814 resultados para Focus on opportunities


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PURPOSE OF REVIEW: Brain metastases are a common clinical problem, and only limited treatment options exist. We review recent advances in medical brain metastasis research with a focus on the most common tumor types associated with secondary brain colonization: melanoma, breast cancer and lung cancer. We speculate on opportunities for drug development in patients with brain metastases, both as a treatment of established disease and as an adjuvant and prophylactic strategy. RECENT FINDINGS: BRAF inhibitors and the immunomodulatory anticytotoxic T-lymphocyte-associated antigen 4 antibody ipilimumab have shown clinically meaningful activity in melanoma patients with brain metastases. In breast cancer, current studies on drug treatment of brain metastases are mainly focusing on human epidermal growth factor receptor 2 targeting agents such as lapatinib. Emerging data seem to implicate a potential role of targeted agents including antiangiogenic compounds, pazopanib, and epithelial growth factor receptor inhibitors for prevention of brain metastasis formation in breast cancer or nonsmall cell lung cancer. SUMMARY: Novel drugs are beginning to enter clinical practice for selected patients with brain metastases. The promising findings from recent studies may fuel more research on brain metastases and their optimal drug treatment.

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Chile is one of the countries with the highest level of income inequality worldwide. Given the association between economic inequality and patterns of social stratification, in such context it would be expected to find a large dispersion of subjective social status' indicators in the population. Nevertheless, analyses from international surveys reveal a strong tendency to the mean of the subjective status i.e. there would be downward and upward biases of the subjective status regarding the objective status. The present research attempts to tackle this phenomenon for the Chilean case, with a focus on the influence of status and class variables on the subjective status. For the analysis we use Chilean data from the social inequality module of the International Social Survey Programme 2009. The results indicate a strong tendency to the mean of the subjective status in the population, particularly from the side of those with higher objective status.

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A lot of research in cognition and decision making suffers from a lack of formalism. The quantum probability program could help to improve this situation, but we wonder whether it would provide even more added value if its presumed focus on outcome models were complemented by process models that are, ideally, informed by ecological analyses and integrated into cognitive architectures.

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This paper deals with the recruitment strategies of employers in the low-skilled segment of the labour market. We focus on low-skilled workers because they are overrepresented among jobless people and constitute the bulk of the clientele included in various activation and labour market programmes. A better understanding of the constraints and opportunities of interventions in this labour market segment may help improve their quality and effectiveness. On the basis of qualitative interviews with 41 employers in six European countries, we find that the traditional signals known to be used as statistical discrimination devices (old age, immigrant status and unemployment) play a somewhat reduced role, since these profiles are overrepresented among applicants for low skill positions. However, we find that other signals, mostly considered to be indicators of motivation, have a bigger impact in the selection process. These tend to concern the channel through which the contact with a prospective candidate is made. Unsolicited applications and recommendations from already employed workers emit a positive signal, whereas the fact of being referred by the public employment office is associated with the likelihood of lower motivation.

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Objective: Impaired blood flow of the gastric tube represents a major cause of anastomotic leakage after esophageal resection. In order to improve local vascularisation, preoperative embolization (PE) of the left gastric artery has recently been proposed. The aimof this study was to assess our initial experience of this novel approach with a particular focus on anastomotic leakage.Methods: A consecutive series of 102 patients (81 male, 21 female, median age 64 years) underwent resection (82 Ivor-Lewis procedures, 9 transhiatal resections, 11 triple incisions) for esophageal malignancies at our institution from 2000 to 2009. Since 2004, PE was used selectively in 19 patients 21 days prior to elective esophagectomy. Selection criteria were normal gastric vascular anatomy, no pre-existing vascular disease, i.e. atheromatosis of the celiac trunk or superior mesenteric artery, and resectability of the tumor. PE was performed under local anesthesia on a dedicated system in a standard fashion. Following percutaneous transfemoral visceral angiography to identify gastric vascular anatomy, embolization was performed either with 5-F or with coaxial 3-F catheters and fibered metal coils. We analyzed retrospectively patient's data, operative data, and outcome from a prospective database.Results: The overall anastomotic leakage rate was 18・6% (19/102 patients); cervical anastomosis had a leak rate of 25% compared to intrathoracic anastomosis leak rate of 18・2%. While 17 of 83 patients without PE developed anastomotic leakage (20・5%), there were only 2 of 19 patients after PE revealing an anastomotic leakage (10・5%). Otherwise, patients with PE had no more other complications. There was only one PE-related complication (i.e. partial splenic necrosis).Mean hospital stay was 25 days versus 27 days for patients with PE and without PE, respectively. The mortality rate was 7・8% (8/102 patients), whereby four deaths were related to anastomotic leakage (1 and 3 patients with PE and without PE, respectively).Conclusion: PE is an interesting novel approach to improve gastric blood flow in order to minimize anastomotic leakage. Its application is safe and technically easy. Our preliminary experience revealed a decrease of the anastomotic leakage rate of almost 50%.

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The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations.

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A new initiative has sprung on the path created by the Open Access (OA) movement: Open Education (OE). The initiative's aim is to open up all educational resources at all learning levels. In order to achieve this goal, several international institutions, like UNESCO and the OECD, have published reports, surveys and documents to help educational institutions in this endeavor. This global initiative needs a legal framework; as a result, efforts thus far have usually resorted to Open Licensing (OL), especially Creative Commons (CC) licensing. In fact, as a response to this new movement, Creative Commons launched a new program, ccLearn , which recognizes open licensing's impact on education and directly supports the idea of open educational resources (OER). However, there still remain a good amount of open questions: What is happening locally with OL in higher education? How are educational institutions receiving the initiative? How is it that the OL initiative relates to educational resources? Are there local examples of open educational resources (OER)? How do these local instances incorporate CC into their educational frameworks?. To this effect, this analysis aims to focus on the legal approach and specifically on the way the educational sector is using open licenses outside the English speaking world. It will do so by looking at the current situation in two specific scenarios, the Colombian and the Catalan experiences with open educational projects at the higher education level.

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En pratique courante, les événements thrombotiques ne sont pas rares. Dans le suivi des grossesses, les gynécologues ont souvent affaire à des pertes foetles chez leurs patientes. Jusqu'à quel point ces événements peuvent-ils être considérés comme "banals" ? Quand et sur quels critères doit-on considérer la possibilité d'un syndrome des antiphospholipides ? Des efforts ont été réalisés ces dernières années en vue de mieux codifier ce syndrome, tant sur le plan du laboratoire, que clinique. En vue d'uniformiser ces éléments, une première conférence de consensus a eu lieu en 1999 à Sapporo, avec mise à jour en 2004 à Sydney. Ces quelques lignes font le point sur les éléments nouveaux liés à la classification actuelle et sur les éléments diagnostiques en découlant, en vue de retenir le diagnostic de syndrome des antiphospholipides de manière rigoureuse, et d'initier le traitement adéquat dans les différentes situations liées à ce syndrome. In current practice, the occurrence of thrombosis--venous or arterial--is not rare. Moreover, during the follow-up of pregnancies, gynecologists often have to deal with fetal losses of their patients. Up to which point can these events be considered as "ordinary"? When and on which criteria can we consider an antiphospholipid syndrome? Efforts have been put these last years to better codify the diagnosis of this syndrome, so much on the laboratory side as on the clinical side. With a view to standardize these elements, a first consensus conference took place in 1999 in Sapporo, with an update in 2004 in Sydney, that has recently been published. The goal of these lines is to focus on new elements connected to the actual classification and on the resulting diagnosis elements, with the aim of obtaining a diagnosis of antiphospholipid syndrome in a rigorous way, and to initiate the appropriate treatment in different situations linked to this syndrome

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Dopaminergic, serotonergic and noradrenergic nuclei form the trimonoamine modulating system (TMMS). This system modulates emotional/motivational activities mediated by the limbic circuitry, where glutamate is the major excitatory neurotransmitter. Two main concepts are the basis of this review. First, since 1950 and the discovery of the antipsychotic activity of the dopamine D2 receptor antagonist chlorpromazine, it appears that drugs that can modulate the TMMS possess therapeutic psychiatric properties. Second, the concept of glutamate/trimonoamine imbalance in the cortico-striato-thalamo-cortical loop that has been so successful in explaining the pathophysiology of Parkinson disease has been applied in the pathophysiology of schizophrenia. This review will focus on the complex interactions between the fast synaptic glutamatergic transmission and the TMMS in specific parts of the limbic lobe and we will try to link these interactions to some psychiatric disorders, mainly depression, schizophrenia and drug addiction.

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Objectives The purpose of this study is to assess short and long term changes in knowledge, attitudes, and skills among medical residents following a short course on cultural competency and to explore their perspectives on the experience. Methods Eighteen medical residents went through a short training programme comprised of two seminars lasting 30' and 60' respectively over two days. Three months later, we conducted three focus groups, with 17 residents to explore their thoughts, perspectives and feedback about the course. To measure changes over time, we carried out a quantitative sequential survey before the seminars, three days after, and three months later using the Multicultural Assessment Questionnaire. Results Residents expressed a wide variety of perspectives on the main themes related to the content of the training - culture, trialogue, stereotypes, status, epidemiology, history and geopolitics - and related to its organization - relevance, volume, timing, target audience, training tools, and working material. Using the MAQ, we observed a higher global performance score (n=16) at three days (median=38) compared to results before the training (median=33) revealing a median difference of 5.5 points (z=2.4, p=0.015). This difference was still present at three months (∆=4.5, z=2.4, p=0.018), mainly due to knowledge acquisition (∆=3) rather than attitudes (∆=0) or skills (∆=1). Conclusions Cross-cultural competence training not only brings awareness of multicultural issues but also helps participants understand their own cultures, perception of others and preconceived ideas. Physicians' education should however also focus on improving implementation of acquired knowledge in cross-cultural competence.

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Macrophage migration inhibitory factor (MIF) is a homotrimeric multifunctional proinflammatory cytokine that has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. Current therapeutic strategies for targeting MIF focus on developing inhibitors of its tautomerase activity or modulating its biological activities using anti-MIF neutralizing antibodies. Herein we report a new class of isothiocyanate (ITC)-based irreversible inhibitors of MIF. Modification by benzyl isothiocyanate (BITC) and related analogues occurred at the N-terminal catalytic proline residue without any effect on the oligomerization state of MIF. Different alkyl and arylalkyl ITCs modified MIF with nearly the same efficiency as BITC. To elucidate the mechanism of action, we performed detailed biochemical, biophysical, and structural studies to determine the effect of BITC and its analogues on the conformational state, quaternary structure, catalytic activity, receptor binding, and biological activity of MIF. Light scattering, analytical ultracentrifugation, and NMR studies on unmodified and ITC-modified MIF demonstrated that modification of Pro1 alters the tertiary, but not the secondary or quaternary, structure of the trimer without affecting its thermodynamic stability. BITC induced drastic effects on the tertiary structure of MIF, in particular residues that cluster around Pro1 and constitute the tautomerase active site. These changes in tertiary structure and the loss of catalytic activity translated into a reduction in MIF receptor binding activity, MIF-mediated glucocorticoid overriding, and MIF-induced Akt phosphorylation. Together, these findings highlight the role of tertiary structure in modulating the biochemical and biological activities of MIF and present new opportunities for modulating MIF biological activities in vivo.

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The first phase of this research involved an effort to identify the issues relevant to gaining a better understanding of the County Engineering profession. A related objective was to develop strategies to attract responsible, motivated and committed professionals to pursue County Engineering positions. In an era where a large percentage of County Engineers are reaching retirement age, the shrinking employment pool may eventually jeopardize the quality of secondary road systems not only in Iowa, but nationwide. As we move toward the 21st century, in an era of declining resources, it is likely that professional staff members in charge of secondary roads will find themselves working with less flexible budgets for the construction and maintenance of roads and bridges. It was important to understand the challenges presented to them, and the degree to which those challenges will demand greater expertise in prioritizing resource allocations for the rehabilitation and maintenance of the 10 million miles of county roads nationwide. Only after understanding what a county engineer is and what this person does will it become feasible for the profession to begin "selling itself", i.e., attracting a new generation of County Engineers. Reaching this objective involved examining the responsibilities, goals, and, sometimes, the frustrations experienced by those persons in charge of secondary road systems in the nine states that agreed to participate in the study. The second phase of this research involved addressing ways to counter the problems associated with the exodus of County Engineers who are reaching retirement age. Many of the questions asked of participants asked them to compare the advantages and disadvantages of public sector work with the private sector. Based on interviews with nearly 50 County Engineers and feedback from 268 who returned surveys for the research, issues relevant to the profession were analyzed and recommendations were made to the profession as it prepares to attract a new generation. It was concluded that both State and Regional Associations for County Engineers, and the National Association of County Engineers are most well-situated to present opportunities for continued professional development. This factor is appealing for those who are interested in competitive advantages as professionals. While salaries in the public sector may not be able to effectively compete with those offered by the private sector, it was concluded that this is only one factor of concern to those who are in the business of "public service". It was concluded, however, that Boards of Supervisors and their equivalents in other states will need to more clearly understand the value of the contributions made by County Engineers. Then the selling points the profession can hope to capitalize on can focus on the strength of state organizations and a strong national organization that act as clearinghouses of information and advocates for the profession, as well as anchors that provide opportunities for staying current on issues and technologies.

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Résumé: Valoriser le géopatrimoine par la médiation indirecte et la visualisation des objets géomorphologiques Le géopatrimoine regroupe des objets géologiques lato sensu auxquels certaines valeurs sont attribuées, en fonction de leur intérêt pour la science, de leur rareté, de leurs particularités culturelles ou écologiques, etc. Valoriser le géopatrimoine signifie avant tout faire partager cette approche aux non-spécialistes, en expliquant ce qui fait la valeur de ces objets. Cette valorisation peut s'effectuer, entre autres, sous la forme d'une activité touristique et contribuer ainsi au développement régional. Faire comprendre l'origine, la singularité et la valeur des formes du relief implique le recours à une communication éducative, désignée par le terme de médiation. Les implications de la dimension éducative du processus, comme la prise en compte des connaissances et attentes du public, la création d'un environnement favorable à l'apprentissage ou l'attractivité du contenu, sont souvent négligées. Du point de vue conceptuel, un modèle de la médiation indirecte (c'est-à-dire au moyen de supports médiatiques) a été proposé et appliqué au développement empirique de produits de médiation et à leur évaluation. Ce modèle ne garantit pas la réussite de la communication éducative, mais contribue à créer un cadre favorable au processus. De plus, plusieurs lignes directrices pour le choix du type de média et sa mise en forme ont été définies sur la base d'une compilation de résultats de la psychologie cognitive sur l'usage des médias pour l'apprentissage. Des méthodes qualitatives et quantitatives variées ont été mobilisées : enquêtes par questionnaire ex situ et in situ, auprès des visiteurs de géomorphosites de montagne, réalisation de médias interactifs testés ensuite auprès de divers publics (parcours enregistré, pré- et post-questionnaires) et entretiens collectifs. Les résultats obtenus éclairent divers aspects de la problématique. L'étude du public a montré, par exemple, que le géotourisme possède un réel public parmi les visiteurs des sites de montagnes : trois-quarts d'entre eux expriment de l'intérêt pour des explications sur la géologie et l'évolution du paysage. Cette thèse a exploré ces aspects liés au processus d'apprentissage en se focalisant sur les médias visuels, surtout interactifs. La plupart des médias visuels couramment utilisés en géomorphologie ont été considérés. Le développement de versions interactives de ces médias sous forme d'applications web a fourni un aperçu concret des possibilités des nouvelles technologies. Les utilisateurs apprécient en particulier a richesse du contenu, le haut degré d'interactivité et la variété de ces applications. De tels médias incitent à visiter le site naturel et semblent aussi répondre aux intérêts de publics variés. Abstract: Geoheritage promotion through non-personal interpretation and visualisation of geomorphological features Geoheritage concerns all geological features lato sensu to which some values are attributed, according to their scientific interest, their rarity, their cultural or ecological dimensions, etc. Geoheritage promotion implies sharing this point of view with non-specialists, explaining what gives value to those objects. Geotourism is one of the many ways to achieve geoheritage promotion, while contributing also to regional development. In order to make non-specialists understand the origin, the specificity and the value of landforms, educational communication is needed, that is called interpretation (French: médiation). This education dimension has several, and often neglected, implications, like taking into account public's knowledge and expectations, creating a favourable learning environment, attractive design, etc. From the conceptual point of view, a model for non-personal interpretation has been proposed and applied for the empirical development and for the assessment of interpretive products. This model does not guarantee success of educational communication, but help creating a favourable environment for this process. Moreover, some guidelines were defined from a compilation of several results of cognitive psychology on media use for learning. They guide the choice of the kind of media and its design. Several qualitative and quantitative methods were applied: survey questionnaires ex situ and in situ by mountain geomorphosites visitors, interactive medias developed and then tested by different kinds of users (with usertracking, pre- and post-survey questionnaires), group interviews. The results answered different aspects of the research questions. Visitor surveys revealed for example that geotourism could attract many visitors of mountain areas: three quarters of them say they are interested in getting explanations about geology and landscape (in particular its dynamic dimensions). This thesis examined those aspects with a focus on visual medias, both statics and interactive. Most of currently used medias in geomorphology were considered. Interactive versions of those medias were developed in web applications; they gave a concrete overview on the opportunities that new technologies offer. The content richness, the high interaction level and the diversity of the applications are the most liked aspects by the users. Such medias drive to visit the natural site and seem to correspond to the interests of various kinds of publics. Zusammenfassung: Aufwertung des erdwissenschaftlichen Erbes durch mediale Vermittlung und Visualisierung von geomorphologischen Objekten Das erdwissenschaftliche Erbe besteht aus geologischen Gegebenheiten lato sensu, denen entsprechend ihrer Bedeutung für die Wissenschaft, ihrer Seltenheit, ihrer kulturellen oder ökologischen Besonderheiten usw. bestimmte Werte zugeordnet werden. Das erdwissenschaftliche Erbe aufzuwerten bedeutet in erster Linie, diesen Ansatz Nichtspezialisten näher zu bringen, indem ihnen erklärt wird, was den Wert dieser Gegebenheiten ausmacht. Dies kann etwa im Rahmen eines touristischen Angebots geschehen und so die regionale Entwicklung unterstützen. Um Entstehung, Besonderheit und Wert von Geländeformen verständlich zu machen, wird eine pädagogische Kommunikationsform verwendet, die als mediale Vermittlung (franz. médiation) bezeichnet wird. Die Bedeutung der pädagogischen Dimension des Vermittlungsprozesses wie etwa der Einbezug des Wissens und der Erwartungen des Publikums, die Gestaltung eines positiven Lernklimas oder die Attraktivität des Inhalts wird oft vernachlässigt. Auf konzeptueller Ebene wurde ein Modell der indirekten Interpretation erarbeitet (d. h. anhand von Medien), das bei der empirischen Entwicklung der Interpretationsprodukte und ihrer Evaluation Anwendung fand. Dieses Modell garantiert zwar nicht den Erfolg der pädagogischen Kommunikation. Es trägt aber dazu bei, einen für den Prozess günstigen Kontext zu schaffen. Des Weiteren wurden mehrere Richtlinien für die Wahl des Medientyps und dessen Ausgestaltung anhand einer Zusammenstellung von Resultaten der kognitiven Psychologie über den Gebrauch von Medien in Lernprozessen definiert. Es wurden verschiedene qualitative und quantitative Methoden eingesetzt: Befragung mittels Fragebogen der Besucher von geomorphologischen Geotopen im Gebirge - ex situ und in situ -, Erarbeitung von interaktiven Medien, die anschliessend anhand verschiedener Zielgruppen gestestet wurden (Aufnahme des Besuchparcours, Vor- und Nachfragebögen) sowie kollektive Interviews. Die Ergebnisse geben Aufschluss zu verschiedenen Aspekten der Fragestellung. Die Befragung des Publikums hat zum Beispiel deutlich gemacht, dass der Geotourismus unter den Besuchern von Berggebieten tatsächlich auf eine Nachfrage stösst: drei Viertel von ihnen zeigen ein Interesse für Erläuterungen zur Geologie und der Landschaftsentwicklung. Die vorliegende Doktorarbeit hat die genannten Aspekte der Lernprozesse untersucht, wobei der Fokus auf visuellen, insbesondere interaktiven Medien lag. Die meisten gängigen visuellen Medien der Geomorphologie wurden berücksichtigt. Die Entwicklung von interaktiven Versionen dieser Medien in Form von Web-Anwendungen hat die Möglichkeiten der neuen Technologien veranschaulicht. Die Benutzer schätzten insbesondere die Vielfalt des Inhalts, die hohe Interaktivität und die Diversität dieser Anwendungen. Solche Medien laden dazu ein, ein Naturgebiet zu besuchen und scheinen den Interessen der verschiedenen Publikumsgruppen entgegenzukommen.

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Purpose: Despite the fundamental role of ecosystem goods and services in sustaining human activities, there is no harmonized and internationally agreed method for including them in life cycle assessment (LCA). The main goal of this study was to develop a globally applicable and spatially resolved method for assessing land-use impacts on the erosion regulation ecosystem service.Methods: Soil erosion depends much on location. Thus, unlike conventional LCA, the endpoint method was regionalized at the grid-cell level (5 arc-minutes, approximately 10×10 km2) to reflect the spatial conditions of the site. Spatially explicit characterization factors were not further aggregated at broader spatial scales. Results and discussion: Life cycle inventory data of topsoil and topsoil organic carbon (SOC) losses were interpreted at the endpoint level in terms of the ultimate damage to soil resources and ecosystem quality. Human health damages were excluded from the assessment. The method was tested on a case study of five three-year agricultural rotations, two of them with energy crops, grown in several locations in Spain. A large variation in soil and SOC losses was recorded in the inventory step, depending on climatic and edaphic conditions. The importance of using a spatially explicit model and characterization factors is shown in the case study.Conclusions and outlook: The regionalized assessment takes into account the differences in soil erosion-related environmental impacts caused by the great variability of soils. Taking this regionalized framework as the starting point, further research should focus on testing the applicability of the method trough the complete life cycle of a product and on determining an appropriate spatial scale at which to aggregate characterization factors, in order to deal with data gaps on location of processes, especially in the background system. Additional research should also focus on improving reliability of the method by quantifying and, insofar as it is possible, reducing uncertainty.

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La igualdad de oportunidades para las mujeres, como factor clave para avanzar en la consecución de calidad de vida preocupa hoy en día a la sociedad en general y alas instituciones en particular. Antes de la elaboración de programas de intervención social es necesario conocer las percepciones de las propias mujeres acerca de sus problemas y de sus necesidades. Siguiendo esta línea de pensamiento presentamos un trabajo empírico en el que analizamos las percepciones de las mujeres de la ciudad de Girona, centrándonos en dos aspectos de manera particular: la percepción de calidad de vida proporcionada por su ciudad y la percepción de desigualdad de oportunidades y/o de discriminación. Los principales resultados, obtenidos a partir de las respuestas a un cuestionario auto-administrado, y proporcionados por una muestra de mujeres seleccionadas aleatoriamente a partir de un muestreo estratificado geográficamente, indican que en general están satisfechas con su ciudad aunque detectamos las principales causas de insatisfacción. Por otra parte, tas principales fuentes de desigualdad se refieren al mundo laboral (menos salario por el mismo trabajo, dificultades de encontrar trabajo si tienen hijos o si son ya mayores), y en la actitud general de la sociedad en el sentido de tener que cumplir el papel que tradicionalmente se les ha asignado