Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

Determinants of school efficiency : The case of primary schools in the State of Geneva, Switzerland

The public primary school system in the State of Geneva, Switzerland, is characterized by centrally evaluated pupil performance measured with the use of standardized tests. As a result, consistent data are collected among the system. The 2010-2011 dataset is used to develop a two-stage data envelopment analysis (DEA) of school efficiency. In the first stage, DEA is employed to calculate an individual efficiency score for each school. It shows that, on average, each school could reduce its inputs by 7% whilst maintaining the same quality of pupil performance. The cause of inefficiency lies in perfectible management. In the second stage, efficiency is regressed on school characteristics and environmental variables;external factors outside of the control of headteachers. The model is tested for multicollinearity, heteroskedasticity and endogeneity. Four variables are identified as statistically significant. School efficiency is negatively influenced by (1) the provision of special education, (2) the proportion of disadvantaged pupils enrolled at the school and (3) operations being held on multiple sites, but positively influenced by school size (captured by the number of pupils). The proportion of allophone pupils; schools located in urban areas and the provision of reception classes for immigrant pupils are not significant. Although the significant variables influencing school efficiency are outside of the control of headteachers, it is still possible to either boost the positive impact or curb the negative impact. Dans le canton de Genève (Suisse), les écoles publiques primaires sont caractérisées par un financement assuré par les collectivités publiques (canton et communes) et par une évaluation des élèves à l'aide d'épreuves standardisées à trois moments distincts de leur scolarité. Cela permet de réunir des informations statistiques consistantes. La base de données de l'année 2010-2011 est utilisée dans une analyse en deux étapes de l'efficience des écoles. Dans une première étape, la méthode d'analyse des données par enveloppement (DEA) est utilisée pour calculer un score d'efficience pour chaque école. Cette analyse démontre que l'efficience moyenne des écoles s'élève à 93%. Chaque école pourrait, en moyenne, réduire ses ressources de 7% tout en conservant constants les résultats des élèves aux épreuves standardisées. La source de l'inefficience réside dans un management des écoles perfectible. Dans une seconde étape, les scores d'efficience sont régressés sur les caractéristiques des écoles et sur des variables environnementales. Ces variables ne sont pas sous le contrôle (ou l'influence) des directeurs d'école. Le modèle est testé pour la multicolinéartié, l'hétéroscédasticité et l'endogénéité. Quatre variables sont statistiquement significatives. L'efficience des écoles est influencée négativement par (1) le fait d'offrir un enseignement spécialisé en classe séparée, (2) la proporition d'élèves défavorisés et (3) le fait d'opérer sur plusieurs sites différents. L'efficience des écoles est influencée positivement par la taille de l'école, mesurée par le nombre d'élèves. La proporition d'élèves allophones, le fait d'être situé dans une zone urbaine et d'offrir des classes d'accueil pour les élèves immigrants constituent autant de variables non significatives. Le fait que les variables qui influencent l'efficience des écoles ne soient pas sous le contrôle des directeurs ne signifie pas qu'il faille céder au fatalisme. Différentes pistes sont proposées pour permettre soit de réduire l'impact négatif soit de tirer parti de l'impact positif des variables significatives.

Understanding the development of the ESDP: Perspectives and insights from historical institutionalism and theories of learning

How can we best understand the emergence of the European Security and Defence Policy (ESDP)? This paper applies the theories of historical institutionalism and experiential learning to offer a dynamic conceptualisation of moves towards an ESDP which highlights some of the causal factors that a more temporally-restricted analysis would miss. It firstly shows how the institutional and functional expansion of European Political Cooperation (EPC) over the course of the 1970s and 80s gave rise to a context in which the development of a security and defence dimension came to be viewed as more logical and even necessary. It then goes on to analyse some of the external factors (in the form of actors, events and institutions) that further pushed in this direction and proved to influence the policy’s subsequent evolution. The paper is therefore intended to act as a first-step to understanding the ESDP’s development from this perspective.

Light-regulated plant growth and development.

Plants are sessile and photo-autotrophic; their entire life cycle is thus strongly influenced by the ever-changing light environment. In order to sense and respond to those fluctuating conditions higher plants possess several families of photoreceptors that can monitor light from UV-B to the near infrared (far-red). The molecular nature of UV-B sensors remains unknown, red (R) and far-red (FR) light is sensed by the phytochromes (phyA-phyE in Arabidopsis) while three classes of UV-A/blue photoreceptors have been identified: cryptochromes, phototropins, and members of the Zeitlupe family (cry1, cry2, phot1, phot2, ZTL, FKF1, and LKP2 in Arabidopsis). Functional specialization within photoreceptor families gave rise to members optimized for a wide range of light intensities. Genetic and photobiological studies performed in Arabidopsis have shown that these light sensors mediate numerous adaptive responses (e.g., phototropism and shade avoidance) and developmental transitions (e.g., germination and flowering). Some physiological responses are specifically triggered by a single photoreceptor but in many cases multiple light sensors ensure a coordinated response. Recent studies also provide examples of crosstalk between the responses of Arabidopsis to different external factors, in particular among light, temperature, and pathogens. Although the different photoreceptors are unrelated in structure, in many cases they trigger similar signaling mechanisms including light-regulated protein-protein interactions or light-regulated stability of several transcription factors. The breath and complexity of this topic forced us to concentrate on specific aspects of photomorphogenesis and we point the readers to recent reviews for some aspects of light-mediated signaling (e.g., transition to flowering).

Determinants of Decentralization within the Firm: Some Empirical Evidence from Spanish Small and Medium- Sized Enterprise

This paper examines empirically the determinants of decentralization of decision- making in the firm for small and medium-sized enterprises (SMEs) that tend to be highly centralized. By decentralization of decisions we mean the delegation of decision rights from the owner or manager to the plant supervisor or even to floor workers. Our findings show that the allocation of authority to basic workers or a team of workers depends on firm characteristics such as firm size, the use of internal networks or the number of workplaces, and workers characteristics, in particular, the composition of the laborforce in terms of education and seniority and whether or not workers receive pay incentives. External factors such as the intensity of competition and the firm s export intensity are also important determinants of the allocation of authority.

Molecular chaperones and associated cellular clearance mechanisms against toxic protein conformers in Parkinson's disease.

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder marked by the loss of dopaminergic neurons (in particular in the substantia nigra) causing severe impairment of movement coordination and locomotion, associated with the accumulation of aggregated α-synuclein (α-Syn) into proteinaceous inclusions named Lewy bodies. Various early forms of misfolded α-Syn oligomers are cytotoxic. Their formation is favored by mutations and external factors, such as heavy metals, pesticides, trauma-related oxidative stress and heat shock. Here, we discuss the role of several complementing cellular defense mechanisms that may counteract PD pathogenesis, especially in youth, and whose effectiveness decreases with age. Particular emphasis is given to the 'holdase' and 'unfoldase' molecular chaperones that provide cells with potent means to neutralize and scavenge toxic protein conformers. Because chaperones can specifically recognize misfolded proteins, they are key specificity factors for other cellular defenses, such as proteolysis by the proteasome and autophagy. The efficiency of the cellular defenses decreases in stressed or aging neurons, leading to neuroinflammation, apoptosis and tissue loss. Thus, drugs that can upregulate the molecular chaperones, the ubiquitin-proteasome system and autophagy in brain tissues are promising avenues for therapies against PD and other mutation-, stress- or age-dependent protein-misfolding diseases.

Non-random fertilization in mice correlates with the MHC and something else

One evolutionary explanation for the success of sexual reproduction assumes that sex is an advantage in the coevolutionary arms race between pathogens and hosts. Accordingly, an important criterion in mate choice and maternal selection thereafter could be the allelic specificity at polymorphic loci involved in parasite-host interactions, e.g. the MHC (major histocompatibility complex). The MHC has been found to influence mate choice and selective abortions in mice and humans. However, it could also influence the fertilization process itself, i.e. (i) the oocyte's choice for the fertilizing sperm, and (ii) the outcome of the second meiotic division after the sperm has entered the egg. We tested both hypotheses in an in vitro fertilization experiment with two inbred mouse strains congenic for their MHC. The genotypes of the resulting blastocysts were determined by polymerase chain reaction. We found nonrandom MHC combinations in the blastocysts which may result from both possible choice mechanisms. The outcome changed significantly over time, indicating that a choice for MHC combinations during fertilization may be influenced by one or several external factors.

Formação dos preços de venda nas Empresas Importadoras de São Vicente

As decisões de preços de venda, é uma das funções com mais relevância no ambiente empresarial para os gerentes, devido o seu carácter estratégico para o sucesso das empresas. O processo de formação de preço (FP) é fundamental para as empresas, embora apresenta graus de dificuldade e de complexidade, por implicar diversos factores. A primeira etapa para a FP consiste na estimativa correcta de custos, para obtenção de preços ideais. Para além dos custos, outros factores internos e externos devem ser analisados para que as decisões possam ser tomadas de forma correcta e obter um preço competitivo. Portanto, os gerentes precisam de informações precisas para poderem tomar decisões com segurança, levando em consideração todos os aspectos relevantes para a FP. O presente trabalho tem como objectivo principal, conhecer uma politica adequada de FP, bem como, descobrir quais os factores mais relevantes considerados na formação desses preços nas empresas e ainda conhecer quais os métodos de FP utilizado pelas empresas de importação de S.Vicente para a FP. A metodologia, consistiu primeiramente numa pesquisa bibliográfica e exploratória. Para a recolha dos dados,foram aplicados questionários com perguntas fechadas múltipla escolha, aos gerentes e aos responsáveis pelos processos de EC e FP e para complementar, foi feita uma entrevista a um especialista da área. Para a análise dos dados, foram utilizadas técnicas qualitativas e quantitativas, feito através das respostas obtidas dos questionários. Os resultados obtidos da pesquisa, mostram que o método de formação de preços de venda adoptado pelas empresas de S.Vicente, é o método baseado no custo e no mercado (método misto), ou seja, o preço é definido com base nos seus custos, mas é ajustado tendo por base o preço da concorrência. The sale prices decisions; it is one of the functions with more relevance in the managerial atmosphere for the managers, due your strategic character for the success of the companies. The process of price formation (FP) it is fundamental for the companies,although it presents degrees of difficulty and of complexity, for implicating several factors. The first stage for FP consists in estimate correct costs, to obtaining ideal prices. Besides the costs, others internal and external factors should be analyzed so that decisions can be made in a correct form to obtain a competitive price. Therefore, the managers need necessary information to make safety decisions, taking in consideration all the important aspects of FP. The main objective of this present work, is to know the appropriate politics of FP, as well as, to discover which the most important factors considered in the formation of those prices to purchases and still to know which of the FP methods used by the import companies in São Vicente. The methodology consisted firstly in a bibliographical and exploratory research. To collect the data, were applied uestionnaires with closed questions, multiple choice to the managers and the responsible for the processes of ECP and EP and to complement, it was made an interview to a specialist. For the analysis of the data, qualitative techniques were used, done through to obtained answers of the questionnaires. The results of the research, show that the method of formation of sale prices adopted for São Vicente's companies, is the method based on the cost and in the market (mixed method), in other words, the price is defined with base in the costs, but it is adjusted tends for base of the competition.

The Spanish motor industry in the first third of the 20th Century: A lost opportunity

The Spanish automobile industry had a late start. Although the country proved capable of short production runs of high-quality vehicles during the first third of the century it never managed to build up its own industry, unlike Great Britain, France, or Italy. What then, were the critical shortcomings that prevented the establishment of large Spanish motor manufacturers? Put another way, why did all of the companies set up during the first half-century fail to survive? This paper attempts to shed some light on these questions, employing a wide-ranging analysis of both internal and external factors affecting the industry. A feeble internal market, lack of resources and production factors are usually adduced as reasons, as are Spain's general economic backwardness and the role played by the public authorities. However, this paper mainly focuses on the internal factors concerning company strategy and organisation. A comparison with the Italian case helps put the traditional arguments in proper perspective and highlights those covering business strategies. Finally, we argue that a broad range of factors needs to be analysed to fully understand why Spain failed to establish a motor industry.

Plan estratégico 2012-2105 para la empresa Automatizaciones Eléctricas, SL

La empresa moderna, se encuentra en una situación actual de incertidumbre en la que además está más expuesta a factores externos con el aumento de la competencia y el impacto de la globalización. Se enfrenta a un panorama que debe ser gestionado adecuadamente para asegurar su supervivencia y el éxito de su existencia. En este TFC, se presenta una de las herramientas ‘buque insignia’ del Management moderno, aquella que está destinada a ser la base de la Gestión de la empresa y que cada vez más se hace imprescindible para la construcción de un futuro cada vez más incierto, la Planificación Estratégica. El Plan Estratégico 2012-2015 de AESL se desarrolla en varios apartados que intentarán dar con las claves de la dirección que la empresa debe seguir y propone los objetivos que encontrará a través de la puesta en marcha de las acciones y estrategias determinadas. La primera etapa, y la más extensa, realiza un Análisis de la situación externa e interna de la empresa además de un Diagnóstico de la misma. Se analizan diversos factores que pueden contribuir o hacer peligrar el futuro de la empresa, y constituye el punto de partida de la planificación. En la segunda etapa, y con la información de la anterior fase, comienza la fijación de los Objetivos Corporativos y la definición de las Decisiones Estratégicas que han de transformar nuestro rumbo actual en el logro de esos objetivos. Las estrategias no sólo comportarán un ámbito corporativo, también se centrarán en estrategias funcionales con un carácter más definitorio en el interior de la empresa. Por último, la tercera y última etapa, aglutinará todas estas Decisiones estratégicas para transformarlas en las Decisiones Operativas, aquellas que se encargarán de gestionar el día a día de la empresa a través de los Planes de Acción, que suponen la etapa de mayor concreción del Plan. Este Plan a 3 años deberá erigirse como la herramienta de planificación más importante de la empresa, debiendo guiar las principales decisiones tomadas y convirtiéndose en un instrumento de consulta no sólo para decidir hoy lo que se hará en el futuro sino también para mantener unos niveles altos de competitividad en el tremendo esfuerzo que supone la gestión de una PYME.

Introduction

Although increasing our knowledge of the properties of networks of cities is essential, these properties can be measured at the city level, and must be assessed by analyzing actor networks. The present volume focuses less on individual characteristics and more on the interactions of actors and institutions that create functional territories in which the structure of existing links constrains emerging links. Rather than basing explanations on external factors, the goal is to determine the extent to which network properties reflect spatial distributions and create local synergies at the meso level that are incorporated into global networks at the macro level where different geographical scales occur. The paper introduces the way to use the graphs structure to identify empirically relevant groups and levels that explain dynamics. It defines what could be called âeurooemulti-levelâeuro, âeurooemulti-scaleâeuro, or âeurooemultidimensionalâeuro networks in the context of urban geography. It explains how the convergence of the network multi-territoriality paradigm collaboratively formulated, and manipulated by geographers and computer scientists produced the SPANGEO project, which is exposed in this volume.

Verbal labels selectively bias brain responses to high-energy foods.

The influence of external factors on food preferences and choices is poorly understood. Knowing which and how food-external cues impact the sensory processing and cognitive valuation of food would provide a strong benefit toward a more integrative understanding of food intake behavior and potential means of interfering with deviant eating patterns to avoid detrimental health consequences for individuals in the long run. We investigated whether written labels with positive and negative (as opposed to 'neutral') valence differentially modulate the spatio-temporal brain dynamics in response to the subsequent viewing of high- and low-energetic food images. Electrical neuroimaging analyses were applied to visual evoked potentials (VEPs) from 20 normal-weight participants. VEPs and source estimations in response to high- and low- energy foods were differentially affected by the valence of preceding word labels over the ~260-300 ms post-stimulus period. These effects were only observed when high-energy foods were preceded by labels with positive valence. Neural sources in occipital as well as posterior, frontal, insular and cingulate regions were down-regulated. These findings favor cognitive-affective influences especially on the visual responses to high-energetic food cues, potentially indicating decreases in cognitive control and goal-adaptive behavior. Inverse correlations between insular activity and effectiveness in food classification further indicate that this down-regulation directly impacts food-related behavior.

Simulation of stromatolite growth using diffusion-limited aggregation and a discrete model of biogeochemical exchanges in microbial mat

Resume : Mieux comprendre les stromatolithes et les tapis microbiens est un sujet important en biogéosciences puisque cela aide à l'étude des premières formes de vie sur Terre, a mieux cerner l'écologie des communautés microbiennes et la contribution des microorganismes a la biominéralisation, et même à poser certains fondements dans les recherches en exobiologie. D'autre part, la modélisation est un outil puissant utilisé dans les sciences naturelles pour appréhender différents phénomènes de façon théorique. Les modèles sont généralement construits sur un système d'équations différentielles et les résultats sont obtenus en résolvant ce système. Les logiciels disponibles pour implémenter les modèles incluent les logiciels mathématiques et les logiciels généraux de simulation. L'objectif principal de cette thèse est de développer des modèles et des logiciels pour aider a comprendre, via la simulation, le fonctionnement des stromatolithes et des tapis microbiens. Ces logiciels ont été développés en C++ en ne partant d'aucun pré-requis de façon a privilégier performance et flexibilité maximales. Cette démarche permet de construire des modèles bien plus spécifiques et plus appropriés aux phénomènes a modéliser. Premièrement, nous avons étudié la croissance et la morphologie des stromatolithes. Nous avons construit un modèle tridimensionnel fondé sur l'agrégation par diffusion limitée. Le modèle a été implémenté en deux applications C++: un moteur de simulation capable d'exécuter un batch de simulations et de produire des fichiers de résultats, et un outil de visualisation qui permet d'analyser les résultats en trois dimensions. Après avoir vérifié que ce modèle peut en effet reproduire la croissance et la morphologie de plusieurs types de stromatolithes, nous avons introduit un processus de sédimentation comme facteur externe. Ceci nous a mené a des résultats intéressants, et permis de soutenir l'hypothèse que la morphologie des stromatolithes pourrait être le résultat de facteurs externes autant que de facteurs internes. Ceci est important car la classification des stromatolithes est généralement fondée sur leur morphologie, imposant que la forme d'un stromatolithe est dépendante de facteurs internes uniquement (c'est-à-dire les tapis microbiens). Les résultats avancés dans ce mémoire contredisent donc ces assertions communément admises. Ensuite, nous avons décidé de mener des recherches plus en profondeur sur les aspects fonctionnels des tapis microbiens. Nous avons construit un modèle bidimensionnel de réaction-diffusion fondé sur la simulation discrète. Ce modèle a été implémenté dans une application C++ qui permet de paramétrer et exécuter des simulations. Nous avons ensuite pu comparer les résultats de simulation avec des données du monde réel et vérifier que le modèle peut en effet imiter le comportement de certains tapis microbiens. Ainsi, nous avons pu émettre et vérifier des hypothèses sur le fonctionnement de certains tapis microbiens pour nous aider à mieux en comprendre certains aspects, comme la dynamique des éléments, en particulier le soufre et l'oxygène. En conclusion, ce travail a abouti à l'écriture de logiciels dédiés à la simulation de tapis microbiens d'un point de vue tant morphologique que fonctionnel, suivant deux approches différentes, l'une holistique, l'autre plus analytique. Ces logiciels sont gratuits et diffusés sous licence GPL (General Public License). Abstract : Better understanding of stromatolites and microbial mats is an important topic in biogeosciences as it helps studying the early forms of life on Earth, provides clues re- garding the ecology of microbial ecosystems and their contribution to biomineralization, and gives basis to a new science, exobiology. On the other hand, modelling is a powerful tool used in natural sciences for the theoretical approach of various phenomena. Models are usually built on a system of differential equations and results are obtained by solving that system. Available software to implement models includes mathematical solvers and general simulation software. The main objective of this thesis is to develop models and software able to help to understand the functioning of stromatolites and microbial mats. Software was developed in C++ from scratch for maximum performance and flexibility. This allows to build models much more specific to a phenomenon rather than general software. First, we studied stromatolite growth and morphology. We built a three-dimensional model based on diffusion-limited aggregation. The model was implemented in two C++ applications: a simulator engine, which can run a batch of simulations and produce result files, and a Visualization tool, which allows results to be analysed in three dimensions. After verifying that our model can indeed reproduce the growth and morphology of several types of stromatolites, we introduced a sedimentation process as an external factor. This lead to interesting results, and allowed to emit the hypothesis that stromatolite morphology may be the result of external factors as much as internal factors. This is important as stromatolite classification is usually based on their morphology, imposing that a stromatolite shape is dependant on internal factors only (i.e. the microbial mat). This statement is contradicted by our findings, Second, we decided to investigate deeper the functioning of microbial mats, We built a two-dimensional reaction-diffusion model based on discrete simulation, The model was implemented in a C++ application that allows setting and running simulations. We could then compare simulation results with real world data and verify that our model can indeed mimic the behaviour of some microbial mats. Thus, we have proposed and verified hypotheses regarding microbial mats functioning in order to help to better understand them, e.g. the cycle of some elements such as oxygen or sulfur. ln conclusion, this PhD provides a simulation software, dealing with two different approaches. This software is free and available under a GPL licence.

Järjestelmäintegraattorin strategisten kasvumahdollisuuksien analyysi

Tämän pro gradu -tutkielman tarkoituksena oli selvittää, mikä on sopivin kasvustrategia omia ohjelmistoja tuottavalle tietojärjestelmäintegraattorille. Tavoitteena oli, että tutkimustuloksia voidaan käyttää konkreettisesti toimeksiantajan, Informa Oy:n, strategisen suunnittelun tukena. Yrityksen strateginen analyysi käsitellään ulkoisten ja sisäisten tekijöiden suhteen. Samalla vertaillaan eri strategiatutkimuksen koulukuntia ja luodaan synteesiä näiden välille. Kolmas teoreettinen kokonaisuus on kasvustrategioiden tarkastelu sekä suuntaus-, että kilpailustrategioiden näkökulmasta. Empiirisen osan aineisto kerättiin kvalitatiivisen haastattelututkimuksen avulla, jossa selvitettiin toimeksiantajayrityksessä eri tehtävissä työskentelevien henkilöiden näkemyksiä. Lisäksi analysoitiinyrityksen teettämiä asiakaskyselyitä ja toimialan kehitystä käsitteleviä lehtiartikkeleita. Toimialan merkittävimmiksi kehitystrendeiksi todettiin kansainvälistyminen, verkostoituminen, keskittyminen, tuotteiden vakioituminen ja ohjelmistorajapintojen avoimuuden lisääntyminen. Informa Oy:lle esitetyistä toimenpide-ehdotuksista tärkeimmät liittyvät resurssien panostamiseen entistä enemmän ydinosaamisen ja ydintuotteiden kehittämiseen. Toimialan keskittyminen tarkoittaa sitä, että pienen lattiatason tietojärjestelmiä toimittavan yrityksen on päästävä mukaan kilpailusta voittajana selviäviin arvoketjuihin. Asiakassegmenteistä potentiaalisimmaksi kasvualueeksi todettiin pk-yritykset, sekä julkinen- ja palvelusektori.

En torno a la integración de lo interno y lo externo en los estudios historiográficos de la lengua inglesa

Aquest estudi és una aproximació crítica a la dicotomia establerta per Saussure entre la lingüística interna i la lingüística externa i l'aplicació que se n'ha fet als tractats historiogràfics de la llengua anglesa. Pel caràcter ontològic de la investigació diacrònica, aquestes consideracions saussurianes posen les bases empíriques per teoritzar sobre el canvi lingüístic en la llengua anglesa. D'altra banda, la distinció més o menys explícita entre la història interna de la llengua anglesa i l'externa és un fet comunament acceptat i utilitzat pels tractats historiogràfics consultats. A l'hora de dur a terme la investigació diacrònica, però, la història interna necessita, per a la delimitació cronològica, les aportacions de l'externa; així, encara que els condicionants sociològics es considerin marginals, els factors externs adquireixen importància no només pel fet d'incloure el context social on s'emmarquen els fenòmens lingüístics, sinó també per les consideracions de tipus sociolingüístic que en resulten, les quals aporten noves línies de recerca historiogràfica, basada en els models de variacions en el registre escrit de la llengua anglesa.