Identifying adaptive genetic divergence among populations from genome scans

The identification of signatures of natural selection in genomic surveys has become an area of intense research, stimulated by the increasing ease with which genetic markers can be typed. Loci identified as subject to selection may be functionally important, and hence (weak) candidates for involvement in disease causation. They can also be useful in determining the adaptive differentiation of populations, and exploring hypotheses about speciation. Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of F-ST. Low outliers relative to an appropriate neutral population-genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection. However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of F-ST estimates, and current methods have not yet been tested in large-scale simulation experiments. Here, we simulate data from a structured population at many unlinked, diallelic loci that are predominantly neutral but with some loci subject to adaptive or balancing selection. We develop a hierarchical-Bayesian method, implemented via Markov chain Monte Carlo (MCMC), and assess its performance in distinguishing the loci simulated under selection from the neutral loci. We also compare this performance with that of a frequentist method, based on moment-based estimates of F-ST. We find that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate. Neither method could reliably distinguish loci under balancing selection in our simulations, even when the selection coefficient is twenty times the migration rate.

The role of the gastrointestinal microbiota in colorectal cancer

Both environmental and genetic factors contribute to cancers of the gastrointestinal tract including, the stomach, colon and rectum. The mechanisms associated with gastrointestinal cancer causation and prevention are largely unknown and the subject of much research. Many of the proposed mechanisms implicate the metabolic activities of the bacterial biota normally resident in the gastrointestinal tract. This review examines both the adverse and beneficial consequences of bacterial activity of the gastrointestinal tract focusing, in particularly on the stomach and large intestine. Studies on the role of the bacterial biota in colon carcinogenesis have also resulted in several useful biomarkers for use in human.

Infant-mother attachment and the growth of externalizing problems across the primary-school years

Background:  Some contend that attachment insecurity increases risk for the development of externalizing behavior problems in children. Method:  Latent-growth curve analyses were applied to data on 1,364 children from the NICHD Study of Early Child Care to evaluate the association between early attachment and teacher-rated externalizing problems across the primary-school years. Results:  Findings indicate that (a) both avoidant and disorganized attachment predict higher levels of externalizing problems but (b) that effects of disorganized attachment are moderated by family cumulative contextual risk, child gender and child age, with disorganized boys from risky social contexts manifesting increases in behavior problems over time. Conclusions:  These findings highlight the potentially conditional role of early attachment in children’s externalizing behavior problems and the need for further research evaluating causation and mediating mechanisms.

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics.

The causes of prescribing errors in English general practices: a qualitative study

Aim: To examine the causes of prescribing and monitoring errors in English general practices and provide recommendations for how they may be overcome. Design: Qualitative interview and focus group study with purposive sampling and thematic analysis informed by Reason’s accident causation model. Participants: General practice staff participated in a combination of semi-structured interviews (n=34) and six focus groups (n=46). Setting: Fifteen general practices across three primary care trusts in England. Results: We identified seven categories of high-level error-producing conditions: the prescriber, the patient, the team, the task, the working environment, the computer system, and the primary-secondary care interface. Each of these was further broken down to reveal various error-producing conditions. The prescriber’s therapeutic training, drug knowledge and experience, knowledge of the patient, perception of risk, and their physical and emotional health, were all identified as possible causes. The patient’s characteristics and the complexity of the individual clinical case were also found to have contributed to prescribing errors. The importance of feeling comfortable within the practice team was highlighted, as well as the safety of general practitioners (GPs) in signing prescriptions generated by nurses when they had not seen the patient for themselves. The working environment with its high workload, time pressures, and interruptions, and computer related issues associated with mis-selecting drugs from electronic pick-lists and overriding alerts, were all highlighted as possible causes of prescribing errors and often interconnected. Conclusion: This study has highlighted the complex underlying causes of prescribing and monitoring errors in general practices, several of which are amenable to intervention.

Acts of estrangement: reading the psoriatic-skin

I am continually surprised by the acts of estrangement in which my body engages. All bodies do this to some extent – lungs breathe, hearts beat and so on, but with psoriasis, which my article is concerned with, these processes are highly visible. As a condition of the skin, it is a pathology which is enacted both within and without, visible to the social world as well emerging from some little understood inflammatory source within the body. This article will undertake a phenomenological exploration of my own skin and how my experience of my body is affected by its lack of compliance with medicine, cosmetics etc. By some unknown causation it flakes, breaks, itches constantly drawing attention to bodily limits and the limits of medical knowledge. I want to think through the meanings we ascribe to such inflammatory conditions in Western society, how my skin materialises at the nexus of industrialisation, medicine, class and capital. This investigation will emerge at the limit point, the thin skin between the subjective and objective, observing and theorising my skin in ways which dissolve disciplinary boundaries, to comprehend the cultural, biological and environmental forces that work upon my body, estranging it from me.

Divine premotion

According to divine premotionism, God does not merely create and sustain the universe. He also moves all secondary causes to action as instruments without undermining their intrinsic causal efficacy. I explain and uphold the premotionist theory, which is the theory of St Thomas Aquinas and his most prominent exponents. I defend the premotionist interpretation of Aquinas in some textual detail, with particular reference to Suarez and to a recent paper by Louis Mancha. Critics, including Molinists and Suarezians, raise various objections to the view that premotion is compatible with genuine secondary causation. I rebut a number of these objections, in the course of which I respond to the central challenge that premotionism destroys free will. I also offer a number of positive reasons for embracing the premotionist theory.

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

Aluminium and the human breast

The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current useage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified.

A Teoria do fortuito externo: um novo estudo

Apresentação histórica dos conceitos de caso fortuito e força maior. Avanço doutrinário em relação aos sistemas de responsabilidade civil. Responsabilidade civil subjetiva e responsabilidade civil objetiva. Perda de importância do elemento subjetivo culpa. Teorias explicativas das situações de caso fortuito e de força maior. Objetivista e subjetivista. Posição adotada pelo legislador. Equiparação dos efeitos de caso fortuito e de força maior. Evolução do estudo do direito consumerista. Fortuito interno. Evolução. Fortuito externo. Rompimento do nexo de causalidade. Externidade. Principais características.

O processo decisório do empreendedor frente à transição da pequena para a média empresa: casos do setor hoteleiro na cidade Curitiba-PR

O presente estudo buscou entender como as mudanças ocasionadas pelo crescimento da empresa afetam o processo decisório, com foco na transição de pequena para média empresa. Buscou-se preencher o gap existente sobre esse período de transição entre pequenas e médias empresas, principalmente sob os aspectos abordados pelas lógicas Effectuation e Causation, descritas por Sarasvathy (2001). Esta pesquisa parte do princípio de que as pequenas empresas possuem poucos níveis hierárquicos e geralmente as decisões estão centralizadas no empreendedor-proprietário. Já quando a empresa cresce e torna-se média empresa, há um aumento nas formalizações dos processos e nas hierarquias. Com isso, há uma necessidade de modificar o processo decisório, que pode ser descentralizada ou envolver mais pessoas, se comparado às pequenas empresas. O referencial teórico da pesquisa, teve como base temas relativos à pequenas e médias empresas; setor hoteleiro, estrutura organizacional; ciclo de vida das organizações; processo decisório; e, por fim, o uso das lógicas causation e effectuation, com foco nas características do processo decisório do empreendedor. A pesquisa teve de caráter qualitativo e exploratório e faz uso do método de estudos de casos, através de entrevistas em profundidade com empreendedores do setor hoteleiro, que é um setor de serviços que tem tido grande visibilidade e crescimento nos últimos anos. Foram analisados dois casos no setor hoteleiro de Curitiba- PR, que passaram recentemente pela fase de transição de pequena para média empresa. Em cada um dos casos foram entrevistados os proprietários-fundadores, os seus sucessores diretos e o gerente-geral. Também levantou-se depoimentos de clientes em sites de avalizações de hospedagem. Para análise dos dados foram atribuídas categorias analíticas, e foi realizada a análise do conteúdo, (contrapondo com o referencial teórico apresentado) e cross-case analysis (comparativo das informações obtidas em cada caso). Ao finalizar a pesquisa, concluiu-se que a transição de pequena para média empresa afeta as decisões no sentido de aumentar a formalização de processos, há uma delegação de pequenos poderes, um maior distanciamento dos funcionários e a cúpula administrativa, há uma preocupação maior com a capacitação dos funcionários, são consideração de aspectos racionais na decisão, há uma equipe de suporte para tomada de decisões, há uma preocupação com o longo prazo, as responsabilidades tornam-se mais claras, e mais autonomia é delegada aos funcionários. Pode-se dizer que não mudou o fato da administração permanecer familiar, o foco das decisões ainda mantém-se no curto prazo, as decisões permanecem flexíveis, mantém-se a centralização do poder de decisões estratégicas; há ainda uma dificuldade em separar o pessoal do profissional, definição de metas e objetivos não muito claras, investimentos em um projeto por vez, e o uso de rede de contatos ainda é importante para o desenvolvimento da empresa.

As desventuras do duty to mitigate the loss no Brasil : nascimento (e morte) de um brocardo

Primeiramente, o trabalho descreve sinteticamente a tradição common law, inserindo o o duty to mitigate the loss em contexto próprio. Então, traça as linhas gerais que, naquele cenário, conformam o instituto. Atenção é dada aos fundamentos do duty to mitigate the loss e às funções por ele desempenhadas, inclusive nos casos subordinados à United Nations Convention on Contracts for the International Sale of Goods (CISG). No contexto próprio, o duty to mitigate the loss tem por fundamento primeiro a causation e funciona como um limitador do quantum indenizatório; não trata de um “dever”; cabe ao demandante; tem na razoabilidade das medidas mitigadoras e no reembolso das despesas incorridas características essenciais. Em segundo lugar, a dissertação investiga o duty to mitigate the loss no Brasil, a partir da doutrina selecionada e de decisões do Superior Tribunal de Justiça e de diversos tribunais estaduais. As pesquisas demonstram que o duty to mitigate the loss, sob o nome de mitigation doctrine, ingressou no Brasil pela doutrina, mas desta forma repercutiu pouco nos tribunais. Desprovido desta influência doutrinária anterior, o duty to mitigate the loss retornou ao Brasil por meio de enunciado do Conselho da Justiça Federal, proposto em documento cujo conteúdo é objeto de reflexões neste trabalho, notadamente na questão da íntima relação entre o duty to mitigate the loss e a boa-fé objetiva. A partir do leading case no Superior Tribunal de Justiça, que adotou o enunciado e o documento que lhe serviu de proposta, o duty to mitigate the loss expandiu rapidamente no Brasil. Em São Paulo, foi alçado à princípio e brocardo. No Superior Tribunal e Justiça, foi considerado sub-princípio da boa-fé e aplicado em questões adjetivas e substantivas criminais. Comparativamente, o duty to mitigate the loss no Brasil guarda remotas semelhanças ao instituto homônimo da common law. Este trabalho aponta as diferenças entre os intitutos e concluí com a sistematização das funções que o duty to mitigate the loss desempenha no Brasil, formulando proposta para a reedição de enunciado do Conselho da Justiça Federal.

We're Chained: an analysis of systemic risk in finance

This dissertation presents two papers on how to deal with simple systemic risk measures to assess portfolio risk characteristics. The first paper deals with the Granger-causation of systemic risk indicators based in correlation matrices in stock returns. Special focus is devoted to the Eigenvalue Entropy as some previous literature indicated strong re- sults, but not considering different macroeconomic scenarios; the Index Cohesion Force and the Absorption Ratio are also considered. Considering the S&P500, there is not ev- idence of Granger-causation from Eigenvalue Entropies and the Index Cohesion Force. The Absorption Ratio Granger-caused both the S&P500 and the VIX index, being the only simple measure that passed this test. The second paper develops this measure to capture the regimes underlying the American stock market. New indicators are built using filtering and random matrix theory. The returns of the S&P500 is modelled as a mixture of normal distributions. The activation of each normal distribution is governed by a Markov chain with the transition probabilities being a function of the indicators. The model shows that using a Herfindahl-Hirschman Index of the normalized eigenval- ues exhibits best fit to the returns from 1998-2013.

Os argumentos transcendentais: kant e o problema de hume

This work whose title is "The transcendental arguments: Kant Andy Hume's problem" has as its main objective to interpret Kant's answer to Hume's problem in the light of the conjunction of the causality and induction themes which is equivalent to skeptical- naturalist reading of the latter. In this sense, this initiative complements the previous treatment seen in our dissertation, where the same issue had been discussed from a merely skeptical reading that Kant got from Hume thought and was only examined causality. Among the specific objectives, we list the following: a) critical philosophy fulfills three basic functions, a founding, one negative and one would argue that the practical use of reason, here named as defensive b) the Kantian solution of Hume's problem in the first critisism would fulfill its founding and negative functions of critique of reason; c) the Kantian treatment of the theme of induction in other criticisms would will fulfill the defense function of critique of reason; d) that the evidence of Kant's answer to Hume's problem are more consistent when will be satisfied these three functions or moments of criticism. The basic structure of the work consists of three parts: the first the genesis of Hume's problem - our intention is to reconstruct Hume's problem, analyzing it from the perspective of two definitions of cause, where the dilution of the first definition in the second match the reduction of psychological knowledge to the probability of following the called naturalization of causal relations; whereas in the second - Legality and Causality - it is stated that when considering Hume in the skeptic-naturalist option, Kant is not entitled to respond by transcendental argument A􀁴B; A⊢B from the second Analogy, evidence that is rooted in the position of contemporary thinkers, such as Strawson and Allison; in third part - Purpose and Induction - admits that Kant responds to Hume on the level of regulative reason use, although the development of this test exceeds the limits of the founding function of criticism. And this is articulated in both the Introduction and Concluding Remarks by meeting the defensive [and negative] function of criticism. In this context, based on the use of so-called transcendental arguments that project throughout the critical trilogy, we provide solution to a recurring issue that recurs at several points in our submission and concerning to the "existence and / or the necessity of empirical causal laws. In this light, our thesis is that transcendental arguments are only an apodictic solution to the Hume s skeptical-naturalist problem when is at stake a practical project in which the interest of reason is ensured, as will, in short, proved in our final considerations

A inferência causal na filosofia moral de Hume.

Starting from the idea that the result of the Humean analysis of causal inferences must be applied coherently to the remaining part of his work, including its moral theory, the present master thesis aims at investigating whether Hume´s moral philosophy is essentially based on feeling, or whether this would not be rather essentially a consequence of our causal inferences in human actions and deliberations. The main idea consists in showing that our moral inferences, to the extent that they are for Hume empirical , depend on our belief in a connexion between something which has been previously observed and something which is not being observed ( but that it is expected to occur or to be observed in the future). Thus, this very belief must base our moral inferences concerning the actions and deliberations of the individuals. Therefore, must e o ipso induce us to associate actions and behaviors, as well as character and moral claims of men to certain moral feelings. Accordingly, the thesis is unfolded in three chapters. In the first chapter Hume´s theory of the perception is reported as essential part of the explanation or the principles that bind ideas in our mind and constitute our inferences. In the second chapter, the Humean analysis of causal inferences is presented and the way they contribute in the formation of our moral inferences is explained. In the third and last chapter, the formation of our moral inferences and the real contribution of the doctrine of freedom and necessity for the examination or our actions are analysed and discussed.