Rare variants in LRRK1 and Parkinson's disease

Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow- up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.

An event-based approach to understanding decadal fluctuations in the Atlantic meridional overturning circulation

Many previous studies have shown that unforced climate model simulations exhibit decadal-scale fluctuations in the Atlantic meridional overturning circulation (AMOC), and that this variability can have impacts on surface climate fields. However, the robustness of these surface fingerprints across different models is less clear. Furthermore, with the potential for coupled feedbacks that may amplify or damp the response, it is not known whether the associated climate signals are linearly related to the strength of the AMOC changes, or if the fluctuation events exhibit nonlinear behaviour with respect to their strength or polarity. To explore these questions, we introduce an objective and flexible method for identifying the largest natural AMOC fluctuation events in multicentennial/multimillennial simulations of a variety of coupled climate models. The characteristics of the events are explored, including their magnitude, meridional coherence and spatial structure, as well as links with ocean heat transport and the horizontal circulation. The surface fingerprints in ocean temperature and salinity are examined, and compared with the results of linear regression analysis. It is found that the regressions generally provide a good indication of the surface changes associated with the largest AMOC events. However, there are some exceptions, including a nonlinear change in the atmospheric pressure signal, particularly at high latitudes, in HadCM3. Some asymmetries are also found between the changes associated with positive and negative AMOC events in the same model. Composite analysis suggests that there are signals that are robust across the largest AMOC events in each model, which provides reassurance that the surface changes associated with one particular event will be similar to those expected from regression analysis. However, large differences are found between the AMOC fingerprints in different models, which may hinder the prediction and attribution of such events in reality.

Global patterns of plant root colonization intensity by mycorrhizal fungi explained by climate and soil chemistry

Aim Most vascular plants on Earth form mycorrhizae, a symbiotic relationship between plants and fungi. Despite the broad recognition of the importance of mycorrhizae for global carbon and nutrient cycling, we do not know how soil and climate variables relate to the intensity of colonization of plant roots by mycorrhizal fungi. Here we quantify the global patterns of these relationships. Location Global. Methods Data on plant root colonization intensities by the two dominant types of mycorrhizal fungi world-wide, arbuscular (4887 plant species in 233 sites) and ectomycorrhizal fungi (125 plant species in 92 sites), were compiled from published studies. Data for climatic and soil factors were extracted from global datasets. For a given mycorrhizal type, we calculated at each site the mean root colonization intensity by mycorrhizal fungi across all potentially mycorrhizal plant species found at the site, and subjected these data to generalized additive model regression analysis with environmental factors as predictor variables. Results We show for the first time that at the global scale the intensity of plant root colonization by arbuscular mycorrhizal fungi strongly relates to warm-season temperature, frost periods and soil carbon-to-nitrogen ratio, and is highest at sites featuring continental climates with mild summers and a high availability of soil nitrogen. In contrast, the intensity of ectomycorrhizal infection in plant roots is related to soil acidity, soil carbon-to-nitrogen ratio and seasonality of precipitation, and is highest at sites with acidic soils and relatively constant precipitation levels. Main conclusions We provide the first quantitative global maps of intensity of mycorrhizal colonization based on environmental drivers, and suggest that environmental changes will affect distinct types of mycorrhizae differently. Future analyses of the potential effects of environmental change on global carbon and nutrient cycling via mycorrhizal pathways will need to take into account the relationships discovered in this study.

The role of industry bodies in changing market practices through self-regulation: commercial property leasing in the UK

The UK government has sought to make changes to commercial property leasing practices. This has been the case since the recession of the 1990s. Industry self-regulation using an industry code of practice has been the vehicle for these changes. However, the code has had little direct success in changing practices. This is despite repeated threats of legislation as a constant backdrop to this initiative. The focus for this research is on the role of the industry bodies in the code initiative. They have been central to self-regulation in commercial leasing. Thus, the aim is to investigate the role of industry bodies in the process of institutional change. The context is industry self-regulation. The specific setting is commercial leasing. The main industry bodies in focus are the British Property Federation and Royal Institution of Chartered Surveyors. An existing model of institutional change forms the framework for the research. A chronological narrative is constructed from secondary data. This is analysed, identifying the actions of the industry bodies within the conceptual stages of the model. The analysis shows that the industry bodies had not acted as convincing agents of change for commercial leasing. In particular there was a lack of theorisation, a key stage in the process. The industry bodies did not develop a framework necessary to guide their members through the change process. These shortcomings of the industry bodies are likely to have contributed to the failure of the Code. However, the main conclusion is that, if industry self-regulation is led by government, then the state must work with industry bodies to harness their potential as champions and drivers of institutional change. This is particularly important in achieving change in institutionalised environments.

ENSO representation in climate models: from CMIP3 to CMIP5

We analyse the ability of CMIP3 and CMIP5 coupled ocean–atmosphere general circulation models (CGCMs) to simulate the tropical Pacific mean state and El Niño-Southern Oscillation (ENSO). The CMIP5 multi-model ensemble displays an encouraging 30 % reduction of the pervasive cold bias in the western Pacific, but no quantum leap in ENSO performance compared to CMIP3. CMIP3 and CMIP5 can thus be considered as one large ensemble (CMIP3 + CMIP5) for multi-model ENSO analysis. The too large diversity in CMIP3 ENSO amplitude is however reduced by a factor of two in CMIP5 and the ENSO life cycle (location of surface temperature anomalies, seasonal phase locking) is modestly improved. Other fundamental ENSO characteristics such as central Pacific precipitation anomalies however remain poorly represented. The sea surface temperature (SST)-latent heat flux feedback is slightly improved in the CMIP5 ensemble but the wind-SST feedback is still underestimated by 20–50 % and the shortwave-SST feedbacks remain underestimated by a factor of two. The improvement in ENSO amplitudes might therefore result from error compensations. The ability of CMIP models to simulate the SST-shortwave feedback, a major source of erroneous ENSO in CGCMs, is further detailed. In observations, this feedback is strongly nonlinear because the real atmosphere switches from subsident (positive feedback) to convective (negative feedback) regimes under the effect of seasonal and interannual variations. Only one-third of CMIP3 + CMIP5 models reproduce this regime shift, with the other models remaining locked in one of the two regimes. The modelled shortwave feedback nonlinearity increases with ENSO amplitude and the amplitude of this feedback in the spring strongly relates with the models ability to simulate ENSO phase locking. In a final stage, a subset of metrics is proposed in order to synthesize the ability of each CMIP3 and CMIP5 models to simulate ENSO main characteristics and key atmospheric feedbacks.

Inferential Implications of Over-Parametrization: A Case Study in Incomplete Categorical Data

P>In the context of either Bayesian or classical sensitivity analyses of over-parametrized models for incomplete categorical data, it is well known that prior-dependence on posterior inferences of nonidentifiable parameters or that too parsimonious over-parametrized models may lead to erroneous conclusions. Nevertheless, some authors either pay no attention to which parameters are nonidentifiable or do not appropriately account for possible prior-dependence. We review the literature on this topic and consider simple examples to emphasize that in both inferential frameworks, the subjective components can influence results in nontrivial ways, irrespectively of the sample size. Specifically, we show that prior distributions commonly regarded as slightly informative or noninformative may actually be too informative for nonidentifiable parameters, and that the choice of over-parametrized models may drastically impact the results, suggesting that a careful examination of their effects should be considered before drawing conclusions.Resume Que ce soit dans un cadre Bayesien ou classique, il est bien connu que la surparametrisation, dans les modeles pour donnees categorielles incompletes, peut conduire a des conclusions erronees. Cependant, certains auteurs persistent a negliger les problemes lies a la presence de parametres non identifies. Nous passons en revue la litterature dans ce domaine, et considerons quelques exemples surparametres simples dans lesquels les elements subjectifs influencent de facon non negligeable les resultats, independamment de la taille des echantillons. Plus precisement, nous montrons comment des a priori consideres comme peu ou non-informatifs peuvent se reveler extremement informatifs en ce qui concerne les parametres non identifies, et que le recours a des modeles surparametres peut avoir sur les conclusions finales un impact considerable. Ceci suggere un examen tres attentif de l`impact potentiel des a priori.

Desdobramento da qualidade em serviços : o caso da biblioteca de engenharia da UFRGS

O presente trabalho introduz o estabelecimento de um modelo para garantia da qualidade, particularmente aplicado ao segmento de prestação de serviços por bibliotecas. O estudo a ser apresentado baseia-se na utilização de um método de planejamento em específico, o Desdobramento da Função Qualidade (QFD), selecionada para viabilizar a análise da qualidade demandada pelo cliente, das características de qualidade críticas, dos serviços críticos e dos recursos críticos. Este trabalho discute o sistema de garantia da qualidade, cuja implantação está em curso, e que é parte integrante do modelo de gestão a ser adotado pela Biblioteca da Escola de Engenharia da Universidade Federal do Rio Grande do Sul. A análise a ser apresentada utiliza o QFD incorporando um conjunto de matrizes que facilita e garante o fluxo de informações através de todas as suas etapas de desenvolvimento.

Responsabilidade social das empresas e valores humanos: um estudo sobre a atitude dos gestores brasileiros

In the last decades of the 21st century, Corporate Social Responsibility (CSR) has become one of the most widely debated issues in business management, concerning researchers, politicians, managers and society at large. With multilateral implications in economic and social life, CSR refers, essentially, to the discussion about the boundaries of business intervention in society and the ethical limits that should regulate that intervention. It questions the impact of business practices in social well-being, the role left for corporations and for the State in attending to community needs, and which are, at last, the responsibilities that tie enterprises to society. In this research, CSR is approached from the perspective of its ethical foundations, based on the moral reasoning of the business manager, as a key organizational leader with relevant decision power. Specifically, the research aims to understand how the personal human value system and the ethical orientation of managers influence their attitude towards CSR, considering this attitude as an indicator of managerial behavior that translates into corporate performance. Theoretically, CSR concept is discussed and presented as a set of social commitments, based on a strict interpretation of its meaning. As to human values, its philosophical roots are briefly analyzed and Schwartz modern motivational theory is addressed as main reference for studying the personal value system of managers in this research. Concerning ethics, based on classical theory from moral philosophy, references are seek in John Stuart Mill¿s utilitarianism, Immanuel Kant¿s deontological absolutism, John Rawls¿s theory of justice and the ethics of virtue inspired by Aristotle¿s moral thoughts. Based on an extended literature review, research hypothesis are proposed as part of a theoretical model of analysis named Individual Attitude Towards Social Responsibility Model. In order to test the theory¿s empirical validity, it was conducted a field study with 252 Brazilian managers, mainly from the metropolitan areas of São Paulo and Rio de Janeiro. Results show that managerial attitude aligned with CSR principles is favored by conservative personal values, protectors of stability and centered on collective will, and by an ethical orientation based on egalitarianism as postulated by distributive justice principles. However, results also show that the influence of values and personal ethics on managerial attitude towards CSR only occur in managers younger than 30 years old. Findings and their meanings are discussed, as well as summarized in the Axiological and Ethical Determinants of Managers¿ Social Commitment Model. Finally, methodological limitations are evaluated and clues for further research are suggested.

Federalismo fiscal: uma análise das relações intergovernamentais quanto ao atendimento das demandas sociais - o caso brasileiro

Este trabalho tem por objetivo analisar as relações entre as esferas de governo no Brasil, quanto ao provimento das demandas sociais. O foco do estudo reside nas relações que resultam em externalidades negativas, significando perdas para o bem-estar coletivo, que vai de encontro às pretensões da nova Carta Constitucional, promulgada em 1988. O exame das relações intergovernamentais é realizado sob a perspectiva de internalização das instituições ao modelo de análise, promovendo uma maior compreensão quanto aos comportamentos adotados pelas unidades federativas e, por conseguinte, seus resultados nos cenários político, econômico e social, em função do jogo federativo que se faz presente.

El sistema de capacitacion de los recursos humanos de la Secretaria Nacional de Desarollo Administrativo - SENDA - um estudio descriptivo y exploratório

Com uma abordagem sistêmica se realizou-se uma análises da capacitação dos Recursos Humanos da Secretaria Nacional de Desarrollo Administrativo do Equador - SENDA-. É apresentada uma descrição da instituição analisada considerando sua origem, fmalidade, objetivos, estrura e resultados obtidos no âmbito da administração pública equatoriana. À luz de uma abordagem de tipo sistêmico da capacitação dos recursos humanos, significou obter um diagnóstico mais completo e propor uma política de administração eficiente do recurso mais importante das organizações, o ser humano.

Análise do mecanismo de transmissão dos preços internacionais de commodities agrícolas sobre o comportamento da taxa de câmbio real no Brasil

This paper examined the transmission mechanism of international prices of agricultural commodities into the real exchange rate in Brazil for the period from January 2000 to February 2010. We used time series models (ARIMA Model, Transfer Model, Intervention Analysis, Johansen Cointegration Test) in determination of the short and long run elasticities. Transfer Function Model results show that changes in international prices of agricultural commodities are transmitted to the real exchange rate in Brazil in the short run, however, that transmission is less than unity, thus configuring the inelastic relationship. Johansen cointegration tests show that these variables are not co-integrated, no longer converge to the long-run equilibrium. These results are in agreement Cashim et al. (2004), which also found no long run relationship between real exchange rate and commodity prices in the case of Brazil. These results show that monetary shocks have greater weight on changes of the real exchange rate than real shocks.

Growth, structural change and technological capabilities Latin America in a comparative perspective

Countries differ in terms of technological capabilities and complexity of production structures. According to that, countries may follow different development strategies: one based on extracting rents from abundant endowments, such as labor or natural resources, and the other focused on creating rents through intangibles, basically innovation and knowledge accumulation. The present article studies international convergence and divergence, linking structural change with trade and growth through a North South Ricardian model. The analysis focuses on the asymmetries between Latin America and mature and catching up economies. Empirical evidence supports that a shift in the composition of the production structure in favor of R&D intensive sectors allows achieving higher rates of growth in the long term and increases the capacity to respond to demand changes. A virtuous export-led growth requires laggard countries to reduce the technological gap with respect to more advanced ones. Hence, abundance of factor endowments requires to be matched with technological capabilities development for countries to converge in the long term.

Fundos de investimento: uma análise da dinâmica entre tamanho, captação e rentabilidade

O presente trabalho tem como objetivo avaliar a relação existente entre o retorno de um fundo, o seu tamanho, o total de recursos sob gestão da instituição gestora, entre outros fatores. Para a realização dos testes propostos, utilizamos o modelo de regressão com dados em painel. Consideramos para a análise os últimos cinco anos de informações disponíveis (maio de 2005 a abril de 2010) para duas categorias de fundos: Multimercados e Renda Variável. Outro ponto que buscamos investigar neste trabalho são os fatores que explicam a captação dos fundos. Neste caso, como possíveis variáveis explicativas, utilizamos, por exemplo, o retorno do fundo e seu Índice de Sharpe nos últimos 6 meses.

Piraí digital e a teoria ator-rede: a trajetória de inclusão e desenvolvimento de Piraí

A cidade de Piraí, no estado do Rio de Janeiro, Brasil, é palco do programa Piraí Digital, um leque de iniciativas, em cinco áreas de atuação – governo, educação, saúde, negócios e cidadania –, com o objetivo de vencer a exclusão digital no município e contribuir para seu desenvolvimento. O programa foi estudado por meio da associação entre um modelo heurístico para análise da inclusão digital e a Teoria Ator-Rede (ANT). O trabalho apresenta a descrição da evolução do programa segundo os atores que o construíram. Entre 1997 e 2009, Piraí Digital contribuiu para uma série de mudanças positivas em Piraí, notadamente nas áreas de educação, a qual adotou a computação 1:1 em toda a rede municipal no ano de 2009; saúde, que utiliza a estrutura de rede de computadores e internet da cidade para disseminar seus sistemas; e governo, onde a administração pública teve ganhos de produtividade e arrecadação por meio da informatização da máquina administrativa. O estudo de Piraí Digital permite compreender a importância da associação de artefatos – rede de computadores, telecentros, Planos Diretores e outros – e das pessoas nos esforços para vencer a exclusão digital e contribuir para o desenvolvimento local. Explorando o contraste entre a grande notoriedade de Piraí Digital fora do município e o baixo conhecimento do programa pela população local, o autor faz a analogia com uma obra de saneamento, pouco conhecida e visível, mas essencial para a população. Em Piraí, o saneamento digital está pronto, com bits jorrando das torneiras nas escolas e a saúde se beneficiando da TI para escoar seu fluxo de informações para benefício dos cidadãos piraienses.

Os bancos brasileiros na internet: um estudo de caso sobre os motivadores para a sua forma de atuação neste ambiente

O objetivo deste estudo é propor um modelo de análise integrada para a forma de atuação dos bancos brasileiros no ambiente da Internet. Para tanto foi conduzido um estudo de caso único com o Banco do Brasil. A maioria das entrevistas foi realizada nas sedes administrativa e de tecnologia do banco na cidade de Brasília, DF. Foi proposto um Modelo de Análise Integrada baseado em várias teorias e estruturas da área de estudos organizacionais e sistemas de informação. Entre as descobertas da pesquisa está a constatação de que o fenômeno estudado pode ser satisfatoriamente compreendido com o emprego de todas as teorias selecionadas, comprovando a complexidade do objeto desta pesquisa. O estudo apresentou entre suas limitações o fato de ter sido um estudo de caso único, como também a impossibilidade de se realizar esta pesquisa em amplo espectro, com um número consideravelmente maior de organizações. O ineditismo e a contribuição deste estudo residem no fato de ter proposto um modelo integrado com teorias e estruturas de análise que facilitam a compreensão do fenômeno observado. Em estudos futuros o pesquisador poderia incluir a pesquisa em um número maior de instituições para enriquecer a análise.