Showing papers by "Ivana Marková published in 2017"

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Abstract: Summary Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT . Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10 −10 ) on chromosome 5 spanning three genes: MSH3, DHFR , and MTRNR2L2 . The genes in this locus were associated with progression in TRACK-HD ( MSH3 p=2·94 × 10 −8 DHFR p=8·37 × 10 −7 MTRNR2L2 p=2·15 × 10 −9 ) and to a lesser extent in REGISTRY ( MSH3 p=9·36 × 10 −4 DHFR p=8·45 × 10 −4 MTRNR2L2 p=1·20 × 10 −3 ). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10 −8 ), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation. Funding The European Commission FP7 NeurOmics project; CHDI Foundation; the Medical Research Council UK; the Brain Research Trust; and the Guarantors of Brain.

The making of the theory of social representations

Abstract: This paper presents the theory of social representations as a model of social scientific theory. In doing so, it attempts to reconstruct the foundations of the theory of social representations by focusing on intellectual resources that were available to Serge Moscovici during the time he was developing the theory. These resources shaped his epistemology, and firmly distinguished the theory of social representations from other social psychological approaches. The focus on these intellectual resources draws attention to two issues. First, in contrast to what Moscovici often called ‘one or two sentence theories’ in social psychology based on the manipulation of variables, the theory of social representations is built on a rich set of presuppositions. Second, an explicit recognition of presuppositions of social representations in their application in professional practices like education, politics and health, among others, enables a unique contribution to social sciences and humanities.

A fabricação da teoria de representações sociais

Abstract: This paper presents the theory of social representations as a model of social scientific theory. In doing so, it attempts to reconstruct the foundations of the theory of social representations by focusing on intellectual resources that were available to Serge Moscovici during the time he was developing the theory. These resources shaped his epistemology, and firmly distinguished the theory of social representations from other social psychological approaches. The focus on these intellectual resources draws attention to two issues. First, in contrast to what Moscovici often called ‘one or two sentence theories’ in social psychology based on the manipulation of variables, the theory of social representations is built on a rich set of presuppositions. Second, an explicit recognition of presuppositions of social representations in their application in professional practices like education, politics and health, among others, enables a unique contribution to social sciences and humanities.

Themata in science and in common sense

Abstract: Abstract Human thinking is heterogeneous, and among its different forms, thinking in dyadic oppositions is associated with the concept of themata. Gerald Holton characterises themata as elements that lie beneath the structure and development of physical theories as well as of non-scientific thinking. Themata have different uses, such as a thematic concept, or a thematic component of the concept; a methodological (or epistemological) thema; and a propositional thema. Serge Moscovici has placed the concept of themata in the heart of his theory of social representations which is based on ‘natural thinking’ and on forms of daily knowing, including common sense. In this article I shall explore some features of thematic concepts and of methodological themata in scientific theories and in common sense. More specifically, I shall refer to the significance of the methodological (or epistemological) thema the Self and Other(s) in common-sense thinking and in social practices.

Case Studies and Dialogicality

Abstract: Dialogicality is one of the dialogical approaches in human and social sciences. It postulates that the nature of the Self-Other interdependence is unique. Uniqueness of the Self-Other interdependence is strongly discernible in communication involving people with congenital deafblindness. This raises a fundamental methodological question: how to transform the unique and dynamic nature of dialogue into an empirical project that would allow general claims to be made about dialogicality? It is argued that while single cases do not allow for statistical generalisation, they allow for theoretical generalisation of research findings, as well as for generalisation of practices in professional services. Examples of theoretical generalisation of concepts such as ‘dialogical learning’ and ‘resilience’ are discussed.

Contemporary challenges to dialogicality

Abstract: In contrast to perspectives fragmenting individuals into elements and studying disengaged cognition, ‘neutral’ and ‘objective’ knowledge, the dialogical approach is holistic, focusing on interactions and interdependencies between the Self and Others (the Ego-Alter). It studies engaged action and experience, daily knowledge, and communication in ordinary life. Interactions involve learning about and acting upon objects. Thus from the Ego-Alter as an irreducible ethical and ontological unit we arrive at the Ego-Alter-Object as an irreducible unit of dialogical epistemology. In this article I discuss two challenges to dialogical epistemology. One concerns the different degrees of commitment within the Ego-Alter-Object relationship. The second challenge refers to the replacement of the epistemological triangle the Ego-Alter-Object of knowledge by the consumerist triangle the Ego-Alter-Thing of desire. I discuss the latter challenge with respect to contemporary bureaucratization of academic and education institutions.