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- Klaric, Lucija, et al.
(author)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Other publication (other academic/artistic)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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- Gustafsson, Mariana S., 1978-, et al.
(author)
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Repairment of Unstable Sociomaterial Relations: A study on librarians’ and social workers’ roles and practices in addressing the complex needs of vulnerable groups
- 2021
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Conference paper (other academic/artistic)abstract
- In this paper we address the increased digitalization of the fabric of modern welfare societies, and the expectations on individuals to be independent and digitally capable that follows from this. We focus on repairment practices aimed at repairing the lives of individuals situated in unstable sociomaterial relations in the context of social care and a public library in Sweden. The aim was to explore repairment practices in two Swedish empirical contexts: one in a municipal library setting, and one in a social service setting. The analysis was conducted with the help of the concept of repairment, understood in relation to feminist STS points of departure of relationality and entanglement of humans and non-humans. We conducted interviews and observations in these two settings and analyzed these with the help of the concept of repair. The analysis shows that in the context of social service, repairment was enacted differently in relation to different interpretations of existing legislation concerning minimal livelihoods, and that in the context of the public library repairment was enacted in relation to expectations of the library visitors to become digitally independent. We also relate these repairment practices to the current pandemic.
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- S. Gustafsson, Mariana, 1978-
(author)
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Integration of RPA in public services: a tension approach and the case of Income support
- 2021
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Conference paper (other academic/artistic)abstract
- Scandinavian welfare services are undergoing advanced digitalization in a context rife with diversified client needs and demands. The political ambition is to draw the benefits from technological developments to address the new demands from society and challenges in health, social care and education [1, 2]. Beyond the municipal organization, technology mediated decision making, also called Robotic Process Automation (RPA), require new, cross-jurisdictional governance and coordination mechanisms, as well as new institutional arrangements. Such transformations entail at least a thorough revision, if not totally new logics on service administration, organization management, professional roles and relation to the clients. Rules and principles for public service provision and administration are now re-designed and implemented as RPA applications are introduced in municipalities. To understand RPA practices, their municipal context and the transformations of services that they set out, as well as their impacts upon societal needs, it is critical to identify and understand the assumptions that underly such arrangements, the different logics at play and the tensions and value conflicts that arise. The Purpose of this paper is to uncover and explain institutional, organization and governance tensions and implications of RPA in income support services.
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