Although worry is a common source of distress in children and adolescents, relatively few studies have focused on understanding worry in both of these age groups (Cartwright-Hatton, 2006). This area of research is of particular relevance, as understanding worry in youth may have implications for the assessment and treatment of adolescent worry and other anxiety-related difficulties. Consequently, the focuses of this study were to examine the validity and relevance of metacognitive measures of worry in an adolescent sample, to determine the degree to which metacognitive worry is associated with worry in adolescents, and to examine the potential association between adolescent metacognitive worry and intolerance of uncertainty, another cognitive variable hypothesized to be associated with worry, in an adolescent sample. A total of 175 adolescents between the ages of 11-17 were recruited from local middle and high schools to complete a series of self-report measures, which included the following: the Metacognitive Questionnaire for Children, the Meta-Worry Questionnaire, the Intolerance of Uncertainty Scale for Children, the Penn State Worry Questionnaire for Children, and the Spence Children‘s Anxiety Scale. The findings of this study suggest that metacognition may play a role in the development and maintenance of excessive worry and related generalized anxiety disorder symptoms in adolescents. Further, current findings provide support for the combined influence of metacognitive beliefs and intolerance of uncertainty in the development and maintenance of worry.

Der Beitrag untersucht auf der Grundlage neuer primärärztlicher Befunde die Versorgungsqualität bei der hinsichtlich Chronizität und Arbeitsausfall schwerwiegendsten Angsterkrankung, der Generalisierten Angststörung. Neben einer knappen Einführung in das Störungsbild werden die an über 20 000 Patienten in 558 Hausarztpraxen gewonnenen Kernbefunde der GAD-P-Studie (Generalisierte Angst und Depression in der Primärärztlichen Versorgung) zusammengefasst und Ansatzpunkte zur Verbesserung der Versorgungsqualität dieses selten adäquat behandelten Störungsbildes diskutiert. Insbesondere wird auf die zentrale Bedeutung einer sichereren diagnostischen Erkennung als Voraussetzung für therapeutische Verbesserungen hingewiesen. In Ergänzung zur Verbesserung bestehender Weiterbildungsangebote wird auf Arzt- und Patientenebene der breitere Einsatz bestehender Screeningverfahren, die Nutzung krankheitsspezifischer Patientenratgeber, sowie eine breitere Öffentlichkeitsarbeit zur Information über dieses bislang vernachlässigte, häufig chronisch verlaufende Krankheitsbild empfohlen. / Based on new empirical findings in a large-scale primary care study, the quality of care for the most chronic and debilitating anxiety problem, generalised anxiety disorder, is examined. Following a brief introduction of this disorder, the core findings of the GAD-P study (generalised anxiety and depression in primary care) with more than 20,000 patients of 558 family doctor practices are summarised and measures to improve the quality of care of patients with generalised anxiety disorder, a disorder which is rarely adequately treated, are discussed. This paper particularly emphasises the standard use of time-efficient diagnostic screening instruments, because improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to increase awareness of this disorder as well as patient education materials to improve compliance and to enhance treatment outcome effects are highlighted.

Comparing the efficacy of different treatments in psychiatry is difficult for many reasons, even when they are investigated in `head-to-head' studies. A consensus meeting was, therefore, held to produce best practice guidelines for such studies. This article presents the conclusions of this consensus and illustrates it using published data in the field of antidepressant treatment of generalized anxiety disorder.

The purpose of this thesis project was to examine the effects of chronic alcohol on the excitability and molecular adaptation of GABA neurons of the ventral tegmental area (VTA). GABA neurons are of interest with regards to ethanol intoxication, reinforcement, and dependence due to their widespread distribution and connectivity to mesocorticolimbic dopamine (DA) neurons implicated in alcohol reward and addiction. Since we have previously shown adaptation of VTA GABA neuron firing rate to chronic ethanol (Gallegos, Criado et al. 1999) and suppression of gap-junction (GJ) mediated coupling between these neurons by acute ethanol (Stobbs, Ohran et al. 2004), we wanted to further characterize the effects of chronic ethanol on VTA GABA neuron excitability, electrical coupling and molecular adaptation. In particular, we analyzed the GJ mediated coupling and protein regulation of VTA GABA neurons following a three week period of continuous ethanol exposure via liquid diet. Although some animals showed tolerance, there was no significant tolerance to ethanol inhibition of GJ-mediated electrical coupling. In addition, we were able to characterize differences in mRNA expression levels for the DA synthesizing enzyme tyrosine hydroxylase (TH), the DA D2 receptor and the NMDAR2B receptor subunit in DA versus GABA neurons, all three of which were expressed at higher levels in DA neurons. We also determined the effects of chronic ethanol on mRNA levels of these same proteins as well as μ-opioid receptors (μORs) and connexin-36 (Cx36) GJs. Most significantly, we found a down-regulation of the DA D2 receptor, confirming that molecular modification occurs in these VTA GABA neurons with chronic alcohol. While we reject our hypothesis that acute ethanol inhibition of VTA GABA neuron electrical coupling would undergo tolerance to chronic ethanol in these non-dependent rats, which was the focus of this thesis, it remains to be determined if tolerance to chronic ethanol might be obtained in ethanol-dependent rats.

Type 1 diabetes affects a person’s life on many levels in terms of quality of life, health, and socioeconomic costs both for the patients but also their families. As of now there is no therapy that targets the underlying mechanism of the disease. Intralymphatic administration of Diamyd® is being evaluated in a phase IIb clinical trial, DIAGNODE-2. The aim was to examine if the intralymphatic administration is feasible for both patients and medical professionals, and to identify any aspects of the procedure that can be improved. This feasibility study is based on interviews and answers received from questionnaires. The medical professionals that were selected were radiologists and study nurses that are involved in the DIAGNODE-2 trial. The radiologists were the prime focus and were thus interviewed through face-to-face/skype or phone and answered a questionnaire. Study nurses, having more contact with the patient, answered a survey in order to gain additional insights into the patient perspective.   The results show that the radiologists has a positive view towards the administration procedure, which was described as easy and safe. According to the study nurses the patients accept the procedure and they agreed that the patients understand the injection procedure once they received the information. In terms of the emotional state of the patients they were a bit nervous, but they became calmer after receiving the first injection. Based on the above-mentioned findings the intralymphatic injection procedure is described as feasible and has the potential to become a part of the standard clinical routine.

The fetal lung epithelium secretes fluid into the potential pulmonary air-spaces by actively transporting chloride (Cl¯) into the lung lumen. This Cl¯-driven fluid secretion declines with the progression of lung development. Recent studies demonstrate that the A-type γ-aminobutyric acid receptor (GABAAR), a Cl¯ channel, and glutamic acid decarboxylase (GAD65/67), key GABA-synthesizing enzymes, are expressed in adult pulmonary epithelial cells (ECs), forming an autocrine GABAAR signaling system. My thesis study revealed that GABAAR π- and β2- subunits are expressed in high levels in the fetal rat lung epithelium and decline at birth, consistent with pattern of fluid secretion. Immunohistochemistry showed distinct profiles of expression for GABAAR subunits and GAD65/67. Treatment of alveolar ECs with dexamethasone reduced the GABAAR π-subunit expression. These results suggest that the GABAAR signaling in the fetal pulmonary epithelium is developmentally regulated and the GABAAR expression and GABAAR-mediated Cl¯ secretion in pulmonary ECs may be regulated by glucosteroids.

The fetal lung epithelium secretes fluid into the potential pulmonary air-spaces by actively transporting chloride (Cl¯) into the lung lumen. This Cl¯-driven fluid secretion declines with the progression of lung development. Recent studies demonstrate that the A-type γ-aminobutyric acid receptor (GABAAR), a Cl¯ channel, and glutamic acid decarboxylase (GAD65/67), key GABA-synthesizing enzymes, are expressed in adult pulmonary epithelial cells (ECs), forming an autocrine GABAAR signaling system. My thesis study revealed that GABAAR π- and β2- subunits are expressed in high levels in the fetal rat lung epithelium and decline at birth, consistent with pattern of fluid secretion. Immunohistochemistry showed distinct profiles of expression for GABAAR subunits and GAD65/67. Treatment of alveolar ECs with dexamethasone reduced the GABAAR π-subunit expression. These results suggest that the GABAAR signaling in the fetal pulmonary epithelium is developmentally regulated and the GABAAR expression and GABAAR-mediated Cl¯ secretion in pulmonary ECs may be regulated by glucosteroids.

The nervous system, including the brain, is the most sophisticated organ in the mammalian body. In such a complex network, neuron-glial interaction is essential and controls most developmental processes, such as stem cell fate determination, migration, differentiation, synapse formation, ensheathment and myelination. Many of these events are critical for the developmental process and small errors can lead to growth retardation, malformation or disease. The understanding of the normal progress of nervous system development is fundamental and will help the discovery of new treatments for disease. This thesis discusses three types of neuron-glia interactions at different developmental stages; neural stem/progenitor cell (NSPC) differentiation, building and maintaining the structure of the sciatic nerve, and myelin formation. In Paper I we show that NSPCs, based upon their morphology and expression of specific protein markers, have the capacity to differentiate into cells of either the peripheral nervous system (PNS) or enteric nervous system (ENS) when grown with PNS or ENS primary cell cultures, or fed with conditioned medium from these. This indicates that soluble factors secreted from the PNS or ENS cultures are important for stem cell differentiation and fate determination. The adhesion protein neuronal cadherin (N-cadherin) is implicated in migration, differentiation and nerve outgrowth in the developing PNS. In Paper II N-cadherin was exclusively found in ensheathing glia (nonmyelinating Schwann cells, satellite cells and enteric glia) in contact with each other or with axons. Functional blocking of N-cadherin in dissociated fetal dorsal root ganglia (DRG) cultures led to a decrease in attachment between Schwann cells. N-cadherin-mediated adhesion of nonmyelinating Schwann cells may be important in encapsulating thin calibre axons and provide support to myelinating Schwann cells. In Paper III the inhibitory gamma aminobutyric acid (GABA) and GABAB receptors were studied in the Schwann cell of the adult sciatic nerve and DRG cultures. GABAB receptors were primarily expressed in nonmyelinating Schwann cells and protein levels decreased during development and myelination. Blocking the GABAB receptor in long-term DRG cultures led to decreased levels of mRNA markers for myelin. These results indicate that the GABA and GABAB receptors may be involved in Schwann cell myelination.

The mood-as-input model of perseverative worrying is a conceptual model that has been developed to explain the perseverative aspect of worry inherent in Generalized Anxiety Disorder (GAD) (Davey, 2006a). The first objective of this study was to provide additional empirical support for the mood-as-input model of perseverative worrying. A second objective of this study was to investigate the association between perseverative worry and GAD symptoms. The final objective of this study was to assist in generating a comprehensive model of worry that incorporated unique predictors of GAD. Results indicated that unique variables, such as ‘as many as can’ stop rules and beliefs about worry, were weak predictors of perseveration, but were significant predictors of worry and GAD symptoms. Therefore, these variables may still contribute to the processes inherent in perseverative worry. Results also indicated that the catastrophic interview was an overall weak predictor of worry and GAD symptoms, suggesting that the catastrophic interview might not be the most suitable measure of perseverative worry. In summary, the current study provides mixed support for the mood-as-input model of perseverative worrying. Future research should further examine the relationship of the catastrophic interview and perseverative worry. In addition, future studies should include measures of GAD symptoms as an outcome variable when studying the mood-as-input model. Keywords: worry, GAD, catastrophic interview, meta-cognition, stop rules

[ES] El presente trabajo de investigación se centra en indagar la interrelación entre la interculturalidad y desarrollo local, factores de su desencuentro en los Gobiernos Autónomos Descentralizados de Otavalo y Cotacachi a fin de incidir en una política pública en beneficio de la población. La pregunta central que conduce la investigación es si el desencuentro intercultural incide en la coexistencia de la discriminación racial y evita el desarrollo local en los cantones de Otavalo y Cotacachi pertenecientes a la provincia de Imbabura. Así como si Otavalo y Cotacachi son unas verdaderas ciudades interculturales inclusivas, verdaderos pueblos de diálogo y convivencia intercultural con respecto a los preceptos constitucionales. Para responder a estas preguntas se procesaron las siguientes fuentes de información: encuestas aplicadas a la ciudadanía de los cantones, objeto de estudio, y entrevistas realizadas a los alcaldes y directivos de los dos municipios. La estrategia metodológica de la investigación es cualitativa, no obstante, contó con una fase de análisis cuantitativo a partir del procesamiento de fuente de datos levantados en el 2019-2020: a la población, encuestas a ciudadanos y ciudadanas residentes en los cantones de Cotacachi y Otavalo. La fase cuantitativa corresponde al procesamiento de las bases de datos citados, cuyos resultados fueron tratados de manera descriptiva a fin de producir una síntesis analítica y representación gráfica de los datos observados, productos de la investigación. Las variables consideradas tienen relación con la gestión de los Gobiernos Autónomos Descentralizados municipales (GAD) para el desarrollo local desde la perspectiva de relación intercultural. Se parte del mandato constitucional a través de la Carta Magna de la República del Ecuador y la normativa específica que guía el quehacer de los GAD locales como el Código Orgánico de Organización Territorial (COOTAD). Dentro del recorrido teórico de la presente investigación se considera la concepción de Catherine Walsh sobre la definición de interculturalidad y la posición sumada de Enrique Ayala Mora, historiador ecuatoriano que coincide en su concepción. Sen (2000) establece como un elemento fundamental para lograr el desarrollo a la libertad del individuo, libertad asumida desde la visión de los derechos humanos y la libertad política, la cual está soslayada y utilizada únicamente en la retórica dominante. Se sustenta además en la base de la teoría del desarrollo endógeno, que se lo concibe como un fenómeno integral, la unión de ideas y supuestos que articulan los diferentes conceptos que se asocian para el desarrollo desde lo local o del territorio, abarcando varias dimensiones de las sociedades como la económica, sociopolítica, cultural, ambiental, institucional, cultural, y simbólica (Romero, 2001). Como conclusión se podría afirmar que el desencuentro intercultural, incide directamente en la coexistencia de la discriminación racial y evita el desarrollo local en los cantones de Otavalo y Cotacachi. El 57,7 % de la población encuestada de Otavalo y el 60 % de Cotacachi reconoce que hay un desencuentro intercultural que impiden aceptar la convivencia en la diversidad y el desarrollo. El 55,2 % de las encuestas aplicadas en Otavalo afirma que persiste el racismo y discriminación a la etnia indígena; el 50,4 % opinan que existe racismo de la población indígena a la mestiza, el 84,50 % consideran que existen espacios específicos para la población mestiza y la población indígena. Asimismo, el 77,6 % de la población cotacachense encuestada opina que persiste la discriminación étnica de doble vía, admite la existencia de espacios diferenciados específicos para mestizos e indígena. La gestión municipal, la gobernanza de los GAD de Otavalo y Cotacachi, no han aportado a la gestión pública intercultural. No cuentan con un soporte de ordenanzas municipales y políticas públicas que fomenten y fortalezcan la interculturalidad. / [CA] Aquest treball d’investigació es centra en la recerca de la interrelació entre la interculturalitat i el desenvolupament local, factors de desencontre entre els Goberns Autónoms Descentralitzats de Otavalo i Cotacachi amb la finalitat de incidir en una política pública en benefici de la población. El interrogant que condueix la investigación es si el desencontre intercultural incideix a la coexisténcia de la discriminiació racial y evita el desenvolupamente als cantons de Otavalo i Cotacachi que pertanyen a la provincia de Imbabura. Així com si Otavalo i Cotacachi son vertaderes ciutats interculturals inclusive, vertaders pobles de diáleg i convivencia intercultural respecte al que fa als preceptes constitucionals. Per a respondre a aquestes questions, es processaren les seguents fonts d’informació: encuestes aplicades a la ciutadanía dels cantons objetcte d’estudi i entrevistes realitzadaes als alcaldes i directius del dos municipis. L estrategia metodológica de l’investigació és cuaitativa. No obstant, va contar amb una fase d’análisi cuantitatiu des del processament de fonts de dades en el 2019-2020. A la población, enquestes a ciutadans i ciutadanes residents als cantons de Cotacachi i Otavalo. La fase cuantitativa correspon al processament de les bases de dades citats, dels quals, els resutats van ser tractats de manera descriptiva amb la finalitat de produir (con dos puntitos la i) una síntesi analítica i representación gráfica de les dades observades, productes de la investigación. Les variables considerades tenen rel.lació amb la gestió dels Goberns Autónoms Descentralitzats Municipals (GAD) per al desenvolupament des de la perspectiva de rel.lació interculturla. El punt de partida és el mandato constitucional a través de la Carta Magna de República de l’Equador i la normativa específica que guía el que ha de fer els GADs locals com el Código Orgánico de Organización Territorial (COOTAD). Dins del recorregut teóric d’aquesta investigación es considera la concepció de Catherine Walsh sobre la definición de interculturalitat i el posicionament sumat de Enrique Ayala Mora, historiador equatoriá que coincideix amn la concepció de Walsh. Sen (2000) estableix com a element fonamental per a lograr el desenvolupament la llibertat de l’individu, llibertat assumida des de la visió dels Drets Humans y la llibertat política, la qual está i utilitzada només a la retórica dominant. A més a més, es fonamenta a la base de la teoría del desenvolupament ? Que es concebut com a fenómeno integral, la unió d’idees i suposts que articulen els diferents concepts que son associats al desenvolupament des de el que és local o del territorio, ‘' varies dimensions de les societats com pot ser la económica, la sociopolítica, cultural, ambiental, institucional i simbólica (Romero, 2001) Com a conclusió, es pot afirmar que el desencontre intercultutal incideix directament a la coexisténcia de la discriminación racial i evita el desenvolupament als cantons Otavalo i Cotacachi. El 57% de la población enquestada de Otavalo i el 60% de Cotacachi reconeix que hi ha un desencontre intercultural que impedeix la convivencia a la diversitat i el desenvolupament. El 55%,2 % de les enquestes aplicades a Otavalo afirmen que persiteix el racismo i la discriminación per part de la etnia indígena a la mestissa, el 84%,50 considera que hi han espais específics per a la población mestissa i la población indígena. Tanmateix, el 77,6% de la población de Cotacachi enquestada opina que persiteix la discriminación étnica de doble vía, admiteix a existencia de espais diferenciats per als mestissos i indigenes. La gestió municipal, el governament dels GADS de Otavalo i Cotacachi no han aportat res a la gestió pública intercultutal. A més a més, no conten amb el soport de les ordenanzes municipals i les polítiques publiques que fomente i fasan més forta la interculturalitat. / [EN] This research work focuses on investigating the interrelation between interculturality and local development, factors of their disagreement in the decentralized autonomous governments of Otavalo and Cotacachi in order to influence a public policy for the benefit of the population, the central question that leads the investigation is yes; Does the intercultural disagreement affect the coexistence of racial discrimination and prevent local development in the Cantons of Otavalo and Cotacachi belonging to the Province of Imbabura? as well as, Could it be that Otavalo and Cotacachi are true inclusive intercultural cities, true peoples of dialogue and intercultural coexistence with respect to constitutional precepts? To answer these questions, the following sources of information were processed: surveys applied to the citizens of the cantons under study, and interviews with the mayors and directors of the two municipalities. The methodological strategy of the research is qualitative, however, It had a quantitative analysis phase from the processing of data sources collected in 2019-2020: to the population, surveys of citizens and citizens residing in the Cantons of Cotacachi and Otavalo. The quantitative phase corresponds to the processing of the aforementioned databases, whose results were treated in a descriptive way in order to produce an analytical synthesis and graphic representation of the observed data, products of the research. The variables considered are related to the management of the Municipal Decentralized Autonomous Governments (GAD) for local development from the perspective of intercultural relations. For which it starts from the constitutional mandate through the Magna Carta of the Republic of Ecuador and specific regulations that guide the work of the Decentralized Autonomous Local Governments such as the Organic Code of Territorial Organization (COOTAD), in addition to considering within the route theoretical of the present investigation the conception of Catherine Walsh on the definition of interculturality, and the combined position of Ayala Mora, Ecuadorian historian that coincide in their conception, and the perspective of Sen (2000), which he considers as a fundamental element to achieve the development to the freedom of the individual, freedom assumed from the vision of human rights and political freedom, which is ignored and used only in the dominant rhetoric. It is also based on the Endogenous Development Theory base, which is conceived as an integral phenomenon, the union of ideas and assumptions that articulate the different concepts that are associated for development from the local or territorial level, encompassing various dimensions of societies. such as the economic, socio-political, cultural, environmental, institutional, cultural, and symbolic (Romero 2001) As a conclusion, it could be stated that the intercultural disagreement directly affects the coexistence of racial discrimination and prevents local development in the Cantons of Otavalo and Cotacachi belonging to the Province of Imbabura; 57.7% of the surveyed population from Otavalo and 60% from Cotacachi recognize that there is an intercultural disagreement that prevents accepting coexistence in diversity, and development 55.2% of the surveys applied in Otavalo affirm that racism and discrimination against the indigenous ethnic group persist, 50.4% believe that there is racism from the indigenous population to the mestizo, 84.50% consider that there are spaces specific for the mestizo population and the indigenous population. Likewise, 77.6% of the surveyed population of the Cotacachi Canton, believes that two-way ethnic discrimination persists, admits the existence of specific differentiated spaces for mestizos and indigenous people, Municipal management, the governance of the decentralized Autonomous Governments of the Municipalities of Otavalo and Cotacachi, have not contributed to intercultural public management. The decentralized Autonomous Governments under study do not have the support of municipal ordinances and public policies that promote and strengthen interculturality. In such circumstances, it could not be said that Otavalo and Cotacachi are truly inclusive intercultural cities, true peoples of dialogue and intercultural coexistence with respect to the constitutional precepts that lead to a harmonious coexistence that favors local development. / Hermoza Vinueza, MM. (2022). Interculturalidad y desarrollo local en los gobiernos autónomos descentralizados de OTavalo y Cotacachi de la provincia de Imbabura, Ecuador [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181686 / TESIS