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. ^

An International Professional Development Collaboration in Literacy Education

An International Professional Development Collaboration in Literacy Education is a report of an international professional development project in Guatemala designed to improve literacy instructional practices and thereby raise student achievement in reading and writing. The opportunity for coaching Guatemalan teachers in teaching literacy strategies and skills provides data for this participatory action research study. This research is intended to contribute to cross-cultural understanding by graduate and undergraduate students in literacy, improved pedagogical techniques, international outreach in developing countries, and student academic success worldwide.

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.

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

The observatory of intelligence and territorial development, tool for innovation in processes of territorial planning in municipalities of the province of Jujuy

El municipio es considerado como un espacio donde sus habitantes comparten no sólo el territorio sino también los problemas y los recursos existentes. La institución municipal -como gobierno local- es el ámbito en el cual se toman decisiones sobre el territorio, que implican a sus habitantes. En cuanto a los actores, estos pueden ser funcionarios, empleados y la comunidad (individual y organizada en ongs), todos aportan sus conocimientos y valores, pero tienen diferentes intereses y diferentes tiempos. Vinculada a las decisiones, encontramos que la forma en que se gestiona la información territorial, es determinante si se pretende apuntar hacia acciones con impacto positivo, y sustentables en lo ambiental y en el tiempo. Este trabajo toma tres municipios: San Salvador de Jujuy, capital de la provincia localizada en los Valles Templados; San Pedro de Jujuy, principal municipio de la región de las Yungas y Tilcara en la Quebrada de Humahuaca. El aporte de la Inteligencia Territorial, a través del observatorio OIDTe, permite analizar los modos de gestión de la información, especialmente mediante el uso de las tecnologías de la información y comunicación (pagina web municipal, equipamiento informático en las oficinas, estrategias de comunicación y vinculación con la población) y mediante la organización de las estructuras administrativas (organigrama) por las cuales circula la información municipal. Además, con la participación enriquecedora de equipos multidisciplinarios en las diferentes etapas. Se busca, a partir de un diagnóstico, generar estrategias para la introducción de innovaciones con los propios actores municipales, a partir de las situaciones y modos culturales propios de cada lugar, incorporando los marcos conceptuales de la Inteligencia Territorial. En este sentido el OIDTe al promover el entendimiento entre los actores, institucionales y la sociedad, facilita la coordinación de diferentes intereses propiciando la toma de decisiones por acuerdos. Asimismo, el método Portulano, puede orientar la introducción de innovaciones en la coordinación de la información cartográfica, para que las diferentes oficinas puedan complementar sus aportes y la comunicación hacia fuera de la institución. En la fase de diagnóstico, se aplicaron entrevistas a informantes claves, se realizó un workshop con técnicos de planta permanente y funcionarios de áreas que manejan información territorial, y de planificación. También por la importancia de la capacidad instalada de recursos humanos, se analizó el nivel de instrucción y la capacitación con que cuenta el personal de planta permanente de cada área

Five growth strategies for Myanmar : re-engagement with the global economy

After decades of isolation, Myanmar is now actively re-engaging with the global economy. For successful re-engagement, Myanmar needs to implement comprehensive economic reforms based on a shared vision for long-term economic development that is characterized by human-centered, high, sustainable, pro-poor, inclusive, and balanced economic growth. In this paper, we propose five growth strategies: "Agriculture Plus Plus," an export-oriented strategy, a foreign direct investment-driven strategy, a two-polar growth strategy, and a strategy to develop domestic economic corridors. These strategies are used as guides to translate these development agendas into a set of implementable policies, programs, and projects.

From school to work : Muslim youths' education and employment strategies in a community in Uttar Pradesh, India

India's Muslim community, which accounts for 14.4 percent of India’s vast population and is thus the largest of all religious minorities, has been the subject of considerable development discourse as Muslims have the lowest level of educational attainment and standard of living among socio-religious groups in the country. This study addresses the meaning of education and career opportunities for Muslim youths in relation to their educational credentials and social position in the hierarchy of Muslim class and caste groups, with particular reference to a community in Uttar Pradesh. The author contends that the career opportunities, possibilities, and strategies of Muslim youths in Indian society depend on multiple factors: social hierarchy, opportunities to utilize economic resources, social networks, cultural capital, and the wider structural disparities within which the Muslims are situated and wherein they question the value of higher education in gaining them admission to socially recognized and established employment sectors.

Innnovation and new business models for the regional development: travel and transportation

Regional development could present different strategies: •Relocation of industry clusters •Foreign Direct Investment attraction •Innovation based on new business models The Regional Government of Madrid (3rd largest GDP in the EU) selected strategic industries to compete & innovate: •Travel & Transportation •Aerospace •Nanotech. & •Biotech. •ICTs. •Energy

Optimization of urban mobility measures to achieve win-win strategies

European cities are essential in the development of Europe as they constitute the living environment of more than 60% of the population in the European Union and are drivers of the European economy – just under 85% of the EU’s gross domestic product is produced in urban areas (EC, 2007a). The car has been one of the main factors of development during the 20th century, but it is at the same time the origin of the key problems cities have to face: traffic increase. This has resulted in chronic congestion with many adverse consequences such as air pollution and noise. This loss of environmental quality is one of the reasons for urban sprawl in European cities during recent decades. But this urban sprawl at the same time worsens the environmental conditions. We must return to the dense city, but clean and competitive, and this implies reducing car use yet provides quality transport alternatives sufficient to recover and maintain the competitiveness of cities (EC, 2007a). Consequently, European cities need to establish an urban transport strategy which helps reduce their environmental problems –mainly emissions and noise – but without decreasing their trip attraction. This aspect is very important because a loss of trip attraction would result in an increase of people moving to more disperse areas, contributing towards worsening the current situation. This thesis is an attempt to contribute solutions to this problem in two ways: 1) The first is to analyze the complementarity and possible synergies of several urban transport measures aimed at improving a modal split to a more sustainable means of transport. This analysis will focus on the three aspects already mentioned: emissions, noise and attractiveness or competitiveness. 2) Once possible synergies and complementarities have been analyzed, the second objective is to propose the best combination of these measures, in terms of level of implementation, to achieve the maximum benefit with respect to the three aspects previously established: emissions, noise and attractiveness or competitiveness. Therefore, within the wide range of measures enhancing sustainable urban transport, three of them have been be selected in this thesis to establish a methodology for achieving these objectives. The analysis will be based on the region of Madrid, which is also the case study selected for this research. Las ciudades europeas son piezas fundamentales para el desarrollo europeo, ya que son el lugar de residencia de más del 60% de la población de la unión europea así como los motores de su economía – casi el 85% del PIB europeo se produce en áreas urbanas (EC, 2007a). El coche ha sido uno de los principales motores de desarrollo de las ciudades durante el siglo XX, pero se ha terminado por convertir a su vez en uno de los principales problemas con los que tiene que lidiar las ciudades: el aumento del tráfico. Esto ha derivado en unos niveles crónicos de congestión, con multitud de efectos adversos, entre los que cabe destacar la contaminación del aire y el ruido. Esta pérdida de calidad ambiental es una de las razones que ha propiciado la dispersión urbana que han experimentado las ciudades europeas en las últimas décadas. Pero esta dispersión urbana a su vez contribuye a empeorar las condiciones ambientales de las ciudades. Debemos retornar a la ciudad densa, pero limpia y competitiva, y esto implica reducir el uso del coche, pero proporcionando alternativas de transporte que permitan recuperar y mantener la competitividad de las ciudades (EC, 2007a). Por lo tanto, las ciudades europeas necesitan encontrar una estrategia de transporte urbano que ayude a reducir sus problemas medio ambientales – principalmente ruido y emisiones – pero sin hacerlas perder atractividad o competitividad. Este aspecto tiene gran importancia porque una pérdida de la misma se traduciría en un aumento de dispersión de la población hacia áreas periféricas, contribuyendo a empeorar la situación actual. Esta tesis contribuye a solucionar este problema de dos maneras: 1) La primera, analizando la complementariedad y posibles sinergias de diferentes medidas de transporte urbano orientadas a promover un reparto modal hacia modos más sostenibles. Este análisis se centrará en los tres aspectos anteriormente citados: emisiones, ruido y atractividad o competitividad. 2) Una vez las posibles sinergias y complementariedades se han analizado, el segundo objetivo es proponer la mejor combinación de estas medidas – en términos de grado de aplicación - para lograr el máximo beneficio en lo que respecta a los tres objetivos previamente establecidos. Para ello, en esta tesis se han seleccionado una serie de medidas que permitan establecer una metodología para alcanzar estos objetivos previamente definidos. El análisis se centra en la ciudad de Madrid y su área metropolitana, la cual se ha escogido como caso de estudio para realizar esta investigación.