Fluorescent Cytidine Analogues

Three luminescent cytidine analogues have been synthesized in order to perform SNP analysis by fluorescence spectroscopy. Herein is described the synthesis of 6-pyrenylpyrrolocytidine (PypdC), its photophysical characterization, and its subsequent incorporation into oligodeoxynucleotides (ODNs). The behavior of PypdC in ODNs is described as well as fluorescence intensity changes with respect to the match and mismatch cases. In order to obtain a greater understanding of pyrene’s interaction with pyrrolocytidine, a congener, pyrenyl ethynyl cytidine (PyEtdC) was synthesized. The congener was photophysically studied and prepared for oligo synthesis. Finally, exploration into indole substituted pyrrolocytidines (pdCs) was undertaken to explore new pdC structures

High-dose-rate brachytherapy boost in prostate cancer: clinical outcomes, late rectal toxicity and uncertainties in organ at risk delineation

Prostate cancer is one of the most commonly diagnosed cancers in the developed world, having caused 293,000 deaths in 2013 (Global Burden of Disease Cancer, et al., 2013). According to the Spanish Network of Cancer Registries (REDECAN), 33,370 new cases were diagnosed in 2015 in Spain. In 2014, prostate cancer was ranked fifth in terms of cancer deaths among Spanish men (Instituto de Salud Carlos III, 2014). High-risk prostate cancer is an aggressive form of the disease with a higher risk of distant metastasis and mortality. This classification represents a significant portion of the nearly 28,000 prostate cancer deaths per year in the United States and the 5,855 deaths in Spain (American Cancer Society 2015; Instituto de Salud Carlos III, 2014). There are different treatment options for locally advanced prostate cancer, such as active surveillance, radical prostatectomy, and radiotherapy. The use of radiotherapy in the radical treatment of intermediate- and high-risk prostate cancer has been well studied in several prospective randomized trials (Zelefsky et al., 2008; Coen et al., 2002). This option can be administered through EBRT, BT, and either HDRBT or LDRBT given alone or combined with EBRT. HDRBT is a brachytherapy technique, and when combined with EBRT, it allows for dose escalation, administration of the complete dose to the target (the prostate), and minimisation of the dose received by the surrounding normal tissues. Current international treatment guidelines recommend the use of HDRBT combined with EBRT, which is also known as “HDRBT boost”. According to the ABS, GEC/ESTRO, and ESTRO/EUA/EORTC, this treatment modality improves local control compared with monotherapy, as well as the outcomes in certain patients with intermediate- and high-risk disease (Zaorsky et al., 2017). There are no specific recommendations about the best dose fractionation scheme for HDRBT boost. Several studies have reported various treatment schemes, which has made it difficult to compare the results of acute and late toxicity. In recent years, there has been a transition in the number of fractions delivered. Initially, as many as four boost fractions were used, but currently, the evidence supports large boost fractions with a single HDRBT boost (Morton et al., 2013). This trend has been accompanied by important biological effects, as well as practical and cost-saving advantages. Furthermore, virtually all-geometric uncertainty is eliminated, as there is no risk of inter-fraction variability. For these reasons, there has been much interest in this technique, which has also been adopted by several centres for high-risk patients. This thesis is motivated by the need for clinical outcomes, including improvements in prevention and decrease of rectal toxicity. The purpose of this thesis was threefold. Firstly, to determine the clinical outcomes of a cohort of patients diagnosed with prostate cancer and treated with HDRBT boost using real-time TRUS based planning in combination with EBRT (see Chapter IV, Paper I). Secondly, determining the occurrence of late rectal toxicity in our patients’ cohort and evaluating its potential relationship with D2cc parameter. This was based in the rectal constraint recommended by GEC/ESTRO, given the absence of another rectal dose constraints from similar studies of HDRBT combined with EBRT for prostate cancer (see Chapter IV, Paper I). Thirdly, we proposed to evaluate the D 2cc robustness in HDRBT for prostate cancer using the interobserver variability in the rectum contouring. A first pilot study was performed with a limited number of patients and physicians of the same center (see Chapter IV, Paper II). Lastly, in order to evaluate the outcomes from the pilot study, a multicentre prospective study was performed (see Chapter IV, Paper III). Below is a summary of the information contained in each of the papers of this thesis. Chapter I provides a summary describing the findings of the research that were carried out by the doctoral candidate. Chapter II provides a general introduction and justification of the thesis. Chapter III contains the general aim, specific objectives and the study design of the thesis. In Chapter IV (Paper I), we review our institution´s experience with HDRBT boost for localized prostate cancer. The first purpose of this study was to analyse the clinical outcomes, particularly local control, overall survival, and late rectal toxicity. The second purpose was to determine the significance of dose-volume histogram parameters for predicting LRT after single-fraction HDRBT boost and EBRT in prostate cancer patients. A cohort of 300 patients diagnosed with locally advanced prostate cancer and treated with HDRBT boost plus EBRT were followed prospectively. The patient data were used for both purposes. The treatment comprised a single-fraction HDRBT boost of 15 Gy plus EBRT ...MedicinaCiencias de la Salu

Three Essays on the Effect of Representation on Governance

Recent research tests and finds support for the hypothesis that an increase in the number of elected representatives in local governments can reduce public expenditures by improving the oversight of the mayor by the council. This result suggests that a system of checks-and-balances is in place at the lowest level of governance in established democracies and is consistent with theories of the role of division-of-powers in improving government accountability. Given the relevance of this result for our understanding of political institutions, this dissertation presents three essays that: 1) test this hypothesis using different samples and alternative measures of government performance and 2) revisit the evidence from the existent literature. The first essay tests the hypothesis by implementing a Regression Discontinuity (RD) design using data from a large panel of local governments in Colombia, South America. I find that additional representatives decrease government expenditures on average; however, there is no evidence that this increase affects the oversight on the mayor. The results persist after accounting for the number of parties with elected representatives, indicating that the estimates are not driven by changes in the party composition. There is also no evidence that the reduction in municipal expenditures affects the provision of services such as potable water, student enrollment in elementary and high school education, and provision of health care to the low income population. Given the findings from the panel of municipal governments in Colombia, the second essay revisits the two empirical studies that report support for the hypothesis. A common feature of both studies is that they present their estimates of the effect of council size as coming from a RD specification. However, after examining the estimated equations, I show that they are inconsistent with a RD design because they do not incorporate information about the data generating process (i.e., discontinuities in the treatment assigning variable). The data from both studies is then used to estimate the effect of changes in the number of representatives using an appropriate RD specification. I find that the parameter estimates from the appropriate RD specification fail to reject the null hypothesis that a change in the number of representatives does not affect the oversight of the manager/major by the council. The last essay provides an additional test for the hypothesis that an increase in the number representatives can increase the oversight of the executive by the council using a panel of municipal governments from Costa Rica. Although this panel is smaller than the one from Colombia, it better represents local governments in many developing countries where municipalities have a limited number of responsibilities with most services being provided through the central government. Using a RD design, I find no evidence that an increase in the number representatives has an impact on fiscal efforts or the allocation of municipal expenses. This is in spite of the fact that changes in the number of representatives lead to an increase in the number of parties in local councils

Development of a novel catalytic membrane reactor: application in wastewater treatment

Los procesos de oxidación químicos son una herramienta universal para el tratamiento de aguas subterráneas, efluentes industriales y aguas residuales. Una de estas técnicas se basa en la generación de radicales hidroxilos (•OH), y se le conoce con el nombre de proceso de oxidación avanzada (AOP). Aunque dicho proceso es considerado una poderosa herramienta para la degradación de contaminantes, este enfrenta varias limitación prácticas especialmente en función del sistema seleccionado para la generación de los •OH. El objetivo de este trabajo fue proponer y poner a prueba una estrategia novedosa con el fin de ampliar la aplicabilidad de la oxidación avazanda, integrando al sistema el uso de reactores de membrana catalítica (CMR). Los esfuerzos fueron enfocados en la aplicación de los CMRs para la oxidación de un compuesto orgánico modelo (fenol), utilizando peróxido de hidrogeno generado in situ como fuente de •OH. Las características de los CMRs permiten la síntesis directa de H2O2.Chemical oxidation processes are the most universal tool for treatment of contaminated groundwater, industrial effluents and wastewater. Oxidation at mild conditions and based on the generation of highly reactive hydroxyl radicals (•OH) is referred to as advanced oxidation process (AOP). Even though this technique is considered as powerful regarding contaminant degradation, it faces several practical limitations in a large scale due to the cost of the system selected for •OH generation. The aim was to propose and test a novel strategy in order to extend the applicability of AOP, whereby the integration of catalytic membrane reactors (CMRs) plays a key role. The efforts were focused on the application of the CMRs for direct oxidation of a model organic compound by the in-situ generated hydrogen peroxide. The inherent properties of the CMRs permit the direct synthesis of hydrogen peroxide starting from H2 and O2 using noble metal as an active phase

Dancing with Culture: A Grounded Theory Study on Latin American and Spanish Speaking Caribbean Women Living in the United States Process for Dealing with Internal Conflicts

This grounded theory study explored the competing cultural expectations and cultural approaches by women from Latin American and Spanish-speaking Caribbean countries living in the United States. The study explored the following questions: In what ways do women from Latin America living in the United States establish priorities among potentially conflicting cultural expectations or roles? What internal conflicts result out of living between two cultures? What does the process for making sense of cultural expectations look like? How do Latin American women living in the United States make sense of this process? Using a constructivist grounded methodology, the research reflects the insights of 20 female participants from various Latin American and Spanish-speaking Caribbean countries. The data analysis resulted in five major findings, illuminating a framework for understanding the process for making sense of conflicting cultural norms, expectations, and cultural approaches. This is presented in four stages, (1) confronting the new norm/expectation, (2) recognition/acknowledgment of the conflicting cultural value/norm/expectation, (3) adapting to the new context/situation and (4) managing from a cultural standpoint. The main decision-making process related to cultural expectations was tied to: (a) what it meant to be a woman from their native country in the United States and (b) what this means when they return to their country of origin. Concluding with “creating a new norm/dynamic,” this becomes the “balancing act” or “the dance between cultures

DEMAND FOR FOOD IN ECUADOR AND THE UNITED STATES: EVIDENCE FROM HOUSEHOLD-LEVEL SURVEY DATA

This thesis consists of two essays focused on the estimation of food demand models from household-level data. The first essay examines the approach developed by Lewbel (1989) for the construction of household level commodity price indices (Stone-Lewbel prices) which can be used for the estimation of price effects in demand models. Stone-Lewbel prices are constructed using information on budget shares and Consumer Price Indices (CPIs) of the goods comprising the commodity groups. We consider three alternative CPIs for the construction of the Stone-Lewbel prices: monthly, quarterly and a constant (unity) price index (by a unity CPI we meant that all households face a unique same price). The unity CPI is used to simulate a scenario where no price index information is available. Data from the United States Consumer Expenditure Survey is used in the analyses. The EASI demand system is used as our parametric demand system. Two-stage estimate procedures are used to account for censoring in the data, and endogeneity of expenditures. Elasticities and marginal effect estimates from the demand models proved to be robust to the alternative CPIs considered in this study. The second essay examines the demand for food commodities in Ecuador. We estimate three demand systems, one for the entire population, and one for urban and rural populations. The AIDS model is used as our parametric demand system. Specialized econometric procedures are used to account for censoring in the data, endogeneity of expenditures and the use of unit values as a proxy for prices. Estimated elasticities and marginal effects for the three systems are consistent with the theory. Substantial differences are observed between estimates for urban and rural populations

The Ethnic Context and Attitudes Toward 9th Grade Math

The present study examined the relations between ethnic context and attitudes about 9th grade math in youth from different ethnic groups who had recently transitioned to high school. The large sample comprised African American, Latino, White, and Asian youth (n = 2265, 55% girls, Mage = 14.6 yrs.) A new questionnaire was developed assessing four math attitudes (perceived competence, feelings of belonging, perceive importance and anxiety in math) and two ethnic context variables (perceived same-ethnic peers in one’s math class and perceptions of the school ethnic climate). Participants listed the math course they were taking in 9th grade and then completed the questionnaire based on that class. Perceiving more same-ethnic classmates in math was related to more positive attitudes about perceived competence and feelings of belonging in math. Significant interactions between the two ethnic context variables were documented suggesting that a positive ethnic climate buffered some of the negative effects of few same-ethnic peers on perceived competence and belonging. Implications of the findings for understanding the social-motivational underpinnings of high school course-taking among multiethnic youth were discussed

Who are the actors and what are the factors that are used in models to map forest fire susceptibility? A systematic review

In the last decades, natural fire regimes have experienced significant alterations in terms of intensity, frequency and severity in fire prone regions of the world. Modelling forest fire susceptibility has been essential in identifying areas of high risk to minimize threats to natural resources, biodiversity and life. There have been significant improvements in forest fire susceptibility modelling over the past two decades 2001–2021. In this study, we conducted a systematic literature review of literature covering forest fire susceptibility modelling published during this period. The review provides insights on the main themes of forest fire susceptibility modelling research, the main base input factors used in models to map forest fire susceptibility, the main researchers, the areas where this type of research were implemented, technology and models used. It also highlights collaboration opportunities, and regions, such as Central America and Africa, where mapping of forest fire susceptibility is needed. We argue that such knowledge is crucial in order to identify critical factors and opportunities which can aid in improving factor selection and forest fire management.Peer Reviewe

Factores protectores y de riesgo asociados al desarrollo de violencia en la adolescencia media y tardía

No existe país ni comunidad a salvo de la violencia; es así como América Latina y el Caribe es la región más violenta del mundo con una tasa de 30 homicidios por 100,00 habitantes(10). Nuestro país no es ajeno a esta realid, siendo después de Colombia, Honduras y Guatemala, el cuarto país de América Latina con la tasa más alta de homicidio