986 resultados para Agonist-antagonist relationship


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Abstract Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.

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In this research we examined, by means of case studies, the mechanisms by which relationships can be managed and by which communication and cooperation can be enhanced in developing sustainable supply chains. The research was predicated on the contention that the development of a sustainable supply chain depends, in part, on the transfer of knowledge and capabilities from the larger players in the supply chain. A sustainable supply chain requires proactive relationship management and the development of an appropriate organisational culture, and trust. By legitimising individuals’ expectations of the type of culture which is appropriate to their company and empowering employees to address mismatches that may occur, a situation can be created whereby the collaborating organisations develop their competences symbiotically and so facilitate a sustainable supply chain. Effective supply chain management enhances organisation performance and competitiveness through the management of operations across organisational boundaries. Relational contracting approaches facilitate the exchange of information and knowledge and build capacity in the supply chain, thus enhancing its sustainability. Relationship management also provides the conditions necessary for the development of collaborative and cooperative relationships However, often subcontractors and suppliers are not empowered to attend project meetings or to have direct communication with project based staff. With this being a common phenomenon in the construction industry, one might ask: what are the barriers to implementation of relationship management through the supply chain? In other words, the problem addressed in this research is the engagement of the supply chain through relationship management.

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This study explored how meta-worry and intolerance of uncertainty relate to pathological worry, generalised anxiety, obsessive compulsive disorder, social phobia, and depression. University students (n = 253) completed a questionnaire battery. A series of regression analyses were conducted. The results indicated that meta-worry was associated with GAD, social phobia, obsessive compulsive, and depressive symptoms. Intolerance of uncertainty was related to GAD, social phobia, and obsessive compulsive symptoms, but not depressive symptoms. The importance of meta-worry and intolerance of uncertainty as predictors of pathological worry, GAD, social phobia, obsessive compulsive and depressive symptoms was also examined. Even though both factors significantly predicted the aforementioned symptoms, meta-worry emerged as a stronger predictor of GAD and obsessive compulsive symptoms than did intolerance of uncertainty. Intolerance of uncertainty, compared with meta-worry, appeared as a stronger predictor of social phobia symptoms. Findings emphasise the importance of addressing meta-worry and/or intolerance of uncertainty not only for the assessment and treatment of generalised anxiety disorder (GAD), but also obsessive compulsive disorder, social phobia, and depression.

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To date, research on P-O fit has focused heavily on the effect of P-O fit on individual and organisational outcomes. Few studies have attempted to explain how or why P-O fit leads to these outcomes. Meglino, Ravlin, and Adkins (1989) and Schein (1985) identified several intervening mechanisms for explaining fit-outcome relationships but only few of these explanations have been tested empirically (Cable & Edwards, 2004; Edwards & Cable, 2009; Kalliath, Bluedorn, & Strube, 1999). This thesis investigates role conflict, cognitive style and organisational justice as three potential mediating mechanisms in the relationship between P-O fit (defined as fit between personal and organisational values – value congruence or value fit) and outcomes including job satisfaction, job performance, service performance, affective commitment and continuance commitment. The study operationalised P-O fit using three measures: subjective fit, perceived fit and objective fit. The mediation model of subjective fit was tested using a Mplus analytical technique, while the mediation models of both perceived and objective fit were tested by modeling the difference between two scores (that is, between personal values and organisational values) using a polynomial regression and response surface analysis (Edwards, 1993). A survey of 558 mid-level managers from seven Brunei public sector organisations provided the data. Our results showed that the relationship between P-O fit and outcomes was partially mediated by organisational justice and cognitive style - for all the three measures of fit, while role conflict had no mediating effects. The findings from this research therefore have both theoretical and practical implications. This research contributes to the literature by combining these theoretical explanations for value congruence effects into one integrated model, and by providing evidence on the partial mediating effects of organisational justice and cognitive style. Future research needs to address and investigate other potential mechanisms by which value congruence affects individual and organisational outcomes. In addition, the study is considered to be the first to test these mediating roles for a value fit-outcomes relationship using three different measures of fit in a non-Western context.

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Many studies into construction procurement methods reveal evidence of a need to change the culture and attitude in the construction industry, transition from traditional adversarial relationships to cooperative and collaborative relationships. At the same time there is also increasing concern and discussion on alternative procurement methods, involving a movement away from traditional procurement systems. Relational contracting approaches, such as partnering and relationship management, are business strategies that align the objectives of clients, commercial participants and stakeholders. It provides a collaborative environment and a framework for all participants to adapt their behaviour to project objectives and allows for engagement of those subcontractors and suppliers down the supply chain. The efficacy of relationship management in the client and contractor groups is proven and well documented. However, the industry has a history of slow implementation of relational contracting down the supply chain. Furthermore, there exists little research on relationship management conducted in the supply chain context. This research aims to explore the association between relational contracting structures and processes and supply chain sustainability in the civil engineering construction industry. It endeavours to shed light on the practices and prerequisites for relationship management implementation success and for supply sustainability to develop. The research methodology is a triangulated approach based on Cheung.s (2006) earlier research where questionnaire survey, interviews and case studies were conducted. This new research includes a face-to-face questionnaire survey that was carried out with 100 professionals from 27 contracting organisations in Queensland from June 2008 to January 2009. A follow-up survey sub-questionnaire, further examining project participants. perspectives was sent to another group of professionals (as identified in the main questionnaire survey). Statistical analysis including multiple regression, correlation, principal component factor analysis and analysis of variance were used to identify the underlying dimensions and test the relationships among variables. Interviews and case studies were conducted to assist in providing a deeper understanding as well as explaining findings of the quantitative study. The qualitative approaches also gave the opportunity to critique and validate the research findings. This research presents the implementation of relationship management from the contractor.s perspective. Findings show that the adaption of relational contracting approach in the supply chain is found to be limited; contractors still prefer to keep the suppliers and subcontractors at arm.s length. This research shows that the degree of match and mismatch between organisational structuring and organisational process has an impact on staff.s commitment level and performance effectiveness. Key issues affecting performance effectiveness and relationship effectiveness include total influence between parties, access to information, personal acquaintance, communication process, risk identification, timely problem solving and commercial framework. Findings also indicate that alliance and Early Contractor Involvement (ECI) projects achieve higher performance effectiveness at both short-term and long-term levels compared to projects with either no or partial relationship management adopted.

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The field of bereavement and grief has been expanding to recognise the potential for growth following the loss of a loved one. This study sought to examine the effect of the relationship to the deceased and perceptions of the severity of the trauma on dimensions of posttraumatic growth. Participants were 146 people who had lost either: a) a first degree relative, b) a second degree relative, or c) a non-related friend. Results demonstrated that both severity and the relationship to the bereaved differentiate posttraumatic growth outcomes. For example, participants who had lost a first degree relative reported higher levels of growth than those who had lost a second degree relative. Consistent with previous research in general trauma populations, the more severe the loss was rated, the higher the levels of growth. Implications for practice are discussed.

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Small business has been shown to contribute significantly to a nation’s economic development. Small business owners typically confront challenges, uncertainty, and risks while operating new businesses. Franchising has become a way to minimize the risks of small business management (Chiou et al., 2004); however, a franchise system is not a guarantee of business success (Lee and Karkovista, 2001). A poor franchising relationship between franchisors and franchisees can result in franchise failure, such as termination and closure, or franchisee exit (Frazer and Winzar, 2005).

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Obesity has been widely regarded as a public health concern because of its adverse impact on individuals’ health. Systematic reviews have been published in examining the effect of obesity on depression, but with major emphasis on general obesity as measured by the body mass index. Despite a stronger effect of abdominal obesity on individuals’ physical health outcomes, to our best knowledge, no systematic review was undertaken with regard to the relationship between abdominal obesity and depression. This paper reports the results of a systematic review and meta-analysis of cross-sectional studies examining the relationship between abdominal obesity and depression in a general population. Multiple electronic databases were searched until the end of September 2009. 15 articles were systematically reviewed and meta-analyzed. The analysis showed that the odds ratio of having depression for individuals with abdominal obesity was 1.38 (95% CI, 1.22–1.57) as compared to those who are not obese. Furthermore, it was found that this relationship did not vary with potential confounders including gender, age, measurement of depression and abdominal obesity, and study quality.