Genetic studies on Finnish lupus erythematosus patients with cutaneous manifestations

Lupus erythematosus (LE) is a chronic, heterogeneous autoimmune disorder with abnormal immune responses, including production of autoantibodies and immune complexes. Clinical presentations of the disease range from mild cutaneous manifestations to a more generalised systemic involvement of internal organs. Cutaneous (CLE) forms are further subclassified into discoid LE (DLE), subacute cutaneous LE (SCLE) and acute cutaneous lupus erythematosus (ACLE), and may later progress to systemic disease (SLE). Both genetic and environmental factors contribute to the disease, although the precise aetiology is still elusive. Furthermore, complex gene-gene or gene-environment interactions may result in different subphenotypes of lupus. The genetic background of CLE is poorly known and only a few genes are confirmed, while the number of robust genetic associations in SLE exceeds 30. The aim of this thesis was to characterise the recruited patients clinically, and identify genetic variants conferring susceptibility to cutaneous variants of LE. Given that cutaneous and systemic disease may share underlying genetic factors, putative CLE candidate genes for genotyping were selected among those showing strong evidence of association in SLE. The correlation between relevant clinical manifestations and risk genotypes was investigated in order to find specific subphenotype associations. In addition, epistatic interactions in SLE were studied. Finally, the role of tissue degrading matrix metalloproteinases (MMP) in LE tissue injury was explored. These studies were conducted in Finnish case-control and family cohort, and Swedish case-control cohort. The clinical picture of the patients in terms of cutaneous, haematological and immunological findings resembled that described in the contemporary literature. However, the proportion of daily smokers was very high supporting the role of smoking in disease aetiology. The results confirmed that, even though clinically distinct entities, CLE and SLE share predisposing genetic factors. For the first time it was shown that known SLE susceptibility genes IRF5 and TYK2 also increase the risk of CLE. A tendency toward gene-gene interaction between these genes was found in SLE. As a remarkable novel finding, it was observed that ITGAM polymorphisms associated even more strongly to DLE than SLE, and the risk estimates were substantially higher than those reported for SLE. Several other recently identified SLE susceptibility genes showed signs of good or modest association especially in DLE. Subphenotype analyses indicated possible associations to clinical features, but marginally significant results reflected lack of sufficient power for these studies. Thorough immunohistochemical analyses of several MMPs demonstrated a role in epidermal changes and dermal tissue remodelling in diseased skin, and suggested that targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues. In conclusion, the results provide an insight into the genetics of CLE and demonstrate that genetic predisposition is at least in part shared between cutaneous and systemic variants of LE. This doctoral study has contributed IRF5, TYK2, ITGAM and several other novel genes to the so far short list of genes implicated in CLE susceptibility. Detailed examination of the function of these genes in CLE pathogenesis warrants further studies. Furthermore, the results support the need of subphenotype analysis with sample sizes large enough to reveal possible specific disease associations in order to better understand the heterogeneous nature and clinical specificities of the disease. Comprehensive analysis of clinical data suggests that smoking is an environmental triggering factor.

Stadilaispojat, rikokset ja lastensuojelu : Viisi tapaustutkimusta kuudelta vuosikymmeneltä

Societal reactions to norm breaking behavior of children reveal, how we understand childhood, the relations between generations and communitie's ratio of tolerance. In Finland the children that repeatedly commit crimes receive social service measures that are based on Child Welfare Act. In the city of Helsinki (Stadi in the slang of Helsinki) existed an agency specifically established for ill-behaving children until the 1980's, agter which an unified agency for the maltreated and maladjusted children was founded. Through five boys' welfare cases, this research aims at defining what kind of positions, social relations and structures are constructed in the social dynamics of these children's everyday lives. The cases cover different decades from the 1940s to the present. At the same time the cases reflect the child welfare and societal practices, and reveal how the communities have participated in constructing deviance in different eras. The research is meta-theoretically based on critical realism and specifically on Roy Bhaskar's transformative model of social activity. The cases are analyzed in the framework of Edwin M. Lemert's societal reaction theory. Thus the focus of the study is on the wide structural context of the institutional and societal definitions of deviance. The research is methodologically based on a qualitative multiple case study research. The primary data consist of classified child welfare case files collected from the archives of the city of Helsinki. The data of the institutional level consist of the annual reports from 1943 to 2004 and the ordinances from 1907 onwards, and of various committee documents produced in the law-making process of child welfare, youth and criminal legislation of the 20th century. Empirical finding are interpreted in a dialogue with previous historical and child welfare research, contemporary literature and studies on the urban development. The analysis is based on Derek Layder's model of adaptive theory. The research forms a viewpoint to the historical study of child welfare, in which the historical era, its agents and the dynamics of their mutual relations are studied through an individual level reconstruction based on the societal reaction theory. The case analyses reveal how the positions of the children form differently in the different eras of child welfare practices. In the 1940s the child is positioned as a psychopath and a criminal type. The measures are aimed at protecting the community from the disturbed child, and at adjusting the individual by isolation. From 1960s to 1980s the child is positioned as a child in need of help and support. The child becomes a victim, a subject that occupies rights, and a target of protection. In the turn of the millennium a norm breaking child is positioned as a dangerous individual that, in the name of the community safety, has to be confined. The case analyses also reveal the prevailing academic and practical paradigms of the time. Keywords: childhood, youth, child protection, child welfare, delinquency, crime, deviance, history, critical realism, case study research

Monumenttikuvista elämyskuviin : Helsinki matkaesitteiden kuvituksessa 1895 - 2005

The purpose of this study is to define how Helsinki has been presented in the pictures of tourist brochures and how their illustration has changed over time. Attention is also paid to the values and meanings that the pictures mediate, as well as their historical and societal connections. The pictures are approached as representations selectively interpreting and illustrating the reality of Helsinki, while constructing mental images of it. An iconological framework structures the study. It proceeds from the description and classification of the physical features towards an analysis of time- and culture-specific meanings. The emergence of meanings and their historical and cultural underpinnings are examined from the perspectives of humanistic geography, semiotics and constructionism. In the analysis attention is paid to the discourses, myths and ideologies that underlie the representations. Information on the physical features of the pictures and their changes is collected with a content analysis. The classified data consists of 1377 photographs. These pictures are collected from 75 tourist brochures of Helsinki that have been published between 1895 and 2005. The deeper meanings of the pictures are studied qualitatively, by paying attention to the mental images that the content elements and visual effects evoke. Research studies, contemporary literature and the texts of the tourist brochures are utilised in the interpretation of the meanings. There has been a permanent core to objects of the pictures during the entire study period. It has consisted mainly of sights that are located close to the Senate and Market Squares. In addition, marine elements have been popular. The area of Helsinki represented in the brochures has extended from the Senate Square towards Töölö Bay. Pictures of monumental buildings and statues have been complemented with snapshots and portraits. In the beginning of the 20th century, brochures were mainly produced for the travelling, educated elite. The style of the pictures was declaratory and educative. They aimed at medating an objective image of the reality that prevailed in Helsinki. In practice, the pictures were connected to a patriotic ideology and the corresponding myth of Finnishness. In the second half of the 20th century the improvement of the standard of living led to a democratisation of consumers and an increase in the tourism demand. Local culture and the everyday life of "ordinary" people became popular themes in the pictures. A new welfare ideology manifested itself in the people of the local residential areas, for instance. The increase in the cultural diversity has led to the recognition of new target groups, expecially since the 1980s. The human figures in the pictures have started to function as objects of identification and a means of constructing mental images. A pronounced emphasis on experience and individuality in the illustration of the tourist brochures mirrors the post-modern change and a new ideology based on consumption. The construction and consumption of the pictures in the tourist brochures is governed by the conventions of representation and interpretaion that are typical of the genre of tourist brochures. The pictures emphasize the perceived positive characteristics of Helsinki and thus construct a skewed view of the reality. However, consumers can knowingly use the pictures as a means of dreaming and detaching themselves from their everyday reality.

A assistência farmacêutica no Brasil contemporâneo: a produção pública de medicamento permite ampliar o acesso da população ao uso racional de medicamentos?

O presente estudo avalia a produção pública de medicamentos no Brasil, abordando as possibilidades de avanços no acesso aos medicamentos essenciais. Fundamentou-se na análise bibliográfica e documental. Esta última análise focou os documentos oficiais, originários dos diversos agentes institucionais vinculados à política de medicamentos do país. A Política Nacional de Medicamentos concentrou-se na provisão da assistência farmacêutica e, em especial, no acesso racional aos medicamentos essenciais. A pesquisa, de caráter histórico, destacou analiticamente o desenvolvimento dessa política desde 2003 até o presente. Nesse contexto, privilegiam-se as características universais do atual sistema de saúde no Brasil e o compromisso do Estado nacional em garantir o acesso a esse direito fundamental. Foram também objeto de destaque nesta pesquisa as alternativas de oferta de medicamentos por intermédio da indústria farmacêutica internacional e nacional. O núcleo deste estudo é a análise da produção dos medicamentos pelos laboratórios oficiais, bem como das dificuldades que esses laboratórios enfrentam em função da descontinuidade histórica de políticas voltadas para o fortalecimento de suas atividades. Assim, permite-se afirmar que a produção dos medicamentos essenciais poderia contribuir de forma decisiva para a inclusão da população historicamente excluída das políticas de saúde a partir de estratégias para o seu fortalecimento continuado, definidas pelo Estado brasileiro.

Trânsitos ficcionais: um estudo sobre a experiência da viagem na ficção contemporânea

Este trabalho se propõe a analisar a experiência da viagem no contexto da ficção contemporânea brasileira. Para tanto, serão utilizadas as constantes viagens do protagonista do romance Budapeste, de Chico Buarque, para discutir as questões que serão apresentadas. Com a ajuda do pensamento de estudiosos como Bauman, Augé, Schutz, Maffesoli, Deleuze e Guattari, este estudo seguirá os trânsitos ficcionais e as linhas de fuga do protagonista para discutir sobre o modo como o homem contemporâneo vivencia a experiência da mobilidade

A ação dos componentes da patronagem sobre a literatura infanto-juvenil brasileira: o efeito sobre a tradução de Do outro mundo de Ana Maria Machado

Esta pesquisa tem como objetivos, (i) verificar a ação dos componentes da patronagem: status, econômico e ideológico sob a tradução e publicação de obras da Literatura Infanto-Juvenil brasileira na hegemônica cultura norte-americana e, (ii) verificar se as estratégias de tradução dos itens de especificidade cultural de Do Outro Mundo de Ana Maria Machado estão em concordância com as normas de tradução de LIJ que, de acordo com Zohar Shavit (2006), pressupõem uma maior liberdade por parte do tradutor para que esse ajuste a trama, os personagens e a língua a capacidade de leitura e ao conhecimento de mundo infantil. A relação entre esses objetivos é verificada na afirmação de Gigeon Toury (1995a, p. 13) de que a posição ocupada pela tradução no sistema da cultura-alvo afeta diretamente as estratégias adotadas pelos tradutores e a composição dos textos traduzidos. Com base nos Estudos Descritivos da Tradução (TOURY, 1995b), o conceito de patronagem introduzido por André Lefevere (1992) associado às considerações feitas por James English (2005) quanto à importância dos prêmios na sociedade atual foram fundamentais para a compreensão da ação dos componentes da patronagem sob a literatura Infanto-juvenil. Outro importante conceito aos objetivos desta pesquisa foi o de item de especificidade cultural de Javier Franco Aixelá (1996). Na análise dos dados desta pesquisa utilizei a reformulação da classificação das estratégias de tradução dos itens de Carla Bentes (2005) nos IEC de Do Outro Mundo e respectiva tradução em inglês From Another World. Os procedimentos de análise do corpus basearam-se no modelo de Lambert e van Gorp (1985) para a análise da tradução literária. Utilizo desse modelo a análise dos dados preliminares e a análise microtextual por atenderem aos objetivos desta pesquisa. O estudo se encerra com considerações a respeito da tradução de literatura Infanto-juvenil brasileira e as implicações sob o público-alvo

Companhia subterrânea: notas de um último leitor acerca da literatura do Não

O presente trabalho adota, como base teórica, uma perspectiva desenvolvida a partir do exame de certas ideias presentes na obra ficcional de Enrique Vila-Matas apresentadas em seus romances Bartleby e companhia (a literatura do Não, pulsão negativa da literatura contemporânea, desistência e mutismo literários, renúncia à escrita) e O mal de Montano (doença literária, doente de literatura, literatose) e na ensaísta de Ricardo Piglia, em O último leitor (último leitor, o leitor viciado, que não consegue deixar de ler, leitor para o qual a leitura não é apenas uma prática, mas uma forma de vida; o leitor como personificação da literatura). A partir dessas noções, a presente Dissertação especula sobre as relações entre a escrita de Machado de Assis, o universo de Franz Kafka e a obra de Murilo Rubião. Adotou-se como metodologia a leitura comparativa desses autores, com destaque para os contos de Murilo Rubião, e de alguns dos escritores lidos pelos três ficcionistas

Distribution and life history of two diminutive flatfishes, Citharichthys gymnorhinus and C. cornutus (Pleuronectiformes: Paralichthyidae), in the western North Atlantic

Citharichthys cornutus and C. gymnorhinus, diminutive flatfishes inhabiting continental shelves in the western Atlantic Ocean, are infrequently reported and poorly known. We identified 594 C. cornutus in 56 different field collections (68–287 m; most between 101–200 m) off the eastern United States, Bahamas, and eastern Caribbean Sea. Historical records and recently captured specimens document the northern geographic range of adults on the shelf off New Jersey (40°N, 70°W). Citharichthys cornutus measured 17.2–81.3 mm standard length (SL); males (20.0–79.1 mm SL) and females (28.0–81.3 mm SL) attain similar sizes (sex could not be determined for fish <20 mm SL). Males reach nearly 100% maturity at ≥60 mm SL. The smallest mature females are 41.5 mm SL, and by 55.1 mm SL virtually all are mature. Juveniles are found with adults on the outer shelf. Only 214 C. gymnorhinus were located in 42 different field collections (35–201 m, with 90% between 61 and 120 m) off the east coast of the United States, Bahamas, and eastern Caribbean Sea. Adults are found as far north as the shelf off Cape Hatteras, NC (35°N, 75°W). This diminutive species (to 52.4 mm SL) is among the smallest flatfishes but males (n=131; 20.3–52.4 mm SL) attain a slightly larger maximum size than that of females (n=58; 26.2–48.0 mm SL). Males begin to mature between 29 and 35 mm SL and reach 100% maturity by 35–40 mm SL. Some females are mature at 29 mm SL, and all females >35.1 mm SL are mature. Overlooked specimens in museum collections and literature enabled us to correct long-standing inaccuracies in northern distributional limits that appear in contemporary literature and electronic data bases for these species. Associated locality-data for these specimens allow for proper evaluation of distributional information for these species in relation to hypotheses regarding shifts in species ranges due to climate change effects.

Formas de argumentación retórica en Sófocles, «Electra», 558-609

[ES] El código retórico adquiere una especial relevancia durante el siglo V ateniense. Su presencia es evidente en la literatura del momento, especialmente en la historiografía y en el drama. Sófocles, «Electra», 558-609 es un buen ejemplo de hasta qué punto dicho código se tiene en cuenta en la elaboración de los discursos literarios. Pero, además, este discurso y la escena de la que forma parte ponen de manifiesto la reflexión de la sociedad ateniense acerca de la oposición entre ese código retórico y público y otro código de índole más privada.

Do imaginário à narrativa: a memória da casa da infância

A casa da infância é uma entidade bipartida: uma, a casa vivida na experiência indiferenciada de ser, um lugar-tempo do inaugural, do espanto, do afeto; outra, aquela que este lugar-tempo produz no imaginário daquele que dela se afastou, geográfica e temporalmente, a casa onírica. No sujeito, memória e imaginação não se dissociam, e somente assim é possível retornar ao lugar-tempo mítico desta casa primeva; a memória é então fonte (ou ponte) para esta celebração da ausência retornada viva através da transmutação da lembrança em narrativa processo constante nos indivíduos que as obras ficcionais buscam reproduzir. A presente tese, Do imaginário à narrativa: a memória da casa da infância, pretende explorar a memória da casa e a ficção indissociável a esta na construção de um pre-texto gerador de narrativa no sujeito e a forma como este processo é ficcionalizado em produções literárias contemporâneas que recorrem a ela como temática e estrutura

An ethnographic interpretation of the work environment within a creative culture in the advertising sector.

Purpose and rationale The purpose of the exploratory research is to provide a deeper understanding of how the work environment enhances or constrains organisational creativity (creativity and innovation) within the context of the advertising sector. The argument for the proposed research is that the contemporary literature is dominated by quantitative research instruments to measure the climate and work environment across many different sectors. The most influential theory within the extant literature is the componential theory of organisational creativity and innovation and is used as an analytical guide (Amabile, 1997; Figure 8) to conduct an ethnographic study within a creative advertising agency based in Scotland. The theory suggests that creative people (skills, expertise and task motivation) are influenced by the work environment in which they operate. This includes challenging work (+), work group supports (+), supervisory encouragement (+), freedom (+), sufficient resources (+), workload pressures (+ or -), organisational encouragement (+) and organisational impediments (-) which is argued enhances (+) or constrains (-) both creativity and innovation. An interpretive research design is conducted to confirm, challenge or extend the componential theory of organisational creativity and innovation (Amabile, 1997; Figure 8) and contribute to knowledge as well as practice. Design/methodology/approach The scholarly activity conducted within the context of the creative industries and advertising sector is in its infancy and research from the alternative paradigm using qualitative methods is limited which may provide new guidelines for this industry sector. As such, an ethnographic case study research design is a suitable methodology to provide a deeper understanding of the subject area and is consistent with a constructivist ontology and an interpretive epistemology. This ontological position is conducive to the researcher’s axiology and values in that meaning is not discovered as an objective truth but socially constructed from multiple realties from social actors. As such, ethnography is the study of people in naturally occurring settings and the creative advertising agency involved in the research is an appropriate purposive sample within an industry that is renowned for its creativity and innovation. Qualitative methods such as participant observation (field notes, meetings, rituals, social events and tracking a client brief), material artefacts (documents, websites, annual reports, emails, scrapbooks and photographic evidence) and focused interviews (informal and formal conversations, six taped and transcribed interviews and use of Survey Monkey) are used to provide a written account of the agency’s work environment. The analytical process of interpreting the ethnographic text is supported by thematic analysis (selective, axial and open coding) through the use of manual analysis and NVivo9 software Findings The findings highlight a complex interaction between the people within the agency and the enhancers and constraints of the work environment in which they operate. This involves the creative work environment (Amabile, 1997; Figure 8) as well as the physical work environment (Cain, 2012; Dul and Ceylan, 2011; Dul et al. 2011) and that of social control and power (Foucault, 1977; Gahan et al. 2007; Knights and Willmott, 2007). As such, the overarching themes to emerge from the data on how the work environment enhances or constrains organisational creativity include creative people (skills, expertise and task motivation), creative process (creative work environment and physical work environment) and creative power (working hours, value of creativity, self-fulfilment and surveillance). Therefore, the findings confirm that creative people interact and are influenced by aspects of the creative work environment outlined by Amabile (1997; Figure 8). However, the results also challenge and extend the theory to include that of the physical work environment and creative power. Originality/value/implications Methodologically, there is no other interpretive research that uses an ethnographic case study approach within the context of the advertising sector to explore and provide a deeper understanding of the subject area. As such, the contribution to knowledge in the form of a new interpretive framework (Figure 16) challenges and extends the existing body of knowledge (Amabile, 1997; Figure 8). Moreover, the contribution to practice includes a flexible set of industry guidelines (Appendix 13) that may be transferrable to other organisational settings.

Japonia w życiu i w twórczości Amélie Nothomb

Wydział Neofilologii: Instytut Filologii Romańskiej

Revising Justice: Punitory Thought and Action in the Work of Atwood, Jordan, and Oates

*Designated as an exemplary master's project for 2015-16*