Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

O Lean Management e os desafios da gestão de recursos humanos na FAP

O estudo que se apresenta teve como objetivo analisar a implementação do modelo de Serviços Partilhados, com recurso à metodologia lean, nos serviços de apoio de pessoal do Complexo de Alfragide que decorreu no contexto da sua implementação na Força Aérea Portuguesa, determinada pelo Despacho do CEMFA n.º 59/2015, de 31 de julho. Para desenvolver este trabalho foi utilizada uma estratégia de investigação mista (quantitativa e qualitativa), seguindo o raciocínio hipotético-dedutivo. O desenho de pesquisa utilizado foi o estudo de caso, recorrendo a entrevistas, à análise documental e a um questionário para recolha de dados. Os resultados apurados através das entrevistas e do inquérito permitem concluir que a implementação do novo modelo alcançou alguns dos objetivos a que se propunha, nomeadamente, a melhoria dos serviços de apoio de pessoal prestados aos militares e civis. Apesar de se antever um elevado potencial ao nível da racionalização de Recursos Humanos, de momento, esse objetivo ainda não foi inteiramente alcançado. Conclui-se a presente investigação sugerindo a reavaliação numa fase mais adiantada da implementação do modelo de Serviços Partilhados no Complexo de Alfragide e o alargamento a outras Unidades de modo a obter uma visão mais abrangente da realidade na Força Aérea. Abstract: The study aimed to analyze the implementation of the Shared Services model, using the lean methodology, in the personnel support services in Complexo de Alfragide. This process took place in the context of implementation of this model in the Portuguese Air Force, determined by CEMFA Order No. 59/2015 of 31 July. To develop this work was used a mixed research strategy (quantitative and qualitative), following the hypothetical-deductive reasoning. The research design used was the case study, interviews, document analysis and a questionnaire. By the results obtained through the views expressed in the interviews and in the investigation, it can be concluded that the implementation of the Shared Services model has achieved some of the goals that it proposed like the improvement in personnel support services. Although foreseen great potential in terms of gains of Human Resources rationalization and due to several factors, has not yet been possible to achieve this goal. This research is concluded suggesting a reevaluation at a later stage of the implementation of the Shared Services model in the Complexo de Alfragide and extension to other Units for a more comprehensive view of reality in the Air Force.

TORP: The Open Robot Project A Framework for Module-Based Robots

The development of robots has shown itself as a very complex interdisciplinary research field. The predominant procedure for these developments in the last decades is based on the assumption that each robot is a fully personalized project, with the direct embedding of hardware and software technologies in robot parts with no level of abstraction. Although this methodology has brought countless benefits to the robotics research, on the other hand, it has imposed major drawbacks: (i) the difficulty to reuse hardware and software parts in new robots or new versions; (ii) the difficulty to compare performance of different robots parts; and (iii) the difficulty to adapt development needs-in hardware and software levels-to local groups expertise. Large advances might be reached, for example, if physical parts of a robot could be reused in a different robot constructed with other technologies by other researcher or group. This paper proposes a framework for robots, TORP (The Open Robot Project), that aims to put forward a standardization in all dimensions (electrical, mechanical and computational) of a robot shared development model. This architecture is based on the dissociation between the robot and its parts, and between the robot parts and their technologies. In this paper, the first specification for a TORP family and the first humanoid robot constructed following the TORP specification set are presented, as well as the advances proposed for their improvement.

Gestão compartilhada de P&D em petróleo:a interação entre a Petrobrás e a Universidade Federal do Rio Grande do Norte

This work addresses the relationship between University-Firm aims to understand the model of shared management of R&D in petroleum of Petrobras with UFRN. This is a case study which sought to investigate whether the model of cooperation established by the two institutions brings innovation to generate technical-scientific knowledge and contribute to the coordination with other actors in the promotion of technological innovation. In addition to desk research the necessary data for analysis were obtained by sending questionnaires to the coordinators of projects in R&D at the company and university. Also, interviews were conducted with subjects who participated in the study since its inception to the present day. This case study were analysed through the Resource-Based View and Interorganizational Networks theory. The sample data also stands that: searches were aligned to the strategic planning and that 29% of R&D projects have been successful on the scope of the proposed objectives (of which 11% were incorporated into business processes); which was produced technical and scientific knowledge caracterized by hundreds of national and international publications; thesis, dissertations, eleven patents, and radical and incremental innovations; the partnership has also brought benefits to the academic processes induced by the improved infrastructure UFRN and changing the "attitude" of the university (currently with national prominence in research and staff training for the oil sector). As for the model, the technical point of view, although it has some problems, it follows that it is appropriate. From the viewpoint of the management model is criticized for containing an excess of bureaucracy. From the standpoint of strategic allocation of resources from the legal framework needs to be reassessed, because it is focused only on the college level and it is understood that should also reach the high school given the new reality of the oil sector in Brazil. For this it is desirable to add the local government to this partnership. The set of information leads to the conclusion that the model is identified and named as a innovation of organizational arrangement here known as Shared Management of R&D in petroleum of Petrobras with UFRN. It is said that the shared management model it is possible to exist, which is a simple and effective way to manage partnerships between firms and Science and Technology Institutions. It was created by contingencies arising from regulatory stand points and resource dependence. The partnership is the result of a process of Convergence, Construction and Evaluation supported by the tripod Simplicity, Systematization and Continuity, important factors for its consolidation. In practice an organizational arrangement was built to manage innovative university-industry partnership that is defined by a dyadic relationship on two levels (institutional and technical, therefore governance is hybrid), by measuring the quarterly meetings of systematic and standardized financial contribution proportional to the advancement of research. These details have led to the establishment of a point of interaction between the scientific and technological-business dimension, demystifying they are two worlds apart

Behavioural outcomes of next-generation family members’ commitment to their firm

Are there variations in behaviours and leadership styles of next-generation family members or descendants who join their family business due to different forms of commitment? Evidence from a dual respondent study of 109 Canadian and Swiss family firms suggests that descendants with affective commitment to their family firms are more likely to engage in discretionary activities going beyond the job description, thereby contributing to organizational performance. Next-generation members with normative commitment are more likely to engage in transformational leadership behaviours. Both affectively and normatively motivated next-generation members use contingent reward forms of leadership. A surprising finding of this study is the binding force of normative commitment on positive leadership behaviours of next-generation members. This study empirically tests the generalizability of the three-component model of commitment to family businesses, a context in which different forms of commitment may play a unique role.

Three-dimensional model for multi-component reactive transport with variable density groundwater flow

PHWAT is a new model that couples a geochemical reaction model (PHREEQC-2) with a density-dependent groundwater flow and solute transport model (SEAWAT) using the split-operator approach. PHWAT was developed to simulate multi-component reactive transport in variable density groundwater flow. Fluid density in PHWAT depends not on only the concentration of a single species as in SEAWAT, but also the concentrations of other dissolved chemicals that can be subject to reactive processes. Simulation results of PHWAT and PHREEQC-2 were compared in their predictions of effluent concentration from a column experiment. Both models produced identical results, showing that PHWAT has correctly coupled the sub-packages. PHWAT was then applied to the simulation of a tank experiment in which seawater intrusion was accompanied by cation exchange. The density dependence of the intrusion and the snow-plough effect in the breakthrough curves were reflected in the model simulations, which were in good agreement with the measured breakthrough data. Comparison simulations that, in turn, excluded density effects and reactions allowed us to quantify the marked effect of ignoring these processes. Next, we explored numerical issues involved in the practical application of PHWAT using the example of a dense plume flowing into a tank containing fresh water. It was shown that PHWAT could model physically unstable flow and that numerical instabilities were suppressed. Physical instability developed in the model in accordance with the increase of the modified Rayleigh number for density-dependent flow, in agreement with previous research. (c) 2004 Elsevier Ltd. All rights reserved.

Proposal for shared services performance management model applied to portugueses public administration

Comunicação apresentada no 8º Congresso Nacional de Administração Pública - Desafios e Soluções, em Carcavelos de 21 a 22 de Novembro de 2011.

Reflexive Space. A Constructionist Model of the Russian Reflexive Marker

This study examines the structure of the Russian Reflexive Marker ( ся/-сь) and offers a usage-based model building on Construction Grammar and a probabilistic view of linguistic structure. Traditionally, reflexive verbs are accounted for relative to non-reflexive verbs. These accounts assume that linguistic structures emerge as pairs. Furthermore, these accounts assume directionality where the semantics and structure of a reflexive verb can be derived from the non-reflexive verb. However, this directionality does not necessarily hold diachronically. Additionally, the semantics and the patterns associated with a particular reflexive verb are not always shared with the non-reflexive verb. Thus, a model is proposed that can accommodate the traditional pairs as well as for the possible deviations without postulating different systems. A random sample of 2000 instances marked with the Reflexive Marker was extracted from the Russian National Corpus and the sample used in this study contains 819 unique reflexive verbs. This study moves away from the traditional pair account and introduces the concept of Neighbor Verb. A neighbor verb exists for a reflexive verb if they share the same phonological form excluding the Reflexive Marker. It is claimed here that the Reflexive Marker constitutes a system in Russian and the relation between the reflexive and neighbor verbs constitutes a cross-paradigmatic relation. Furthermore, the relation between the reflexive and the neighbor verb is argued to be of symbolic connectivity rather than directionality. Effectively, the relation holding between particular instantiations can vary. The theoretical basis of the present study builds on this assumption. Several new variables are examined in order to systematically model variability of this symbolic connectivity, specifically the degree and strength of connectivity between items. In usage-based models, the lexicon does not constitute an unstructured list of items. Instead, items are assumed to be interconnected in a network. This interconnectedness is defined as Neighborhood in this study. Additionally, each verb carves its own niche within the Neighborhood and this interconnectedness is modeled through rhyme verbs constituting the degree of connectivity of a particular verb in the lexicon. The second component of the degree of connectivity concerns the status of a particular verb relative to its rhyme verbs. The connectivity within the neighborhood of a particular verb varies and this variability is quantified by using the Levenshtein distance. The second property of the lexical network is the strength of connectivity between items. Frequency of use has been one of the primary variables in functional linguistics used to probe this. In addition, a new variable called Constructional Entropy is introduced in this study building on information theory. It is a quantification of the amount of information carried by a particular reflexive verb in one or more argument constructions. The results of the lexical connectivity indicate that the reflexive verbs have statistically greater neighborhood distances than the neighbor verbs. This distributional property can be used to motivate the traditional observation that the reflexive verbs tend to have idiosyncratic properties. A set of argument constructions, generalizations over usage patterns, are proposed for the reflexive verbs in this study. In addition to the variables associated with the lexical connectivity, a number of variables proposed in the literature are explored and used as predictors in the model. The second part of this study introduces the use of a machine learning algorithm called Random Forests. The performance of the model indicates that it is capable, up to a degree, of disambiguating the proposed argument construction types of the Russian Reflexive Marker. Additionally, a global ranking of the predictors used in the model is offered. Finally, most construction grammars assume that argument construction form a network structure. A new method is proposed that establishes generalization over the argument constructions referred to as Linking Construction. In sum, this study explores the structural properties of the Russian Reflexive Marker and a new model is set forth that can accommodate both the traditional pairs and potential deviations from it in a principled manner.

What is reflection? A conceptual analysis of major definitions and a proposal of a five-component definition and model

La réflexion est considérée comme un élément significatif de la pédagogie et de la pratique médicales sans qu’il n’existe de consensus sur sa définition ou sur sa modélisation. Comme la réflexion prend concurremment plusieurs sens, elle est difficile à opérationnaliser. Une définition et un modèle standard sont requis afin d’améliorer le développement d’applications pratiques de la réflexion. Dans ce mémoire, nous identifions, explorons et analysons thématiquement les conceptualisations les plus influentes de la réflexion, et développons de nouveaux modèle et définition. La réflexion est définie comme le processus de s’engager (le « soi » (S)) dans des interactions attentives, critiques, exploratoires et itératives (ACEI) avec ses pensées et ses actions (PA), leurs cadres conceptuels sous-jacents (CC), en visant à les changer et en examinant le changement lui-même (VC). Notre modèle conceptuel comprend les cinq composantes internes de la réflexion et les éléments extrinsèques qui l’influencent.

Incorporation of a physically based melt pond scheme into the sea ice component of a climate model

The extent and thickness of the Arctic sea ice cover has decreased dramatically in the past few decades with minima in sea ice extent in September 2005 and 2007. These minima have not been predicted in the IPCC AR4 report, suggesting that the sea ice component of climate models should more realistically represent the processes controlling the sea ice mass balance. One of the processes poorly represented in sea ice models is the formation and evolution of melt ponds. Melt ponds accumulate on the surface of sea ice from snow and sea ice melt and their presence reduces the albedo of the ice cover, leading to further melt. Toward the end of the melt season, melt ponds cover up to 50% of the sea ice surface. We have developed a melt pond evolution theory. Here, we have incorporated this melt pond theory into the Los Alamos CICE sea ice model, which has required us to include the refreezing of melt ponds. We present results showing that the presence, or otherwise, of a representation of melt ponds has a significant effect on the predicted sea ice thickness and extent. We also present a sensitivity study to uncertainty in the sea ice permeability, number of thickness categories in the model representation, meltwater redistribution scheme, and pond albedo. We conclude with a recommendation that our melt pond scheme is included in sea ice models, and the number of thickness categories should be increased and concentrated at lower thicknesses.

Home, meaning and identity: learning from the English model of shared ownership

This article explores the problematic nature of the label “home ownership” through a case study of the English model of shared ownership, one of the methods used by the UK government to make home ownership affordable. Adopting a legal and socio-legal analysis, the article considers whether shared ownership is capable of fulfilling the aspirations households have for home ownership. To do so, the article considers the financial and nonfinancial meanings attached to home ownership and suggests that the core expectation lies in ownership of the value. The article demonstrates that the rights and responsibilities of shared owners are different in many respects from those of traditional home owners, including their rights as regards ownership of the value. By examining home ownership through the lens of shared ownership the article draws out lessons of broader significance to housing studies. In particular, it is argued that shared ownership shows the limitations of two dichotomies commonly used in housing discourse: that between private and social housing; and the classification of tenure between owner-occupiers and renters. The article concludes that a much more nuanced way of referring to home ownership is required, and that there is a need for a change of expectations amongst consumers as to what sharing ownership means.

A new model of outbred genetically selected mice which present a strong acute inflammatory response in the absence of complement component C5

Mice selected for a strong (AIRmax) or weak (AIRmin) acute inflammatory response present different susceptibilities to bacterial infections, autoimmune diseases and carcinogenesis. Variations in these phenotypes have been also detected in AIRmax and AIRmin mice rendered homozygous for Slc11a1 resistant (R) and susceptible (S) alleles. Our aim was to investigate if the phenotypic differences observed in these mice was related to the complement system. AIRmax and AIRmin mice and AIRmax and AIRmin groups homozygous for the resistance (R) or susceptibility (S) alleles of the solute carrier family 11a1 member (Slc11a1) gene, formerly designated Nramp-1. While no difference in complement activity was detected in sera from AIRmax and AIRmin strains, all sera from AIRmax Slc11a1 resistant mice (AIRmax(RR)) presented no complement-dependent hemolytic activity. Furthermore, C5 was not found in their sera by immunodiffusion and, polymerase chain reaction and DNA sequencing of its gene demonstrated that AIRmax(RR) mice are homozygous for the C5 deficient (D) mutation previously described in A/J. Therefore, the C5D allele was fixed in homozygosis in AIRmax(RR) line. The AIRmax(RR) line is a new experimental mouse model in which a strong inflammatory response can be triggered in vivo in the absence of C5.

Shared decision-making in mental health care : a user perspective on decisional needs in community-based services

BACKGROUND: Shared decision-making (SDM) is an emergent research topic in the field of mental health care and is considered to be a central component of a recovery-oriented system. Despite the evidence suggesting the benefits of this change in the power relationship between users and practitioners, the method has not been widely implemented in clinical practice. OBJECTIVE: The objective of this study was to investigate decisional and information needs among users with mental illness as a prerequisite for the development of a decision support tool aimed at supporting SDM in community-based mental health services in Sweden. METHODS: Three semi-structured focus group interviews were conducted with 22 adult users with mental illness. The transcribed interviews were analyzed using a directed content analysis. This method was used to develop an in-depth understanding of the decisional process as well as to validate and conceptually extend Elwyn et al.'s model of SDM. RESULTS: The model Elwyn et al. have created for SDM in somatic care fits well for mental health services, both in terms of process and content. However, the results also suggest an extension of the model because decisions related to mental illness are often complex and involve a number of life domains. Issues related to social context and individual recovery point to the need for a preparation phase focused on establishing cooperation and mutual understanding as well as a clear follow-up phase that allows for feedback and adjustments to the decision-making process. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The current study contributes to a deeper understanding of decisional and information needs among users of community-based mental health services that may reduce barriers to participation in decision-making. The results also shed light on attitudinal, relationship-based, and cognitive factors that are important to consider in adapting SDM in the mental health system.

A systematic component of the jump-risk premium in an AJD model

We develop an affine jump diffusion (AJD) model with the jump-risk premium being determined by both idiosyncratic and systematic sources of risk. While we maintain the classical affine setting of the model, we add a finite set of new state variables that affect the paths of the primitive, under both the actual and the risk-neutral measure, by being related to the primitive's jump process. Those new variables are assumed to be commom to all the primitives. We present simulations to ensure that the model generates the volatility smile and compute the "discounted conditional characteristic function'' transform that permits the pricing of a wide range of derivatives.