Cystoscopy and the development of invasive bladder cancer in patients presenting with superficial urinary bladder cancer

The objective of this study was to determine the impact of different follow-up cystoscopy frequencies on time to development of invasive bladder cancer in a cohort of 3,658 eligible patients 65 and older with an initial diagnosis of superficial bladder cancer between 1994 and 1998. Bladder cancer patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were used as the study population. ^ It was hypothesized that superficial bladder cancer patients receiving less frequent cystoscopy follow-up would develop invasive bladder cancer sooner after initial diagnosis and treatment than patients seen more frequently for cystoscopy follow-up. Cox Proportional Hazard Regression revealed that patients seen for cystoscopy every 3 or more months were 83–89% less likely to develop invasive cancer than patients seen every 1 to 2 months. A comparison of the 2 groups (1 to 2 months vs. 3≥ months) revealed that the 1 to 2 month group may have had more aggressive disease, and they are seen more frequently as a result. ^ These findings suggest that there are two groups of superficial bladder cancer patients: those at high risk of developing invasive bladder cancer and those at low risk. Patients who developed invasive bladder cancer sooner after initial diagnosis and treatment were seen more frequently for cystoscopy follow-up. The recommendation is that cystoscopy should be based on disease status at 3 months. Standardized schedules give all patients the same number of cystoscopies regardless of their risk factors. This could lead to unnecessary cystoscopies in low risk patients, and fewer than optimal cystoscopies in high risk patients. ^

11beta-hydroxysteroid dehydrogenases as regulators of pulmonary corticosterone during the granulomatous response to trehalose 6,6'-dimycolate

Protection against Mycobacterium tuberculosis requires development and maintenance of granulomatous lesions, a feature considered to be the pathological hallmark of Tuberculosis (TB) disease. Upon encountering Mtb or mycobacterial antigens, specifically trehalose 6,6'-dimycolate (TDM), a strong local pro-inflammatory response is initiated. Systemic production of anti-inflammatory glucocorticoids (GCs) is also induced. Emergence of these antagonists at the inflammatory foci is counterproductive to development of the granulomatous structure and detrimental to host protection against TB. Therefore, it was hypothesized that local enzymatic regulation of GCs occurs locally at the site of granulomatous inflammation. The experiments described here strongly suggest that 11β-hydroxysteroid dehydrogenases (11βHSDs) shuttle GCs between active and inert forms during the acute granulomatous response, supporting the net reduction of corticosterone. The patterns of GC and 11βHSD regulation were specific to the lung (the site of inflammation) and were not observed in other tissues. Furthermore, 11βHSD2, which decreases corticosterone concentrations, was not expressed in models of dysregulated granulomatous inflammation. These findings suggest that cellular exposure to local active GC concentrations is restricted via 11βHSDs as a mechanism to initiate and maintain granuloma formation. The information derived from the experiments outlined in this dissertation provides a better understanding of the events required for establishment and maintenance of the protective granulomatous response. As a practical consequence, exploiting 11βHSD2 modulation of GCs at the site of Mtb infection may lead to improvement of Tuberculosis treatment strategies.^

ROLE OF SOX9 IN UTERINE GLAND DEVELOPMENT AND DISEASE INITIATION

The female reproductive tract (FRT) develops midway through embryogenesis, and consists of oviducts, uterine horns, cervix and upper part of the vagina. The uterine horns are composed of an epithelial layer, luminal (LE) and glandular epithelium (GE), surrounded by a mesenchymal layer, the stroma and myometrium. Interestingly, in most mammals the GE forms after birth and it only becomes fully differentiated as the female reaches sexual maturity. Uterine glands (UG) are made up of GE and are present in all mammals. They secrete nutrients, cytokines and several other proteins, termed histotroph, that are necessary for embryo implantation and development. Experiments in ewes and mice have revealed that females who lack UGs are infertile mainly due to impaired implantation and early pregnancy loss, suggesting that UGs are essential for fertility. Fortunately for us, UGs develop after birth allowing us to peer into the genetic mechanism of tubulogenesis and branching morphogenesis; two processes that are disrupted in various adenocarcinomas (cancer derived from glands). We created 3D replicas of the epithelium lining the FRT using optical projection tomography and characterized UG development in mice using lineagetracing experiments. Our findings indicate that mouse UGs develop as simple tubular structures and later grow multiple secretory units that stem from the main duct. The main aim of this project was to study the role of SOX9 in the UGs. Preliminary studies revealed that Sox9 is mostly found in the nucleus of the GE. vii This observation led to the hypothesis that Sox9 plays a role in the formation and/or differentiation of the GE. To study the role of Sox9 in UGs differentiation, we conditionally knocked out and overexpressed Sox9 in both the LE and GE using the progesterone receptor (Pgr) promoter. Overexpressing Sox9 in the uterine epithelium, parts of the stroma, and myometrium led to formation of multiple cystic structures inside the endometrium. Histological analysis revealed that these structures appeared morphologically similar to structures present in histological tissue sections obtained from patients with endometrial polyps. We have accounted for the presence of simple and complex hyperplasia with atypia, metaplasia, thick-walled blood vessels, and stromal fibrosis; all “hallmarks” that indicate overexpressing Sox9 leads to development of a polyp-like morphology. Therefore, we can propose the use of Sox9-cOE mice to study development of endometrial cystic lesions and disease progression into hyperplastic lesions.

Development of HIF-1α/HIF-1β heterodimerization inhibitors using a novel bioluminescence reporter assay system for in vitro high throughput screening and in vivo imaging

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study. Using this screening platform, we identified a promising lead candidate and further chemically derivatized the lead candidate to assess the structure-activity relationship (SAR). The most effective first generation drug inhibitors were selected and their pharmacodynamics and anti-tumor efficacy in vivo were verified by bioluminescence imaging (BLI) of HIF-1α/β heterodimerization in the xenograft tumor model. Furthermore, the first generation drug inhibitors, M-TMCP and D-TMCP, demonstrated efficacy as monotherapies, resulting in tumor growth inhibition via disruption of HIF-1 signaling-mediated tumor stromal neoangiogenesis.

Targeted Deletion Of Functionally Validated Enhancers Defines Their Role in Mouse Limb Development

Transcriptional enhancers are genomic DNA sequences that contain clustered transcription factor (TF) binding sites. When combinations of TFs bind to enhancer sequences they act together with basal transcriptional machinery to regulate the timing, location and quantity of gene transcription. Elucidating the genetic mechanisms responsible for differential gene expression, including the role of enhancers, during embryological and postnatal development is essential to an understanding of evolutionary processes and disease etiology. Numerous methods are in use to identify and characterize enhancers. Several high-throughput methods generate large datasets of enhancer sequences with putative roles in embryonic development. However, few enhancers have been deleted from the genome to determine their roles in the development of specific structures, such as the limb. Manipulation of enhancers at their endogenous loci, such as the deletion of such elements, leads to a better understanding of the regulatory interactions, rules and complexities that contribute to faithful and variant gene transcription – the molecular genetic substrate of evolution and disease. To understand the endogenous roles of two distinct enhancers known to be active in the mouse embryo limb bud we deleted them from the mouse genome. I hypothesized that deletion of these enhancers would lead to aberrant limb development. The enhancers were selected because of their association with p300, a protein associated with active transcription, and because the human enhancer sequences drive distinct lacZ expression patterns in limb buds of embryonic day (E) 11.5 transgenic mice. To confirm that the orthologous mouse enhancers, mouse 280 and 1442 (M280 and M1442, respectively), regulate expression in the developing limb we generated stable transgenic lines, and examined lacZ expression. In M280-lacZ mice, expression was detected in E11.5 fore- and hindlimbs in a region that corresponds to digits II-IV. M1442-lacZ mice exhibited lacZ expression in posterior and anterior margins of the fore- and hindlimbs that overlapped with digits I and V and several wrist bones. We generated mice lacking the M280 and M1442 enhancers by gene targeting. Intercrosses between M280 -/+ and M1442 -/+, respectively, generated M280 and M1442 null mice, which are born at expected Mendelian ratios and manifest no gross limb malformations. Quantitative real-time PCR of mutant E11.5 limb buds indicated that significant changes in transcriptional output of enhancer-proximal genes accompanied the deletion of both M280 and M1442. In neonatal null mice we observed that all limb bones are present in their expected positions, an observation also confirmed by histology of E18.5 distal limbs. Fine-scale measurement of E18.5 digit bone lengths found no differences between mutant and control embryos. Furthermore, when the developmental progression of cartilaginous elements was analyzed in M280 and M1442 embryos from E13.5-E15.5, transient development defects were not detected. These results demonstrate that M280 and M1442 are not required for mouse limb development. Though M280 is not required for embryonic limb development it is required for the development and/or maintenance of body size – adult M280 mice are significantly smaller than control littermates. These studies highlight the importance of experiments that manipulate enhancers in situ to understand their contribution to development.

Minors’ Access to Contraceptive Services

Over the past 30 years, states have expanded minors’ authority to consent to health care, including care related to sexual activity. This trend reflects U.S. Supreme Court rulings extending the constitutional right to privacy to a minor’s decision to obtain contraceptives and concluding that rights do not “come into being magically only when one attains the state-defined age of majority.” It also reflects the recognition that while parental involvement is desirable, many minors will remain sexually active but not seek services if they have to tell their parents. As a result, confidentiality is vital to ensuring minors’ access to contraceptive services. Even when a state has no relevant policy or case law, physicians may commonly provide medical care to a mature minor without parental consent, particularly if the state allows a minor to consent to related health services.

Gentrificación liderada por el Estado y empresarialismo urbano en la Ciudad Autónoma de Buenos Aires

A partir de la experiencia de la Ciudad Autónoma de Buenos Aires, el artículo reflexiona sobre la gentrificación como una estrategia de desarrollo urbano impulsada por diversos gobiernos locales de la región, en un contexto de difusión del empresarialismo urbano. En este marco, el Gobierno de la Ciudad Autónoma de Buenos Aires impulsó, desde 1990, un intenso proceso de transformación urbana en el área central y en los barrios del sudeste, generando un tipo particular de interrelación con el sector privado que promueve la gentrificación en barrios del sudeste de la ciudad. Como consecuencia, han emergido recurrentemente conflictos urbanos que se oponen al modelo de desarrollo urbano impulsado desde el GCABA y reivindican el derecho a la ciudad para las mayorías. No obstante, todos estos conflictos mantienen un elevado nivel de fragmentación y no han logrado hasta el momento articularse en un único movimiento social urbano, lo que va en detrimento de las capacidades para modificar la orientación de las políticas urbanas locales.

Manipulación de la crisis a través de la acumulación por desposesión en México

La acumulación por desposesión es un ejercicio de poder que se ha expresado en el devenir histórico del capitalismo, aunque la acumulación por desposesión, cobra fuerza ideológica a partir del modelo neoliberal y representa, sino la única forma, si la más importante actualmente para sostener o incrementar la acumulación de capital en la geografía glocal (lograr el establishment del sistema bancario y de las grandes corporaciones y centros de poder -BM-FMI y BCE). El rasgo económico-político que definiría dicha acumulación por desposesión, es que su instrumentación para llevarse a cabo, necesita obligatoriamente que el Estado y los dueños de capital (productivo, comercial, financiero) tengan el interés común “contubernio" de que los espacios receptores sirvan para que el capital incremente su capital; esto sólo se logra expropiando el derecho del trabajador de vivir dignamente con un empleo bien remunerado. En palabras de David Harvey (2003, 2004, 2204b, 2007a, 2007b 2007c) quien posibilita la acumulación por desposesión es la liberación de un conjunto de activos, incluida la fuerza de trabajo a un coste muy bajo y en algunos casos, nulo.

El juego recreativo y el deporte social como política de derecho : Su relación con la infancia en condiciones de vulnerabilidad social

Actualmente son reconocidos los beneficios del deporte, la actividad física y la recreación para el desarrollo humano y social de las poblaciones y su afirmación como derechos humanos en diferentes instrumentos legales. Este derecho al deporte y al juego recreativo en la infancia se hace explícito en la Convención de los Derechos del Niño (ONU, 1989), en la Ley de Educación Nacional, y en la Ley de Protección Integral (Ley 26.061). El propósito de este trabajo es estudiar la implementación de políticas públicas mediante el estudio de caso en el Partido de La Matanza, en tres espacios socio-residenciales de villa o asentamientos urbanos, que tuvieron como población participante principal niños/as entre 4 y 14 años. Mediante la triangulación de perspectivas cualitativas se realizó un análisis en paralelo entre el enfoque teórico y metodológico del programa, y las prácticas objetivas desarrolladas en el territorio. Se reconocen los límites que tienen los programas orientados al "deporte social" para traducir en prácticas concretas el ideario del desarrollo humano desde un enfoque de derechos, los desafíos de cobertura y en particular de construcción e implementación de ofertas educativas de calidad en el campo del juego recreativo y el deporte

El juego recreativo y el deporte social como política de derecho : Su relación con la infancia en condiciones de vulnerabilidad social

Actualmente son reconocidos los beneficios del deporte, la actividad física y la recreación para el desarrollo humano y social de las poblaciones y su afirmación como derechos humanos en diferentes instrumentos legales. Este derecho al deporte y al juego recreativo en la infancia se hace explícito en la Convención de los Derechos del Niño (ONU, 1989), en la Ley de Educación Nacional, y en la Ley de Protección Integral (Ley 26.061). El propósito de este trabajo es estudiar la implementación de políticas públicas mediante el estudio de caso en el Partido de La Matanza, en tres espacios socio-residenciales de villa o asentamientos urbanos, que tuvieron como población participante principal niños/as entre 4 y 14 años. Mediante la triangulación de perspectivas cualitativas se realizó un análisis en paralelo entre el enfoque teórico y metodológico del programa, y las prácticas objetivas desarrolladas en el territorio. Se reconocen los límites que tienen los programas orientados al "deporte social" para traducir en prácticas concretas el ideario del desarrollo humano desde un enfoque de derechos, los desafíos de cobertura y en particular de construcción e implementación de ofertas educativas de calidad en el campo del juego recreativo y el deporte

El juego recreativo y el deporte social como política de derecho : Su relación con la infancia en condiciones de vulnerabilidad social

Actualmente son reconocidos los beneficios del deporte, la actividad física y la recreación para el desarrollo humano y social de las poblaciones y su afirmación como derechos humanos en diferentes instrumentos legales. Este derecho al deporte y al juego recreativo en la infancia se hace explícito en la Convención de los Derechos del Niño (ONU, 1989), en la Ley de Educación Nacional, y en la Ley de Protección Integral (Ley 26.061). El propósito de este trabajo es estudiar la implementación de políticas públicas mediante el estudio de caso en el Partido de La Matanza, en tres espacios socio-residenciales de villa o asentamientos urbanos, que tuvieron como población participante principal niños/as entre 4 y 14 años. Mediante la triangulación de perspectivas cualitativas se realizó un análisis en paralelo entre el enfoque teórico y metodológico del programa, y las prácticas objetivas desarrolladas en el territorio. Se reconocen los límites que tienen los programas orientados al "deporte social" para traducir en prácticas concretas el ideario del desarrollo humano desde un enfoque de derechos, los desafíos de cobertura y en particular de construcción e implementación de ofertas educativas de calidad en el campo del juego recreativo y el deporte

TNCs in Perplexity over How to Meet Local Suppliers: The Case of Philippine Export Processing Zone

Transnational Corporations (TNCs) have played a vital role in fostering rapid industrialisation in many developing countries. The Philippines is the case. However, the country has been far lagging behind other ASEAN members in economic performance. The present study examines this issue, mainly focusing on the linkage formation between TNCs affiliates and Philippine local suppliers. Three factors are proposed to determine the overall performance of linkage formation; i.e., outsourcing strategies of TNCs’ local affiliates, local entrepreneurial response, and host government policies. An economic enclave structure is clearly identified in the Philippines, in which only a few locally-owned suppliers have emerged.　Extremely weak local entrepreneurship in the Philippines is identified to explain the poor performance of linkage formation.

Toward an inclusive and a little bit ethical world trading system : listening to the voices of the people in LDCs

Many specialists in international trade have started saying that the era of a mega FTA is approaching. If the three poles of the global economy, namely East Asia, EU and the United States, form mega FTAs, most of the volume of global trade will be covered. That may be fine, but there will be many countries left out of the mega FTA, most of which will be the least developed countries (LDCs). Since the inception of the Doha Development Agenda (DDA) negotiations in 2001, the WTO and its member countries have tried to include LDCs in the world trading system through various means, including DFQF and AfT. Although these means have some positive impact on the economic development of LDCs, most of the LDCs will never feel comfortable with the current world trading system. To overcome the stalemate in the DDA and to create an inclusive world trading system, we need more commitment from both LDCs and non-LDCs. To surmount the prolonged stalemate in the DDA, we should understand how ordinary people in LDCs feel and think about the current world trading system. Those voices have seldom been listened to, even by the decision makers of their own countries. So as to understand the situation of the people in LDCs, IDE-JETRO carried out several research projects using macro, meso and micro approaches. For the micro level, we collected and analyzed statements from ordinary people concerning their opinions about the world trading system. The interviewees are ordinary people such as street vendors, farmers and factory workers. We asked about where they buy and sell daily necessities, their perception of imported goods, export promotion and free trade at large, etc. These ‘voices of the people’ surveys were conducted in Madagascar and Cambodia during 2013. Based on this research, and especially the findings from the ‘voices of the people’ surveys, we propose a ‘DDA-MDGs hybrid’ strategy to conclude DDA negotiations and develop a more inclusive and a little bit more ethical world trading system. Our proposal may be summarized in the following three points. (1) Aid for Trade (AfT) ver. 2 Currently AfT is mainly focused on coordinating several aid projects related to LDCs’ capacity building. However, this is inadequate; for the proposed ‘DDA-MDGs hybrid’, a super AfT is needed. The WTO, other development agencies and LDC governments will not only coordinate but also plan together aid projects for trade capacity building. AfT ver. 2 includes infrastructure projects either gran aid, ODA loans and private investment. This is in accordance with the post-MDGs argument which emphasizes the role of the private sector. (2) Ethical Attitude Reciprocity is a principle of multilateral agreement, and it has been a core promise since GATT. However, for designing an inclusive system, special and differential treatment (S&D) is still needed for disadvantaged members. To compromise full reciprocity and less than full reciprocity, an ethical attitude on the part of every member is needed in which every member refrains from insisting on the full rights and demands of its own country. As used herein, the term ‘ethical’ implies more consideration for LDCs, and it is almost identical to S&D but with a more positive attitude from developed countries (super S&D). (3) Collect Voices of the People In order to grasp the real situation of the people, the voices of the people on free trade will continue to be collected in other LDCs, and the findings and leanings will be fed back to the WTO negotiation space.

From foot-draggers to strategic counter-partners : the dynamics of U.S. and Chinese policies for tackling climate change

As can been seen from the U.S.'s non-ratification of the Kyoto Protocol, together with the negotiations toward the post-Kyoto Protocol framework, the U.S. and China have been quarrelling over their responsibilities and have contradicted one another over the introduction of compulsory domestic greenhouse gases emission reduction targets. Therefore, for a long time, it has been argued that the controversy between the two countries has hindered the process of forging an international agreement to deal with climate change. On the other hand, Sino-U.S. bilateral cooperation on climate change has significantly increased in recent years in summit talks and their Strategic & Economic Dialogue (S&ED), especially after the 15th Conference of Parties (COP) of the United Nations Framework Convention on Climate Change (UNFCCC) in Copenhagen, one of whose aims was to facilitate positive negotiations for the post-Kyoto Protocol agreement. Analyzing this in the light of recent developments, we find that the U.S. and China have tended to address climate change and related issues from a pluralistic viewpoint and approach, by regarding the achievement of bilateral cooperation and global agreements as their common strategic objective.

Producción y gestión habitacional de los pobladores : articulación con la política de vivienda y barrio : trayectoria y problemática actual

Esta tesis analiza las acciones de los pobladores en la creación, consolidación y transformación de su hábitat y en su relación con la política pública de vivienda y barrio en Chile. A partir de la observación directa en terreno y de la revisión de material proveniente de diversas fuentes afirmamos que, aunque los pobladores han hecho un trabajo de producción del hábitat de gran magnitud y generalizado, las políticas públicas no han reconocido suficientemente su papel en la construcción de la ciudad, no han incorporado a cabalidad las potencialidades e innovaciones surgidas de sus prácticas y estrategias, y nunca les han abierto un espacio claro en la toma de decisiones y en la puesta en obra de los programas habitacionales. En el contexto latinoamericano, la política habitacional chilena de los últimos 20 años se ha considerado un éxito y un ejemplo a seguir, puesto que ha demostrado ser eficaz en la disminución del déficit habitacional. Sin embargo, ha tenido efectos urbanos y sociales nefastos, como la construcción de extensos bolsones periféricos de pobreza que se degradan aceleradamente, y la desintegración social que genera la expulsión de los sin casa a la periferia, donde pierden sus redes familiares y sociales. Desde una trinchera opuesta, los allegados, los sin casa que viven al alero de otras familias y representan la mayoría de la demanda por vivienda, exigen quedarse en barrios ya consolidados y evitan las periferias, en parte por mantener una red familiar y social que se sustenta en la proximidad física, en parte por los equipamientos y servicios con que cuentan estos barrios y la cercanía a las fuentes de empleo. Al mismo tiempo, los responsables de diseñar la política habitacional no han buscado establecer una forma de colaboración con los pobladores —principales receptores de la política— con el fin ajustar los programas públicos a las necesidades de las familias de bajos ingresos y a las realidades socioculturales de sus barrios. Por el contrario, han privilegiado una alianza con el sector privado, que conoce muy limitadamente las demandas de las familias. Así, en lugar de construir ciudades más justas, la política habitacional ha alimentado un mercado inmobiliario sustentado en la especulación del suelo y fomentado la industria de la construcción. La pregunta que guía esta investigación es cómo incorporar el conocimiento acumulado y los procedimientos probados por los pobladores al diseño y la implementación de programas habitacionales y urbanos que promuevan procesos de regeneración de las poblaciones y mejoren la distribución de la vivienda social en la ciudad. Sostenemos que los pobladores, a lo largo de una trayectoria de más de medio siglo, han adquirido y consolidado todas las competencias para construir vivienda, mejorar sus barrios e incorporarse a la discusión sobre ordenamiento territorial. Así, hoy están capacitados para asumir un papel protagónico en la definición de políticas públicas que apunte a la construcción de ciudades más sostenibles y equitativas. La producción social del hábitat vinculada al derecho a la ciudad y a la participación de los pobladores «desde abajo» está bastante documentada en la literatura latinoamericana. En Chile se han escrito numerosos trabajos y evaluaciones sobre la política habitacional, pero los estudios sobre el movimiento de pobladores, enfocados desde las ciencias sociales o multidisciplinares, tienen un auge primero, durante los años 60 y principios de los 70 y luego, en la segunda mitad de los 80, pero posteriormente dejan de publicarse, a excepción de algunas investigaciones de historia urbana o social. En cuanto a los estudios que abordan las acciones de los pobladores desde una mirada puesta en los resultados de la producción y la gestión habitacional y urbana, estos han sido especialmente escasos y ninguno abarca un período largo. La tesis aborda entonces las acciones específicas que emprenden los pobladores a distintas escalas territoriales —el conjunto, el barrio, la población, la ciudad y el país—, su relación con la política habitacional y su articulación con los demás actores que intervienen en la producción material del hábitat. Lo realizado por los pobladores se estudia a la luz del largo plazo, desde la promulgación de la primera ley de vivienda en 1906 hasta nuestros días, con el énfasis puesto entre los años 1990 y 2010, período de producción masiva y sostenida de vivienda social, financiada por el Estado y construida por el sector privado en la periferia urbana, y más detalladamente entre 2006 y 2010, cuando los pobladores irrumpen con la «gestión vecinal» y la «autogestión» como medios para implementar los programas habitacionales del gobierno. Para ello se recorre toda la trayectoria y se complementa con procesos particulares, a la manera de un lente de acercamiento con el cual se focalizan y amplifican trece casos de estudios, para ilustrar modos de producción y gestión concretos y mostrar cómo estos se inscriben en modos de hacer genéricos de los pobladores. Finalmente, con el lente centrado en el último ciclo de este proceso escribimos el capítulo inédito de los últimos veinte años de esta historia. Primero se realiza la reconstrucción de tres casos de estudio «en profundidad», que incluyen la génesis, la consolidación y las transformaciones del conjunto o barrio. Estos casos de estudio «en profundidad» se ponen en perspectiva reconstruyendo la trayectoria histórica de la producción y gestión realizada por los pobladores. Esta reconstrucción de largo período se profundiza con tres casos de estudio «específicos», de dimensión histórica, que tratan el conflicto del acceso a suelo. Finalmente se analizan las interrogantes que plantean estos procesos hoy en día para la producción y gestión de vivienda y barrio a futuro, a partir de entrevistas a actores claves y de la reconstrucción de siete casos de estudio «específicos» de acceso a suelo ilustrativos del período actual. La tesis sustenta que los pobladores, con las acciones de gestión y autogestión que realizan desde 2006, e interviniendo en la discusión sobre los instrumentos de planificación territorial a partir del mismo año, se sitúan actualmente en una nueva plataforma de acción y negociación desde la cual pueden incorporarse, con todas las competencias necesarias, a la definición de las políticas públicas y así dotarlas de pertinencia y coherencia para contribuir a superar la pobreza con respuestas más acorde a sus realidades. ABSTRACT This thesis analyzes the actions of pobladores in the creation, consolidation and transformation of their habitat and their relationship with Chilean public housing and neighbourhood policy. Through direct observation in the field and the review of material from various sources we can affirm that although the pobladores have undertaken widespread work in the production of their environment, public policies have not sufficiently recognized their role in the construction of the city. Public policy has failed to fully incorporate the potential and innovation arising from practices and strategies employed by social housing recipients and has never opened a clear space for them in decision-making or the commissioning work of the housing programs. Within the Latin America context, the Chilean housing policy of the past 20 years has been considered a success and an example to follow given that it has proven effective in reducing the housing deficit. However it has had disastrous urban and social effects, such as construction of large peripheral pockets of poverty that degrade rapidly, and generates social disintegration through the expulsion of the homeless to the periphery, where they lose their family and social networks. On another front those homeless who live under the roof of relatives and who represent the majority of demand for social housing, request to stay in consolidated neighbourhoods avoiding the periphery, partly to maintain family and social networks based on physical proximity and partly because of the facilities and services available in these neighbourhoods and their adjacency to sources of employment. At the same time, those responsible for designing housing policy have not sought to establish a form of collaboration with the pobladores in order to adjust the public programs to the needs of low-income families and the socio-cultural realities of their neighbourhoods. On the contrary an alliance with the private sector has been favored, a sector which has very limited knowledge of the demands of the recipients. Therefore instead of building more equal cities, housing policy has fueled a housing market which supports land speculation and promotes the construction industry. The question leading this research is how to incorporate the accumulated knowledge and proven procedures of the pobladores in the design and implementation of programs that promote housing and urban regeneration processes and which could improve the distribution of social housing in the city. We maintain that social housing recipients over the course of half a century have acquired and consolidated all the skills to build housing, improve neighborhoods and join the discussion on city planning. These residents are now capable of assuming a leading role in defining public policies that aim to build more sustainable and equitable cities. The social production of the environment linked to the right to the city and resident participation from the «bottom-up» is well documented in Latin American literature. In Chile there are extensive written works and assessments on housing policy with multidisciplinary or social science studies on the movement of the pobladores peaking during the 60’s and early 70’s and then again in the second half of the 80’s but afterwards this stops, with the exception of some research on social or urban history. As for studies that address the actions of the pobladores looking at the results of production and housing and urban management these have been particularly scarce and none of which cover a long period of time. The thesis then addresses the specific actions undertaken by the pobladores at different territorial levels; the housing development, the neighbourhood, the community, the city and State, and their relation to housing policy and its coordination with other actors involved in the production process of the built environment. The accomplishments of the pobladores is studied over the long term, since the enactment of the first housing law in 1906 to the present, with an emphasis between 1990 and 2010, a period of mass production and sustained social housing which was State-funded and built by the private sector in the urban periphery, and in particular between 2006 and 2010, when the pobladores break with the «neighborhood management» and «self-management» as a means to implement the housing programs of the government. To this end the entire process is outlined and is complemented by specific processes which are placed under a lens in order to focus and amplify thirteen case studies illustrating actual ways of production and management and to show how these ways of doing things are generic to the pobladores. Finally, with the lens focused on the last cycle of this process we write the new chapter of the last twenty years of this history. First there is a reconstruction of three case studies «in depth», including their origins, consolidation and the transformation of the sector or neighborhood. These «in depth» case studies are put into perspective reconstructing the historical trajectory of the production and management by the pobladores. This reconstruction over a long period is given great depth by three «specific» case studies, of historical importance, dealing with the conflict of access to land. Finally we analyze the questions raised by these processes for the production and management of housing and neighborhood in the future, based on interviews with key players and the reconstruction of seven case studies specifically regarding access to land and which are illustrative of current practice. The thesis maintains that since 2006 the pobladores through actions of management and selfmanagement and their intervention in the debate on territorial planning has placed them on a new platform for action and negotiation from which they can incorporate themselves, with all the necessary capacities, in the definition of public policy and therefore provide it with a pertinence and coherence to help towards overcoming poverty with answers more according to their realities.