Strategies to the success of Online Course Development

Introduction Online courses provide flexible access to education from a distance. However, learners may encounter frustration and disappointment in the learning process for various reasons. Faculties might not be familiar with adult learning principles. The online course developer may have no knowledge, experience, or the skills necessary for developing online courseware. Online course development can take longer time and more resources. It can also take longer time to deliver the course. It is, therefore, important that online course development be made efficient and effective for best student learning. [See PDF for complete abstract]

Determining acquisition and cessation antecedents to adolescent cigarette smoking for development of intervention strategies

Our national focus and emphasis on the promotion of healthy behavior choices regarding tobacco and other drugs continues to target adolescents. Multiple studies have shown that adolescence is the optimum period for the prevention of substance use initiation as life-long patterns of health behaviors are established during this critical developmental stage. Tobacco use is associated with an increase in morbid and mortal health conditions of which prevalence increases throughout the lifespan. Attention to the antecedents of preventable health conditions aims to modify the risks and identify health promotion factors. Modifying antecedent factors for tobacco initiation in youth and identifying protective factors for successful smoking cessation has major public health implications across the lifespan. Of foremost interest are those risk factors and resultant behaviors that predict a youth's probability of initiating cigarette use and their cessation of cigarette use. Specifically, this dissertation supports previous results identifying intervention variables on the initiation/cessation continuum model especially with the established predictors of smoking (decisional balance and susceptibility) and with more recently identified predictors of smoking (nicotine dependence and withdrawal symptoms) in current and former smokers in a sample of high school students in Austin and Houston, Texas. These results offer insight for the development of appropriate intervention program strategies for our youth. ^

STRATEGIES FOR THE TRANSFER OF APPROPRIATE TECHNOLOGY TO DEVELOPING COUNTRIES: THE IMPLEMENTATION AND DEVELOPMENT OF ENVIRONMENTAL HEALTH PROGRAMS IN TUNISIA

This dissertation focuses on Project HOPE, an American medical aid agency, and its work in Tunisia. More specifically this is a study of the implementation strategies of those HOPE sponsored projects and programs designed to solve the problems of high morbidity and infant mortality rates due to environmentally related diarrheal and enteric diseases. Several environmental health programs and projects developed in cooperation with Tunisian counterparts are described and analyzed. These include (1) a paramedical manpower training program; (2) a national hospital sanitation and infection control program; (3) a community sewage disposal project; (4) a well reconstruction project; and (5) a solid-waste disposal project for a hospital.^ After independence, Tunisia, like many developing countries, encountered several difficulties which hindered progress toward solving basic environmental health problems and prompted a request for aid. This study discusses the need for all who work in development programs to recognize and assess those difficulties or constraints which affect the program planning process, including those latent cultural and political constraints which not only exist within the host country but within the aid agency as well. For example, failure to recognize cultural differences may adversely affect the attitudes of the host staff towards their work and towards the aid agency and its task. These factors, therefore, play a significant role in influencing program development decisions and must be taken into account in order to maximize the probability of successful outcomes.^ In 1969 Project HOPE was asked by the Tunisian government to assist the Ministry of Health in solving its health manpower problems. HOPE responded with several programs, one of which concerned the training of public health nurses, sanitary technicians, and aids at Tunisia's school of public health in Nabeul. The outcome of that program as well as the strategies used in its development are analyzed. Also, certain questions are addressed such as, what should the indicators of success be, and when is the time right to phase out?^ Another HOPE program analyzed involved hospital sanitation and infection control. Certain generic aspects of basic hospital sanitation procedures were documented and presented in the form of a process model which was later used as a "microplan" in setting up similar programs in other Tunisian hospitals. In this study the details of the "microplan" are discussed. The development of a nation-wide program without any further need of external assistance illustrated the success of HOPE's implementation strategies.^ Finally, although it is known that the high incidence of enteric disease in developing countries is due to poor environmental sanitation and poor hygiene practices, efforts by aid agencies to correct these conditions have often resulted in failure. Project HOPE's strategy was to maximize limited resources by using a systems approach to program development and by becoming actively involved in the design and implementation of environmental health projects utilizing "appropriate" technology. Three innovative projects and their implementation strategies (including technical specifications) are described.^ It is advocated that if aid agencies are to make any progress in helping developing countries basic sanitation problems, they must take an interdisciplinary approach to progrm development and play an active role in helping counterparts seek and identify appropriate technologies which are socially and economically acceptable. ^

THE ROLE OF TAK1 IN PANCREATIC CANCER DEVELOPMENT

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States and the fifth leading cause of cancer-related mortality worldwide. Pancreatic cancer is a big challenge in large due to the lack of early symptoms. In addition, drug resistance is a major obstacle to the success of chemotherapy in pancreatic cancer. The underlying mechanism of drug resistance in human pancreatic cancers is not well understood. Better understanding of the mechanism of molecular pathways in human pancreatic cancers can help to identify the novel therapeutic target candidates, and develop the new preventive and clinic strategies to improve patient survival. We discovered that TAK1 is overexpressed in pancreatic cancer cell lines and patient tumor tissues. We demonstrated that the elevated activity of TAK1 is caused by its binding partner TAB1. Knocking down of TAK1 in pancreatic cancer cells with RNAi technique resulted in cell apoptosis and significantly reduces the size of tumors in mice and made a chemotherapy drug more potent. Targeting the kinase activity of TAK1 with the selective inhibitor LY2610956 strongly synergized in vitro with the antitumor activity of gemcitabine, oxaliplatin, or irinotecan on pancreatic cancer cells. These findings highlighted that TAK1 could be a potential therapeutic target for pancreatic cancer. We also demonstrated that TAK activity is regulated by its binding protein TAB1. We defined a minimum TAB1 sequence which is required and sufficient for TAK1 kinase activity. We created a recombinant TAK1-TAB1 C68 fusion form which has highly kinase activity. This active form could is used for screening TAK1 inhibitors. In addition, several posttranslational modifications were identified in our study. The acetylation of lysine 158 on TAK1 is required for kinase activity. This site is conserved throughout all of kinase. Our findings may reveal a new mechanism by which kinase activity is regulated.

Development of prostate cancer gene therapy

Osseous metastases account for most of the morbidity and mortality associated with prostate cancer, for which there are currently no effective therapies. In the skeletal metastatic environment, neoplastic prostatic epithelial cells interact in a bidirectional stimulatory manner with osteoblastic stromal cells. Similarly, the presence of osteoblastic cells is essential for the survival and maintenance of intraosseous prostate cancer cells. In this thesis, I have developed novel gene therapy strategies for the treatment of androgen-independent human prostate cancers in experimental animal models. First, Ad-CMV-p53, a recombinant adenovirus (Ad) containing p53 tumor suppressor gene driven by the universal cytomegalovirus promoter, was effective in inhibiting prostate cancer cell growth, and direct intratumoral injections of Ad-CMV-p53 resulted in tumor regression. Second, because prostate cancer cells as well as osteoblastic cells produce osteocalcin (OC), OC promoter mediated tissue/tumor specific toxic gene therapy is developed to interrupt stromal-epithelial communications by targeting both cell types. Ad-OC-TK, a recombinant Ad containing the herpes simplex virus thymidine kinase (TK) gene driven by the OC promoter, was generated to inhibit the growth of osteoblastic osteosarcoma with prodrug acyclovir (ACV). Ad-OC-TK/ACV also inhibited the growth of prostate cancer cells and suppressed the growth of subcutaneous and intraosseous prostate tumor. In order to combine treatment modalities to maximize tumor cell-kill with minimized host toxicities, Ad-OC-TK/ACV was applied in combination with low dose methotrexate to eradicate osteoblastic osteosarcoma. In targeting of micrometastatic disease, intravenous Ad-OC-TK/ACV treatment resulted in significant tumor nodule reduction and prolonged the survival of animals harboring osteosarcoma lung metastases without significant host toxicity. Ad-OC-TK is a rational choice for the treatment of prostate cancer skeletal metastasis because OC is uniformly detected in both primary and metastatic human prostate cancer specimens by immunohistochemistry. Ad-OC-TK/ACV inhibits the growth not only of prostate cancer cells but also of their supporting bone stromal cells. Targeting both prostate cancer epithelium and its supporting stroma may be most efficacious for the treatment of prostate cancer osseous metastases. ^

Development of a protective vaccine against Helicobacter pylori

Helicobacter pylori, which colonizes the stomach and causes the most common chronic infection in man, is associated with peptic ulceration, gastric carcinoma and gastric lymphoma. Studies in animals demonstrated that mucosal immunization could induce immune response against H. pylori and prevent H. pylori infection only if powerful mucosal adjuvants such as cholera toxin (CT) or heat-labile toxin of E. coli (LT) were used along with an H. pylori protein antigen. Adjuvants such as CT or LT cannot be used for humans because of their toxicity. Finding non-toxic alternative adjuvants/immunomodulators or immunization strategies that eliminates the use of adjuvants is critical for the development of efficacious human Helicobacter vaccines. We investigated whether several new adjuvants such as Muramyl Tripeptide Phosphatidylethonolamine (MTP-PE), QS21 (a Quil A derivative), Monophosphoryl lipid A (MPL) or heat shock proteins (HSP) of Mycobacterium tuberculosis could be feasible to develop a safe and effective mucosal vaccine against H. pylori using a murine model. C57/BL6 mice were immunized with liposomes incorporating each adjuvant along with urease, a major antigenic protein of H. pylori, to test their mucosal effectiveness. Since DNA vaccination eliminates both the use of adjuvants and antigens we also investigated whether immunization with plasmid DNA encoding urease could induce protective immunity to H. pylori infection in the same murine model. We found that oral vaccination with liposomal MTP-PE (6.7 m g) and urease, (100 m g) induced antigen-specific systemic and mucosal immune response and protected mice against H. pylori challenge when compared to control groups. Parenteral and mucosal immunizations with as little as 20 m g naked or formulated DNA encoding urease induced systemic and mucosal immune response against urease and partially protected mice against H. pylori infection. DNA vaccination provided long-lasting immunity and serum anti-urease IgG antibodies were elevated for up to 12 months. No toxicity was detected after immunizations with either liposomal MTP-PE and urease or plasmid DNA and both were well tolerated. We conclude that immunization liposomes containing MTP-PE and urease is a promising strategy deserving further investigation and may be considered for humans. DNA vaccination could be used to prime immune response prior to oral protein vaccination and may reduce the dose of protein and adjuvant needed to achieve protective immunity. ^

Development and evaluation of a cervical cancer screening program for Chinese women

Despite of the proven efficacy of the Pap test, Asian populations still have low Pap screening compliance. The purpose of this dissertation was to investigate factors that influencing women's decision to obtain a Pap test, and to describe the development and evaluation of a cervical cancer educational program promoting the Pap screening behavior among women in Taiwan. ^ The first study examined factors associated with Pap screening compliance. Psychometric properties of measurement instruments were also assessed. The scale reliabilities were as the follows: Cronbach alpha 0.70 for knowledge scale, 0.88 for pros scale, 0.68 for cons scale, and 0.72 for perceived norms scale. Results from multiple logistic regression analysis, after adjusted for marital status, showed women who compliant to Pap screening guidelines had significantly higher knowledge, higher perceived benefits (pros), lower perceived barriers (cons), and higher perceived norms to receive a Pap test. ^ The second study described the development of a program called “Love yourself before you take care of your family”, designed to increase Pap screening behavior among women in Taiwan. The development of this program was guided by Intervention Mapping (IM), an innovative process of intervention design. The program used methods such as information transmission, modeling, persuasion, and facilitation. Strategies included direct mail campaigns, role model stories with women's testimonials, and phone intervention. ^ The third study examined the effectiveness of a randomized trial of the carefully-designed intervention (N = 424). Participants were female family members of inpatients admitted to one of the major teaching hospitals in Taiwan during August and September 1999. Women in the intervention group reported a higher rate of receiving a Pap test than women in the control group (50% versus 32%) after a three-month intervention (p = 0.002). Women in the intervention group showed increased knowledge (p = .016), perceived pros (p = 0.008), and susceptibility (p = .011) between baseline and follow-up. They also showed higher perceived pros of Pap tests than women in control group at follow-up (p = .031). This result suggested that program development based on theories and evidences could maximize the intervention impact for a specific target population. ^

Vasculogenesis: A process of vessel formation and its role during Ewing's sarcoma development

Vasculogenesis is the process by which Endothelial Precursor Cells (EPCs) form a vasculature. This process has been traditionally regarded as an embryological process of vessel formation. However, as early as in the 60's the concept of postnatal vasculogenesis was introduced, with a strong resurface of this idea in recent years. Similarly, previous work on a mouse skin tumor model provided us with the grounds to consider the role of vasculogenesis during tumor formation. ^ We examined the contribution of donor bone marrow (BM)-derived cells to neovascularization in recipient nude mice with Ewing's sarcoma. Ewing's sarcoma is a primitive neuroectodermal tumor that most often affects children and young adults between 5 and 30 years of age. Despite multiple attempts to improve the efficacy of chemotherapy for the disease, the 2-year metastases-free survival rate for patients with Ewing's sarcoma has not improved over the past 15 years. New therapeutic approaches are therefore needed to reduce the mortality rate. ^ The contribution of BM endothelial precursor cells in the development of Ewing's sarcoma was examined using different strategies to track the donor-derived cells. Using a BMT model that takes advantage of MHC differences between donor and recipient mice, we have found that donor BM cells were involved in the formation of Ewing's sarcoma vasculature. ^ Cells responsible for this vasculogenesis activity may be located within the stem cell population of the murine BM. These stem cells would not only generate the hematopoietic lineage but they would also generate ECs. Bone marrow SP (Side Population) cells pertain to a subpopulation that can be identified using flow cytometric analysis of Hoechst 33342-stained BM. This population of cells has HSC activity. We have tested the ability of BM SP cells to contribute to vasculogenesis in Ewing's sarcoma using our MHC mismatched transplant model. Mice transplanted with SP cells developed tumor neovessels that were derived from the donor SP cells. Thus, SP cells not only replenished the hematopoietic system of the lethally irradiated mice, but also differentiated into a non-hematopoietic cell lineage and contributed to the formation of the tumor vasculature. ^ In summary, we have demonstrated that BM-derived cells are involved in the generation of the new vasculature during the growth of Ewing's sarcoma. The finding that vasculogenesis plays a role in Ewing's sarcoma development opens the possibility of using genetically modified BM-derived cells for the treatment of Ewing's sarcomas. ^

A qualitative assessment of multi-level nutrition strategies for reducing racial and ethnic disparities in diabetes

The purpose of this study is to examine the stages of program realization of the interventions that the Bronx Health REACH program initiated at various levels to improve nutrition as a means for reducing racial and ethnic disparities in diabetes. This study was based on secondary analyses of qualitative data collected through the Bronx Health REACH Nutrition Project, a project conducted under the auspices of the Institute on Urban Family Health, with support from the Centers for Disease Control and Prevention (CDC). Local human subjects' review and approval through the Institute on Urban Family Health was required and obtained in order to conduct the Bronx Health REACH Nutrition Project. ^ The study drew from two theoretical models—Glanz and colleagues' nutrition environments model and Shediac-Rizkallah and Bone's sustainability model. The specific study objectives were two-fold: (1) to categorize each nutrition activity to a specific dimension (i.e. consumer, organizational or community nutrition environment); and (2) to evaluate the stage at which the program has been realized (i.e. development, implementation or sustainability). ^ A case study approach was applied and a constant comparative method was used to analyze the data. Triangulation of data based was also conducted. Qualitative data from this study revealed the following principal findings: (1) communities of color are disproportionately experiencing numerous individual and environmental factors contributing to the disparities in diabetes; (2) multi-level strategies that targeted the individual, organizational and community nutrition environments can appropriately address these contributing factors; (3) the nutrition strategies greatly varied in their ability to appropriately meet criteria for the three program stages; and (4) those nutrition strategies most likely to succeed (a) conveyed consistent and culturally relevant messages, (b) had continued involvement from program staff and partners, (c) were able to adapt over time or setting, (d) had a program champion and a training component, (e) were integrated into partnering organizations, and (f) were perceived to be successful by program staff and partners in their efforts to create individual, organizational and community/policy change. As a result of the criteria-based assessment and qualitative findings, an ecological framework elaborating on Glanz and colleagues model was developed. The qualitative findings and the resulting ecological framework developed from this study will help public health professionals and community leaders to develop and implement sustainable multi-level nutrition strategies for addressing racial and ethnic disparities in diabetes. ^

Marketing physical activity and healthy eating: A literature review of recent social marketing campaigns and development of a social marketing plan for the CATCH program

Background. This culminating experience project was inspired by an independent study conducted at The University of Texas School of Public Health with Dr. Andrew Springer, DrPH, who works on the evaluation of the Coordinated Approach to Child Health (CATCH) program in Travis County, Texas. It was indicated that a social marketing plan could enhance current efforts for the CATCH program. The aims of the project were to (1) review and synthesize literature on social marketing, with a specific focus on diet, physical activity, and obesity prevention; and (2) apply the gained knowledge toward a practical solution – a social marketing plan for the CATCH program.^ Methods. The literature review aimed to answer the following questions: (1) What audiences (ethnic and age groups), settings, health behaviors, and behavioral science theories have been used in social marketing campaigns? (2) What features of social marketing were used (e.g. formative research, segmentation, and the marketing mix - including promotional strategies and communication channels)? (3) What were the outcomes of the social marketing campaigns? The search aimed to identify studies that met the following inclusion criteria: (a) The study explicitly stated that social marketing was used; (b) The intervention promoted physical activity and/or healthy eating; (c) The population was children, adolescents, young adults, and/or parents; (d) Results of the intervention were available in the published literature The literature review includes studies from the past five years (2004 to 2009). After reviewing the social marketing literature, the insight and knowledge gained was applied to develop a social marketing plan for the CATCH program. The plan was guided by Hands-on Social Marketing, A Step-by-Step Guide and the Center for Disease Control and Prevention's Social Marketing web course.^

A summative evaluation of a HIV/AIDS Early Childhood Care, Education and Development Teacher Training Workshop in Mongu, Zambia

Objective. To conduct a summative evaluation of an Early Childhood Care, Education and Development (ECCED) Teacher Training Workshop in Mongu, Zambia by assessing changes in knowledge, attitudes and intent to use the information. ^ Study design. A matched cohort survey design was used with additional qualitative data collected by structured observation of workshop sessions, daily facilitator and participant debriefs and participant interviews. ^ Results. Matching pre and post tests were completed by 27 individuals in addition to daily debriefs, structured workshop observation and participant interviews with 22% of the group. The participant population was predominantly female individuals aged 15-44 years old that had completed high school and additional post-secondary training, been teaching children aged 0 – 8 years for 2-5 years in the Western Province and received other HIV/AIDS and ECCED education. Pre-tests indicated a strong understanding of ECCED principles and misconceptions regarding HIV transmission, prevention and the disease's impact on early childhood development. The workshop was found to significantly increase the participants' knowledge of topics covered by the curriculum (paired t-test, N=27, p = 0.004, 95% CI 1.8, 8.6). Participants began with a more limited understanding of HIV/AIDS than ECCED, but the mean gain was much greater at 7.4 +/- 12.3 points. Significantly more participants believed at post-test that HIV/AIDS education should increase for future educators. The 77.8% of participants that increased their knowledge scores at post-test expressed significantly less fear of having a child with HIV/AIDS in the classroom (Independent Samples t-test, N= 27, p = 0.011). Overall participant fear decreased 15.5%. 92.6% and 88.9% of participants planned at post-test to respectively use and share the taught information in their daily professional lives and reported on innovative strategies to communicate with the community. ^ Conclusions. Teacher training workshops can significantly increase HIV/AIDS awareness and promote positive attitudes in educators working with children affected by HIV/AIDS. Using participant suggested teaching techniques such as poems and songs and translating the materials to the local language could assist future facilitators to both culturally and professionally relate to the workshop audience as well as increase participant capacity to share the information with the local community. ^

OXIDATIVE STRESS BASED STRATEGIES FOR ENHANCING THE EFFICACY OF HISTONE DEACETYLASE INHIBITORS (HDACi)

Histone deacetylase inhibitors (HDACi) are anti-cancer drugs that primarily act upon acetylation of histones, however they also increase levels of intracellular reactive oxygen species (ROS). We hypothesized that agents that cause oxidative stress might enhance the efficacy of HDACi. To test this hypothesis, we treated acute lymphocytic leukemia cells (ALL) with HDACi and adaphostin (ROS generating agent). The combination of two different HDACi (vorinostat or entinostat) with adaphostin synergistically induced apoptosis in ALL. This synergistic effect was blocked when cells were pre-treated with the caspase-9 inhibitor, LEHD. In addition, we showed that loss of the mitochondrial membrane potential is the earliest event observed starting at 12 h. Following this event, we observed increased levels of superoxide at 16 h, and ultimately caspase-3 activation. Pre-treatment with the antioxidant N-acetylcysteine (NAC) blocked ROS generation and reversed the loss of mitochondrial membrane potential for both combinations. Interestingly, DNA fragmentation and caspase-3 activity was only blocked by NAC in cells treated with vorinostat-adaphostin; but not with entinostat-adaphostin. These results suggest that different redox mechanisms are involved in the induction of ROS-mediated apoptosis. To further understand these events, we studied the role of the antioxidants glutathione (GSH) and thioredoxin (Trx). We found that the combination of entinostat-adaphostin induced acetylation of the antioxidant thioredoxin (Trx) and decreased intracellular levels of GSH. However, no effect on Trx activity was observed in either combination. In addition, pre-treatment with GSH ethyl ester, a soluble form of GSH, did not block DNA fragmentation. Together these results suggested that GSH and Trx are not major players in the induction of oxidative stress. Array data examining the expression of genes involved in oxidative stress demonstrated a differential regulation between cells treated with vorinostat-adaphostin and entinostat-adaphostin. Some of the genes differentially expressed between the combinations include aldehyde oxidase 1, glutathione peroxidase-5, -6, peroxiredoxin 6 and myeloperoxidase. Taken together, these experimental results indicate that the synergistic activity of two different HDACi with adaphostin is mediated by distinct redox mechanisms in ALL cells. Understanding the mechanism involved in these combinations will advance scientific knowledge of how the action of HDACi could be augmented in leukemia models. Moreover, this information could be used for the development of effective clinical trials combining HDACi with other anticancer agents.