Program Evaluation of the Living Well With Diabetes Program of Prince William County, Virginia

Presented to the Faculty of the University of Alaska Anchorage in Partial Fulfillment of the Requirements for the Degree of MASTER OF PUBLIC HEALTHApproximately 25.8 million US residents are living with diabetes. Research has demonstrated that healthy lifestyles can significantly reduce the onset of diabetes. Various community-based programs have been implemented nationally to address diabetes through lifestyle changes. One such program is the Living Well with Diabetes (LWwD) program of Prince William County, Virginia. The goal of this project practicum was to conduct a process evaluation of the Living Well with Diabetes (LWwD) Program of Prince William County, Virginia. Semi-structured interviews were conducted with LWwD program educators. Qualitative data analysis on secondary, post-course evaluations was performed using a thematic method to coding on all short string responses. Results indicate that the intended delivery of the program curriculum resulted in positive changes in the knowledge, attitudes, and applied behaviors of the LWwD program participants. Overall, the continued support of the LWwD program goals would significantly improve the public health and safety of the community.Signature Page / Title Page / Abstract / List of Figures / List of Tables / List of Appendices / Acknowledgements / Introduction / Background / Goals, Objectives, and Research Questions / Methods / Results / Data Source 1: LWwD Participant Registration Database / Worksheet 1: Interview Template for Program Educators / Worksheet 2: LWwD Post-Course Evaluation / Worksheet 3: LWwD Post-Course Evaluation (January 2016) / Discussion / Strengths and Limitations / Public Health Implications / Conclusions and Recommendations / References / Appendice

An Exploratory Analysis of Factors Affecting Participation in Air Force Knowledge Now Communities of Practice

As the AF continues to lose its knowledge base through retirements and downsizing, the need to get maximum use from the remaining knowledge base becomes increasingly important. In their efforts to help the Department of Defense and the Air Force Chief Information Officer (AFCIO) meet their knowledge management goals, Air Force Material Command (AFMC) has been working to implement the use of communities of practice. A primary goal of AFMC/DRW , the AF Knowledge Now program office, and the office of the AFCIO is to increase effectiveness and participation within communities of practice. The goal of this research is to identify factors from the literature that may affect knowledge transfer, information sharing, and technology acceptance, and compare those factors with AFKN hosted communities of practice (CoPs) exhibiting high and low levels of participation. Additionally, factors of interest identified in interviews with AFKN personnel will be researched. This research used a cross-sectional research instrument to survey CoP members within all AFKN hosted CoPs containing 20 or more members. This research suggests there are differences in the way members within high and low use CoPs perceive these factors: trust, willingness to share information, job fit, outcome expectations, social factors, facilitating conditions, anonymity, security constraints, knowledge champion, facilitator. The results of these findings may allow AFKN to focus on these factors when the goal is to improve participation in future CoPs

Determinants of Variation in Perioperative Red Blood Cell Transfusion During Adult Coronary Artery Bypass Graft Surgery

Background: Despite evidence-based guidelines informing indications for transfusions, unwarranted variability in performance exists across cardiac surgical programs. We aimed to identify to what extent distinguishing patient and procedural characteristics can explain center- level transfusion variation during coronary artery bypass grafting (CABG) surgery. Methods: We evaluated 22,272 adult patients undergoing isolated CABG using cardiopulmonary bypass between July 1, 2011 and July 1, 2017 across 43 centers. Iterative multilevel logistic regression models were constructed using patient demographic, preoperative risk factors, and intraoperative conservation strategies to progressively explain center-level transfusion variation. Results: Nearly one-third (n=7241, 32.5%) of patients received at least one transfusion. Rates varied between 10.9% to 59.9% across centers. Among the models explaining center-level transfusion variability, the intraclass correlation coefficients varied between 0.072 to 0.136, while the coefficient of variation varied between 0.29 to 0.40. Conclusion: The results suggest that variation in center-level RBC transfusion cannot be explained by patient and procedural factors alone. Investigating organizational culture and programmatic infrastructure may be necessary to better understand variation in transfusion practices

Materials for phantoms for terahertz pulsed imaging

Phantoms are commonly used in medical imaging for quality assurance, calibration, research and teaching. They may include test patterns or simulations of organs, but in either case a tissue substitute medium is an important component of the phantom. The aim of this work was to identify materials suitable for use as tissue substitutes for the relatively new medical imaging modality terahertz pulsed imaging. Samples of different concentrations of the candidate materials TX151 and napthol green dye were prepared, and measurements made of the frequency-dependent absorption coefficient (0.5 to 1.5 THz) and refractive index (0.5 to 1.0 THz). These results were compared qualitatively with measurements made in a similar way on samples of excised human tissue (skin, adipose tissue and striated muscle). Both materials would be suitable for phantoms where the dominant mechanism to be simulated is absorption (similar to ∼100 cm(-1) at 1 THz) and where simulation of the strength of reflections from boundaries is not important; for example, test patterns for spatial resolution measurements. Only TX151 had a frequency-dependent refractive index close to that of tissue, and could therefore be used to simulate the layered structure of skin, the complexity of microvasculature or to investigate frequency-dependent interference effects that have been noted in terahertz images

DNA Microarray Genotyping and Virulence and Antimicrobial Resistance Gene Profiling of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates from Renal Patients.

Thirty-six methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates from renal patients were genetically characterized by DNA microarray analysis and spa typing. The isolates were highly clonal, belonging mainly to ST22-MRSA-IV. The immune evasion and enterotoxin gene clusters were found in 29/36 (80%) and 33/36 (92%) of isolates, respectively

Comparative genomics of Drosophila and human core promoters

BACKGROUND: The core promoter region plays a critical role in the regulation of eukaryotic gene expression. We have determined the non-random distribution of DNA sequences relative to the transcriptional start site in Drosophila melanogaster promoters to identify sequences that may be biologically significant. We compare these results with those obtained for human promoters. RESULTS: We determined the distribution of all 65,536 octamer (8-mers) DNA sequences in 10,914 Drosophila promoters and two sets of human promoters aligned relative to the transcriptional start site. In Drosophila, 298 8-mers have highly significant (p ≤ 1 × 10(-16)) non-random distributions peaking within 100 base-pairs of the transcriptional start site. These sequences were grouped into 15 DNA motifs. Ten motifs, termed directional motifs, occur only on the positive strand while the remaining five motifs, termed non-directional motifs, occur on both strands. The only directional motifs to localize in human promoters are TATA, INR, and DPE. The directional motifs were further subdivided into those precisely positioned relative to the transcriptional start site and those that are positioned more loosely relative to the transcriptional start site. Similar numbers of non-directional motifs were identified in both species and most are different. The genes associated with all 15 DNA motifs, when they occur in the peak, are enriched in specific Gene Ontology categories and show a distinct mRNA expression pattern, suggesting that there is a core promoter code in Drosophila. CONCLUSION: Drosophila and human promoters use different DNA sequences to regulate gene expression, supporting the idea that evolution occurs by the modulation of gene regulation

Antitumor effects of B3-PE and B3-lysPE40 in a nude mouse model of human breast cancer and the evaluation of B3-PE toxicity in monkeys

B3 is a tumor-reactive monoclonal antibody (mAb) that binds to a limited number of normal tissues.Immunotoxins made with B3 coupled to either Pseudomonas exotoxin (PE) or recombinant forms of PE with a deletion of the cell-binding domain (LysPE40) have been shown to cause complete tumor regression in nude mice bearing a rapidly growing A431 (L. H. Pai et al., Proc. Natl. Acad. Sci. USA, 88: 3358-3362, 1991) human epidermoid carcinoma. In this study we show that an immunotoxin composed of mAb B3 when chemically coupled to LysPE40 (B3-LysPE40) led to complete regression of a slowly growing breast cancer, MCF-7, in nude mice when given i.v. every other day for five doses. mAb B3 coupled to native PE also produced significant regression of the MCF-7 tumor. The reactivity of mAb B3 was evaluated using an immunohistochemical method on the two responsive tumors, MCF-7 and A431, and compared with a typical human colon carcinoma specimen that has B3 antigen on its surface. The results showed that both A431 and MCF-7 xenograft tumors have similar reactivity to B3 when compared with the human colon carcinoma specimen. To evaluate the toxicity of B3-PE in primates, Cynomolgus monkeys received escalating doses of B3-PE i.v. on Days 1, 3, and 5. Based on antibody localization studies using frozen sections of normal human and monkey tissue, gastric, trachea, and bladder mucosal injury could have occurred. However, no clinical signs of injury or histological damage to these organs were seen at the doses administered. Chemical hepatitis due to PE was transient and well tolerated at doses up to 50 μg/kg for three doses. The lethal dose was about 100 μg/kg, and the cause of death was liver necrosis, as shown by necropsy. We conclude that m Ab B3, when coupled to PE40 or PE, can produce strong antitumor activity in vivo. The similar level of reactivity of the B3 antibody in our tumor models with a surgical specimen of a human colon carcinoma and the toxicity study in monkeys indicate that therapeutic doses of B3-PE and B3-LysPE40 can be delivered without causing toxicity to normal organs that express B3 antigen. Although both B3-PE and B3-LysPE40 have antitumor activity in nude mice bearing a human xenograft, B3-LysPE40 is better tolerated and should be further evaluated as a therapeutic agent for cancer patients

Induction of p38- and gc1qr-Dependent IL-8 Expression in Pulmonary Fibroblasts by Soluble Hepatitis c Core Protein

Background: Recent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies have addressed the inflammatory aspects of HCV-associated pulmonary disease. Because IL-8 plays a fundamental role in reactive airway diseases, we examined IL-8 signaling in normal human lung fibroblasts (NHLF) in response to the HCV nucleocapsid core protein, a viral antigen shown to modulate intracellular signaling pathways involved in cell proliferation, apoptosis and inflammation. Methods: NHLF were treated with HCV core protein and assayed for IL-8 expression, phosphorylation of the p38 MAPK pathway, and for the effect of p38 inhibition. Results: Our studies demonstrate that soluble HCV core protein induces significant increases in both IL-8 mRNA and protein expression in a dose- and time-dependent manner. Treatment with HCV core led to phosphorylation of p38 MAPK, and expression of IL-8 was dependent upon p38 activation. Using TNFα as a co-stimulant, we observed additive increases in IL-8 expression. HCV core-mediated expression of IL-8 was inhibited by blocking gC1qR, a known receptor for soluble HCV core linked to MAPK signaling. Conclusions: These studies suggest that HCV core protein can lead to enhanced p38- and gC1qR-dependent IL-8 expression. Such a proinflammatory role may contribute to the progressive deterioration in pulmonary function recently recognized in individuals chronically infected with HCV

Predisposing Factors Associated With Development of Persistent Compared With Paroxysmal Atrial Fibrillation

Background: Once atrial fibrillation (AF) progresses to sustained forms, adverse outcomes increase and treatment success rates decrease. Therefore, identification of risk factors predisposing to persistence of AF may have a significant impact on AF morbidity. Methods and Results: We prospectively examined the differential associations between traditional, lifestyle, and biomarker AF risk factors and development of paroxysmal versus nonparoxysmal AF (persistent/permanent) among 34 720 women enrolled in the Women's Health Study who were free of cardiovascular disease and AF at baseline. AF patterns were defined based on current guidelines and classified according to the most sustained form of AF within 2 years of diagnosis. During a median follow‐up of 16.4 years, 690 women developed paroxysmal AF and 349 women developed nonparoxysmal AF. In multivariable time‐varying competing risk models, increasing age (hazard ratio [HR] 1.11, 95% CI 1.10 to 1.13, versus HR 1.08, 1.07 to 1.09, per year), body mass index (HR 1.07, 1.05 to 1.09, versus HR 1.03, 1.02 to 1.05, per kg/m2), and weight (HR 1.30, 1.22 to 1.39, versus HR 1.14, 1.08 to 1.20, per 10 kg) were more strongly associated with the development of nonparoxysmal AF compared with paroxysmal AF. Hemoglobin A1c levels at baseline were directly related to the development of nonparoxysmal AF but inversely associated with paroxysmal AF in multivariable competing risk models (P for nonequal association=0.01). Conclusions: In women without AF or CVD at baseline, increasing age, adiposity, and higher hemoglobin A1c levels were preferentially associated with the early development of nonparoxysmal AF. These data raise the hypothesis that efforts aimed at weight reduction or glycemic control may affect the proportion of the population with sustained AF