| 1. |
- Córdoba Doña, Juan Antonio, 1962-
(författare)
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Withstanding austerity : economic crisis and health inequalities in Spain
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Along with the austerity measures introduced in many countries, the economic crisis affecting Europe since 2008 seems to have impacted many aspects of the health of the Spanish population and has had a negative effect on the provision health services. An increasing body of knowledge has shown a clear impact of the current crisis on suicidal behaviour and mental health, and a less consistent effect on physical health and access to healthcare. However, little is known about the impact of the crisis on social inequalities in health and healthcare access, an area on which the present study seeks to shed light in the context of Spain, and specifically Andalusia, a region hit very hard by the crisis.Objective: To study the impact of the economic crisis starting in 2008 on health, health inequalities and health service utilisation in Spain and Andalusia and the roles of socio-demographic factors in these associations.Methods: Death rates were analysed to study the annual percent change in overall and cause-specific mortality in Spain between 1999 and 2011, and the Longitudinal Database of the Andalusian Population was used to study educational inequalities in overall mortality from 2002 to 2010 (study 1). To calculate suicide attempt rates, information from 2003 to 2012 on 11,494 men and 12,886 women provided by the Health Emergencies Public Enterprise Information System in Andalusia was utilised. The association between unemployment and suicide attempts was studied through linear regression models (study 2). Two waves of the Andalusian Health Survey (2007 and 2011–12) provided data for the third and fourth studies of this thesis. Educational and employment status inequalities in poor mental health in relation with the crisis were analysed through Poisson regression models (study 3). The change in inequalities (pre-crisis–crisis) in health care utilisation outcomes (general practitioner, specialist, hospitalisation and emergency attendance) was measured by the change in horizontal inequality indices. A decomposition analysis of change in inequality between periods was performed using the Oaxaca approach (study 4).Results: Study 1: Overall mortality in Spain decreased steadily during the period, with annual percent changes of -2.44% in men and -2.20% in women. An increase in educational inequality in mortality was observed in men in Andalusia. In women, the inequalities instead remained stable. Suicide mortality showed a downward trend in both sexes in Spain. Study 2: A sharp increase in suicide attempts in Andalusia was detected after the onset of the crisis in both sexes, with adults aged 35 to 54 years being the most affected. Suicide attempts were associated with unemployment rates only in men. Study 3: Poor mental health increased in working individuals with secondary and primary studies during the crisis compared to the pre-crisis period, while it decreased in the university study group. However, in unemployed individuals poor mental health increased only in the secondary studies group. Financial strain could partly explain the crisis effect on mental health among the unemployed. Study 4: Horizontal inequality in utilisation changed to a greater equality or a more pro-poor inequality in both sexes. In the decomposition analysis, socioeconomic position and health status showed greater contributions to the changes in inequalities.Conclusion: This thesis illustrates the complexity of the influences of the current economic crisis on health inequalities in a Southern European region. Specifically, no noticeable effects of the crisis on overall and suicide mortality were detected; instead, increasing educational inequalities in mortality in men and a large increase in suicide attempts in middle aged men and women were observed. The deterioration in poor mental health was mainly detected in those of intermediate educational level. Economic conditions such as unemployment and financial strain proved to be relevant. Finally, in the light of no increased inequalities in healthcare utilisation, the universal coverage health system seems to buffer the deleterious effect of the crisis and austerity policies in this context.
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| 2. |
- Gustafsson, Stefan
(författare)
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Adiponectin : genetic determinants and relations with subclinical cardiovascular disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease (CVD) is a major cause of morbidity and premature death in Sweden and globally, which besides the substantial individual suffering, puts large restraints on the public health system. Adiponectin is a highly heritable trait, which is strongly associated with metabolic disturbances such as obesity and insulin resistance. Previous studies indicate that adiponectin may play a fundamental role in the development of CVD. However, further knowledge about pathways linking circulating adiponectin, genetic loci, and markers of early CVD is needed. Therefore, the overall aim of this thesis was to assess the genetic determinants of adiponectin, and the role of adiponectin in the development of subclinical CVD. In Study I, we investigated the association between adiponectin and cardiac geometry and function in two cross-sectional samples of elderly and found that high adiponectin levels were associated with poorer cardiac function in men. This association was dependent on N-terminal pro-brain natriuretic peptide and this was more pronounced in individuals with prior CVD, which could indicate a counter-active effect in response to decreased cardiac function, potentially mediated by natriuretic peptides. In Study II, we examined the role of adiponectin in vascular pathology in a cross-sectional study design where higher adiponectin levels were associated with a lower lipid-content in plaques and higher vessel wall elasticity, indicating less arterial pathology. In Study III, we assessed oxidative stress and inflammatory markers in relation to adiponectin, where adiponectin was positively associated with the anti-oxidant glutathione and inversely associated with lipid peroxidation as well as epidermal growth factor. Our findings suggest that adiponectin is associated with a more beneficial oxidative stress profile. In Study IV, we explored the impact of rare genetic loci on circulating adiponectin levels on a genome-wide scale. Besides several independent variants around the adiponectin gene, we found a rare coding variant in a gene upstream of adiponectin receptor 2 that was associated with higher adiponectin levels. If replicated in an independent sample, these findings can provide new insight to adiponectin biology. In conclusion, we found that individuals with poor cardiac function had higher levels of adiponectin and the results suggested that natriuretic peptides had an important role in a potentially counter-active mechanism. In contrast, high adiponectin levels were associated with a more beneficial arterial, oxidative stress and inflammation profile. Finally, rare variation around the adiponectin gene and a potentially novel locus upstream of the adiponectin receptor 2 gene was associated with adiponectin levels.
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| 3. |
- Gustafsson, Stefan
(författare)
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Electromagnetic Dispersion Modeling and Analysis for Power Cables
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses electromagnetic wave propagation in power cables. It consists of five papers, where the three first papers are based on one and the same model, and the last two papers are based on a similar but slightly different model. The first model considers electromagnetic modeling in connection with basic transmission line theory with a mismatch calibration of the scattering parameters, while the second model is based on a magnetic frill generator with calibration on the input current.The two models describe the dispersion characteristics of an 82 km long High Voltage Direct Current (HVDC) power cable, and the results are validated with Time Domain Reflectometry (TDR) measurements. In both models the relevant bandwidth is 100 kHz, with the result that the fields inside the metallic layers must be calculated due to a large skin-depth. The present study is concerned with Transversal Magnetic (TM) modes of order zero. Higher order TM modes, including the Transversal Electric (TE) modes, will essentially be cut-off in this low-frequency regime.An asymptotic analysis regarding the low-frequency dispersion characteristics is provided in Paper I. Comparing the result with a numerical solution shows that the low-frequency characteristics of the power cable is complicated, and an asymptotic solution is only valid at frequencies below 1 Hz.Paper II presents a sensitivity analysis of the propagation constant. It is concluded that some of the electrical parameters of the metallic layers, and of the insulating layer, have a large impact on the model, while other parameters do not perturb the model in any substantial way.In Paper III a general framework for the electromagnetic modeling is provided. The paper addresses sensitivity analysis, computation, and measurements regarding wave propagation characteristics in power cables.The asymptotic behavior of the non-discrete radiating mode, the branch-cut, is presented in Paper IV. The result is compared with the first and second propagating Transversal Magnetic (TM) mode.Finally, Paper V addresses the numerical problems associated with large arguments in the Bessel functions, which are due to the large conductivity parameters of the metallic layers. The introduction of a perfect electric conductor (PEC) and a short illustration of an inverse problem are also discussed in the paper. At the end an analysis is presented regarding uncertainties in the model parameters, which shows that temperature is an important parameter to consider.
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| 4. |
- Gustafsson, Stefan
(författare)
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Nuclear Magnetic Resonance Spectroscopy and Spin Relaxation in Amphiphilic Liquid Crystals
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spin relaxation theory and nuclear magnetic resonance spectroscopy in amphiphilic liquid crystals are presented. Group theory is used to determine the information content and the orientation dependence in spin relaxation experiments, and to investigate the combined effect of crystal and local symmetries and the effect of symmetry on multiple timescales. From lineshapes of a deuterated decanol and SdS molecules the distribution within and aspect ratio of rodlike aggregates in the rectangular phase of the system SdS/decanol/water are determined. The results reveal the importance of electrostatic interactions in stabilisation of the rectangular phase. A geometry independent theory is developed for spin relaxation by diffusion on a biaxial rod. The most striking result of this theory is the strong geometry dependence of the spinrelaxation functions. A theoretical investigation of spinrelaxation in coupled membrane system are presented. The coupled membrane theory reveals a strong dependence of spectral density functions on membrane coupling. The second and fourth order spectral density functions are calculated. The effective diffusion coefficient for a particle diffusing on a random surface is related to the degree of roughness of the surface. An exact result for the diffusion coefficient is obtained in the limit of fast surface fluctuations, for a static surface upper and lower bounds and an effective medium approximation are derived. From diffusion measurements the surface configuration can then be determined. For particle diffusion in one dimensional random geometry an exact results for the diffusion coefficient is obtained for rapidly fluctuating geometry, a static geometry and in the general case.
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| 5. |
- Gustafsson, Stefan, 1976
(författare)
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Silicon Carbide Reinforced Alumina and Mullite Ceramics
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this work was to develop homogeneous ceramic nanocomposite materials with good thermal and structural stability as well as good mechanical properties. The development of microstructure was related to the material properties. This thesis reports on the electron microscopy characterization of alumina (Al2O3) and mullite (3Al2O3·2SiO2) reinforced with 5 vol % SiC nanoparticles. Al2O3 / 5 vol% SiC nanocomposite materials were pressureless sintered to near full density at 1780 °C. Smaller additions of MgO promoted densification at lower temperatures. The addition of both MgO and SiO2 resulted in a slightly reduced density and a larger Al2O3 grain size as compared to doping with MgO only. Transmission electron microscopy revealed that the SiC particles were located predominantly to the interior of the matrix grains and well distributed throughout the composite microstructures. The hardness varied in the range 17.0-18.5 GPa and the indentation fracture toughness varied between 2.3 and 2.6 MPam1/2 when the material was sintered at 1780 °C. The crack front propagated transgranularly without interacting with intragranular SiC. Crack bridging was observed but not crack deflection. Al2O3 / 5 vol% SiC composites were also fabricated by the in-situ synthesis of nano-sized SiC particles. It was found that SiC and mullite formed during sintering. SiC nanoparticles with a size ranging from a few ten nanometers up to ~300 nm were located predominantly to the interior of both mullite and alumina matrix grains.The relationship between the fine-scale micro- and nanostructure and the creep deformation process in single-phase mullite and mullite reinforced with 5 vol% nano-sized SiC particles was investigated. Creep deformation of polycrystalline mullite was dominated by diffusional processes and unaccomodated grain boundary sliding facilitated by softening of the intergranular glass. Diffusional creep in the nanocomposite was inhibited by the slower diffusional transport in the SiC particles compared to self diffusion of the matrix, leading to an enhanced creep resistance by grain boundary pinning. Grain boundary sliding due to softening of the intergranular glass reduced the beneficial effect of the nanoparticles at higher stresses.
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| 6. |
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| 7. |
- Nilsson, Miriam, 1984-
(författare)
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Studies of the chromatin form of yeast Mediator and the function of its tail module
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mediator is a large, multifunctional complex that is conserved in eukaryotes. It was first discovered in Saccharomyces cerevisiaeas required for transcriptional activators to function in a reconstituted in vitro system. Mediator is also important for stimulation of basal, unregulated transcription, and transcriptional repression. In yeast, Mediator consists of 25 subunits divided into head, middle, and tail modules, and is intermittently associated with a Cdk8 kinase module (CKM). The head and middle bind to the RNA polymerase II (Pol II) while the tail is responsible for binding to gene-specific transcriptional regulators. Most head and middle subunits are essential, whereas all tail module subunits are encoded by non-essential genes. CKM is mostly involved in transcriptional repression by binding Mediator in a way that sterically blocks the binding of Pol II to Mediator. Mediator is traditionally purified from the ‘non-chromatin’ fraction of whole-cell extracts. Since most Mediator functions occur in a chromatin context, we set out to purify Mediator from the chromatin fraction of cell extracts. We performed affinity-purification using strains expressing epitope-tagged Mediator subunits, combined with mass spectrometry to reveal the composition of chromatin-bound Mediator. We found that Mediator in chromatin interacts with several protein complexes involved in different aspects of gene expression. Several of them, such as CPF, CF IA, and TFIIB have been shown to be involved in gene looping. Using Chromatin immunoprecipitation (ChIP)-seq experiments, we localized Mediator occupancy genome-wide. As expected, we found enrichment of Mediator at gene promoters, but also at Chromatin Interaction Domain boundaries (CIDBs), which are important for chromatin organization and transcriptional regulation. We also investigated the yeast Tail module function in detail. Individually, Tail subunit mutants are non-essential, but med15/med16 or med5/med15 strain are lethal. We used the N-degron system to conditionally deplete Med15/Med16 or Med5/Med15 and studied their effects on global gene expression using MicroArray assays. Several meiosis and sporulation genes were upregulated in the med5/med15 and med15/med16. In support of this, Rck1 which is a repressor of meiosis and sporulation rate in diploid cells, was downregulated in both strains. All strains where Med15 expression was depleted showed downregulation of several target genes for the Ace2 transcription factor which is important for cell cycle progression through the G1 cell cycle phase. Accordingly, all our med15-degron strains showed a G1-phase arrest in flow cytometry assays. Finally, we investigated the tail module subunit Med2 which has a phosphorylation site at position S208. We found that point mutations of S208A led to downregulation of several genes that are usually expressed during anaerobic growth. We also found that a med2 strain was unable to grow under anaerobic conditions.
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| 8. |
- O'Farrell, Fergal
(författare)
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A screen for mutations affecting PNS development in Drosophila identifies the trim gene, dappled
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The peripheral nervous system of Drosophila melanogaster contains a variety of sense organs, ranging from the relatively simple four celled bristle organ to the more complex compound eye. The development of each organ type is well described, providing a useful backdrop for functional studies of genes acting in one or more of the many processes involved in organogenesis. We have used the bristle organ to screen for genes affecting PNS development. Two of the candidates recovered via this approach, string (stg, Drosophila cdc25, the universal regulator of the G2 to M phase mitotic transition), and dappled (dpld, a poorly described gene implicated in tumor suppression) were selected for further study. Examination of stg mis-expression phenotypes in the adult bristle organ revealed cell fate transformations corresponding to the generation of two pIIa structural precursor cells at the expense of a neural precursor cell. This transformation most reasonably resulted from an abnormally short G2 arrest, indicating that the time spent in the G2 phase is crucial to correct cell fate determination. dpld is a member of the Tripartite Motif (TRIM) superfamily, members of which are involved in diverse biological processes e.g. proliferation, apoptosis and immune response. dpld belongs to a subgroup of NHL domain containing TRIM proteins, that are known to be involved in tumor suppression. Phylogenetic analysis placed dpld in the lin-41 sub-clade of the TRIM superfamily. A combination of insilico, genetic and cell culture assay approaches showed dpld to be susceptible to miRNA regulation. As homologous genes are also miRNA regulated this regulatory mechanism may be conserved throughout this sub-clade, between vertebrates and invertebrates. Pre-existing loss of function dpld alleles were characterized, however, subsequent complementation studies revealed that characteristic aspects of the described dpld phenotype, in fact mapped outside the dpld locus, and were caused by mutations of nearby genes. The tumor-causing locus was mapped to the Cytb5 gene (mutated in both pre-existing dpld alleles), while the embryonic lethality and PNS phenotype was mapped to the scraps locus. scraps encodes for Drosophila Anillin, known to be required during cytokinesis. We provide the first characterization of scraps null alleles and detail a biased requirement for scraps within neural precursor cells of the embryonic PNS. A novel loss of function dpld allele was recovered. This mutation is lethal, however it does not have an associated tumor phenotype. This finding, together with our complementation study indicates that the existing classification of dpld as a tumor suppressor is inaccurate. Subsequent studies detail dpld requirements in the developing fly retina. There, dpld mutation resulted in excessive proliferation, while conversely, mis-expression caused a reduction. Additionally, and perhaps consequently, cell differentiation was affected. Thus, regulation of proliferation by NHL-TRIM genes seems a conserved feature. We additionally identified a novel Drosophila TRIM gene of the same class as dpld, which we have dubbed another bbox affiliate (abba), bringing the number of NHL containing TRIM genes in Drosophila to four.
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| 9. |
- Owman, Caroline, 1966-
(författare)
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det meränmänskliga museet : Konservatorns bevarandepraktik som flyktlinje i modernitetens museum
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis takes the conservator as a starting point to explore more-than-human aspects of the museum of modernity. Assuming that built-in obstacles impinge when museums today deal with environmental issues‚ it investigates new and alternative perspectives on the engagement with our immediate surroundings, in this case the museum objects. The objective of this study is to map museum processes hidden in the anthropocentric museum of modernity. The aim is to broaden the perspective on the museum to include what the museum structures of modernity have pushed aside: ongoing processes and becomings, and the myriad of energetic more-than-human agencies and temporalities constantly at work in a museum.The main empirical material consists of interviewes with conservators working in different departements and museums in Sweden. This material also includes my own experiences of working as a conservator and as an exhibition producer in various museums. There is a particular focus on the care of objects performed by conservators. The material also includes Swedish Government Official Reports (SOU) and one central text from the Ministry Publications Series (Ds). Furthermore, more-than-human agencies play an important role: enacted through the museum apparatus in shape of humidity and silverfish.Posthuman theory, environmental humanities and material feminism form the overarching theoretical framework as well as provide the analytical tools. Three main themes from these theoretical areas run throughout the entire thesis: anthropocentrism, more-than-human agency, dualistic thinking and dichotomies. All of which are applied to the empirical material. To conclude, museums have been part of modernity’s ambitions and ideals since they were established just over 100 years ago. This thesis shows how, in the structures of the museum, modernity’s ideas have persisted. Furthermore, these structures of thought appear and interfere, inter alia, in the conservator’s experiences of and thoughts about their work and professional identity. However, when working intimately with the museum objects more-than-human relational processes and other productive connections emerge, whereby the structures, derived from moderity’s thinking, are challenged in productive ways. This forms the line of flight that the title refers to; here perceived as a possibility for change, in a direction that could promote new ways for museums to tackle complex more-than-human issues, such as climate change and environmental matters.
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