16,974 research outputs found

    In her own words: exploring the subjectivity of Freud’s ‘teacher’ Anna von Lieben

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    This project is inspired by Roy Porter (1985), who draws attention to the patient-shaped gap in medical history, and Rita Charon (2006), who emphasises the need to bring the patient’s narrative to the fore in the practice of medicine. The principal aim was to devise a means of accessing the lived experience of a patient who is no longer alive in order to gain an understanding of her narrative. Anna von Lieben was identified as a suitable subject as she wrote a substantial quantity of autopathographical poetry suitable for analysis and her status as Freud’s patient makes her a person of significant interest to the history of medicine. The poems were analysed using Interpretative Phenomenological Analysis (IPA), an idiographic and inductive method of qualitative research, based on Heideggerian hermeneutic phenomenology, which explores the lived experience of individuals and is committed to understanding the first-person perspective from the third-person position. The main findings from the IPA study reveal that Anna experienced a prolonged period of malaise, starting in late adolescence which she believed to result, at least partly, from a traumatic experience which occurred at that time. The analysis also indicates that Anna suffered from deep and lasting feelings of guilt and shame. The discovery of additional family documentation enabled me to contextualise and add substance to the findings of the IPA study. Anna’s husband’s diaries in particular reveal that Anna: • had a severe and longstanding gynaecological disorder • suffered from severe morphinism • did not benefit from Freud’s treatment which seemed neither to ease her symptoms nor identify any cause • was treated in Paris, not by Jean-Martin Charcot as previously supposed, but by a French hydrotherapist, Theodore Keller, who appears to have become a person of considerable significance in her life. The above findings led me to investigate Anna’s comorbidities (gynaecological disease and morphinism) and to show how those could be responsible for much of the symptomatology identified by Freud as ‘hysteria’. I then explore the possibility that her psychotic-like experiences could have been iatrogenically induced by her treatment first by Keller and then by Freud. Finally, I propose a fourfold set of hypotheses as an alternative to Freud’s diagnosis of hysteria

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    How to Be a God

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    When it comes to questions concerning the nature of Reality, Philosophers and Theologians have the answers. Philosophers have the answers that can’t be proven right. Theologians have the answers that can’t be proven wrong. Today’s designers of Massively-Multiplayer Online Role-Playing Games create realities for a living. They can’t spend centuries mulling over the issues: they have to face them head-on. Their practical experiences can indicate which theoretical proposals actually work in practice. That’s today’s designers. Tomorrow’s will have a whole new set of questions to answer. The designers of virtual worlds are the literal gods of those realities. Suppose Artificial Intelligence comes through and allows us to create non-player characters as smart as us. What are our responsibilities as gods? How should we, as gods, conduct ourselves? How should we be gods

    Interactive Sonic Environments: Sonic artwork via gameplay experience

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    The purpose of this study is to investigate the use of video-game technology in the design and implementation of interactive sonic centric artworks, the purpose of which is to create and contribute to the discourse and understanding of its effectiveness in electro-acoustic composition highlighting the creative process. Key research questions include: How can the language of electro-acoustic music be placed in a new framework derived from videogame aesthetics and technology? What new creative processes need to be considered when using this medium? Moreover, what aspects of 'play' should be considered when designing the systems? The findings of this study assert that composers and sonic art practitioners need little or no coding knowledge to create exciting applications and the myriad of options available to the composer when using video-game technology is limited only by imagination. Through a cyclic process of planning, building, testing and playing these applications the project revealed advantages and unique sonic opportunities in comparison to other sonic art installations. A portfolio of selected original compositions, both fixed and open are presented by the author to complement this study. The commentary serves to place the work in context with other practitioners in the field and to provide compositional approaches that have been taken

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock séptico

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    La sepsis es una afección potencialmente mortal causada por una respuesta anormal del huésped a una infección, produciendo respuestas fisiológicas alteradas que dañan los propios tejidos del paciente y pueden provocar disfunción orgánica e incluso la muerte. Asimismo, algunos pacientes sépticos progresan a shock séptico, caracterizado por alteraciones circulatorias, celulares y metabólicas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunológico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresión, la alta complejidad de la fisiopatología de la sepsis requiere una mayor investigación para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citotóxicos en la sepsis, ya que actúan como patrones moleculares asociados a daño, que inducen estrés oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activación de la piroptosis, un mecanismo de muerte celular programada que produce inflamación mediante la expresión de IL-18, IL-1β and IL-1α. Sin embargo, a pesar de la evidencia de activación del inflamasoma en las células inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activación del inflamasoma NLRP3 y la piroptosis en las células endoteliales, contribuyendo a la disfunción endotelial y la desregulación de la respuesta inmune mediada por el endotelio. Asimismo, también demostramos cómo la acetilación de histonas disminuye la activación de la piroptosis. Además, demostramos que la piroptosis se produce en pacientes con shock séptico y los niveles de histonas circulantes se correlacionan con la expresión de citoquinas proinflamatorias y citoquinas piroptóticas, la liberación de factores de adhesión endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones clínicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes críticamente enfermos no sépticos, sépticos y de shock séptico. Nuestro enfoque ayudará a caracterizar rápidamente las respuestas inmunes alteradas en pacientes sépticos y de shock séptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilación del ADN en el control del sistema inmune séptico. Nuestros resultados demostraron el papel central de la metilación del ADN modulando la respuesta molecular en los pacientes de shock séptico y contribuyendo a la inmunosupresión, a través de la alteración de los patrones de metilación de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1β and IL-1α. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

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    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives

    Strung pieces: on the aesthetics of television fiction series

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    As layered and long works, television fiction series have aesthetic properties that are built over time, bit by bit. This thesis develops a group of concepts that enable the study of these properties, It argues that a series is made of strung pieces, a system of related elements. The text begins by considering this sequential form within the fields of film and television. This opening chapter defines the object and methodology of research, arguing for a non-essentialist distinction between cinema and television and against the adequacy of textual and contextual analyses as approaches to the aesthetics of these shows. It proposes instead that these programmes should be described as televisual works that can be scrutinised through aesthetic analysis. The next chapters propose a sequence of interrelated concepts. The second chapter contends that series are composed of building blocks that can be either units into which series are divided or motifs that unify series and are dispersed across their pans. These blocks are patterned according to four kinds of relations or principles of composition. Repetition and variation are treated in tandem in the third chapter because of their close connection, given that variation emerges from established repetition. Exception and progression are also discussed together in the fourth chapter since they both require a long view of these serial works. The former, in order to be recognised as a deviation from the patterns of repetition and variation. The latter, In order to be understood in Its many dimensions as the series advances. Each of these concepts is further detailed with additional distinctions between types of units, motifs, repetitions, variations, and exceptions, using illustrative examples from numerous shows. In contrast, the section on progression uses a single series as case study, Carnivàle (2003-05), because this is the overarching principle that encompasses all the others. The conclusion considers the findings of the research and suggests avenues for their application

    Drivers and barriers to Sustainability practices in the Zambian Construction Industry

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    Zambia, and Sub-Sahara Africa (SSA) generally, is lagging behind in the area of sustainable construction due to several barriers to the implementation of sustainable construction. This study therefore explored drivers and barriers to the adoption of sustainable construction practices in Zambia. The study could inform stakeholders on measures which could improve the implementation of sustainable construction. The study used an online quantitative questionnaire survey of construction professionals and clients. A total of 112 responses were received representing various stakeholder groups in the construction industry. The data were subjected to factor analysis and ranked using the relative importance index. The data show that drivers to sustainable construction cluster into three constructs namely, environment and health-related factors, regulatory and industry-related factors and, economy and firm related factors. Barriers clustered into three groups namely, awareness and knowledge related factors, regulatory and industry-related factors and, economy and cost-related factors. Therefore, measures aimed at improving sustainable construction in Zambia should focus attention on these broad clusters

    Recent Hong Kong cinema and the generic role of film noir in relation to the politics of identity and difference

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    This thesis identifies a connection in Hong Kong cinema with classical Hollywood film noir and examines what it will call a 'reinvestment' in film noir in recent films. It will show that this reinvestment is a discursive strategy that both engages the spectator-subject in the cinematic practice and disengages him or her from the hegemony of the discourse by decentring the narrative. The thesis argues that a cinematic practice has occurred in the recent reinvestment of film noir in Hong Kong, which restages the intertextual relay of the historical genre that gives rise to an expectation of ideas about social instability. The noir vision that is seen as related to the fixed categories of film narratives, characterizations and visual styles is reassessed in the course of the thesis using Derridian theory. The focus of analysis is the way in which the constitution of meanings is dependent on generic characteristics that are different. Key to the phenomenon is a film strategy that destabilizes, differs and defers the interpretation of crises-personal, social, political and/or cultural-by soliciting self-conscious re-reading of suffering, evil, fate, chance and fortune. It will be argued that such a strategy evokes the genre expectation as the film invokes a network of ideas regarding a world perceived by the audience in association with the noirish moods of claustrophobia, paranoia, despair and nihilism. The noir vision is thus mutated and transformed when the film device differs and defers the conception of the crises as tragic in nature by exposing the workings of the genre amalgamation and the ideological function of the cinematic discourse. Thus, noirishness becomes both an affect and an agent that contrives a self-reflexive re-reading of the tragic vision and of the conventional comprehension of reality within the discursive practice. The film strategy, as an agent that problematizes the film form and narrative, gives rise to what I call a politics of difference, which may also be understood as the Lyotardian 'language game' or a practice of 'pastiche' in Jameson's terminology. Under the influence of the film strategy, the spectator is enabled to negotiate his or her understanding of recent Hong Kong cinema diegetically and extra-diegetically by traversing different positions of cinematic identification. When the practice of genre amalgamation adopts the visual impact of the noirish film form, the film turns itself into a playing field of 'fatal' misrecognition or a site of question. Through cinematic identification and alienation from the identification, the spectator-subject is enabled to experience the misrecognition as the film slowly foregrounds the way in which the viewer's presence is implicated in the narrative. This thesis demonstrates that certain contemporary Hong Kong films introduce this selfconscious mode of explication and interpretation, which solicits the spectator to negotiate his or her subject-position in the course of viewing. The notions of identity and subjectivity under scrutiny will thus be reread. With reference to The Private Eye Blue, Swordsman II, City a/Glass and Happy Together, the thesis shall explore the ways in which the Hong Kong films enable and facilitate a negotiation of cultural identity

    In search of 'The people of La Manche': A comparative study of funerary practices in the Transmanche region during the late Neolithic and Early Bronze Age (250BC-1500BC)

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    This research project sets out to discover whether archaeological evidence dating between 2500 BC - 1500 BC from supposed funerary contexts in Kent, flanders and north-eastern Transmanche France is sufficient to make valid comparisons between social and cultural structures on either side of the short-sea Channel region. Evidence from the beginning of the period primarily comes in the form of the widespread Beaker phenomenon. Chapter 5 shows that this class of data is abundant in Kent but quite sparse in the Continental zones - most probably because it has not survived well. This problem also affects the human depositional evidence catalogued in Chapter 6, particularly in Fanders but also in north-eastern Transmanche France. This constricts comparative analysis, however, the abundant data from Kent means that general trends are still discernible. The quality and volume of data relating to the distribution, location, morphology and use of circular monuments in all three zones is far better - as demonstrated in Chapter 7 -mostly due to extensive aerial surveying over several decades. When the datasets are taken as a whole, it becomes possible to successfully apply various forms of comparative analyses. Most remarkably, this has revealed that some monuments apparently have encoded within them a sophisticated and potentially symbolically charged geometric shape. This, along with other less contentious evidence, demonstrates a level of conformity that strongly suggests a stratum of cultural homogeneity existed throughout the Transmanche region during the period 2500 BC - 1500 BC. The fact that such changes as are apparent seem to have developed simultaneously in each of the zones adds additional weight to the theory that contact throughout the Transmanche region was endemic. Even so, it may not have been continuous; there may actually have been times of relative isolation - the data is simply too course to eliminate such a possibility
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