| 1. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 2. |
- Cort, Rebecca, 1988-
(författare)
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Getting Work Done : The Significance of the Human in Complex Socio-Technical Systems
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aims to deepen the understanding of the role and relevance of the worker in the functioning of complex socio-technical systems. The perspective adopted is profoundly human-centred and the worker is considered as a resource. This stands in stark contrast to the performance-related measurements and accident investigations which have typically formed much research on work in complex safety-critical systems and conveyed a perspective of the human as merely a system cog. The empirical material in this thesis is based on ethnographic fieldwork in the shape of workplace studies conducted across two distinct work domains: manufacturing and operational train traffic. The studies are informed by distributed cognition (DCog) and activity theory (AT) as prominent theoretical approaches for developing in-depth understandings of how work activities are accomplished in situations where the interplay between humans and their socio-cultural and material environment is of interest. The findings are illustrated by empirical work that provides detailed accounts of work practices derived from a total of four work settings. It is illustrated how acquired experiences and skills allow the workers to simultaneously use and create resources in the socio-material environment. The findings also reveal novel characteristics of adaptations as driven by a human agency rather than being a result of external demands, which is the common view in literature on work in safety-critical domains. Based on the findings, the role of the worker is illustrated as a meaning-making actor – not only participating in, but also actively contributing to the system and its functioning. In that capacity, the worker is acting as a driving force for a process of continuous development, allowing the system to continue to function although frequently exposed to uncertainties and unexpected events. This thesis contributes to a deepened understanding of the role of human workers in socio-technical systems, highlighting how workers are an invaluable asset when it comes to managing large variations and unexpected events in technology-mediated complex work. This contribution is complementary to the current understanding of how to uphold system safety and provides insight into what underlies a mutually beneficial relationship between humans and technology to which both parties can contribute with what they do best.
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| 3. |
- Grim, Katarina, 1971-, et al.
(författare)
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Legitimizing user knowledge in mental health services : Epistemic (in)justice and barriers to knowledge integration
- 2022
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Ingår i: Frontiers in Psychiatry. - Lausanne : Frontiers Media S.A.. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Including the voices and knowledge of service users is essential for developing recovery-oriented and evidence-based mental health services. Recent studies have however, suggested that challenges remain to the legitimization of user knowledge in practice. To further explore such challenges, a co-production study was conducted by a team of researchers and representatives from user organizations in Sweden. The aim of the study was to explore the barriers and facilitators to the legitimacy of user knowledge, as a central factor in sustainably implementing user influence in mental health practice. A series of workshops, with representatives of mental health services and user organizations were conducted by the research team to explore these issues. The analysis built on the theoretical framework of epistemic injustice, and the underlying aspects, testimonial, hermeneutic and participation-based injustice, were utilized as a framework for a deductive analysis. Results suggest that this is a useful model for exploring the complex dynamics related to the legitimacy of user knowledge in mental health systems. The analysis suggests that the legitimacy of user knowledge is related to the representativeness of the knowledge base, the systematic formulation of this knowledge inapplicable methods, access to resources and positions within the mental health system and participation in the process of integrating this knowledge-base in mental health contexts. Legitimizing user knowledge in practice additionally challenges mental health systems to support readiness for change in working environments and to address the power and role issues that these changes involve. Copyright © 2022 Grim, Näslund, Allaskog, Andersson, Argentzell, Broström, Jenneteg, Jansson, Schön, Svedberg, Svensson, Wåhlstedt and Rosenberg.
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| 4. |
- Havsed, Kristian, et al.
(författare)
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Bacterial Composition and Metabolomics of Dental Plaque From Adolescents
- 2021
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Supragingival dental plaque samples were collected from 40 Swedish adolescents, including 20 with caries lesions (CAR) and 20 caries-free (CF). Fresh plaque samples were subjected to an ex vivo acid tolerance (AT) test where the proportion of bacteria resistant to an acid shock was evaluated through confocal microscopy and live/dead staining, and the metabolites produced were quantified by 1H Nuclear Magnetic Resonance (1H NMR). In addition, DNA was extracted and the 16S rRNA gene was sequenced by Illumina sequencing, in order to characterize bacterial composition in the same samples. There were no significant differences in AT scores between CAR and CF individuals. However, 7 out of the 10 individuals with highest AT scores belonged to the CAR group. Regarding bacterial composition, Abiotrophia, Prevotella and Veillonella were found at significantly higher levels in CAR individuals (p=0.0085, 0.026 and 0.04 respectively) and Rothia and Corynebacterium at significantly higher levels in CF individuals (p=0.026 and 0.003). The caries pathogen Streptococcus mutans was found at low frequencies and was absent in 60% of CAR individuals. Random-forest predictive models indicate that at least 4 bacterial species or 9 genera are needed to distinguish CAR from CF adolescents. The metabolomic profile obtained by NMR showed a significant clustering of organic acids with specific bacteria in CAR and/or high AT individuals, being Scardovia wiggsiae the species with strongest associations. A significant clustering of ethanol and isopropanol with health-associated bacteria such as Rothia or Corynebacterium was also found. Accordingly, several relationships involving these compounds like the Ethanol : Lactate or Succinate : Lactate ratios were significantly associated to acid tolerance and could be of predictive value for caries risk. We therefore propose that future caries risk studies would benefit from considering not only the use of multiple organisms as potential microbial biomarkers, but also their functional adaptation and metabolic output.
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| 5. |
- Jansson, Malin, 1978-, et al.
(författare)
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Stromal type I collagen in breast cancer : correlation to prognostic biomarkers and prediction of chemotherapy response
- 2024
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Ingår i: Clinical Breast Cancer. - : Elsevier. - 1526-8209 .- 1938-0666.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fibrillar collagens accumulate in the breast cancer stroma and appear as poorly defined spiculated masses in mammography imaging. The prognostic value of tissue type I collagen remains elusive in treatment-naïve and chemotherapy-treated breast cancer patients. Here, type I collagen mRNA and protein expression were analysed in 2 large independent breast cancer cohorts. Levels were related to clinicopathological parameters, prognostic biomarkers, and outcome.Method: COL1A1 mRNA expression was analysed in 2509 patients with breast cancer obtained from the cBioPortal database. Type I collagen protein expression was studied by immunohistochemistry in 1395 women diagnosed with early invasive breast cancer.Results: Low COL1A1 mRNA and protein levels correlated with poor prognosis features, such as hormone receptor negativity, high histological grade, triple-negative subtype, node positivity, and tumour size. In unadjusted analysis, high stromal type I collagen protein expression was associated with improved overall survival (OS) (HR = 0.78, 95% CI = 0.61-0.99, p = .043) and trended towards improved breast cancer–specific survival (BCSS) (HR = 0.65, 95% CI = 0.42-1.01, P = 0.053), although these findings were lost after adjustment for other clinical variables. In unadjusted analysis, high expression of type I collagen was associated with better OS (HR = 0.70, 95% CI = 0.55-0.90, P = .006) and BCSS (HR = 0.55, 95% CI = 0.34-0.88, P = .014) among patients not receiving chemotherapy. Strikingly, the opposite was observed among patients receiving chemotherapy. There, high expression of type I collagen was instead associated with worse OS (HR = 1.83, 95% CI = 0.65-5.14, P = .25) and BCSS (HR = 1.72, 95% CI = 0.54-5.50, P = .357).Conclusion: Low stromal type I collagen mRNA and protein expression are associated with unfavourable tumour characteristics in breast cancer. Stromal type I collagen might predict chemotherapy response.
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| 6. |
- Kvedaraite, Egle, et al.
(författare)
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Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142−/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.
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| 7. |
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| 8. |
- Randrup, Thomas, et al.
(författare)
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Urban open space management in the Nordic countries. Identification of current challenges based on managers' perceptions
- 2021
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Ingår i: Cities. - : Elsevier BV. - 0264-2751. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on how Nordic practise relates to, and perceives contemporary challenges to urban open space management. The study used a case study approach, via interviews. The studied Nordic cities experience the effects of densification in inner city areas. This is often resulting in higher pressure on existing urban open spaces, but also generating new spaces which tend to be small and fragmented, not meeting the many wishes and demands asked for by the diverse user groups. While budgets are sufficiently allocated in new development projects, it is a challenge to withstand the maintenance budgets, forcing managers to prioritise. Due to primary political interest in inner city areas, there is a risk of managers not prioritising the more peripheral areas, from where resources are often transferred to the newly developed areas. This creates a new type of urban nature, primarily in the urban peripheral areas, with increased amounts of biodiversity and higher amounts of multi-functionality, compared to the smaller and more intensively programmed inner-city areas. Urban open space managers are relying on the existing municipal planning tools, and to varying degrees act strategically in terms of developing own sector oriented plans and strategies.
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| 9. |
- Svännel, Jessica, et al.
(författare)
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Digital systems and tools to support urban open space governance and management
- 2020
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Ingår i: Urban Open Space Governance and Management. - 9780367173029 ; , s. 168-189
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Bokkapitel (refereegranskat)abstract
- This chapter outlines how digital systems and tools can support urban open space (UOS) governance and management and discusses important factors to consider when building a strategy in relation to future trends and routes to progress. A key conclusion is that digital technology can aid in documenting and analysing data, generating new knowledge for UOS governance and management and presenting and communicating the values and benefits that UOS provide. However, the use of digital technology needs to be underpinned by clear aims and well-structured and well-developed data infrastructure.
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