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- Bolin, Sara
(författare)
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Mechanisms of Medulloblastoma Dissemination and Novel Targeted Therapies
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Medulloblastomas are the most frequent malignant childhood brain tumors, arising in the posterior fossa of children. The overall 5-year survival is 70%, although children often suffer severe long-term side effects from standard medical care. To improve progression-free survival and quality of life for these children, finding new therapeutic targets in medulloblastoma is imperative.Medulloblastoma is divided in to four molecular subgroups (WNT, SHH, Group 3 and Group 4) based on key developmental pathways essential for the initiation and maintenance of tumor development. The MYC family of proto-oncogenes regulates cell proliferation and differentiation in normal brain. Aberrant expression of MYC proteins occurs commonly in medulloblastoma.Our studies on Group 3 medulloblastoma identify the transcription factor SOX9 as a novel target for the E3 ubiquitin ligase FBW7, and show that increased stability of SOX9 confers an increased metastatic potential in medulloblastoma. Moreover, SOX9-positive cells drive distant recurrences in medulloblastoma when combining two regulatable TetON/OFF systems. MYCN depletion leads to increased SOX9 expression in Group 3 medulloblastoma cells, and the recurring tumor cells are more migratory in vitro and in vivo. Segueing to treatment of medulloblastoma, we show that BET bromodomain inhibition specifically targets MYC-amplified medulloblastoma cells by downregulating MYC and MYC-transcriptional targets, and that combining BET bromodomain- and cyclin-dependent kinase- inhibition improves survival in mice compared to single therapy. Combination treatment results in decreased MYC levels and increased apoptosis, and RNA-seq confirms upregulation of apoptotic markers along with downregulated MYC target genes in medulloblastoma cells.This thesis addresses novel findings in transcription factor biology, recurrence and treatment in Group 3 medulloblastoma, the most malignant subgroup of the disease.
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- Kjellgren, Maria, 1973-
(författare)
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Skolkuratorns samtalspraktik : en studie om individuella samtal med barn i den svenska grundskolan
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis fills part of the existing knowledge gap regarding school social workers (SSW) individual counselling practice. The overall aim is to investigate the individual SSW counselling in Swedish elementary schools, as part of the pupil health team (PHT). This will be achieved by exploring the following three basic research questions: What characterizes school social work regarding structure, process and interventions in individual counselling sessions held by SSWs with children? How do SSWs describe the difficulties and opportunities in school social work, interventions and performance, and collaboration with other actors in pupil health teams? What characterises SSWs’ individual counselling according to the adolescents’ experiences and expressed needsThis thesis consisted of four research studies. The first one concentrated on SSWs personal experiences of counselling children, in which focus group studies were conducted with 22 SSWs (four groups). In the second study, the SSWs described their experiences of being a part of a multi-disciplinary team, the PHT, during the focus group interviews. These two studies were analysed by content analysis. The third study consisted of a quantitative protocol study regarding child characteristics, counselling strategies and interventions analysed by descriptive statistics. The purpose on the fourth study was to increase knowledge about the individual counselling from the adolescents’ perspective. Individual interviews were conducted and analysed through content analysis.This thesis highlighted the necessity for children to express themselves, in regards to their life situation, concerns and problems. SSWs could be one prominent actor in the children’s lives by providing individual counselling sessions. SSWs are described as the PHT psychosocial expert with specialised knowledge regarding the impact of negative psychosocial factors on children.In addition, this thesis concluded that available regulations and guidelines meant insure that children are listened and able to express their narrative in a safe and trustful school counselling environment are limited.
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- Kjölstad, Henrik, 1980-
(författare)
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A European Declaration of Fascism? : En analys av Anders Behring Breiviks manifest 2083
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The terror attacks in Oslo, July 22, 2011, executed by Anders Behring Breivik, showed the deadliest outbreak of political violence in Norway since World War II. After the subsequent apprehension of Breivik, discussions about his ideological positioning soon emerged. While Breivik was initially described as an Islamophobic, right wing-extremist, a few expert witnesses and scholars labeled him and his manifesto 2083: A Declaration of European Independence as fascist. Some analysts disagreed with such a categorization and argued that Breivik's views had little to do with fascism. Other commentators and academics partly agreed with the fascist label but added that Breivik's ideology differed from classical fascism in several ways. The aim of this research is to examine whether the manifesto 2083 can be classified as fascist according to various established definitions and ideal types of fascism. In particular, this research draws on the theories, definitions, and ideal types of fascism of established scholars Roger Griffin, Stanley G. Payne, and Emilio Gentile to inform a content analysis of 2083.The study's relevance concerns the ideology of and behind certain violent political activism, and if fascism is undergoing a transformation which urges updates of established definitions of the phenomenon. 2083 is treated as an outlier or deviant case of fascism.This research finds that 2083 does fulfill several fascist criteria, and even concepts central to the ideal types. However, the results are at times ambiguous and open to further interpretation. Fascist concepts such as national rebirth, a glorification of violence, and religiously tinged activism are expressed in the manifesto, but crucial details regarding them remain unexplored or unspecified. 2083's violent strategies for achieving desired societal change have striking similarities with certain contemporary race radicalism; while descriptions of societal condition and utopian goals share certain fascism characteristics, but also resemble late 19th Century German revolutionary conservatism or proto-fascism. Thus, one might rather see 2083 as hybrid form of different, already existing, fascist ideological traits rather than a “new” form of fascism.
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