In response to improving quality patient care, combined with the growing rates of surgical site infections (SSIs) in vascular patients, the need to explore current practice trends with current evidence has been identified. SSIs affect quality patient care and compromise patient safety. Empirical evidence has recommended the use of a chlorhexidine wash preoperatively to reduce SSIs. Despite this recommended practice, vascular patients were not receiving it in their routine plan of care within a hospital organization in southern Ontario. Guided by Lewin's theory of planned change, this project explored how the planning of a chlorhexidine preoperative surgical skin preparation protocol impacted progress toward improved care of vascular patients. The project was designed as a quality improvement project examining approximately 110 vascular surgical procedures over a 1-month period and staff surveys that were provided to staff in the preoperative (n = 88), same day surgery (n = 68), and inpatient (n = 47) units. These data were analyzed and demonstrated a reduction in vascular SSIs from 4.9% pre-implementation to 2.8% 1-month post-implementation. Major themes generated from the staff surveys demonstrated the nursing staff had a good understanding of the content that was presented in the in-service provided. These findings have implications for social change by highlighting the benefits of incorporating evidence in to practice and further informing the preoperative practice in other surgical specialties.

Few investigators have used robust analytic methods to assess risk factors and outcomes for surgical site infections (SSIs) after craniotomy and craniectomy (CRANI) procedures. We performed a retrospective study among patients undergoing CRANI procedures between 2006 and 2010 at the University of Iowa Hospitals and Clinics (UIHC) to assess the effect of an intervention (e.g., limiting Gliadel wafer use among patients with malignant brain tumors) on the trend of SSI rates, to identify independent risk factors for SSIs, and to evaluate one-year postoperative patient outcomes associated with these SSIs. We abstracted demographic data and clinical data from medical records or from the UIHC's Health information Management System. We identified 104 patients with SSIs and selected 312 controls. Of SSIs, 88% were deep incisional or organ space infections, 70% were identified after patients were discharged from their initial hospitalizations, 32% were caused by Staphylococcus aureus alone or in combination with other organisms, and 27% were caused by Gram-negative organisms alone or in combination with other organisms. Significant independent risk factors for SSIs were: previous chemotherapy (odds ratio [OR], 10.0; 95% confidence interval [CI] 1.1, 92.1), preoperative length of stay ≥ 1 day (OR, 2.1; 95% CI 1.3, 3.5), preoperative serum glucose ≥ 100 mg/dL (OR, 1.7; 95% CI, 1.0, 3.0), Gliadel® wafer use (OR, 8.6; 95% CI 3.2, 23.1), and postoperative cerebrospinal fluid leak (OR, 4.0; 95% CI, 1.6, 10.3). Gliadel® wafer use was the strongest risk factor; however, limiting Gliadel® wafer use did not decrease SSI rate significantly among patients with brain tumors. Perioperative ventricular drains or lumbar drains were not independently associated with an increased risk of SSIs, but drains may have clinical significance. An SSI risk index that included the significant preoperative patient-related risk factors had a better predictive power than the National Healthcare Safety Network (NHSN) risk index. After adjusting for preoperative length of stay, age, comorbidity score, severity of illness score, the reason for the procedure, and procedure month, patients with SSIs were hospitalized longer postoperatively than were controls during their readmissions (2.3 days; P < 0.0001). After controlling for the same covariates and treating SSI as a time-varying factor, patients with SSIs were more likely than controls to: die (hazard ratio [HR], 3.3; 95% CI, 1.8, 5.8), be readmitted (HR, 4.1; 95% CI, 2.9, 5.8), and have reoperations (HR, 56.6; 95% CI, 38.1, 84.0). In conclusion, surgeons could predict patients' risk of SSIs based on their preoperative risk factors and surgeons could modify some processes of care to lower the SSI risk. Preventing SSIs after CRANI procedures could improve patient outcomes and decrease healthcare utilization.

Background. Surgical site infections (SSIs) cause many adverse outcomes for patients including increased length of hospital stay, hospital costs, morbidity, and psychological distresses. Staphylococcus aureus is one of the most common causes of SSIs in the United States. Objective. Identify risk factors for Staphylococcus aureus SSIs following breast operations. Design. Retrospective nested case-control study of SSIs among women undergoing breast operations. Setting. An academic health center. Patients. We studied patients undergoing breast operations at the University of Iowa Hospitals and Clinics from 7/1/2004 through 9/30/2015. Cases were patients who acquired SSIs meeting the National Healthcare Safety Network definition and whose SSIs were caused by S. aureus. We randomly selected two controls for each case from patients who had breast operation during the study period and did not meet the SSI definition. Controls were selected randomly from uninfected patients whose operations occurred during the same month and year as a case. Results. Forty two (1.2%) patients acquired S. aureus SSIs after 3494 breast operations. SSIs were identified a mean of 27.8 days after the breast operations; 54.76% were deep incisional infections. Poisson regression analysis revealed that S. aureus SSIs following breast operations at UIHC have been increasing at a statistically significant rate. Bivariable analysis identified several patient and procedure related risk factors that increased the risk for S. aureus SSIs. Patient-related factors included a diabetes mellitus, active skin disease, prior chemotherapy, breast cancer, hypertension, and preoperative hemoglobin. Procedure-related factors included ASA score > 2, a mastectomy followed by immediate reconstruction, sentinel lymph node biopsy (SLN), drain placement, procedure time, and estimated blood loss. A multivariable analysis of patient factors found only breast cancer maintained significance. A similar analysis of procedure factors found that drain placement remained significant. The combined model contained breast cancer, drain placement, and mastectomy followed by immediate reconstruction as significant variables. Conclusions. S. aureus SSIs following breast operations have been increasing at UIHC. Possible remediable risk factors include blood glucose levels, blood pressure, timing of chemotherapy, and drain placement and care. These results will help doctors at UIHC design interventions to prevent S. aureus SSIs following these procedures.

Scholars have suggested that landscape become the main ordering device in the development of the built environment. Traditional methods of urban planning have categorized landscape as a cosmetic application, the purpose of which is to beautify the urban environment after the planning and development phases. The problems associated with globalization and rapid urbanization at present includes the commoditization of urban form. As a result of this trend, many cities are becoming less and less distinguishable from one another, as urban form is generated without considering the particularities of site and context. The lack of a more specific understanding of a site in its environmental, social and cultural dimensions, has led to the phenomenon of "universal" urban form. Landscape has new found relevance in contemporary urbanism becoming the medium that defines urban form; inserting the built environment within the context of complex natural, social and cultural environments. Landscape has the potential to design relationships between dynamic environmental processes and urban form, and become more of a functional system. In the island of Trinidad there exists the opportunity to explore the potential of landscape as a driver of urban form. The island is currently experiencing rapid urbanization and dynamic growth due to a boost in the economy, and an unprecedented government agenda to take the island to a developed nation status by the year 2020. Due to this emerging urbanity, there is the need to implement urban development approaches that protect the environmental integrity of the island, and preserve the social and cultural influences that give identity to the island. The investigation led to the development of a landscape infrastructure that is implemented in an effort to achieve sustainable urban development and preserve the natural integrity of the site. Through an in-depth analysis of the landscape, identifying the natural, social and cultural processes occurring, a plan of intervention is developed that is integrated with the dynamics of the site, and serves as an example of the potential of landscape in urbanism.

This project aimed to reanalyse two large historical data sets from two different locations in New Zealand (Fiordland in the South Island and Pureora Forest Park in the North Island). The data describe populations of mice (Mus musculus), rats (Rattus rattus and R. norvegicus), and stoats (Mustela erminea) collected using standard monitoring techniques from five distinct types of forest habitat. The new analysis methods selected were an index of patchiness and Site Occupancy analysis. The objectives of the analysis were (1) to evaluate whether the patchiness index and Site Occupancy analysis methods might contribute to improved protocols for monitoring small mammal populations in the future, and (2) to use formal tests of five hypotheses to evaluate two of the assumptions made by the conventional density index often used in small mammal studies. I describe the results of the analyses for each species, including any problems encountered (such as the inability of the Site Occupancy method to analyse very sparse data sets). I also describe the results pooled from each of the two study locations and potential consequences for small mammal monitoring and control. This analysis has suggested that in most cases the density index is not a rigorous measure of small mammal populations. However, both the index of patchiness and Site Occupancy analysis provided useful, new information about these populations of rodents and stoats, despite the fact that these historical data sets were not designed for use with modern methods of analysis. Please note: some figures and tables were printed separately and added to the thesis as unnumbered pages. These can be found in the file 03Plates_and_Tables.pdf.

Thesis (Ph. D.)--Georgia State University, 2007. / Naveen Donthu, committee chair; Detmar Straub, Corliss Thornton, Sevo Eroglu, committee members. Electronic text (149 p. : ill.) : digital, PDF file. Title from file title page. Description based on contents viewed Dec. 10, 2007. Includes bibliographical references (p. 142-149).

Thesis (M.S.)--University of Nevada, Reno, 2005. / "December, 2005." Includes bibliographical references (leaves 73-77). Online version available on the World Wide Web.

Among the genetic mutations involved in carcinogenesis, TP53 mutation is a frequent event in many types of cancer. P53 is a transcription factor that regulates activities such as cell cycle arrest, apoptosis, DNA repair and angiogenesis. The majority of TP53 mutations are missense mutations that accumulate in cancer and are often retained in distant metastases. The effects of the mutant p53 proteins include loss of function, dominant-negative effects over wild-type (WT) p53 and possible acquisition of new properties (gain-of-function). However, some of these properties may differ from one mutant p53 protein to another. These differences could have implications for the in vivo behaviour of tumours carrying particular mutations and hence patient prognosis. The aim of this project was to investigate the phenotypic variation between cells transformed with different p53 mutants. This was achieved by constructing a range of TP53 mutants (R175H, G245S, R248W, R248Q, R273H, R282W) using PCR-based mega-primer site directed mutagenesis. These mutants were cloned into a mammalian bi-cistronic expression vector (designed for the co-expression of WT and mutant TP53 from a single plasmid) to allow transient expression in NCI-H358 cells (p53 null). Regard to the method for PCR site directed mutagenesis, the main technical difficulty with conventional methods was the insufficiency of the mutant TP53 product yield (75%). This thesis has modified these methods by carrying over the start template to a second round of PCR and increasing the MgCl2 concentration. This modified PCR-based site directed mutagenesis method has demonstrated an increased mutant TP53 product yield (100%). The tetracycline expression system is the most widely used for conditional inducible systems in mammalian cells, although high background expression has been a main problem. The ecdysone inducible system potentially allows for the study of the conditional expression of the exogenous reporter gene even though it may be cell lethal or alter the phenotype during the selection of transfectants. This system relies on two independent transfections of two plasmids namely pVgRXR and pIND. However, disruption of the regulatory element within the plasmid during stable integration can result in silence or high background expression of the exogenous reporter gene. A previous study reported a transient luciferase reporter assay to screen the cell line stably transfected with pVgRXR plasmid. However, there is no suitable method to screen the subsequent pIND transfection. This thesis has demonstrated a real time RT-PCR strategy to screen for the background expression problem associated with the ecdysone expression system. However, due to the project’s time limitations, a transient expression system rather than a stable expression system was used. The metastasis related cellular activity of WT/mutant TP53 transfected NCI-H358 cells was examined using a range of in vitro functional assays including a proliferation assay, a p21 promoter binding activity assay, a colony formation assay, and a migration assay. To extend the study, this thesis also employed real-time RT-PCR to examine the mRNA expression level of three metastatic related genes, VEGF, HER-2, and E-cadherin, in the WT/mutant TP53 transfected NCI-H358 cells. The results showed that different WT/mutant TP53 transfected cell linse could contribute to markedly different cellular activity. Among these mutants, R175H produced the highest cellular proliferation activity, the strongest dominant-negative activity over the WT on the p21 promoter binding activity and apoptosis activity, and the greatest effect on cellular migration. Furthermore, the real-time PCR results showed that the WT p53 inhibited transcription of key metastasis-related genes such as VEGF and HER-2. Considered with recent literature, this led me to postulate a feedback amplification cycle involving defective p53 and HER-2 mRNA expression. In conclusion, cancer cells with the R175H mutant could contribute to aggressive tumours. This conclusion, based on the in vitro data, is consistent with some clinical observations and animal model experiments. In the past few years it has become apparent that epigenetic changes also play a vitally important role in the cancer developmental process. Recent studies have reported the p53 protein can contribute in methylation which is one of the processes involved in epigenetic modification. This thesis employed a very new PCR-based AMP technique to examine the change of the global genome methylation pattern as a result of knocked-out p53 protein. The results showed defective p53 protein expression may associate with the global genome methylation pattern changes. However, it is important to note that antibiotic reagents, which were used for stable transfectant selection, could also contribute to the global genome methylation changes. In conclusion, this thesis has successfully developed two new methods. One allows the generation of a genetic mutant construct using PCR-based site directed mutagenesis while the other screens the tightly regulated ecdysone reporter system. In terms of effect of p53 in in vitro cell activity, this thesis has postulated that the R175H mutation is associated with much more aggressive metastatic cellular activity. Finally, this thesis also reported that loss of p53 expression could also result in changes in the global genome methylation pattern.

<p>Probably no group of organisms has been as important as bacteriophages when it comes to the understanding of fundamental biological processes like transcriptional control, DNA replication, site-specific recombination, e.t.c.</p><p>The work presented in this thesis is a contribution towards the complete understanding of these organisms. Two proteins, integrase, and Cox, which are important for the choice of the life mode of bacteriophage P2, are investigated. P2 is a temperate phage, i.e. it can either insert its DNA into the host chromosome (by site-specific recombination) and wait (lysogeny), or it can produce new progeny with the help of the host protein machinery and thereafter lyse the cell (lytic cycle). The integrase protein is necessary for the integration and excision of the phage genome. The Cox protein is involved as a directional factor in the site-specific recombination, where it stimulates excision and inhibits integration. It has been shown that the Cox protein also is important for the choice of the lytic cycle. The choice of life mode is regulated on a transcriptional level, where two mutually exclusive promoters direct whether the lytic cycle (Pe) or lysogeny (Pc) is chosen. The Cox pro-tein has been shown to repress the Pc promoter and thereby making tran-scription from the Pe promoter possible, leading to the lytic cycle. Further, the Cox protein can function as a transcriptional activator on the parasite phage, P4. P4 has gained the ability to adopt the P2 protein machinery to its own purposes.</p><p>In this work the importance of the native size for biologically active integrase and Cox proteins has been determined. Further, structure-function analyses of the two proteins have been performed with focus on the protein-protein interfaces. In addition it is shown that P2 Cox and the P2 relative Wphi Cox changes the DNA topology upon specific binding. From the obtained results a mechanism for P2 Cox-DNA interaction is discussed.</p><p>The results from this thesis can be used in the development of a gene delivery system based on the P2 site-specific recombination system.</p>

The scientific endeavors that took place at Hanford Engineer Works, beginning in World War II and continuing thereafter, are often overlooked in the literature on the Manhattan Project, the Atomic Energy Commission, and in regional histories. To historians of science, Hanford is described as an industrial facility that illustrates the perceived differences between academic scientists on the one hand and industrial scientists and engineers on the other. To historians of the West such as Gerald Nash, Richard White, and Patricia Limerick, Hanford has functioned as an example of the West's transformation during in World War II, the role of science in this transformation, and the recurring impacts of industrialization on the western landscape. This thesis describes the establishment and gradual expansion of a multi-disciplinary research program at Hanford whose purpose was to assess and manage the biological and environmental effects of plutonium production. By drawing attention to biological research, an area in which Hanford scientists gained distinction by the mid 1950s, this study explains the relative obscurity of Hanford's scientific research in relation to the prominent, physics-dominated national laboratories of the Atomic Energy Commission. By the mid 1960s, with growing public concern over radiation exposure and changes in the government's funding patterns for science, Hanford's ecologically relevant research provided a recognizable and valuable identity for the newly independent, regionally-based research laboratory. With funding shifts favoring the biological and environmental sciences in the latter half of the twentieth-century, Hanford scientists were well prepared to take advantage of expanding opportunities to carve out a permanent niche on the border of American science. / Graduation date: 2003