| 1. |
- Dalin, Martin, 1982, et al.
(författare)
-
Massive parallel sequencing questions the pathogenic role of missense variants in dilated cardiomyopathy
- 2017
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 228, s. 742-748
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Germline genetic variants are an important cause of dilated cardiomyopathy (DCM). However, recent sequencing studies have revealed rare variants in DCM-associated genes also in individuals without known heart disease. In this study, we investigate variant prevalence and genotype-phenotype correlations in Swedish DCM patients, and compare their genetic variants to those detected in reference cohorts. Methods and results: We sequenced the coding regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM and found 102 protein-altering variants with an allele frequency of <0.04% in reference cohorts; the majority were missense variants not previously described in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two or more variants in the analysed genes. Detection of genetic variants in any gene, and in LMNA, MYII7 or TTN alone, was associated with early onset disease and reduced transplant-free survival. As expected, nonsense and frameshift variants were more common in DCM patients than in healthy individuals of the reference cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation and pathogenicity scores, and localization of missense variants were similar in DCM patients and healthy reference individuals. Conclusion: To our knowledge, this is the first study to identify correlations between genotype and prognosis when sequencing a large number of genes in unselected DCM patients. The similar distribution of missense variants in DCM patients and healthy reference individuals questions the pathogenic role of many variants, and suggests that results from genetic testing of DCM patients should be interpreted with caution.
|
|
| 2. |
- Engström, Pär, 1954
(författare)
-
Samtal och ledarskap - En studie av medarbetarsamtal i grundskolan : Dialogue and Leadership. A study staff dialogue in compulsory school.
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study deals with collaborative conversations (medarbetarsamtal) between headmaster and teachers in Swedish compulsory schooling. The dialogues have been investigated in terms of three aims that concern the headmaster's leadership, institutionai and intra-institutional dialogue, and staff dialogue. On the basis of these aims, the study has tried to answer questions about the interaction in dia logues, their content and their signit1cance for the participants.' The study's theoretical points of departure are taken from leadership research (e.g. a dyad theory and leadership's sources of power), from previous research on staff dialogue (a perspective of evaluation and of development), and discourse theory (which includes e.g. coordination between the speakers and an initiative-response dimension). The empirical foundation of the study comprises 12 taped staff dialogues as weil as follow-up inter views with those involved. Totally 19 persons took part in the study (12 teachers and 7 headmasters). The analysis consists of a quantitative and a qualitative part. The former is an IR analysis that tries to clarify the dominance relationships in the dialogues, while the qualitative analysis is a search for meanings in the interaction and in the content of dialogue. One result of the study is that the dialogues exhibit a variation in patterns of interaction. The explanation for this variation is that the dialogue parcicipants distinguish among themselves mainly in regard to the time length of their relations and professionallives. If the relation is new, the headmaster tends to guide the dialogues (primarily through questions), whereas the interaction pattern becomes more egalitarian if the participants have known each other for some years. Another result is that the headmasters see the staff dialogues as an opportunity to build trust in the teachers, and a way to get information about both the individual teachers and the school activities. The teachers appreciate the headmaster's attention to what they have to say, and feel strenghtened by praise when they receive it. Beneath these meanings, the study has also revealed a controi aspect of the dialogues, whereby the headmaster as chief verifies that the teachers carry out their mission in a purposive manner. The study's contribution to leadership research is a theoretical framework that can illuminate both the professional and personal relations between headmaster and teachers. In addition, numerous empirical examples are presented of how the headmaster and teachers converse about their activities. To dialogue research, the study contributes agreater understanding of variation in the symmetri -asymmetri dimension of institutionai as weil as intra-institutional dialogues..This variation can be understood through the three components of position, relation and profession. Finally, the study contributes to development of theory about staff dialogue by connecting the sources of power that the participants activate in the dialogue with the meanings that the dialogue has for the participants and with pattems of interaction.
|
|
