| 1. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 2. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Kelsoe, John, et al.
(författare)
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Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 5. |
- Bauer, Fredric, et al.
(författare)
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Petrochemicals and climate change: Powerful fossil fuel lock-ins and interventions for transformative change
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- With the risk of climate breakdown, pressure is increasing for all sectors of the economy to break with fossil fuel dependence and reduce greenhouse gas emissions. In this context, the chemical industry requires more focused attention as it uses more fossil-fuel based energy than any other industry and the production of chemicals is associated with very large emissions. Beyond the climate crisis, the chemical industry significantly impacts several critical dimensions of sustainability, including the planetary boundaries for novel entities, biosphere integrity, and ocean acidification. In this report, we focus on the petrochemical sector, which represents the largest share of the chemicals industry and is generally understood to refer to the part of the industry that relies on fossil-fuel feedstocks from oil, gas, and coal. The petrochemicals sector produces chemicals mainly used for plastics and fertilisers, but the products also end up in paints, pharmaceuticals, pesticides, and other applications. This report provides a critical exploration of the petrochemical sector to strengthen awareness of its relevance to the climate crisis and to provide tools and recommendations for decision-makers in different domains to initiate, support, and accelerate much-needed transformation. The report highlights the rapid expansion of the petrochemical sector as well as the range and growth of economic, infrastructural, and political interlinkages with the fossil fuel extraction sector. It argues that these developments and dynamics are crucial to understanding pathways, strategies, and interventions for a low-carbon transition for petrochemicals.
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| 6. |
- Bauer, Fredric, et al.
(författare)
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Petrochemicals and Climate Change : Tracing Globally Growing Emissions and Key Blind Spots in a Fossil-Based Industry
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- With the risk of climate breakdown becoming ever more pressing as the world is on track for 2.7 degrees warming, pressure is increasing on all sectors of the economy to break with fossil fuel dependence and reduce greenhouse gas (GHG) emissions. In this context, the chemical industry and the production of important basic chemicals is a key sector to consider. Although historically a driver of economic development, the sector is highly dependent on fossil resources for use as both feedstock and fuel in the production of as well organic as inorganic chemicals. The chemical industry demands both petroleum fractions and natural gas. Petroleum fractions such as naphtha and petroleum gases are used as feedstocks for building block chemicals and polymers (e.g., benzene and polyethylene), while natural gas is used for methanol and ammonia. Indeed, the sector is associated with both large process emissions as well as energy related emissions. Our results demonstrate that in 2020 direct GHG emissions from the petrochemical sector amounted to 1.8 Gt CO2eq which is equivalent to 4% of global GHG emissions. Indirect GHG emissions resulting from the activities in other industries supplying inputs for the petrochemical industry accounted for another 3.8 Gt CO2eq. The petrochemical industry is thus associated with a total of 5.6Gt CO2eq of GHG emissions, equivalent to ~10% of global emissions. Over the past 25 years, emissions associated with petrochemicals have doubled and the sector is the third most GHG emitting industry. This increase is fueled by large growth of petrochemicals production as well as growth in regions with high indirect emissions, i.e., in energy systems with high dependence on coal and other fossil fuels. Over the past decades, the industry has grown rapidly in the Asia-Pacific region especially in China which in 2020 was the source for about 47% of global GHG emissions associated with petrochemicals. USA accounts for 6% of the emissions from the industry and Europe for 5%. The BRIC group of countries, which except for China also includes Brazil, India, and Russia, currently accounts for 57% of GHG emissions from petrochemicals, showing that the emissions from this sector are more geographically clustered in these countries than emissions from other sectors.Proper disaggregated and comparative analyses of key products is currently not possible. Data confidentiality and a high reliance on proxy data limit the reliability of LCA and stands in the way of mapping climate impacts. A strong demand of chemicals life cycle inventory (LCI) data for environmental footprinting has resulted in a general increase of chemicals data in many LCI databases, but the energy demands both for heat and electricity are typically not well-documented for production processes outside the main bulk chemicals. If incinerated at end-of-life plastics and other chemical products will emit embodied carbon as CO2 and if landfilled there is a risk of slow degradation with associated methane emissions. Global estimates based on most LCA datasets will thus significantly underestimate emissions from the chemical industry.The multitude of value chains dependent on the petrochemical industry makes it an important contribution to life cycle emissions in many sectors of the economy. Petrochemicals are used as an intermediate input in many industries and the emissions associated with them thus propagate through the economy, with final demand in manufacturing industries and services being associated with the largest shares of emissions from chemicals. The impacts and emissions downstream in value chains is however poorly understood and disclosure by petrochemical producers is lacking and insufficient. While disclosure of emissions in the industry has increased over the past decades, it remains partial and shows inconsistencies over time. This is due to issues such as different reporting standards, large discrepancies in the extent of disclosure as well as various other gaps and inconsistencies in reporting. This holds for all scopes, although Scope 1 emissions are better covered. Only some firms disclose information about downstream Scope 3 emissions including end-of-life for final products. Emission targets set by firms in the industry do not correspond to the challenge of large and rapid emission reductions. Many targets include only parts of operations and transparent, standardized target-setting is lacking. Reported emission reduction initiatives to achieve targets are far from sufficient focusing mainly on efficiency improvements or insubstantial parts of the operation. Shifting to renewable energy is a key for rapid emission reductions in the industry, yet few firms report strategic targets for this shift. As the industry has historically been closely linked to and integrated with the energy sector it holds a great potential for engaging with the deployment and adoption of renewable energy, although this implies a transformation of the knowledge base and resource allocation in the industry which is still focused on fossil fuels. Roadmaps and scenario analyses show that apart from a shift to renewable energy, a transformation of the industry relies on the deployment of key technologies which are not yet fully developed. This includes new technologies for hydrogen production, e.g., electrolytic (green) hydrogen or hydrogen produced with carbon capture and storage (CCS). New chemical synthesis pathways based on captured carbon, so called carbon capture and utilization (CCU) is also highlighted, but the massive demand for renewable energy associated with this pathway is a significant barrier to its adoption in the near term. The report shows how efficiency improvements continues to be the main focus for reducing the climate impact of petrochemicals, but that this is a completely inadequate approach for achieving the emissions reductions necessary in the coming decades. Breakthrough technologies are unlikely to be deployed at a rate consistent with international climate targets, and there is a great risk in relying on the promises of technologies which are yet to be proven at scale. The large knowledge gaps that remain are key barriers for effective governance of the transition.
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| 7. |
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| 8. |
- Bauer, Peter, 1992-
(författare)
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När slutar invandrarna vandra? : Integrationsfrågan i statlig, kommunal och skolpolitisk diskurs 1967–2000
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last three decades of the 20th century Swedish immigrant policy went through a profound change. In the late 1960s immigrant policy were based on assimilation but during the 1970’s and 1980’s this policy was exchanged to multicultural guidelines. These multicultural guidelines were however abandoned in the late 1990s when integration became a key word in the debate about immigrants. This thesis investigates how these changes were made possible by a shifting understanding of immigrants in state and local discourse (the last represented by Malmö municipality) by operationalizing Carol Lee Bacchis What’s the problem represented to be analysis. Previous research has shown that the social category of immigrants during the first six decades of the 20th century understood immigrants as a threat towards the Swedish race and later the welfare state. From this perspective immigrant policy can be seen as the result of the creation of a problematized immigrant subject, a tendency that is also the case for later decades. The investigation shows that immigrants in the early 1970’s were mainly understood from a class and welfare perspective. During this period immigrants were seen as a threat towards the social cohesion of the welfare state as well as the social democratic ambitions of a raised standard of living for the working class. This understanding led to the development of a multicultural policy where immigrant culture was supported within state and local politics and by structural changes in the education system, aiming to include the category in civic life and improve their living conditions. In the years between 1976 and 1985 the understanding of immigrants however changed. During this period immigrants became increasingly problematized for their lack of employment and a cultural difference. During the end of this period the multicultural policy changed from an emphasis on culture as a resource for social inclusion to that some parts of of a Swedish identity were not subject of choice. Furthermore, this period also lead to increased efforts at the individual level, were the policy aimed to give individual immigrants increased chances at the labor market. During the last fifteen years the 20th century immigrant policy became increasingly politicized, and immigrants became understood as radically culturally different from swedes. In this period immigrant culture were constructed as oppressive towards women and outdated when compared to the modern Swedish culture. Furthermore, the notion of immigrants as unemployed from previous decades continued to play an important part and immigrants were also conceived as living segregated. This view resulted in the creation of integration policies aiming to not handle immigrants as a from the general population different group. Instead, immigrants should become integrated in Swedish society through the general welfare with an emphasis that not all parts of a Swedish identity were choose able.The result of the investigation show that European culture became increasingly normative in the development of Swedish migrant policy, thus excluding European immigrants from the problematized immigrant subject. Thereby the globalization of migration towards Sweden led to a development were immigrant policy shifted focus from class to cultural perspectives.
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| 9. |
- Bauer, Tobias
(författare)
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Structural and sedimentological reconstruction of the inverted Vargfors basin : a base for 4D-modelling
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Palaeoproterozoic Skellefte mining district in northern Sweden covers an area of 120 by 30 km and is one of the most important mining districts in Europe, producing mainly Zn, Cu, Pb, As and Au from volcanogenic massive sulfide (VMS) and orogenic gold deposits.Detailed mapping of structures and stratigraphy within the sedimentary Vargfors Group combined with a structural analysis revealed a syn-extensional fault pattern of NW-SE-trending normal faults and associated NE-SW-trending transfer faults, creating the segmented sedimentary Vargfors basin. It comprises distinct fault-bound compartments, which incluence the sedimentary stratigraphy in each of these compartments.Syn-rift subsidence affected the sedimentary conditions from near-shore to shallow submarine environment.Intensive fault movements associated with mafic volcanic activity along these faults resulted in the rapid uplift of the oldest phase of the Jörn intrusive complex and/or subsidence of its surrounding areas. Subsequent erosion of the intrusive rocks led to the formation of a tonalite to granodiorite bearing conglomeratic sequence, representing an alluvial fan. Further uplift to the north of the district resulted in the erosion of Arvidsjaur volcanic rocks and the formation of a braided river system. Subsidence of the intrusive complex and/or a sedimentary coverage on top of the same caused a break in sedimentation of tonalite to granodiorite clasts. Stratigraphical evolution of the sedimentary rocks and the Vargfors Group - Skellefte Group contact relationships show that rifting started in the centre and proceeded with time towards SE and NW. Subsequent basin inversion resulted in the reactivation of the existing normal faults along a carbonate-rich basal layer forming asymmetric synclines. Primary geometries of sedimentary strata within each fault-bound compartment controlled their deformation styles. Furthermore, strain was partitioned into the faults, forming high strain zones along the basin margins, where foliations parallel the main faults, and low strain domains in the core of the basin, where foliation is oblique to the main structural grain of the basin. This oblique foliation is either a result of a rotating stress field or a transpressional regime. This case study on basin inversion gives implications for accretion processes along the Svecokarelian Craton margin as well as forthe formation of VMS-deposits and their possible transposition. Basic modelling of the main geological boundaries in the central Skellefte district was performed by integrating data from regional to outcrop scale using the GoCAD (Paradigm) software platform. Available data included geographical and geological data, which were imported from ArcGIS (ESRI) as well as drill-hole data, seismic profiles, resistivity and gravimetry profiles and EM-profiles. Creation of the main geological boundaries utilized GoCAD and SPARSE (Mirageoscience) algorithms, whereas structural geological data was exclusively modelled with SPARSE. Furthermore, this study provides a base for refining the 3-dimensional model and developing a 4-dimensional model, showing the geological evolution of the Skellefte district.
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| 10. |
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