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- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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- Berg, Christoffer, 1986-
(författare)
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Public Planning, Neoliberal Hybridity and Local Activism in Sundbyberg : Epochal Reconfiguration of Urban Development in Greater Stockholm
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Which urban policy responses are deployed when a small social democratic municipality in a greater city region aims to be competitive for private investments in housing and the built environment? Which new institutional development arrangements are implemented for this purpose, in the wake of a decades-long hegemonic position of the municipal public housing company? This thesis draws on a qualitative case study design to approach such questions, and investigates recent urban development in Sundbybergs stad in Greater Stockholm to answer them. Theoretically, the thesis draws on a theory of neoliberal localization in combination with Henri Lefebvre’s theory of the social production of space. The thesis is thereby able to explain how the municipality consolidated political power, institutional infrastructures, and administrative capacities with a view to introducing a market-based paradigm of urban development. It argues that this paradigm became characterized by a neoliberal hybridity. It supports this argument by analyzing three major development projects targeting three areas with very different sociospatial characteristics. The thesis thereby demonstrates how market-based developments integrated a number of regulatory features and public planning interventions in accordance with certain objectives, concerns, and conditions. E.g., it reveals how the development of a 1970s Million Homes Programme area, Hallonbergen, relied both on an extended sale of public assets to support private developers’ investments with the objective of comprehensively transforming the area, and on extraordinary measures for ‘social sustainability’. It also reveals how the development of the original municipal town, Central Sundbyberg, was arranged in a municipal development company. This established a business-like format for political control and external expertise, while undermining public planning and clouding democratic accountability. This point is further emphasized by analyzing local inhabitants’ methods for contesting certain development features and land use proposals in this project, enforcing a re-politicization of a largely depoliticized development project. Ultimately, the thesis contributes new knowledge on the variegating forms of neoliberal urbanism through an atypical case of a subordinate city region municipality that historically has been characterized by social democracy, a large public rental housing structure, a public housing company with control of spatial planning, and working-class populations and industries.
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- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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- Harling, Martin, 1972-
(författare)
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Välja vara : En studie om gymnasieval, mässor och kampen om framtiden
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Avhandlingen kartlägger och analyserar i fyra empiriska artiklar hur elevsubjekt konstrueras i skolans vardag och vilken roll marknadens principer spelar i dessa konstruktioner. I synnerhet fokuseras vilka logiker som konstituerar gymnasievalets praktiker, samt hur dessa legitimeras, tolkas och utmanas. Resultatet visar att gymnasievalets praktiker delar upp både nuet och framtiden för eleverna, som valet mellan en uttalad utopi eller en underförstådd dystopi, där eleverna i hög grad själva görs ansvariga för att lyckas eller misslyckas med att förverkliga den utopi som iscensätts i valets praktiker. Denna uppdelning framstår för aktörerna till stor del som naturlig och apolitisk, vilket i sin tur legitimerar dess effekter i termer av exkludering, ojämlikhet och segregering, ofta på basis av social klass. Den marknadsstyrda skolans diskurser konstruerar och delar också upp eleverna som om de vore varor med olika värde. Begreppet fantasmatiska logiker kan förklara hur elever greppas av marknadsliknande diskurser, samt hur de hanterar motsägelsefulla villkor. Exempelvis hur gymnasievalet för eleverna både innebär att förändras och bli vad man vill, samtidigt som man formas att bli mer av den man redan är, genom att välja att vara den man är. Elevernas problematisering och destabilisering av dominerande marknadslogiker i skolan förekommer i alla undersökta sammanhang, och beskrivs i avhandlingen som både genomskådanden och ifrågasättanden av hur skola och utbildning kopplas samman med marknadens logiker. Genom att genomskåda gymnasievalets förmenta neutralitet synliggör eleverna hur marknadsstyrningen av utbildning i allmänhet och iscensättningen av mässorna i synnerhet tycks ligga i skolornas, snarare än elevernas intresse.
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