Non-normally distributed data and non-parametric statistics

Different types of numerical data can be collected in a scientific investigation and the choice of statistical analysis will often depend on the distribution of the data. A basic distinction between variables is whether they are ‘parametric’ or ‘non-parametric’. When a variable is parametric, the data come from a symmetrically shaped distribution known as the ‘Gaussian’ or ‘normal distribution’ whereas non-parametric variables may have a distribution which deviates markedly in shape from normal. This article describes several aspects of the problem of non-normality including: (1) how to test for two common types of deviation from a normal distribution, viz., ‘skew’ and ‘kurtosis’, (2) how to fit the normal distribution to a sample of data, (3) the transformation of non-normally distributed data and scores, and (4) commonly used ‘non-parametric’ statistics which can be used in a variety of circumstances.

A study of magnetic non-linearity and finite length effects in solid iron subjected to a travelling MMF wave

This thesis describes an experimental and analytic study of the effects of magnetic non-linearity and finite length on the loss and field distribution in solid iron due to a travelling mmf wave. In the first half of the thesis, a two-dimensional solution is developed which accounts for the effects of both magnetic non-linearity and eddy-current reaction; this solution is extended, in the second half, to a three-dimensional model. In the two-dimensional solution, new equations for loss and flux/pole are given; these equations contain the primary excitation, the machine parameters and factors describing the shape of the normal B-H curve. The solution applies to machines of any air-gap length. The conditions for maximum loss are defined, and generalised torque/frequency curves are obtained. A relationship between the peripheral component of magnetic field on the surface of the iron and the primary excitation is given. The effects of magnetic non-linearity and finite length are combined analytically by introducing an equivalent constant permeability into a linear three-dimensional analysis. The equivalent constant permeability is defined from the non-linear solution for the two-dimensional magnetic field at the axial centre of the machine to avoid iterative solutions. In the linear three-dimensional analysis, the primary excitation in the passive end-regions of the machine is set equal to zero and the secondary end faces are developed onto the air-gap surface. The analyses, and the assumptions on which they are based, were verified on an experimental machine which consists of a three-phase rotor and alternative solid iron stators, one with copper end rings, and one without copper end rings j the main dimensions of the two stators are identical. Measurements of torque, flux /pole, surface current density and radial power flow were obtained for both stators over a range of frequencies and excitations. Comparison of the measurements on the two stators enabled the individual effects of finite length and saturation to be identified, and the definition of constant equivalent permeability to be verified. The penetration of the peripheral flux into the stator with copper end rings was measured and compared with theoretical penetration curves. Agreement between measured and theoretical results was generally good.

Does normal processing provide evidence of specialised semantic subsystems?

Category-specific disorders are frequently explained by suggesting that living and non-living things are processed in separate subsystems (e.g. Caramazza & Shelton, 1998). If subsystems exist, there should be benefits for normal processing, beyond the influence of structural similarity. However, no previous study has separated the relative influences of similarity and semantic category. We created novel examples of living and non-living things so category and similarity could be manipulated independently. Pre-tests ensured that our images evoked appropriate semantic information and were matched for familiarity. Participants were trained to associate names with the images and then performed a name-verification task under two levels of time pressure. We found no significant advantage for living things alongside strong effects of similarity. Our results suggest that similarity rather than category is the key determinant of speed and accuracy in normal semantic processing. We discuss the implications of this finding for neuropsychological studies. © 2005 Psychology Press Ltd.

Evolution of non-uniformly seeded warm clouds in idealized turbulent conditions

We present a mean-field model of cloud evolution that describes droplet growth due to condensation and collisions and droplet loss due to fallout. The model accounts for the effects of cloud turbulence both in a large-scale turbulent mixing and in a microphysical enhancement of condensation and collisions. The model allows for an effective numerical simulation by a scheme that is conservative in water mass and keeps accurate count of the number of droplets. We first study the homogeneous situation and determine how the rain-initiation time depends on the concentration of cloud condensation nuclei (CCN) and turbulence level. We then consider clouds with an inhomogeneous concentration of CCN and evaluate how the rain initiation time and the effective optical depth vary in space and time. We argue that over-seeding even a part of a cloud by small hygroscopic nuclei, one can substantially delay the onset and increase the amount of precipitation.

Identifying and correcting non-Markov states in peptide conformational dynamics

Conformational transitions in proteins define their biological activity and can be investigated in detail using the Markov state model. The fundamental assumption on the transitions between the states, their Markov property, is critical in this framework. We test this assumption by analyzing the transitions obtained directly from the dynamics of a molecular dynamics simulated peptide valine-proline-alanine-leucine and states defined phenomenologically using clustering in dihedral space. We find that the transitions are Markovian at the time scale of ˜ 50 ps and longer. However, at the time scale of 30–40 ps the dynamics loses its Markov property. Our methodology reveals the mechanism that leads to non-Markov behavior. It also provides a way of regrouping the conformations into new states that now possess the required Markov property of their dynamics.

Non-linear hierarchical visualisation

This thesis applies a hierarchical latent trait model system to a large quantity of data. The motivation for it was lack of viable approaches to analyse High Throughput Screening datasets which maybe include thousands of data points with high dimensions. High Throughput Screening (HTS) is an important tool in the pharmaceutical industry for discovering leads which can be optimised and further developed into candidate drugs. Since the development of new robotic technologies, the ability to test the activities of compounds has considerably increased in recent years. Traditional methods, looking at tables and graphical plots for analysing relationships between measured activities and the structure of compounds, have not been feasible when facing a large HTS dataset. Instead, data visualisation provides a method for analysing such large datasets, especially with high dimensions. So far, a few visualisation techniques for drug design have been developed, but most of them just cope with several properties of compounds at one time. We believe that a latent variable model (LTM) with a non-linear mapping from the latent space to the data space is a preferred choice for visualising a complex high-dimensional data set. As a type of latent variable model, the latent trait model can deal with either continuous data or discrete data, which makes it particularly useful in this domain. In addition, with the aid of differential geometry, we can imagine the distribution of data from magnification factor and curvature plots. Rather than obtaining the useful information just from a single plot, a hierarchical LTM arranges a set of LTMs and their corresponding plots in a tree structure. We model the whole data set with a LTM at the top level, which is broken down into clusters at deeper levels of t.he hierarchy. In this manner, the refined visualisation plots can be displayed in deeper levels and sub-clusters may be found. Hierarchy of LTMs is trained using expectation-maximisation (EM) algorithm to maximise its likelihood with respect to the data sample. Training proceeds interactively in a recursive fashion (top-down). The user subjectively identifies interesting regions on the visualisation plot that they would like to model in a greater detail. At each stage of hierarchical LTM construction, the EM algorithm alternates between the E- and M-step. Another problem that can occur when visualising a large data set is that there may be significant overlaps of data clusters. It is very difficult for the user to judge where centres of regions of interest should be put. We address this problem by employing the minimum message length technique, which can help the user to decide the optimal structure of the model. In this thesis we also demonstrate the applicability of the hierarchy of latent trait models in the field of document data mining.

Investigation of chromatic function in the normal and abnormal eye

This study examined the use of non-standard parameters to investigate the visual field, with particular reference to the detection of glaucomatous visual field loss. Evaluation of the new perimetric strategy for threshold estimation - FASTPAC, demonstrated a reduction in the examination time of normals compared to the standard strategy. Despite an increased within-test variability the FASTPAC strategy produced a similar mean sensitivity to the standard strategy, reducing the effects of patient fatigue. The new technique of Blue-Yellow perimetry was compared to White-White perimetry for the detection of glaucomatous field loss in OHT and POAG. Using a database of normal subjects, confidence limits for normality were constructed to account for the increased between-subject variability with increase in age and eccentricity and for the greater variability of the Blue-Yellow field compared to the White-White field. Effects of individual ocular media absorption had little effect on Blue-Yellow field variability. Total and pattern probability analysis revealed five of 27 OHTs to exhibit Blue-Yellow focal abnormalities; two of these patients subsequently developed White-White loss. Twelve of the 24 POAGs revealed wider and/or deeper Blue-Yellow loss compared with the White-White field. Blue-Yellow perimetry showed good sensitivity and specificity characteristics, however, lack of perimetric experience and the presence of cataract influenced the Blue-Yellow visual field and may confound the interpretation of Blue-Yellow visual field loss. Visual field indices demonstrated a moderate relationship to the structural parameters of the optic nerve head using scanning laser tomography. No abnormalities in Blue-Yellow or Red-Green colour CS was apparent for the OHT patients. A greater vulnerability of the SWS pathway in glaucoma was demonstrated using Blue-Yellow perimetry however predicting which patients may benefit from B-Y perimetric examination is difficult. Furthermore, cataract and the extent of the field loss may limit the extent to which the integrity of the SWS channels can be selectively examined.

Non-standard techniques for the investigation of the visual field

The study investigated the potential applications and the limitations of non-standard techniques of visual field investigation utilizing automated perimetry. Normal subjects exhibited a greater sensitivity to kinetic stimuli than to static stimuli of identical size. The magnitude of physiological SKD was found to be largely independent of age, stimulus size, meridian and eccentricity. The absence of a dependency on stimulus size indicated that successive lateral spatial summation could not totally account for the underlying mechanism of physiological SKD. The visual field indices MD and LV exhibited a progressive deterioration during the time course of a conventional central visual field examination both for normal subjects and for ocular hypertensive patients. The fatigue effect was more pronounced in the latter stages and for the second eye tested. The confidence limits for the definition of abnormality should reflect the greater effect of fatigue on the second eye. A 330 cdm-2 yellow background was employed for blue-on-yellow perimetry. Instrument measurement range was preserved by positioning a concave mirror behind the stimulus bulb to increase the light output by 60% . The mean magnitude of SWS pathway isolation was approximately 1.4 log units relative to a 460nm stimulus filter. The absorption spectra of the ocular media exhibited an exponential increase with increase in age, whilst that of the macular pigment showed no systematic trend. The magnitude of ocular media absorption was demonstrated to reduce with increase in wavelength. Ocular media absorption was significantly greater in diabetic patients than in normal subjects. Five diabetic patients with either normal or borderline achromatic sensitivity exhibited an abnormal blue-on-yellow sensitivity; two of these patients showed no signs of retinopathy. A greater vulnerability of the SWS pathway to the diabetic disease process was hypothesized.

Une étude générique du metteur en scène au théâtre:son émergence et son rôle moderne et contemporain

The theatre director (metteur en scene in French) is a relatively new figure in theatre practice. It was not until the I820s that the term 'mise en scene' gained currency. The term 'director' was not in general use until the I880s. The emergence and the role of the director has been considered from a variety of perspectives, either through the history of theatre (Allevy, Jomaron, Sarrazac, Viala, Biet and Triau); the history of directing (Chinoy and Cole, Boll, Veinstein, Roubine); semiotic approaches to directing (Whitmore, Miller, Pavis); the semiotics of performance (De Marinis); generic approaches to the mise en scene (Thomasseau, Banu); post-dramatic approaches to theatre (Lehmann); approaches to performance process and the specifics of rehearsal methodology (Bradby and Williams, Giannachi and Luckhurst, Picon-Vallin, Styan). What the scholarly literature has not done so far is to map the parameters necessarily involved in the directing process, and to incorporate an analysis of the emergence of the theatre director during the modem period and consider its impact on contemporary performance practice. Directing relates primarily to the making of the performance guided by a director, a single figure charged with the authority to make binding artistic decisions. Each director may have her/his own personal approaches to the process of preparation prior to a show. This is exemplified, for example, by the variety of terms now used to describe the role and function of directing, from producer, to facilitator or outside eye. However, it is essential at the outset to make two observations, each of which contributes to a justification for a generic analysis (as opposed to a genetic approach). Firstly, a director does not work alone, and cooperation with others is involved at all stages of the process. Secondly, beyond individual variation, the role of the director remains twofold. The first is to guide the actors (meneur de jeu, directeur d'acteurs, coach); the second is to make a visual representation in the performance space (set designer, stage designer, costume designer, lighting designer, scenographe). The increasing place of scenography has brought contemporary theatre directors such as Wilson, Castellucci, Fabre to produce performances where the performance space becomes a semiotic dimension that displaces the primacy of the text. The play is not, therefore, the sole artistic vehicle for directing. This definition of directing obviously calls for a definition of what the making of the performance might be. The thesis defines the making of the performance as the activity of bringing a social event, by at least one performer, providing visual and/or textual meaning in a performance space. This definition enables us to evaluate four consistent parameters throughout theatre history: first, the social aspect associated to the performance event; second, the devising process which may be based on visual and/or textual elements; third, the presence of at least one performer in the show; fourth, the performance space (which is not simply related to the theatre stage). Although the thesis focuses primarily on theatre practice, such definition blurs the boundaries between theatre and other collaborative artistic disciplines (cinema, opera, music and dance). These parameters illustrate the possibility to undertake a generic analysis of directing, and resonate with the historical, political and artistic dimensions considered. Such a generic perspective on the role of the director addresses three significant questions: an historical question: how/why has the director emerged?; a sociopolitical question: how/why was the director a catalyst for the politicisation of theatre, and subsequently contributed to the rise of State-funded theatre policy?; and an artistic one: how/why the director has changed theatre practice and theory in the twentieth-century? Directing for the theatre as an artistic activity is a historically situated phenomenon. It would seem only natural from a contemporary perspective to associate the activity of directing to the function of the director. This is relativised, however, by the question of how the performance was produced before the modern period. The thesis demonstrates that the rise of the director is a progressive and historical phenomenon (Dort) rather than a mere invention (Viala, Sarrazac). A chronological analysis of the making of the performance throughout theatre history is the most useful way to open the study. In order to understand the emergence of the director, the research methodology assesses the interconnection of the four parameters above throughout four main periods of theatre history: the beginning of the Renaissance (meneur de jeu), the classical age (actor-manager and stage designer-manager), the modern period (director) and the contemporary period (director-facilitator, performer). This allows us properly to appraise the progressive emergence of the director, as well as to make an analysis of her/his modern and contemporary role. The first chapter argues that the physical separation between the performance space and its audience, which appeared in the early fifteenth-century, has been a crucial feature in the scenographic, aesthetic, political and social organisation of the performance. At the end of the Middle Ages, French farces which raised socio-political issues (see Bakhtin) made a clear division on a single outdoor stage (treteau) between the actors and the spectators, while religious plays (drame fiturgique, mystere) were mostly performed on various outdoor and opened multispaces. As long as the performance was liturgical or religious, and therefore confined within an acceptable framework, it was allowed. At the time, the French ecclesiastical and civil authorities tried, on several occasions, to prohibit staged performances. As a result, practitioners developed non-official indoor spaces, the Theatre de fa Trinite (1398) being the first French indoor theatre recognized by scholars. This self-exclusion from the open public space involved breaking the accepted rules by practitioners (e.g. Les Confreres de fa Passion), in terms of themes but also through individual input into a secular performance rather than the repetition of commonly known religious canvases. These developments heralded the authorised theatres that began to emerge from the mid-sixteenth century, which in some cases were subsidised in their construction. The construction of authorised indoor theatres associated with the development of printing led to a considerable increase in the production of dramatic texts for the stage. Profoundly affecting the reception of the dramatic text by the audience, the distance between the stage and the auditorium accompanied the changing relationship between practitioners and spectators. This distance gave rise to a major development of the role of the actor and of the stage designer. The second chapter looks at the significance of both the actor and set designer in the devising process of the performance from the sixteenth-century to the end of the nineteenth-century. The actor underwent an important shift in function in this period from the delivery of an unwritten text that is learned in the medieval oral tradition to a structured improvisation produced by the commedia dell 'arte. In this new form of theatre, a chef de troupe or an experienced actor shaped the story, but the text existed only through the improvisation of the actors. The preparation of those performances was, moreover, centred on acting technique and the individual skills of the actor. From this point, there is clear evidence that acting began to be the subject of a number of studies in the mid-sixteenth-century, and more significantly in the seventeenth-century, in Italy and France. This is revealed through the implementation of a system of notes written by the playwright to the actors (stage directions) in a range of plays (Gerard de Vivier, Comedie de la Fidelite Nuptiale, 1577). The thesis also focuses on Leoni de' Sommi (Quatro dialoghi, 1556 or 1565) who wrote about actors' techniques and introduced the meneur de jeu in Italy. The actor-manager (meneur de jeu), a professional actor, who scholars have compared to the director (see Strihan), trained the actors. Nothing, however, indicates that the actor-manager was directing the visual representation of the text in the performance space. From the end of the sixteenth-century, the dramatic text began to dominate the process of the performance and led to an expansion of acting techniques, such as the declamation. Stage designers carne from outside the theatre tradition and played a decisive role in the staging of religious celebrations (e.g. Actes des Apotres, 1536). In the sixteenth-century, both the proscenium arch and the borders, incorporated in the architecture of the new indoor theatres (theatre a l'italienne), contributed to create all kinds of illusions on the stage, principally the revival of perspective. This chapter shows ongoing audience demands for more elaborate visual effects on the stage. This led, throughout the classical age, and even more so during the eighteenth-century, to grant the stage design practitioner a major role in the making of the performance (see Ciceri). The second chapter demonstrates that the guidance of the actors and the scenographic conception, which are the artistic components of the role of the director, appear to have developed independently from one another until the nineteenth-century. The third chapter investigates the emergence of the director per se. The causes for this have been considered by a number of scholars, who have mainly identified two: the influence of Naturalism (illustrated by the Meiningen Company, Antoine, and Stanislavski) and the invention of electric lighting. The influence of the Naturalist movement on the emergence of the modem director in the late nineteenth-century is often considered as a radical factor in the history of theatre practice. Naturalism undoubtedly contributed to changes in staging, costume and lighting design, and to a more rigorous commitment to the harmonisation and visualisation of the overall production of the play. Although the art of theatre was dependent on the dramatic text, scholars (Osborne) demonstrate that the Naturalist directors did not strictly follow the playwright's indications written in the play in the late nineteenth-century. On the other hand, the main characteristic of directing in Naturalism at that time depended on a comprehensive understanding of the scenography, which had to respond to the requirements of verisimilitude. Electric lighting contributed to this by allowing for the construction of a visual narrative on stage. However, it was a master technician, rather than an emergent director, who was responsible for key operational decisions over how to use this emerging technology in venues such as the new Bayreuth theatre in 1876. Electric lighting reflects a normal technological evolution and cannot be considered as one of the main causes of the emergence of the director. Two further causes of the emergence of the director, not considered in previous studies, are the invention of cinema and the Symbolist movement (Lugne-Poe, Meyerhold). Cinema had an important technological influence on the practitioners of the Naturalist movement. In order to achieve a photographic truth on the stage (tableau, image), Naturalist directors strove to decorate the stage with the detailed elements that would be expected to be found if the situation were happening in reality. Film production had an influence on the work of actors (Walter). The filmmaker took over a primary role in the making of the film, as the source of the script, the filming process and the editing of the film. This role influenced the conception that theatre directors had of their own work. It is this concept of the director which influenced the development of the theatre director. As for the Symbolist movement, the director's approach was to dematerialise the text of the playwright, trying to expose the spirit, movement, colour and rhythm of the text. Therefore, the Symbolists disengaged themselves from the material aspect of the production, and contributed to give greater artistic autonomy to the role of the director. Although the emergence of the director finds its roots amongst the Naturalist practitioners (through a rigorous attempt to provide a strict visual interpretation of the text on stage), the Symbolist director heralded the modem perspective of the making of performance. The emergence of the director significantly changed theatre practice and theory. For instance, the rehearsal period became a clear work in progress, a platform for both developing practitioners' techniques and staging the show. This chapter explores and contrasts several practitioners' methods based on the two aspects proposed for the definition of the director (guidance of the actors and materialisation of a visual space). The fourth chapter argues that the role of the director became stronger, more prominent, and more hierarchical, through a more political and didactic approach to theatre as exemplified by the cases of France and Germany at the end of the nineteenth-century and through the First World War. This didactic perspective to theatre defines the notion of political theatre. Political theatre is often approached by the literature (Esslin, Willett) through a Marxist interpretation of the great German directors' productions (Reinhardt, Piscator, Brecht). These directors certainly had a great influence on many directors after the Second World War, such as Jean Vilar, Judith Molina, Jean-Louis Barrault, Roger Planchon, Augusto Boal, and others. This chapter demonstrates, moreover, that the director was confirmed through both ontological and educational approaches to the process of making the performance, and consequently became a central and paternal figure in the organisational and structural processes practiced within her/his theatre company. In this way, the stance taken by the director influenced the State authorities in establishing theatrical policy. This is an entirely novel scholarly contribution to the study of the director. The German and French States were not indifferent to the development of political theatre. A network of public theatres was thus developed in the inter-war period, and more significantly after the Second World War. The fifth chapter shows how State theatre policies establish its sources in the development of political theatre, and more specifically in the German theatre trade union movement (Volksbiihne) and the great directors at the end of the nineteenth-century. French political theatre was more influenced by playwrights and actors (Romain Rolland, Louise Michel, Louis Lumet, Emile Berny). French theatre policy was based primarily on theatre directors who decentralised their activities in France during both the inter-war period and the German occupation. After the Second World War, the government established, through directors, a strong network of public theatres. Directors became both the artistic director and the executive director of those institutionalised theatres. The institution was, however, seriously shaken by the social and political upheaval of 1968. It is the link between the State and the institution in which established directors were entangled that was challenged by the young emerging directors who rejected institutionalised responsibility in favour of the autonomy of the artist in the 1960s. This process is elucidated in chapter five. The final chapter defines the contemporary role of the director in contrasting thework of a number of significant young theatre practitioners in the 1960s such as Peter Brook, Ariane Mnouchkine, The Living Theater, Jerzy Grotowski, Augusto Boal, Eugenio Barba, all of whom decided early on to detach their companies from any form of public funding. This chapter also demonstrates how they promoted new forms of performance such as the performance of the self. First, these practitioners explored new performance spaces outside the traditional theatre building. Producing performances in a non-dedicated theatre place (warehouse, street, etc.) was a more frequent practice in the 1960s than before. However, the recent development of cybertheatre questions both the separation of the audience and the practitioners and the place of the director's role since the 1990s. Secondly, the role of the director has been multifaceted since the 1960s. On the one hand, those directors, despite all their different working methods, explored western and non-western acting techniques based on both personal input and collective creation. They challenged theatrical conventions of both the character and the process of making the performance. On the other hand, recent observations and studies distinguish the two main functions of the director, the acting coach and the scenographe, both having found new developments in cinema, television, and in various others events. Thirdly, the contemporary director challenges the performance of the text. In this sense, Antonin Artaud was a visionary. His theatre illustrates the need for the consideration of the totality of the text, as well as that of theatrical production. By contrasting the theories of Artaud, based on a non-dramatic form of theatre, with one of his plays (Le Jet de Sang), this chapter demonstrates how Artaud examined the process of making the performance as a performance. Live art and autobiographical performance, both taken as directing the se(f, reinforce this suggestion. Finally, since the 1990s, autobiographical performance or the performance of the self is a growing practical and theoretical perspective in both performance studies and psychology-related studies. This relates to the premise that each individual is making a representation (through memory, interpretation, etc.) of her/his own life (performativity). This last section explores the links between the place of the director in contemporary theatre and performers in autobiographical practices. The role of the traditional actor is challenged through non-identification of the character in the play, while performers (such as Chris Burden, Ron Athey, Orlan, Franko B, Sterlac) have, likewise, explored their own story/life as a performance. The thesis demonstrates the validity of the four parameters (performer, performance space, devising process, social event) defining a generic approach to the director. A generic perspective on the role of the director would encompass: a historical dimension relative to the reasons for and stages of the 'emergence' of the director; a socio-political analysis concerning the relationship between the director, her/his institutionalisation, and the political realm; and the relationship between performance theory, practice and the contemporary role of the director. Such a generic approach is a new departure in theatre research and might resonate in the study of other collaborative artistic practices.

A deficit in encoding the order of visual sequences in developmental dyslexia: a non -phonological deficit

The present thesis tested the hypothesis of Stanovich, Siegel, & Gottardo (1997) that surface dyslexia is the result of a milder phonological deficit than that seen in phonological dyslexia coupled with reduced reading experience. We found that a group of adults with surface dyslexia showed a phonological deficit that was commensurate with that shown by a group of adults with phonological dyslexia (matched for chronological age and verbal and non-verbal IQ) and normal reading experience. We also showed that surface dyslexia cannot be accounted for by a semantic impairment or a deficit in the verbal learning and recall of lexical-semantic information (such as meaningful words), as both dyslexic subgroups performed the same. This study has replicated the results of our published study that surface dyslexia is not the consequence of a mild retardation or reduced learning opportunities but a separate impairment linked to a deficit in written lexical learning, an ability needed to create novel lexical representations from a series of unrelated visual units, which is independent from the phonological deficit (Romani, Di Betta, Tsouknida & Olson, 2008). This thesis also provided evidence that a selective nonword reading deficit in developmental dyslexia persists beyond poor phonology. This was shown by finding a nonword reading deficit even in the presence of normal regularity effects in the dyslexics (when compared to both reading and spelling-age matched controls). A nonword reading deficit was also found in the surface dyslexics. Crucially, this deficit was as strong as in the phonological dyslexics despite better functioning of the sublexical route for the former. These results suggest that a nonword reading deficit cannot be solely explained by a phonological impairment. We, thus, suggested that nonword reading should also involve another ability relating to the processing of novel visual orthographic strings, which we called 'orthographic coding'. We then investigated the ability to process series of independent units within multi-element visual arrays and its relationship with reading and spelling problems. We identified a deficit in encoding the order of visual sequences (involving both linguistic and nonlinguistic information) which was significantly associated with word and nonword processing. More importantly, we revealed significant contributions to orthographic skills in both dyslexic and control individuals, even after age, performance IQ and phonological skills were controlled. These results suggest that spelling and reading do not only tap phonological skills but also order encoding skills.

Development of a multicellular co-culture model of normal and cystic fibrosis human airways in vitro

Cystic fibrosis (CF) is the most common lethal inherited disease among Caucasians and arises due to mutations in a chloride channel, called cystic fibrosis transmembrane conductance regulator. A hallmark of this disease is the chronic bacterial infection of the airways, which is usually, associated with pathogens such as Pseudomonas aeruginosa, S. aureus and recently becoming more prominent, B. cepacia. The excessive inflammatory response, which leads to irreversible lung damage, will in the long term lead to mortality of the patient at around the age of 40 years. Understanding the pathogenesis of CF currently relies on animal models, such as those employing genetically-modified mice, and on single cell culture models, which are grown either as polarised or non-polarised epithelium in vitro. Whilst these approaches partially enable the study of disease progression in CF, both types of models have inherent limitations. The overall aim of this thesis was to establish a multicellular co-culture model of normal and CF human airways in vitro, which helps to partially overcome these limitations and permits analysis of cell-to-cell communication in the airways. These models could then be used to examine the co-ordinated response of the airways to infection with relevant pathogens in order to validate this approach over animals/single cell models. Therefore epithelial cell lines of non-CF and CF background were employed in a co-culture model together with human pulmonary fibroblasts. Co-cultures were grown on collagen-coated permeable supports at air-liquid interface to promote epithelial cell differentiation. The models were characterised and essential features for investigating CF infections and inflammatory responses were investigated and analysed. A pseudostratified like epithelial cell layer was established at air liquid interface (ALI) of mono-and co-cultures and cell layer integrity was verified by tight junction (TJ) staining and transepithelial resistance measurements (TER). Mono- and co-cultures were also found to secrete the airway mucin MUC5AC. Influence of bacterial infections was found to be most challenging when intact S. aureus, B. cepacia and P. aeruginosa were used. CF mono- and co-cultures were found to mimic the hyperinflammatory state found in CF, which was confirmed by analysing IL-8 secretions of these models. These co-culture models will help to elucidate the role fibroblasts play in the inflammatory response to bacteria and will provide a useful testing platform to further investigate the dysregulated airway responses seen in CF.

Sparse signal representation by adaptive non-uniform B-spline dictionaries on a compact interval

Non-uniform B-spline dictionaries on a compact interval are discussed in the context of sparse signal representation. For each given partition, dictionaries of B-spline functions for the corresponding spline space are built up by dividing the partition into subpartitions and joining together the bases for the concomitant subspaces. The resulting slightly redundant dictionaries are composed of B-spline functions of broader support than those corresponding to the B-spline basis for the identical space. Such dictionaries are meant to assist in the construction of adaptive sparse signal representation through a combination of stepwise optimal greedy techniques.

Multispectral retinal image analysis:a novel non-invasive tool for retinal imaging

Purpose-To develop a non-invasive method for quantification of blood and pigment distributions across the posterior pole of the fundus from multispectral images using a computer-generated reflectance model of the fundus. Methods - A computer model was developed to simulate light interaction with the fundus at different wavelengths. The distribution of macular pigment (MP) and retinal haemoglobins in the fundus was obtained by comparing the model predictions with multispectral image data at each pixel. Fundus images were acquired from 16 healthy subjects from various ethnic backgrounds and parametric maps showing the distribution of MP and of retinal haemoglobins throughout the posterior pole were computed. Results - The relative distributions of MP and retinal haemoglobins in the subjects were successfully derived from multispectral images acquired at wavelengths 507, 525, 552, 585, 596, and 611?nm, providing certain conditions were met and eye movement between exposures was minimal. Recovery of other fundus pigments was not feasible and further development of the imaging technique and refinement of the software are necessary to understand the full potential of multispectral retinal image analysis. Conclusion - The distributions of MP and retinal haemoglobins obtained in this preliminary investigation are in good agreement with published data on normal subjects. The ongoing development of the imaging system should allow for absolute parameter values to be computed. A further study will investigate subjects with known pathologies to determine the effectiveness of the method as a screening and diagnostic tool.

A comparison of beta-amyloid deposition in the medial temporal lobe in sporadic Alzheimer's disease, Down's syndrome and normal elderly brains

The density of beta-amyloid (A beta) deposits was studied in the medial temporal lobe in non-demented individuals and in sporadic Alzheimer's disease (SAD) and Down's syndrome (DS). No A beta deposits were recorded in six of the non-demented cases, while in a further eight cases, these were confined to either the lateral occipitotemporal or parahippocampal gyrus. The mean density of A beta deposits in the cortex was greater in SAD and DS than in non-demented cases but with overlap between patient groups. The mean density of A beta deposits was greater in DS than SAD consistent with a gene dosage effect. The ratio of primitive to diffuse A beta deposits was greater in DS and in non-demented cases than in SAD and the ratio of classic to diffuse deposits was lowest in DS. In all groups, A beta deposits occurred in clusters which were often regularly distributed. In the cortex, the dimension of the A beta clusters was greater in SAD than in the non-demented cases and DS. The data suggest that the development of A beta pathology in the hippocampus could be a factor in the development of DS and SAD. Furthermore, the high density of A beta deposits, and in particular the high proportion of primitive type deposits, may be important in DS while the development of large clusters of A beta deposits may be a factor in SAD.

A quantitative study of abnormally enlarged neurons in cognitively normal brain and neurodegenerative disease

Abnormally enlarged neurons (AEN) occur in many neurodegenerative diseases. To define AEN more objectively, the frequency distribution of the ratio of greatest cell diameter(CD) to greatest nuclear diameter (ND) was studied in populations of cortical neurons in tissue sections of seven cognitively normal brains. The frequency distribution of CD/ND deviated from a normal distribution in 15 out of 18 populations of neurons studied and hence, the 95th percentile (95P) was used to define a limit of the CD/ND ratio excluding the5% most extreme observations. The 95P of the CD/ ND ratio varied from 2.0 to 3.0 in different cases and regions and a value of 95P = 3.0 was chosen to define the limit for normalneurons under non-pathological conditions. Based on the 95P = 3.0 criterion, the proportion of AEN with a CD/ND ≥ 3 varied from 2.6% in Alzheimer's disease (AD) to 20.3% in Pick's disease (PiD). The data suggest: (1) that a CL/ND ≥ 3.0 may be a useful morphological criterion for defining AEN, and (2) AEN were most numerous in PiD and corticobasal degeneration (CBD) and least abundant in AD and in dementia with Lewy bodies (DLB). © 2013 Dustri-Verlag Dr. K. Feistle.