Invasive Pulmonary Apsergillosis (IPA) is caused by inhalation of fungal conidia to the deep lung followed by germination and invasive hyphal growth in heavily immunosuppressed patients (e.g. those with hematologic malignancies, hematopoietic stem cell transplant recipients, and those undergoing solid organ transplantation). Hyphal growth into pulmonary capillaries often leads to dissemination of the infection and high mortality rates despite current treatment and prophylactic modalities. In addition, systemic antifungal therapy is often limited by drug toxicities, low and variable bioavailability, erratic pharmacokinetics, and drug interactions. Although targeted drug delivery to the lungs has been investigated to reduce adverse events and promote drug efficacy, inconsistent pharmacokinetic properties following inhalation of poorly water soluble antifungals has prompted variable drug efficacy. In this dissertation, inhaled voriconazole was investigated through in vitro and in vivo testing to evaluate pharmacokinetic properties, characterize drug safety and, determine drug efficacy as prophylaxis against IPA. In Chapter 2, the in vitro evaluation of solution properties and aerosol characterization of aqueous voriconazole was evaluated. Subsequent in vivo single and multiple dose pharmacokinetic studies demonstrated high drug concentrations were achieved in lung tissue and plasma following inhalation in contrast to previous reports of inhaled antifungals. Inhaled voriconazole was then administered twice daily (BID, at 08:00 and 16:00) in a murine model of IPA as described in Chapter 3 with significant improvements in animal survival over 12 days compared to both positive and negative control groups. As described in Chapter 4, voriconazole was then chronically administered BID at a high and low dose to rats over 21 days with a 7 day recovery period to assess dose tolerability through laboratory tests and histopathological changes to lung, liver, kidney, and spleen tissues. Inhaled voriconazole was well tolerated through all assessments but with signs of mild acute histiocytosis in lung tissue without other signs of inflammation. Chapter 5 expanded the single inhaled dose pharmacokinetic profile in lung tissue and plasma with determination of additional pharmacokinetic parameters through compartmental modeling. Peak and trough voriconazole concentrations were also evaluated in mice as well as rats following multiple doses administered over 12 hours (Q12H) as opposed to BID. / text

Although the process by which fertilization occurs in bryozoans is well described, the ability to self-fertilize and the subsequent ecological consequences are poorly understood. Culturing experiments were conducted examining the effects of selfing on offspring survival and reproduction in the simultaneous hermaphrodite Bugula stolonifera collected from Eel Pond, Woods Hole, MA. Results from these experiments document significant decreases in survival and fecundity of selfed offspring, compared to outcrossed controls, suggesting that these animals are not routinely self-fertilizing in Eel Pond. How these arborescent colonies minimize selfing remains unclear, but it is hypothesized that conspecific aggregations could serve to minimize the chances that a colony utilizes its own sperm for fertilization. The genetic composition of these aggregations was investigated using a newly developed microsatellite library. As larvae routinely metamorphose on conspecific colonies, the possibility that larvae select or avoid their maternal colony was also investigated. Analyses of genetic structure document homogeneity throughout these aggregations on extremely small spatial scales, suggesting high amounts of larval dispersal within aggregations. When combined with results from parentage-exclusion and kinship analyses, these results indicate that a colony's nearest neighbors are not composed of siblings, potentially minimizing inbreeding. Molecular analyses were then used to determine if the high larval dispersal within aggregations resulted in high mixing between aggregations. Sites within Eel Pond separated by 100-300 m were routinely sampled from 2009 to 2011, and analyses were conducted to investigate potential inter- and intra-annual genotypic differentiation within and between aggregations. Results document that although low levels of mixing could result in increased homogeneity between some aggregations, barriers to genetic exchange prevent mixing between most sites. Further, inter-annual comparisons within sites document that significant differentiation can occur between reproductive seasons. Hence, any potential homogeneity achieved between sites during one reproductive season will likely be lost by the beginning of the next reproductive season. Additionally, while sampling in Eel Pond in 2010, I document the first occurrence from the western Atlantic Ocean of another aggregating arborescent bryozoan, Tricellaria inopinata. The growth and reproductive biology of these animals was monitored throughout 2011; results suggest that this introduction is likely to persist.

Buffelgrass (Pennisetum ciliare) is a perennial bunchgrass native to Africa that has invaded ecologically intact areas of the Sonoran Desert in southern Arizona. It threatens many native plant species by means of competitive exclusion as well as increased fire frequency and intensity. Since the 1990s, efforts have been underway in southern Arizona to control buffelgrass using manual removal. A problem with this method is that the resulting bare, disturbed soil provides a favorable environment for buffelgrass seed germination. This study examined whether thatch composed of uprooted buffelgrass parent plants spread over disturbed areas reduces the density of progeny seedlings. A secondary goal was to determine whether light attenuation and/or autoallelopathy were major factors involved in the effect of thatch on buffelgrass seedling density. The effect of light attenuation on seedling density was tested in containers in the field and in the greenhouse. The propensity of thatch to produce autoallelopathic chemicals was tested in the greenhouse. Field plots with thatch had 1.9 buffelgrass seedlings/m² which was significantly fewer (p= 0.03) than the 2.9 seedlings/ m² in plots without thatch. These results suggest that the placement of thatch over areas disturbed during manual treatment of dense stands of buffelgrass will increase the efficiency of follow-up control of buffelgrass progeny seedlings in these areas. Results of the field container study suggest that light attenuation does not play a significant role (p= 0.39) in the reduction of seedling density by thatch, whereas those of the greenhouse shade treatment study indicated that light attenuation is a significant factor (p= 0.004). However, because percent germination was very low in the field container study, those results may be of little value compared to the greenhouse shade treatment study results which indicate that light attenuation is a mechanism by which thatch reduces buffelgrass seedling emergence. Chemicals leached from decomposed buffelgrass thatch did not have a significant effect (p= 0.09) on buffelgrass seedling density. Only the combination of thatch and leached chemicals significantly reduced (p= 0.014) seedling density. Thatch may also increase the activity of other factors that could reduce seedling density such as pathogens, and predators of seeds and seedlings.

The historically introduced House Rock Valley bison herd has, in recent years, migrated from the eastern Arizona Strip onto the Kaibab Plateau within Grand Canyon National Park. Bison are considered a nonnative species to the southern Colorado Plateau, and the animals adversely impact sensitive ecosystems prompting National Park Service wildlife managers to pursue their removal. Archaeofaunal evidence of bison in the Grand Canyon and neighboring regions, however, raises concern that bison may in fact be native. Assessing the evidence within a zooarchaeological interpretive framework is critical since mere presence/absence lists of bison remains do not address the potentially complex cultural processes involved in the formation of archaeofaunal assemblages. Inter-assemblage comparisons illustrate a decline in relative abundance and skeletal completeness correlated to distance from traditionally understood historical bison distribution. If bison were present in the Southwest, as the evidence suggests, they likely entered the region only occasionally as small, dispersed herds.

Invasive species such as quagga mussel (Dreisseina bugensis) alter native ecosystems around the world. This study uses genetic markers to examine historical lineages for quagga mussels in lakes (reservoirs) of the Colorado River System. Specimens were collected from Lake Mead, Lake Mohave, Lake Pleasant, Lake Havasu, Lower Otay Reservoir, Yuma Area, and two Central Arizona Project pumping stations. Objectives of this project were to perform analyses of genetic variability within populations and determine if relatedness among individuals could resolve whether they originate from a single, or multiple, invasion events and genetically distinguish the populations at each water body. Analyses examined the mitochondrial DNA COI region and eight microsatellite DNA markers. Three populations were characterized in the study area and compelling information gathered about gene flow between them. Results indicate that microsatellite markers are useful to track quagga mussel invasions and provide insights into migration patterns that would otherwise be missed.

Buffelgrass (Cenchrus ciliaris L.) is an invasive, perennial, C₄ bunchgrass. Buffelgrass has a rapid invasion rate, a tendency to displace native vegetation, and presents a fire risk to native plant communities, adjacent developed areas and their associated infrastructure. Mechanical control is impractical and unable to keep pace with regional spread. Chemical control has offered the most promise for successful and cost-effective management on a regional scale. The predominant herbicide used to control buffelgrass is glyphosate, which requires active vegetative growth when applied for optimum uptake and translocation to meristematic tissue. The timing and duration of active growth is difficult to predict. In this dissertation I addressed three related topics to improve effectiveness of buffelgrass management in the Sonoran Desert. First, I used digital time-lapse photography and weather data to predict the timing and length of future active growth based on day of year and antecedent weather at three sites in the Sonoran Desert near Tucson, AZ that were representative of habitats currently infested by buffelgrass in the region. I was able to correctly predict greenness above or below a threshold of herbicide susceptibility at 81 to 95% for a basin floor site and at 61-88% for slope sites. Second, I evaluated the effects of different rates of two herbicides (imazapic and clethodim), alone or in combination with different rates of glyphosate, for pre- (imazapic only) and postemergence control of buffelgrass. I found a minimum glyphosate application rate of 2.52 kg ae ha⁻¹ glyphosate consistently killed mature buffelgrass plants; clethodim at had no effect on mature buffelgrass; and imazapyr was successful in killing mature plants when applied during the dormant season at 0.56 kg ae ha⁻¹ and provided preemergence control. Imazapic severely damaged but did not kill mature buffelgrass plants at the maximum label rate of 0.21 kg ae ha⁻¹. Finally, we evaluated results from a helicopter broadcast herbicide application trial conducted in the Tucson Mountains. We demonstrated that most species and life forms were less affected than buffelgrass to glyphosate deposition rates achieved in the study, but asserted that procedural changes were necessary to achieve effective buffelgrass control.

Shifting patterns of precipitation associated with climate change may affect water-limited ecosystems to a greater degree than atmospheric CO2 or temperature changes, yet we lack a mechanistic understanding of the effects of water in these ecosystems. In water-limited ecosystems, annual net primary productivity correlates strongly with total annual precipitation. However, precipitation in these ecosystems arrives in episodic events, suggesting that biophysical investigations should focus on the implications of discrete precipitation events. Further, examining dynamics of ecosystem processes over a period of days or weeks promises to link our leaf-level mechanistic understandings with larger scale patterns and temporal dynamics of ecosystem photosynthetic CO2 uptake, respiration and evapotranspiration.The objectives of this dissertation were to quantify: (1) the influence of biotic and abiotic features of an ecosystem (e.g., species composition and soil physical characteristics) on short-term patterns of resilience and resistance to a precipitation pulse; (2) the role of antecedent climatic conditions and the seasonal timing of rainfall in limiting ecosystem carbon exchange in response to precipitation events; and (3) the effect of changes in woody plant abundance on seasonal ecosystem carbon dynamics in relation to the North American Monsoon.Major findings and contributions of this research include defining the concepts of ecosystem functional resistance and resilience and their implications in the presence of a dominant nonnative bunchgrass in semi-arid grasslands (Appendix A); a better understanding of the influence of warm-season precipitation variability and the seasonal timing of rainfall on ecosystem carbon dynamics in a semi-arid grassland (Appendix B); the use of flux duration analysis, a novel approach to analyzing ecosystem carbon and water flux time-series data to distinguish between "pulse-driven" or "steady-state" ecosystems (Appendix C); and, finally, the application of flux duration analysis to quantify the sensitivity of ecosystem carbon exchange in response to seasonal rainfall in a riparian grassland and shrubland and the role that plant functional type diversity may play in constraining carbon exchange sensitivity (Appendix D).

Species distribution models must balance the need for model generality with that for precision and accuracy. This is critical when modelling range-expanding species such as invasive species. Given the increased use of species distribution models to study invasive species-landscape relationships, a better understanding of the effect of spatial scales, sampling biases, model transferability and discrepancies between different models’ future predictions is necessary. This dissertation addresses these knowledge gaps using mute swans (Cygnus olor) as a case study species. I specifically examine mute swan’s distributions in parts of their native range of Britain and their non-native range of Ontario, Canada. I first investigate which environmental variables at which spatial scales best explain mute swan’s distribution in its non-native range. Second, I perform a sample selection bias study to examine predictive accuracy when species distribution models are built using varying ranges of environmental variables and applied to broader spatial extents. Third, I examine the potential for, and limitations of model transferability between native and non-native regions. Finally, I use two different modelling approaches and three different climate change and land use change scenarios to predict future mute swan habitat suitability. The results indicate that (1) models with better predictive accuracy include environmental variables from multiple ecologically-meaningful scales and measured at spatial extents that include a broad range of environmental variable values; (2) models can exhibit asymmetrical transferability; (3) climate change will facilitate mute swan range expansion in the future more than land use change; and (4) mute swans are often found near urban waterbodies. When modelling invasive species distributions, I suggest that ecologists consider: (I) spatial scale of the underlying landscape processes and species’ use of the landscape; (II) variability and range of each environmental variable used for building models; and (III) stage of establishment of the invasive species.

Species distribution models must balance the need for model generality with that for precision and accuracy. This is critical when modelling range-expanding species such as invasive species. Given the increased use of species distribution models to study invasive species-landscape relationships, a better understanding of the effect of spatial scales, sampling biases, model transferability and discrepancies between different models’ future predictions is necessary. This dissertation addresses these knowledge gaps using mute swans (Cygnus olor) as a case study species. I specifically examine mute swan’s distributions in parts of their native range of Britain and their non-native range of Ontario, Canada. I first investigate which environmental variables at which spatial scales best explain mute swan’s distribution in its non-native range. Second, I perform a sample selection bias study to examine predictive accuracy when species distribution models are built using varying ranges of environmental variables and applied to broader spatial extents. Third, I examine the potential for, and limitations of model transferability between native and non-native regions. Finally, I use two different modelling approaches and three different climate change and land use change scenarios to predict future mute swan habitat suitability. The results indicate that (1) models with better predictive accuracy include environmental variables from multiple ecologically-meaningful scales and measured at spatial extents that include a broad range of environmental variable values; (2) models can exhibit asymmetrical transferability; (3) climate change will facilitate mute swan range expansion in the future more than land use change; and (4) mute swans are often found near urban waterbodies. When modelling invasive species distributions, I suggest that ecologists consider: (I) spatial scale of the underlying landscape processes and species’ use of the landscape; (II) variability and range of each environmental variable used for building models; and (III) stage of establishment of the invasive species.

INTRODUCTION: National obesity rates are leading to higher rates of Type 2 Diabetes, increasing the number of people at risk of invasive infections with Methicillin Resistant Staphylococcus aureus (iMRSA) upon onset of ESRD and hemodialysis. However, an association between adiposity and risk of iMRSA has not been researched. AIM: The purpose of this study is to describe the epidemiological characteristics of an iMRSA cohort in the Atlanta metro area between 2005-2008; to examine BMI-related health outcomes within the cohort; and to compare proportions of BMI categories in this cohort to BRFSS data. METHODS: Surveillance data collected by the CDC EIP program on iMRSA in Atlanta, Georgia was used. BMI was calculated for each eligible case. Statistical analysis was carried out in SPSS. Univariate and multivariate binary logistic regression analysis was performed on select variables. A p-value of < 0.05 and a 95% confidence interval (CI) were used to determine significance. BRFSS BMI data for Georgia was compared to the study population. RESULTS: Overweight and obese cases were more likely to be diagnosed with diabetes by regression analysis. Cases with diabetes were at greater odds of having undergone dialysis within the previous year (univariate OR=2.3, p=0.000; multivariate OR=2.5, p=0.000). The proportion of iMRSA patients with diabetes is much greater (42.8%) than in the general population of the United States (7.8-10.7%). DISCUSSION: The results indicate that there may be a higher risk for iMRSA in overweight and obese individuals, particularly if other adiposity-related health problems are present.