Genetic analysis of chromosomal regions 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS) affecting 0.1-0.2% of Northern European descent population. MS is considered to be a multifactorial disease, both environment and genetics play a role in its pathogenesis. Despite several decades of intense research, the etiological and pathogenic mechanisms underlying MS remain still largely unknown and no curative treatment exists. The genetic architecture underlying MS is complex with multiple genes involved. The strongest and the best characterized predisposing genetic factors for MS are located, as in other immune-mediated diseases, in the major histocompatibility complex (MHC) on chromosome 6. In humans MHC is called human leukocyte antigen (HLA). Alleles of the HLA locus have been found to associate strongly with MS and remained for many years the only consistently replicable genetic associations. However, recently other genes located outside the MHC region have been proposed as strong candidates for susceptibility to MS in several studies. In this thesis a new genetic locus located on chromosome 7q32, interferon regulatory factor 5 (IRF5), was identified in the susceptibility to MS. In particular, we found that common variation of the gene was associated with the disease in three different populations, Spanish, Swedish and Finnish. We also suggested a possible functional role for one of the risk alleles with impact on the expression of the IRF5 locus. Previous studies have pointed out a possible role played by chromosome 2q33 in the susceptibility to MS and other autoimmune disorders. The work described here also investigated the involvement of this chromosomal region in MS predisposition. After the detection of genetic association with 2q33 (article-1), we extended our analysis through fine-scale single nucleotide polymorphism (SNP) mapping to define further the contribution of this genomic area to disease pathogenesis (article-4). We found a trend (p=0.04) for association to MS with an intronic SNP located in the inducible T-cell co-stimulator (ICOS) gene, an important player in the co-stimulatory pathway of the immune system. Expression analysis of ICOS revealed a novel, previously uncharacterized, alternatively spliced isoform, lacking the extracellular domain that is needed for ligand binding. The stability of the newly-identified transcript variant and its subcellular localization were analyzed. These studies indicated that the novel isoform is stable and shows different subcellular localization as compared to full-length ICOS. The novel isoform might have a regulatory function, but further studies are required to elucidate its function. Chromosome 19q13 has been previously suggested as one of the genomic areas involved in MS predisposition. In several populations, suggestive linkage signals between MS predisposition and 19q13 have been obtained. Here, we analysed the role of allelic variation in 19q13 by family based association analysis in 782 MS families collected from Finland. In this dataset, we were not able to detect any statistically significant associations, although several previously suggested markers were included to the analysis. Replication of the previous findings on the basis of linkage disequilibrium between marker allele and disease/risk allele appears notoriously difficult because of limitations such as allelic heterogeneity. Re-sequencing based approaches may be required for elucidating the role of chromosome 19q13 with MS. This thesis has resulted in the identification of a new MS susceptibility locus (IRF5) previously associated with other inflammatory or autoimmune disorders, such as SLE. IRF5 is one of the mediators of interferons biological function. In addition to providing new insight in the possible pathogenetic pathway of the disease, this finding suggests that there might be common mechanisms between different immune-mediated disorders. Furthermore the work presented here has uncovered a novel isoform of ICOS, which may play a role in regulatory mechanisms of ICOS, an important mediator of lymphocyte activation. Further work is required to uncover its functions and possible involvement of the ICOS locus in MS susceptibility.

Asuntopolitiikka ja vieraskielisen väestön alueellinen keskittyminen Helsingissä vuosina 1992-2005

The aim of the thesis was to study the extent of spatial concentration of immigrant population in Helsinki and to analyse the impact of housing policy on ethnic residential segregation in 1992-2005. For the purpose of the study, immigrant population was defined based on the language spoken at home. The theory of residential segregation by Andersson and Molina formed the main theoretical framework for the study. According to Andersson and Molina ethnic residential segregation results from different dynamic intra-urban migration processes. Institutionally generated migration, i.e. migration patterns generated by various housing and immigrant policies and procedures, is one of the central factors in the development of ethnic segregation. The data of the study consisted of population and housing statistics and housing and immigrant policy documents of Helsinki municipality. Spatial concentration of immigrant population was studied both at district and building levels using GIS-methods and statistical methods. The housing policy of Helsinki municipality was analysed using a method created by Musterd et al. Musterd et al. categorise two types of policy approaches to residential segregation: spatial dispersion policy and compensating policy. The housing policy of Helsinki has a strong focus on social mixing and spatial dispersion of housing stock. Ethnic segregation is regarded as a threat. The importance of ethnic communities and networks is, however, acknowledged and small-scale concentration is therefore not considered harmful. Despite the spatial dispersion policy, the immigrant population is concentrated in the eastern, north-eastern and north-western suburbs of Helsinki. The spatial pattern of concentration was formed already at the beginning of the 1990's when immigration to Finland suddenly peaked. New immigrant groups were housed in the neighbourhoods where public housing was available at the time. Housing policy, namely the location of new residential areas and public housing blocks and the policies of public housing allocation were key factors influencing the residential patterns of immigrant population in the 1990's. The immigration and refugee policies of the state have also had an impact on the development. The concentration of immigrant population has continued in the same areas in the beginning of the 2000's. Dispersion to new areas has mainly taken place within the eastern and north-eastern parts of the city or in the adjacent areas. The migration patterns of native population and the reasonably rapid changes in the housing market have emerged as new factors generating and influencing the ethnic residential segregation in Helsinki in the 2000's. Due to social mixing and spatial dispersion policies, ethnic segregation in Helsinki has so far been fairly small-scale, concentrated in particular housing blocks. The number of residential buildings with a high share of immigrant population is very modest. However, the number of such buildings has doubled between 1996-2002. The concentration of immigrant population concerns mainly the public housing sector. The difference in the level of concentration between the public housing sector and privately owned housing companies is remarkable.

CANCIONES ARGENTINAS (SONGS OFARGENTINA): A RECORDING PROJECT

This Dissertation Project comprises recordings of Argentine art songs. The discs are approximately 40-60 minutes in length and consist of songs from the traditional art-song repertoire for voice and piano. This project is particularly appropriate because of the very limited number of recordings of Argentine songs, which are notable both not only for their high quality but for their accessibility of performance for voice teachers, students, and professional singers alike. Art songs in the Spanish language are a welcome resource, and the poetry included in this project is of an outstanding quality. Some of the poets set to music are Gabriela Mistral (a poet laureate of Chile and the first Latin American woman to win the Nobel Prize for Literature), Pablo Neruda (also a Nobel laureate), Luis Cernuda, and Leon Benar6s. The lyrics of some songs are based on traditional sources, and the melodies and rhythms of all are representative of South American-indigenous and European­ immigrant cultures. The composers represented here will be familiar to some listeners but more than likely unfamiliar to most. Yet Alberto Ginastera (1916-1983) is considered to be the greatest of all Argentine composers. Alberto Williams (1862-1952) is known as the father of the Nationalist School of composition in Argentina, and Carlos Lopez Buchardo (1881-1963) is a most influential composer and pedagogue after whom the national Conservatory of Music in Buenos Aries is named. Two composers who remain relatively unknown outside of South America, Abraham Jurafsky (1906- 1993) and Julio Perceval (1903-1963) are also represented in this project. A complete compact disc is devoted to the works of Carlos Guastavino. Known as the "Argentine Schubert", Guastavino has over 250 songs to his credit. Chiefly a composer for piano and voice, his recent death (October 2000) makes a recording of his works especially appropriate. This project also includes a written component, a supportive dissertation briefly describing the history of the Argentine art song and the lives and influences of the composers and poets represented in the studio recordings. The CD recordings are held in the Michelle Smith Performing Arts Library at the University of Maryland.

Migrations and gradations : reappraising the health profile of immigrants to Canada

New immigrants to Canada typically have a more favourable health profile than the non-immigrant population. This phenomenon, known as the 'healthy immigrant effect', has been attributed to both the socioeconomic advantage (ie. educational attainment, occupational opportunity) of non-refugee immigrants and existing screening protocols that admit only the healthiest of persons to Canada. It has been suggested that this health advantage diminishes as the time of residence in Canada increases, due in part to the adoption of health-risk behaviours such as alcohol and cigarette use, an increase in excess body weight, and declining rates of physical activity. However, the majority of health research concerning immigrants to Canada has been limited to cross-sectional studies (Dunn & Dyck, 2000; Newbold & Danforth, 2003), which may mask an immigrant-specific cohort effect. Furthermore, the practice of aggregating foreign-bom persons by geographical regions or treating all immigrants as a homogeneous group may also obfuscate intra-immigrant differences in health. Accordingly, this study uses the Canadian National Population Health Surveys (NPHS) and data from the United Nations Development Program (UNDP) to prospectively evaluate factors that predict health status among immigrants to Canada. Each immigrant in the NPHS was linked to the UNDP Human Development Index of their country of birth, which uses a combined measure of health, education, and per capita income of the populace. The six-year change in health function, psychological distress, and self-rated health were considered from a population health perspective (Evans, 1994), using generalized-estimating equations (GEE) to examine the compounding effect of past and recent predictors of health. Demographic

La régionalisation de l’immigration au Québec : évolution de 1982 à 2006 des flux et des caractéristiques sociodémographiques

Tout comme la plupart des pays industrialisés, le Canada, et plus particulièrement, le Québec, est caractérisé par une forte concentration de la population immigrante sur son territoire. Encore aujourd’hui, la région métropolitaine de Montréal accueille la majorité des immigrants internationaux admis dans la province, ce qui sous-entend que le reste de la province n’attire qu’une part négligeable de l’immigration. En 1992, le gouvernement du Québec a mis en place une politique de régionalisation dans le but de mieux répartir la population immigrante sur le territoire. Cette politique visait d’une part, à encourager les immigrants internationaux à s’établir en dehors de Montréal et, d’autre part, à faire partager les bénéfices de l’immigration à toutes les régions. Mais qu’en est-il des résultats et des effets de cette politique? Jusqu’à maintenant, on connaît toujours peu de choses sur le sujet et sur les caractéristiques des immigrants qui décident de s’établir en « région ». L’objectif de cette recherche est donc de faire le bilan quantitatif et qualitatif de l’immigration au Québec afin de vérifier si cette politique a eu des répercussions sur le choix de destination des immigrants internationaux. Le premier chapitre est essentiellement consacré à la recension des écrits au sujet de la régionalisation de l’immigration, notamment en ce qui à trait au phénomène de concentration géographique et des tendances à l’échelle nationale et internationale. Un premier portrait des immigrants établis au Canada et au Québec complètera ce chapitre. Le deuxième chapitre analyse l’évolution des flux migratoires et de la régionalisation au Québec de 1982 à 2006. Le dernier chapitre a pour objectif d’évaluer la capacité de rétention des régions. Cela permettra de dresser le portrait actuel de la population immigrée, c’est-à-dire de connaître la région de destination réelle des immigrants. Les résultats de cette recherche nous permettent de croire que les effets de cette politique tardent à se manifester et que les efforts déployés dans le but d’une répartition mieux équilibrée de l’immigration ont porté fruit davantage à la banlieue de Montréal.

Immigration et sport : l’impact de la pratique du soccer amateur sur l’intégration sociale des minorités à Montréal

Fondée sur une étude ethnographique de la pratique du soccer amateur au sein d’une population immigrante associée politiquement à des minorités visibles, discernables par rapport au groupe majoritaire que forment les Québécois francophones, cette thèse cherche à élucider le rapport pratique et fonctionnel entre corps, connaissance et société à la lumière de la théorie de la pratique élaborée par Bourdieu. Dans cette voie, elle cherche à concevoir la pratique sportive comme vecteur d’intégration sociale susceptible de former l’habitus propice à l’intégration, à la sociabilité et à la participation sociale requises pour développer le sentiment d’appartenance à la société d’accueil dans les rangs de ces sportifs. Dans la veine de la théorisation enracinée, et en s’appuyant sur l’observation systématique du style de jeu et des représentations sociales autour de l’intégration élaborés par un groupe d’adeptes du soccer dans une étude combinant observation, vidéo, notes de terrain et interviews, recueillies dans une ligue amateur de Montréal, la thèse a pour objectif de débusquer la logique sociale que sous-tend la pratique sportive en décelant le sens pratique à l’œuvre dans cette dimension de l’espace social. Sur la lancée, l’étude de la pratique du soccer et de la matérialité du corps de l’immigrant en tant que « fait social total » nous amène à concevoir l’intégration du nouveau venu à la société d’accueil comme la combinaison de l’« extériorité » et de l’« intériorité » responsable des dispositions propres à donner corps à l’intégration. On est fondé à penser que la pratique du sport permet à ses adeptes de nouer avec leurs vis-à-vis des relations sociales qui, leur conférant des positions distinctes et distinctives, permettent de comprendre et d’expliquer l’intégration par les enjeux que cela soulève. Sous ce chef, l’ethnicisation en acte dans ce contexte s’opère sous la médiation du corps conçu comme « vecteur de connaissances », « forme de présentation de soi » (Sayad, 1999, p. 301), et « emblème de l’ethnicité » (Defrance, 2009, p. 26). Le corps, aux yeux des joueurs et des supporteurs, devient objet de représentations fondées sur la performance sportive, le jugement de l’habileté physique et l’attitude personnelle comme indicateurs de la compétence du joueur et, plus généralement, les éléments symboliques nés de l’interaction sociale sur le terrain de jeu comme à l’extérieur. En dernière analyse, le soccer, par sa pratique, fait office de médiation, voire de levier, susceptible d’aplanir les entraves à l’intégration à la société d’accueil sous les traits de l’acculturation. La thèse au programme vient donc enrichir l’explication sociologique du processus d’intégration en contexte multiethnique à la lumière du concept d’habitus afin de concevoir théoriquement la dialectique entre acculturation et incorporation sous les traits d’un jeu de relations objectives en vertu duquel le participant s’y engage de son propre chef, sans être tout à fait conscient que par la pratique il est soumis au jugement social, à l’inculcation de dispositions culturellement légitimes, etc. Il s’en dégage l’hypothèse que le joueur de soccer manifeste la « connaissance par corps » que requiert son intégration à la société dans laquelle il a décidé d’évoluer de son plein gré (Bourdieu, 2003). La pratique sportive se révèle donc une « stratégie identitaire synthétique » susceptible de mettre au diapason son identité et les « conditions objectives d’existence » du milieu auquel il est en passe de s’intégrer (Manço, 1999).

A Grey Area of Rights and Knowledge: Displacement in Colombia, South-South Migration and Health Equity

Globalization and liberalization of the economies have produced among others drastic effects on the human mobility, generating confusion, enhancing discrimination and a lack of respect to the rights of several migrant collectives. In this article we analyse several challenges for the study of these phenomena, based on the case of the neglected health rights of Colombian women, who have been forced to displace by the country's internal conflict, and are thus pushed to cross the border to Ecuador. The article identifies several knowledge gaps that could allow and advance a better understanding of these critical subjects. The paper - a think piece -is based upon a general review of documents and studies on the relation between migration and health. The supporting theory on the research comes from international organisations such as the WHO and IOM, NGOs, grass-roots organisations and academic research. This paper shows the need for focusing on the reality of supra states which globalization has generated, and t e urgency of securing the access to essential health preconditions to migrant populations. These issues can no longer be neglected and should be included on agendas at international level, widening the approach of programs to the displaced/immigrant population by taking into account the need to ensure the essential health preconditions (equity), prevention, and protection. Further, it is clear that women and children require a better protection with enhanced prevention and responding measures to sexual abuse, stigmatisation, violence and the respect of their rights.

Evidence for an apartheid-like social structure in early Anglo-Saxon England

The role of migration in the Anglo-Saxon transition in England remains controversial. Archaeological and historical evidence is inconclusive, but current estimates of the contribution of migrants to the English population range from less than 10 000 to as many as 200 000. In contrast, recent studies based on Y-chromosome variation posit a considerably higher contribution to the modern English gene pool (50-100%). Historical evidence suggests that following the Anglo-Saxon transition, people of indigenous ethnicity were at an economic and legal disadvantage compared to those having Anglo-Saxon ethnicity. It is likely that such a disadvantage would lead to differential reproductive success. We examine the effect of differential reproductive success, coupled with limited intermarriage between distinct ethnic groups, on the spread of genetic variants. Computer simulations indicate that a social structure limiting intermarriage between indigenous Britons and an initially small Anglo-Saxon immigrant population provide a plausible explanation of the high degree of Continental male-line ancestry in England.

Technologies that motivates healthy toothbrushing: practices through social translucence

Fifty percent of the European Union’s population suffers from an oral disease. Studies have repeatedly shown that while acquiring healthy toothbrushing practices early on in one’s life is of significance, children and adults often fail to adhere to those. In this thesis we attempt to design and prototype interactive technologies that motivate healthy tooth brushing habits on individuals. Rather than focusing on the technologies’ persuasive power over individuals, we tap on the social mechanisms employed by families. In this sense, we think of these technologies as social translucent rather than persuasive, whose goal is to raise awareness within the family on each other’s habits and that aim at leveraging families’ existing social mechanisms for behavior change, rather than replacing them. More specifically, we aim to gain insights with respect to the following questions: a) What are the drivers and barriers towards adhering to healthy tooth brushing behaviors? b) Can we effectively measure toothbrushing behaviors? c) How can technologies leverage family communication practices in motivating proper toothbrushing behaviors? First, we present two studies about children and adults’ tooth brushing behaviors and how these are influenced by social interactions within the family. Secondly, we present the design and prototyping of two systems that sense toothbrushing practices and provide feedback, using the Social Translucence Framework as a design lens. We conclude with an overview of lessons learnt from the prototyping of these systems supported by an analysis of the strengths and pitfalls of the developed technologies.

Study of the timber constructive systems that are more commercialized in Brazil

The Brazilian houses in wood are executed with several techniques and species, in function of the areas they are located, therefore, it is treated of regional traditional houses, built practically without modem technological resources. These houses are the ones of the tropical areas, where there is abundance of this material, or the ones of the south region, prevailing the European immigrant's constructive techniques. Nowadays, in the urbanized centers of the country it is observed that this type of house can be found sheltering the most lacking populations, in the slums; or in highly sophisticated residential units which are conceived and executed by specialist professionals for a social class of high purchasing power; or still, those that are marketed by companies of small load, that offer standardized residences, usually acquired by the middle class as second residence, in the field or in the coast. The work has for objective to study the houses of these companies that are consolidated at the market, identifying the constructive system, the product; as well as, its production process, trying to verify which technologies are incorporated to these processes. The analysis that was made allows a larger understanding of the product, wood house, that exists in the market and identification of the technological degree in the productive process of those constructive systems.

Socialists vs. fascists and communists in Italian São Paulo in the 1920s

The action of São Paulo's Italian reformist socialists at the beginning of the 20th century had a political impact on the way of considering the question of democracy both in the state of São Paulo and the whole of Brazil. In fact not only did the socialists oppose the fascist political project and the symbolic roots of its aggressive behavior, but they also faced the opposition of the theoretical proposals coming from other leftist groups. This article intends to present the main interlocutors of these socialists and understand how this theoretical dispute has developed.

O pensamento vivo de Mário de Andrade: dos parques infantis aos CEUs da cidade de São Paulo

Pós-graduação em Artes - IA

Imigração e médicos italianos em São Paulo na primeira república

A imigração européia para a região sudeste do país, que foi responsável pela introdução da mão-de-obra assalariada, para atender às necessidades da cultura cafeeira, nas últimas décadas do século XIX e primeiras do século XX, tem sido suficientemente estudada pela historiografia da imigração. O que tem sido explorado em menor grau, é a inter-relação entre a imigração e a reforma sanitária que ocorreu no período. O estado de São Paulo, particularmente, foi palco de uma triste história de imigrantes italianos chegados e expostos à virulência das epidemias. Esse foi o ponto de partida para o início do movimento de reforma da saúde pública. Os fazendeiros consideravam a imigração uma necessidade vital para a economia cafeeira, havendo um consenso bastante forte entre as elites e o governo da necessidade de mostrar ao mundo que o Brasil estava disposto a combater sua má reputação em matéria de saúde pública. O pensamento reformista e a ação elegeramos imigrantes como principal alvo da política de saúde. Desta forma, o presente trabalho apresenta dados sobre essas ações e discute a maneira como os países estrangeiros – particularmente a Itália – enviaram ao Brasil agentes e inspetores, médicos, engenheiros e outros profissionais, no sentido de verificarem as reais condições de vida, de trabalho e de saúde de seus conterrâneos tanto nas áreas rurais como nas urbanas. Um dos fenômenos que resultaram dos esforços dos inspetores sanitários foi a consolidação de um mercado de trabalho para médicos italianos e a abertura de hospitais italianos em São Paulo e outras regiões do estado. O impacto da imigração e a consolidação da profissão médica, afetados pela vinda desses profissionais a São Paulo, são os focos principais deste trabalho.

Predictability in Social Science, The statistical mechanics approach.

The subject of this work concerns the study of the immigration phenomenon, with emphasis on the aspects related to the integration of an immigrant population in a hosting one. Aim of this work is to show the forecasting ability of a recent finding where the behavior of integration quantifiers was analyzed and investigated with a mathematical model of statistical physics origins (a generalization of the monomer dimer model). After providing a detailed literature review of the model, we show that not only such a model is able to identify the social mechanism that drives a particular integration process, but it also provides correct forecast. The research reported here proves that the proposed model of integration and its forecast framework are simple and effective tools to reduce uncertainties about how integration phenomena emerge and how they are likely to develop in response to increased migration levels in the future.

Stable virulence levels in the HIV epidemic of Switzerland over two decades

OBJECTIVE: To determine whether the virulence of HIV-1 has been changing since its introduction into Switzerland. DESIGN: A prospective cohort study of HIV-1 infected individuals with well-characterized pre-therapy disease history. METHODS: To minimize the effect of recently imported viruses and ethnicity-associated host factors, the analysis was restricted to the white, north-west-European majority population of the cohort. Virulence was characterized by the decline slope of the CD4 cell count (n = 817 patients), the decline slope of the CD4:CD8 ratio (n = 815 patients) and the viral setpoint (n = 549 patients) in untreated patients with sufficient data points. Linear regression models were used to detect correlations between the date of diagnosis (ranging between 1984 and 2003) and the virulence markers, controlling for gender, exposure category, age and CD4 cell count at entry. RESULTS: We found no correlation between any of the virulence markers and the date of diagnosis. Inspection of short-term trends confirmed that virulence has fluctuated around a stable level over time. CONCLUSIONS: The lack of long-term time trends in the virulence markers indicates that HIV-1 is not evolving towards increasing or decreasing virulence at a perceptible rate. Both highly virulent and attenuated strains have apparently been unable to spread at the population level. This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host.