[indice inférieur 2]S et l'ammoniac NH[indice inférieur 3], Sous l'effet des paramètres météorologiques et topographiques, ces polluants peuvent se propager et causer des nuisances sur un rayon d'action jusqu'à environ 1 km autour d'un élevage. Cette situation avait amené le gouvernement provincial à adopter un moratoire de deux ans et demi sur les mégaporcheries pour contenir le mécontentement des populations qui n'hésitent plus à organiser des marches de protestation contre des projets d'agrandissement et/ou de construction de nouvelles porcheries. Notre zone d'étude est la MRC de L'Érable. Elle est située dans la région centre du Québec.Avec soixante-huit fermes porcines, le secteur du porc est un de ceux qui ont affiché la plus forte progression depuis deux décennies dans l'économie de la MRC. Notre étude a pour objectif final de trouver les emplacements potentiels dans la MRC de L'Érable pour implanter des élevages porcins qui ne nuisent pas aux populations riveraines. En premier lieu, nous avons établi une zone tampon de 1 km autour de chaque élevage pour vérifier la vulnérabilité des bâtiments et des routes. Cette opération a montré que bon nombre de bâtiments et de portions de routes sont potentiellement soumis à la pollution issue des élevages voisins. Pour confirmer cette assertion, nous avons ensuite utilisé le modèle de dispersion AERMOD. Les concentrations maximales trouvées lors de la simulation du modèle sont confrontées aux normes de qualité de l'air du MDDEP pour trouver les distances sécuritaires autour des routes et des résidences. Ces distances sont utilisées conjointement avec les normes de protection de l'hydrographie, des zones humides, des prises d'eau potable dans un modèle spatial pour identifier les meilleurs emplacements. Comme résultats, les concentrations maximales issues du modèle de dispersion sont pour un élevage individuel de 283,2 [micro]g/m[indice supérieur 3] en NH[indice inférieur 3], et 32,4 [micro]g/m[indice supérieur 3] en H[indice inférieur 2]S. Ces valeurs maximales dépassent respectivement le descripteur de toxicité chronique qui est de 100 [micro]g/m[indice supérieur 3] en NH[indice inférieur 3], ainsi que la norme horaire de 14 [micro]g/m[indice supérieur 3] de H[indice inférieur 2]S définie par le MDDEP. Pour mettre les résidences et les routes à l'abri des nuisances des élevages, il faudra les placer au-delà de 800 m de l'élevage porcin. Les emplacements potentiels résultant du modèle spatial montrent que les problèmes de nuisance d'odeurs que vivent actuellement les populations de la MRC de L'Érable viennent du fait que les élevages actuels ne respectent pas les distances séparatrices du MDDEP et ne sont pas localisés dans les lieux adéquats. L'aspect innovateur de notre étude réside dans l'utilisation de six outils d'analyse spatiale supporté par un modèle de dispersion des odeurs et les résultats satisfaisants obtenus à l'échelle locale. De la sorte, nous pensons que notre étude va contribuer à réduire les tensions sociales reliées à la problématique de la nuisance d'odeur par les élevages porcins. En outre, notre méthodologie pourra être utilisée ailleurs en l'adaptant au milieu d'étude vu que les problèmes de pollution de l'air dépassent les frontières des pays.