Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.

Standard errors of fitted component means of normal mixtures

In this paper use consider the problem of providing standard errors of the component means in normal mixture models fitted to univariate or multivariate data by maximum likelihood via the EM algorithm. Two methods of estimation of the standard errors are considered: the standard information-based method and the computationally-intensive bootstrap method. They are compared empirically by their application to three real data sets and by a small-scale Monte Carlo experiment.

Small volume resuscitation with 3% hypertonic saline solution decrease inflammatory response and attenuates end organ damage after controlled hemorrhagic shock

BACKGROUND: Recently, studies have been conducted examining the efficacy of 3% hypertonic saline solution (HS) for the treatment of traumatic brain injury; however, few studies have analyzed the effects of 3% hemorrhagic shock during hemorrhagic shock. The aim of this study was to test the potential immunomodulatory benefits of 3% hemorrhagic shock resuscitation over standard fluid resuscitation. METHODS: Wistar rats were bled to a mean arterial pressure of 35 mm Hg and then randomized into 3 groups: those treated with lactated Ringer`s solution (LR; 33 mL/kg, n = 7), 3% HS (10 mL/kg, n = 7), and 7.5% HS (4 mL/kg, n = 7). Half of the extracted blood was reinfused after fluid resuscitation. Animals that did not undergo shock served as controls (n = 5). Four hours after hemorrhagic shock, blood was collected for the evaluation of tumor necrosis factor-a and interleukin-6 by enzyme immunoassay. Lung and intestinal samples were obtained for histopathologic analysis. RESULTS: Animals in the HS groups had significantly higher mean arterial pressure than those in the LR group 1 hour after treatment. Osmolarity and sodium levels were markedly elevated in the HS groups. Tumor necrosis factor-alpha and interleukin-6 levels were similar between the control and HS groups but significantly higher in the LR group (P < .05). The lung injury score was significantly higher in the LR group compared with the 7.5% HS and 3% HS groups (5.7 +/- 0.7, 2.1 +/- 0.4, and 2.7 +/- 0.5, respectively). Intestinal injury was attenuated in the 7.5% HS and 3% HS groups compared with the LR group (2.0 +/- 0.6, 2.3 +/- 0.4, and 5.9 +/- 0.6, respectively). CONCLUSIONS: A small-volume resuscitation strategy modulates the inflammatory response and decreases end-organ damage after HS. Three percent HS provides immunomodulatory and metabolic effects similar to those observed with conventional concentrations of HS. (C) 2009 Elsevier Inc. All rights reserved.

Local dispersion of the Eucalyptus leaf beetle Chrysophtharta bimaculata (Coleoptera: Chrysomelidae), and implications for forest protection

1. Chrysophtharta bimaculata is a native chrysomelid species that can cause chronic defoliation of plantation and regrowth Eucalyptus forests in Tasmania, Australia. Knowledge of the dispersion pattern of C. bimaculata was needed in order to assess the efficiency of an integrated pest management (IPM) programme currently used for its control. 2. Using data from yellow flight traps, local populations of C. bimaculata adults were monitored over a season at spatial scales relevant to commercial forestry: within a 50-ha operational management unit (a forestry 'coupe') and between coupes. In addition, oviposition was monitored over a season at a subset of the between-coupe sites. 3. Dispersion indices (Taylor's Power Law and Iwao's Mean Crowding regression method) demonstrated that C. bimaculata adults were spatially aggregated within and between coupes, although the number of egg-batches laid at the between-coupe scale was uniform. Spatial autocorrelation analysis showed that trap-catches at the within-coupe level were similar (positively autocorrelated) to a radius distance of approximately 110 m, and then dissimilar (negatively autocorrelated) at approximately 250 m. At the between-coupe scale, no repeatable spatial autocorrelation patterns were observed. 4. For any individual site, rapid changes in beetle density were observed to be associated with loosely aggregated flights of beetles into and out of that site. Peak adult catches (> the weekly mean plus standard deviation trap-catch) for a site occurred for a period of 2.0 +/- 0.22 weeks at a time (n = 37), with normally only one or two peaks per site per season. Peak oviposition events for a site occurred on average 1.4 +/- 0.11 times per season and lasted 1.5 +/- 0.12 weeks. 5. Analysis of an extensive data set (n = 417) demonstrated that adult abundance at a site was positively correlated with egg density, but negatively correlated with tree damage (caused by conspecifics) and the presence of conspecific larvae. There was no relationship between adult abundance and a visual estimate of the amount of young foliage on trees. 6. Adults of C. bimaculata are show n to occur in relatively small, mobile aggregations. This means that pest surveys must be both regular (less than 2 weeks apart) and intensive (with sampling points no more than 150 m apart) if beetle populations are to be monitored with confidence. Further refinement of the current IPM strategy must recognize the problems posed by this temporal and spatial patchiness, particularly with regard to the use of biological insecticides, such as Bacillus thuringiensis, for which only a very short operational window exists.

Transdermal Pharmacology of Small Molecule Cyclic C5a Antagonists

Overproduction or underregulation of the proinflammatory complement component C5a has been implicated in numerous immune and inflammatory conditions. Therefore, targeting the C5a receptor (C5aR) has become an innovative strategy for antiinflammatory drug development. The novel cyclic peptide C5aR antagonist, AcF-[OP(D-Cha)WR] (PMX53), attenuates injury in numerous animal models of inflammation following intravenous, subcutaneous, intraperitoneal, and oral administration. In the present study the transdermal pharmacology of PMX53 and three analogs designed with increased lipophilicity, hydrocinnamate-[OP(D-Cha)WCit] (PMX200), AcF-[OP(D-Cha)WCit] (PMX201) and hydrocinnamate-[OP(D-Cha)WR] (PMX205), have been examined in order to assess their transdermal permeability and inhibitory effect on C5a-mediated lipopolysaccharide (LPS)-induced systemic responses. In the rat, PMX53, PMX201, and PMX205, were bioavailable following topical dermal administration (10 mg/50 cm(2) site/rat). All analogs functionally antagonized neutropenia and hypotension induced by systemic challenge with LPS (I mg/kg i.v.). Interestingly, PMX200 attenuated LPS-induced neutropenia more effectively than other analogs, despite undetectable (< 5 ng/ml) circulating levels following topical administration. In conclusion, we have demonstrated that cyclic peptide C5aR antagonists can penetrate transdermally sufficiently to have systemic effects. However, increasing lipophilicity in these compounds did not result in increased blood levels. Nonetheless, topical application of C5aR antagonists produced circulating levels of the drugs that antagonized the LPS-induced systemic responses of neutropenia and hypotension. This suggests that these small-molecule C5aR antagonists may be developed for topical administration for the treatment of local and systemic inflammatory conditions in the human and veterinary pharmaceutical markets.

Residents’ perceptions on impacts of hosting the “Guimarães 2012 European Capital of Culture”: comparisons of the pre-and post-2012 ECOC

The nomination of Guimarães, a small city located in the northwest of Portugal, as European capital of culture (ECOC) in 2012 raised great expectations in the local community towards its socio-economic and cultural benefits. As noted by various authors, namely Kim and Petrick (2005), Kim, Gursoy and Lee (2006) and Gursoy, Chi, Ai and Chen (2011), residents tend to have high expectations about the benefits of hosting a mega-event, although they tend to recognize that some costs will result from it. Therefore, the present research was designed to examine the Guimarães residents’ perceptions on the impacts of the 2012 European capital of culture (2012 ECOC) on the city and the municipality of Guimarães before and after the mega-event and the differences found between the two time periods.

Linking strategy and the knowledge of the firm

Discovering the ways through which firms develop and maintain competitive advantage is a central research stream in management theory. The objective of this paper is to present a contribution to the discussion of the knowledge of the firm as a source of competitive advantage. The paper states that a firm's success is a consequence of its ability in the continuous development of core competencies that will sustain its competitiveness over time. Core competencies are understood as the sets of knowledge that differentiate a company strategically. The firm must discover, develop, share and update the knowledge that sustains the present and future core competencies. Knowledge management, through processes of knowledge creation and integration, is one way of doing this.

How middle managers contribute to strategy formation process: connection of strategy processes and strategy practices

The role of middle management is essential when managing integrative and emergent strategy formation processes. We stand out the importance of its role connecting micro and macro organizational level offering a very important contribution when examining the strategy-as-practice perspective and integrative strategy formation process. The main goal of this research is to analyse the relationship between the integrative strategy formation process and the roles of middle management under the strategy-as-practice perspective. To check it out we adopted a qualitative methodology droving a case analysis in a Spanish University. Data was collected by means of personal interviews with members of different levels of the Institution, documents analysis and direct observation. In advance of some results we find out that the University develops an integrative strategy formation process and confers to middle management an important role extended all over the organization.

Competitiveness of tourist destinations: the study of 65 key destinations for the development of regional tourism

Tourism has reached world importance in the economy. The competition in tourism has intensified between destinations, whether the destinations are cities, regions or countries. In this sense, the evaluation of the tourism competitiveness of these destinations may be helpful in planning and prioritizing actions that will benefit the industry. This article discusses the concept of competitiveness by the multidimensional view of performance, efficiency and unit analysis. Using the theoretical framework lifted, this article shows the 'Study on the competitiveness of the 65 destinations inducers of regional tourism development' prepared by the Tourism Ministry, the Brazilian Support Service to Micro and Small Enterprises (Sebrae) and Getulio Vargas Foundation (FGV), its assumptions that guided this study as well its methodological aspects. Based on this methodology, it was carried out a diagnosis of these 65 destinations selected by the Brazilian Ministry of Tourism to be inducers of tourism in their respective regions. The result of competitiveness reached by these 65 inductors destinations is presented in this article, providing a map of the level of competitiveness of tourism in Brazil.

A incubação das micro, pequenas e médias empresas (MPMEs) em Portugal : uma discussão sobre custos de transacção, dimensão competitiva e a cadeia de valor

RESUMO: Este trabalho tem por objectivo discutir as formas como as incubadoras de empresas contribuem para a criação da cadeia de valores de Micros, Pequenas e Médias Empresas (MPMEs) permitindo a redução dos seus custos de transacção. Para melhor compreender a forma como se reduzem os custos de transacção é importante conhecer os pressupostos comportamentais que provocam a existência de tais custos: a racionalidade limitada, porque a nossa forma de pensar tem limitações; e o oportunismo, porque há pessoas com comportamentos desonestos envolvidas no negócio. O verdadeiro poder explicativo da teoria dos custos de transacção está, no entanto, na análise de três variáveis que determinam se esses custos serão mais baixos numa estrutura hierárquica ou num mercado. Estas três variáveis são: a especificidade de activos - se uma transacção envolve ou não activos específicos à actividade da empresa; a incerteza - qual o grau de incerteza em encontrar um produto ou serviço externo à empresa; e a frequência - e se um bem ou serviço é frequentemente utilizado ou não. As incubadoras de empresas são actualmente consideradas como uma iniciativa essencial ao desenvolvimento socioeconómico regional, e nacional. Estas instituições contribuem para corrigir ineficiências no mercado, conferindo às empresas uma capacidade de inovação tecnológica que garante empregos e a criação de riquezas, aumentando o bem-estar da sociedade. O sucesso da sua actuação resume-se à capacidade para gerar dimensões virtuais que contribuem para a cadeia de valores, permitindo as MPMEs, a redução dos seus custos de transacção. ABSTRACT: This work aims to discuss the relevant forms how incubators contribute to the value chain of a in micro, small and medium enterprises (MSME´s) reducing their transaction costs. To better understand how transaction costs can be reduced one must recognize the behavioral assumptions that are behind there existence; bounded rationality - because our way of thinking has limitations and opportunism - because there are dishonest people involved in the business. The true cost theory´s explanatory power comes from the analyses of the three variables that determine whether those costs will be lower in a hierarchical structure or a market structure. These three variables are: specificity of assets - if the transaction involves or not specific assets in for the firm´s activity; the uncertainty - what is the degree of uncertainty in finding a product or service external to the firm; and the frequency - what is the frequency of the good or service use. Business incubators are currently regarded as a key initiative for the national or regional economic development. The institutions contribute to correct market inefficiencies, improving the capacity of firms to produce technological innovations that guaranty jobs and wealth creation increasing welfare. The success of this all boils down to the capacity to create virtual dimensions that contributes to the MSME´s value chain reducing transaction costs.

O impacto energético e as emissões de CO2 dos veículos eléctricos em Portugal

Para a diminuição da dependência energética de Portugal face às importações de energia, a Estratégia Nacional para a Energia 2020 (ENE 2020) define uma aposta na produção de energia a partir de fontes renováveis, na promoção da eficiência energética tanto nos edifícios como nos transportes com vista a reduzir as emissões de gases com efeito de estufa. No campo da eficiência energética, o ENE 2020 pretende obter uma poupança energética de 9,8% face a valores de 2008, traduzindo-se em perto de 1800 milhões de tep já em 2015. Uma das medidas passa pela aposta na mobilidade eléctrica, onde se prevê que os veículos eléctricos possam contribuir significativamente para a redução do consumo de combustível e por conseguinte, para a redução das emissões de CO2 para a atmosfera. No entanto, esta redução está condicionada pelas fontes de energia utilizadas para o abastecimento das baterias. Neste estudo foram determinados os consumos de combustível e as emissões de CO2 de um veículo de combustão interna adimensional representativo do parque automóvel. É também estimada a previsão de crescimento do parque automóvel num cenário "Business-as-Usual", através dos métodos de previsão tecnológica para o horizonte 2010-2030, bem como cenários de penetração de veículos eléctricos para o mesmo período com base no método de Fisher- Pry. É ainda analisado o impacto que a introdução dos veículos eléctricos tem ao nível dos consumos de combustível, das emissões de dióxido de carbono e qual o impacto que tal medida terá na rede eléctrica, nomeadamente no diagrama de carga e no nível de emissões de CO2 do Sistema Electroprodutor Nacional. Por fim, é avaliado o impacto dos veículos eléctricos no diagrama de carga diário português, com base em vários perfis de carga das baterias. A introdução de veículos eléctricos em Portugal terá pouca expressão dado que, no melhor dos cenários haverão somente cerca de 85 mil unidades em circulação, no ano de 2030. Ao nível do consumo de combustíveis rodoviários, os veículos eléctricos poderão vir a reduzir o consumo de gasolina até 0,52% e até 0,27% no consumo de diesel, entre 2010 e 2030, contribuindo ligeiramente uma menor dependência energética externa. Ao nível do consumo eléctrico, o abastecimento das baterias dos veículos eléctricos representará até 0,5% do consumo eléctrico total, sendo que parte desse abastecimento será garantido através de centrais de ciclo combinado a gás natural. Apesar da maior utilização deste tipo de centrais térmicas para produção de energia, tanto para abastecimento das viaturas eléctricas, como para o consumo em geral, verifica-se que em 2030, o nível de emissões do sistema electroprodutor será cerca de 46% inferior aos níveis registados em 2010, prevendo-se que atinja as 0,163gCO2/kWh produzido pelo Sistema Electroprodutor Nacional devido à maior quota de produção das fontes de energia renovável, como o vento, a hídrica ou a solar.

The European challenge of KMN and innovation: a skills and competence portfolio for knowledge worker in SME's

Versão editor: http://www.isegi.unl.pt/docentes/acorreia/documentos/European_Challenge_KM_Innovation_2004.pdf

Identificação de compostos que modulam a patogénese da doença de Machado-Joseph em C.elegans: autofagia como alvo terapêutico: identification of small compounds that modulate pathogenesis of Machado-Joseph disease in a C.elegans model: targeting autophagy

A doença de Machado-Joseph (DMJ) ou ataxia espinocerebelosa do tipo 3 (SCA3), conhecida por ser a mais comum das ataxias hereditárias dominantes em todo o mundo, é uma doença neurodegenerativa autossómica dominante que leva a uma grande incapacidade motora, embora sem alterar o intelecto, culminando com a morte do doente. Atualmente não existe nenhum tratamento eficaz para esta doença. A DMJ é resultado de uma alteração genética causada pela expansão de uma sequência poliglutamínica (poliQ), na região C-terminal do gene que codifica a proteína ataxina-3 (ATXN3). Os mecanismos celulares das doenças de poliglutaminas que provocam toxicidade, bem como a função da ATXN3, não são ainda totalmente conhecidos. Neste trabalho, usamos, pela sua simplicidade e potencial genético, um pequeno animal invertebrado, o nemátode C. elegans, com o objetivo de identificar fármacos eficazes para o combate contra a patogénese da DMJ, analisando simultaneamente o seu efeito na agregação da ATXN3 mutante nas células neuronais in vivo e o seu impacto no comportamento motor dos animais. Este pequeno invertebrado proporciona grandes vantagens no estudo dos efeitos tóxicos de proteínas poliQ nos neurónios, uma vez que a transparência das suas 959 células (das quais 302 são neurónios) facilita a deteção de proteínas fluorescentes in vivo. Para além disso, esta espécie tem um ciclo de vida curto, é económica e de fácil manutenção. Neste trabalho testámos no nosso modelo transgénico da DMJ com 130Qs em C.elegans dois compostos potencialmente moduladores da agregação da ATXN3 mutante e da resultante disfunção neurológica, atuando pela via da autofagia. De modo a validar a possível importância terapêutica da ativação da autofagia os compostos candidatos escolhidos foram o Litío e o análogo da Rapamicina CCI-779, testados independentemente e em combinação. A neuroproteção conferida pelo Litío e pelo CCI-779 independentemente sugere que o uso destes fármacos possa ser considerado uma boa estratégia como terapia para a DMJ, a testar em organismos evolutivamente mais próximos do humano. A manipulação da autofagia, segundo vários autores, parece ser benéfica e pode ser a chave para o desenvolvimento de novos tratamentos para várias doenças relacionadas com a agregação proteica e o envelhecimento.

Internacionalização do vinho do Porto – estudo de caso Grupo Sogevinus

Dissertação apresentada ao Instituto Superior de Contabilidade para a obtenção do Grau de Mestre em Empreendedorismo e Internacionalização Orientada por Professor Doutor José Freitas Santos

Construção de vantagens competitivas nas estratégias de internacionalização: estudo do caso da EFACEC

Dissertação apresentada ao Instituto Politécnico do Porto para obtenção do Grau de Mestre em Gestão das Organizações, Ramo de Gestão de Empresas Orientador: Professor Doutor Orlando Manuel Martins Marques de Lima Rua