Over the past thirty years, clinical research has benefited substantially from the adoption of electronic medical record systems. As deployment has increased, so too has the number of researchers seeking to improve the overall analytical environment by way of tools and models. Although much work has been done, there are still many uninvestigated areas; two of which are explored in this dissertation. The first pertains to the physical storage of the data itself. There are two generally accepted storage models: relational and entity-attribute-value (EAV). For clinical data, EAV systems are preferred due to their natural way of managing many-to-many relationships, sparse attributes, and dynamic processes along with minimal conversion effort and reduction in federation complexities. However, the relational database management systems on which they are implemented, are not intended to organize and retrieve data in this format; eroding their performance gains. To combat this effect, we present the foundation for an EAV Database Management System (EDBMS). We discuss data conversion methodologies, formulate the requisite metadata and partitioned type-sensing index structures, and provide detailed runtime and experimental analysis with five extant methods. Our results show that the prototype, EAVDB, reduces space and conversion requirements while enhancing overall query performance. The second topic concerns query performance in a federated environment. One method used to decrease query execution time, is to pre-compute and store "beneficial" queries (views). The View Selection Problem (VSP) identifies these views subject to resource constraints. A federated model, however, has yet to be developed. In this dissertation, we submit three advances in view materialization. First, a more robust optimization function, the Minimum-Maintenance View Selection Problem (MMVSP), is derived by combining existing approaches. Second, the Federated View Selection Problem (FVSP), built upon the MMVSP, and federated data cube lattice are formalized. The FVSP allows for multiple querying nodes, partial and full materialization, and data propagation constriction. The latter two are shown to greatly reduce the overall number of valid solutions within the solution space and thus a novel, multi-tiered approach is given. Lastly, EAV materialization, which is introduced in this dissertation, is incorporated into an expanded, multi-modal variant of the FVSP. As models and heuristics for both the federated and EAV VSP, to the best of our knowledge, do not exist, this research defines two new branches of data warehouse optimization. Coupled with our EDBMS design, this dissertation confronts two main challenges associated with clinical data warehousing and federation.

Creating a database to manage medical data is not the easiest. We create a database to be used for a presentation tool that presents medical data about patients that is stored in the database. We examine which of the three databases, MySQL with relational design, MySQL with EAV design and MongoDB that are best suited for storing medical data. The analysis i performed in two steps. The first step handles the database that is most effective to retriev data. The second step examines how easy it is to change the structure of the various databases. The results show that depending on whether efficiency or maintenance is most important, different databases are the best choise. MySQL with relational design proves to be most effective while MongoDB is the easiest to maintain.

EHV-1 is a double-stranded DNA virus whereas EAV is a positive sense, single-stranded RNA virus. Therefore, genetically, they are very different from one another. However, both these viruses are endotheliotropic and thus, infect and replicates in equine endothelial cells resulting in vasculitis. Vasculitis is central to the pathogenesis of these two viruses. Thus, the main objective of this thesis was to investigate the inflammatory and innate immune responses of EECs that contribute towards the development of vasculitis following infection with EHV-1 and EAV in-vitro. Since proinflammatory cytokines and chemokines produced by endothelial cells play a significant role in the development of vasculitis, we investigated their gene expression as well as secretion. Results from this study showed that the proinflammatory response of EECs induced by EAV is relatively less when compared with the corresponding results from EHV-1 infected EECs. Furthermore, EAV elicits a lower type I interferon response in EECs when compared with EHV-1. Further investigations revealed an active role played by TLR 3 in inducing the proinflammatory response in EHV-1 infected EECs during the first 6 hours of infection but not in EAV infected EECs. Analyzing the whole transcriptome of EHV-1 and EAV infected EECs revealed a complex pattern of gene regulation and cellular pathways related to cellular immune, inflammatory and apoptotic responses. Finally, we investigated host genetic factors associated with EHV-1 induced myeloencephalopathy but found no evidence for a recessive allele influencing the development of EHM following EHV-1 infection for any genetic locus was identified. However, more complex host-pathogen interactions are possible.

The objectives of this thesis were: (1) to evaluate the downregulation of the stallion hypothalamic-pituitary-gonadal (HPG) axis by a GnRH antagonist (acyline) based upon endocrine, seminal, testicular and behavioral effects, and (2) to assess recovery after treatment. Stallions were treated for 50 days (n=4; 330µg/kg acyline q 5d) and controls (n=4) received vehicle alone. Stallions were assessed pre-treatment and for 72 days after last treatment. Treatment induced declines (p<0.05) in FSH, LH, testosterone (to castrate levels) and estrone sulfate. Gonadotropins and testosterone returned to control values within nine days and estrone sulfate by 14 days after treatment discontinuation. Acyline-treated stallions failed to respond with FSH, LH and testosterone increase after exogenous GnRH stimulation (25µg gonadorelin, IV) compared to pre-treatment and control stimulation. Total sperm numbers and motility were reduced in acyline-treated stallions, as well as total seminal plasma protein and testicular volume (p<0.05). Time to ejaculation was increased in acyline group (p<0.5). Testicular, sexual behavior and most seminal parameters regained normal levels within 72 days after treatment ceased. Sperm output of acyline-treated stallions was regained within seven months after ending treatment. Acyline reversibly suppressed the stallion HPG axis, thus has potential for treating the androgen-dependent Equine-Arteritis-Virus carrier state and as behavior modulator.