| 1. |
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| 2. |
- Furberg, Maria, 1970-
(författare)
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Towards the Limits – Climate Change Aspects of Life and Health in Northern Sweden : studies of tularemia and regional experiences of changes in the environment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIndigenous peoples with traditional lifestyles worldwide are considered particularly vulnerable to climate change effects. Large climate change impacts on the spread of infectious vector-borne diseases are expected as a health outcome. The most rapid climate changes are occurring in the Arctic regions, and as a part of this region northernmost Sweden might experience early effects. In this thesis, climate change effects on the lives of Sami reindeer herders are described and 30 years of weather changes are quantified. Epidemiology of the climate sensitive human infection tularemia is assessed, baseline serologic prevalence of tularemia is investigated and the disease burden is quantified across inhabitants in the region.MethodsPerceptions and experiences of climate change effects among the indigenous Sami reindeer herders of northern Sweden were investigated through qualitative analyses of fourteen interviews. The results were then combined with instrumental weather data from ten meteorological stations in a mixed-methods design to further illustrate climate change effects in this region. In two following studies, tularemia ecology and epidemiology were investigated. A total of 4,792 reported cases of tularemia between 1984 and 2012 were analysed and correlated to ecological regions and presence of inland water using geographical mapping. The status of tularemia in the Swedish Arctic region was further investigated through risk factor analyses of a 2012 regional outbreak and a cross-sectional serological survey to estimate the burden of disease including unreported cases.ResultsThe reindeer herders described how the winters of northern Sweden have changed since the 1970s – warmer winters with shorter snow season and cold periods, and earlier spring. The adverse effects on the reindeer herders through the obstruction of their work, the stress induced and the threat to their lifestyle was demonstrated, forcing the reindeer herders towards the limit of resilience. Weather data supported the observations of winter changes; some stations displayed a more than two full months shorter snow cover season and winter temperatures increased significantly, most pronounced in the lowest temperatures. During the same time period a near tenfold increase in national incidence of tularemia was observed in Sweden (from 0.26 to 2.47/100,000 p<0.001) with a clear overrepresentation of cases in the north versus the south (4.52 vs. 0.56/100,000 p<0.001). The incidence was positively correlated with the presence of inland water (p<0.001) and higher than expected in the alpine and boreal ecologic regions (p<0.001). In the outbreak investigation a dose-response relationship to water was identified; distance from residence to water – less than 100 m, mOR 2.86 (95% CI 1.79–4.57) and 100 to 500 m, mOR 1.63 (95% CI 1.08–2.46). The prevalence of tularemia antibodies in the two northernmost counties was 2.9% corresponding to a 16 times higher number of cases than reported indicating that the reported numbers represent only a minute fraction of the true tularemia.ConclusionsThe extensive winter changes pose a threat to reindeer herding in this region. Tularemia is increasing in Sweden, it has a strong correlation to water and northern ecoregions, and unreported tularemia cases are quite common.
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| 3. |
- Petersen, Zainonisa, 1976-
(författare)
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Smoking cessation during pregnancy : a person-centred approach among disadvantaged women in South Africa
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Smoking remains a leading cause of premature, preventable death in South Africa killing 44 000 South Africans each year. Through the introduction of comprehensive tobacco control policies, the South African government has tried to reduce the death toll and a significant reduction in tobacco use has been recorded since its peak in the 1990’s. Smoking among women, however have remained unchanged, which calls for actions. Pregnant mothers are specifically vulnerable as their smoking detrimentally affects their own health as well as the health of their babies. This thesis gives an account of the role the antenatal care system could play in reducing the burden caused by cigarette smoking. The overall aim was to contribute to an understanding of how a person-centred approach to smoking cessation among disadvantaged pregnant women with high smoking rates may influence smoking behaviour. The specific objectives were to confirm the high smoking rates of the target population, assess their readiness to quit, explore existing barriers and promoting factors towards smoking cessation efforts within the public antenatal health care system, and to qualitatively assess the attitudes and perceptions of disadvantaged pregnant women regarding a personcentred smoking cessation intervention. The high smoking rates of the target population was confirmed based on a cross-sectional study at antenatal clinics in four main cities of South Africa. It focused on the prevalence of smoking during pregnancy and used the stages of change theory to identify their readiness to quit. Additional questions concerned pregnancy related disease experiences, socio-economic determinants of continued smoking as well as attitudes towards the existing clinic services and its possible role in smoking cessation. A qualitative interview study analyzed more in-depth barriers for two-way communication between pregnant mothers and midwives. Both these studies informed the design and development of a person-centred smoking cessation intervention delivered at four public sector antenatal clinics in Cape Town. The intervention was subjected to a comprehensive evaluation based on a combination of quantitative and qualitative measures. This thesis utilizes data from the qualitative process assessment part, comprising individual interviews and focus group discussions with pregnant women during the implementation period of the intervention. The survey results pointed out a high prevalence of smoking of 46% amongst disadvantaged pregnant women, with varying readiness for behaviour change. Most women were in the contemplation stage of behaviour change and thus ready to quit. Many of the women felt positive about the role of the midwife as an antenatal care provider, but they did not have confidence in midwives concerning encouraging or supporting women to change addictive behaviour be it smoking, alcohol or other illegal substances. The qualitative research highlighted the need for revised curricula for health education and counselling. The analysis illustrated how the current situation created tension between clinic staff and pregnant women making women feel unworthy and thus leaving little room for changing behaviour. The in-depth interviews and the focus group discussions provided an analytical account of how the person-centred approach in this population was perceived by the women themselves. It illustrated that a multifaceted intervention programme, using peer counselors and educational material designed specifically for a given target population, can successfully bring about behaviour change. The intervention succeeded in shifting women’s perceptions of hopelessness into feelings of being empowered to face their addictions and competent to make a change. Though the intervention meant greater rapport with the midwives, involving peer counsellors was rated highly by the participating women. The women reported having used the educational material and attached a great value to the appropriateness of the material to their life situations, and the effectiveness of having it combined with counselling from a peer counsellor. This qualitative evaluation showed the importance of a multifaceted intervention approach, in helping women identify with their behaviour change. The thesis highlights the importance of designing smoking cessation interventions that are specific to the needs of target populations. When smoking cessation efforts are included into routine antenatal services it is important that the target group inform the nature and specific components of the intervention.
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| 4. |
- Skeppstedt, Maria, 1977-
(författare)
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Extracting Clinical Findings from Swedish Health Record Text
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Information contained in the free text of health records is useful for the immediate care of patients as well as for medical knowledge creation. Advances in clinical language processing have made it possible to automatically extract this information, but most research has, until recently, been conducted on clinical text written in English. In this thesis, however, information extraction from Swedish clinical corpora is explored, particularly focusing on the extraction of clinical findings. Unlike most previous studies, Clinical Finding was divided into the two more granular sub-categories Finding (symptom/result of a medical examination) and Disorder (condition with an underlying pathological process). For detecting clinical findings mentioned in Swedish health record text, a machine learning model, trained on a corpus of manually annotated text, achieved results in line with the obtained inter-annotator agreement figures. The machine learning approach clearly outperformed an approach based on vocabulary mapping, showing that Swedish medical vocabularies are not extensive enough for the purpose of high-quality information extraction from clinical text. A rule and cue vocabulary-based approach was, however, successful for negation and uncertainty classification of detected clinical findings. Methods for facilitating expansion of medical vocabulary resources are particularly important for Swedish and other languages with less extensive vocabulary resources. The possibility of using distributional semantics, in the form of Random indexing, for semi-automatic vocabulary expansion of medical vocabularies was, therefore, evaluated. Distributional semantics does not require that terms or abbreviations are explicitly defined in the text, and it is, thereby, a method suitable for clinical corpora. Random indexing was shown useful for extending vocabularies with medical terms, as well as for extracting medical synonyms and abbreviation dictionaries.
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| 5. |
- Abelius, Martina, 1980-
(författare)
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Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pregnancy and allergic disease have both been postulated as T-helper 2 (Th2) phenomena. Thus, the increased propensity of allergic mothers to mount Th2-responses might generate favourable effects on the maintenance of pregnancy, but might also be unfavorable, as fetal exposure to a strong Th2 environment could influence the immune development in the offspring to a Th2-like phenotype, favouring IgE production and possibly allergy development later in life. The influence of the intrauterine environment on the immunity and allergy development in the offspring needs to be further investigated.Aim: The aim of this thesis was to explore the Th1/Th2 balance in allergic and non-allergic women during pregnancy and its influence on the shaping of the Th1/Th2 profile in the neonate and the development of allergic diseases in the offspring.Material and methods: The study group included 20 women with and 36 women without allergic symptoms followed during pregnancy (gestational week 10-12, 15-16, 25, 35, 39) and 2 and 12 months postpartum, and their children followed from birth to 6 years of age. The circulating Th1-like chemokines CXCL9, CXCL10, CXCL11, Th2-like chemokines CCL17, CCL18 and CCL22, and the allergen-induced secretion of interleukin-4 (IL-4), IL-5, IL-10, IL-13, Interferon-γ (IFN-γ), CXCL10 and CCL17 were measured by Luminex and ELISA. The allergen-specific and total IgE levels were quantified using ImmunoCAP Technology. mRNA expression of Th1-, Th2-, Treg- and Th17-associated genes were measured by PCR arrays and real-time PCR.Results: We found that sensitised women with allergic symptoms had increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy as compared with postpartum. The non-sensitised women without allergic symptoms had elevated cat-induced IL-5 and IL-13 responses and lower birch- and cat-induced IFN-γ during pregnancy, but similar IgE levels as compared with postpartum.Maternal total IgE levels during and after pregnancy correlated with cord blood (CB) IgE and CCL22 levels (regardless of maternal allergy status). Circulating CXCL11, CCL18 and CCL22 levels during pregnancy and postpartum correlated with the corresponding chemokine levels in the offspring at various time points during childhood. Maternal IL-5 expression in peripheral blood mononuclear cells (PBMC) was associated with neonatal Galectin-1, and placental p35 expression was negatively associated with neonatal Tbx21 expression. Increased mRNA expression of CCL22 in cord blood mononuclear cells (CBMC), and increased CCL17 and CCL22 levels in CB were observed in children later developing allergic symptoms and sensitisation as compared with children who did not. Development of allergic symptoms and sensitisation were associated with increased total IgE, CCL17, CCL18 and CCL22 levels during childhood.Conclusions: Maternal allergy was associated with a pronounced Th2 deviation during pregnancy, shown as increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy, possibly exposing their fetuses to a particular strong Th2 environment during gestation.Correlations were shown between the maternal immunity during pregnancy and the offspring’s immunity at birth and later during childhood, indicating an interplay between the maternal and fetal immunity.Allergy development during the first 6 years of life was associated with a marked Th2 deviation at birth and a delayed down-regulation of this Th2-skewed immunity during childhood.
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| 6. |
- Allbrand, Marianne, 1958-
(författare)
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Gene expression of inflammatory markers and growth factors in placenta in relation to maternal obesity and foetal and postnatal growth
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Maternal obesity is a growing health problem, that contributes to obstetrical complications in pregnancy, as well as neonatal morbidity and mortality. The placenta serves for gas and nutrient exchange between the mother and the foetus, and obesity may influence and modify placental growth and function. The aims of this thesis were to investigate associations between maternal obesity without associated morbidity and gene expression of inflammatory markers and growth factors in the placenta, as well as offspring birth weight and postnatal growth. Study I and III were designed as matched case-control studies including 32 obese women with an early pregnancy body mass index (BMI) ≥ 35.0 kg/m2, study II was an experimental study examining twelve placentas of normal weight women, and study IV was a cohort study including 109 obese women with a BMI ≥ 34.5 kg/m2. In studies I-IV analyses of gene expression were performed and in study III additionally cord blood concentrations were determined. No difference was found in the occurrence of placental gene expression of inflammatory markers or growth factors between obese and normal weight women, nor did the sampling site in placentas of normal weight women influence gene expression of these markers, except for leptin gene (LEP) and insulin receptor gene (INSR) expression. Ghrelin gene (GHRL) and LEP expression, as well as cord blood ghrelin and adiponectin levels, was not altered in maternal obesity, and a negatively U-shaped relationship between LEP expression and infant birth weight (BW) z-scores was observed in the placentas of obese women.In conclusion, no statistically significant difference in gene expressions of inflammatory markers and growth factors in the placenta between severely obese and normal weight women was found. These results are in contrast with earlier studies and could be due to the fact that we examined mainly healthy obese women. The correlations we found between gene expression of leptin in the placenta and the birth weight of the infants warrants further studies.
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| 7. |
- Berglund, Maria, 1975-
(författare)
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Biomolecular Aspects of Flexor Tendon Healing
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Flexor tendon injuries in zone II of the hand (i.e. between the distal volar crease and the distal interphalangeal joint) can be costly for both the afflicted individual and society because of the high cost of a long rehabilitation period, complicated by tendon ruptures or scarring with adhesion formation, causing impaired range of motion. The aim of the present thesis was to characterize more fully the deep flexor tendon, the tendon sheath and their response to injury in a rabbit model in order to find potential targets to improve the outcome of repair. The intrasynovial rabbit deep flexor tendon differed from the extrasynovial peroneus tendon in the expression of collagens and transforming growth factor-β1 gene expression. Differences were also found in collagen III and proteoglycans between regions of the flexor tendon subjected to either compressive or tensile load. After laceration and subsequent repair of the flexor tendon, a shift in collagen gene expression from type I to type III occurred. Proteoglycans were generally increased with the notable exception of decorin, a potential inhibitor of the profibrotic transforming growth factor-β1 which was markedly increased during the first two weeks after repair in tendon tissue but remained unaltered in the sheaths. Both vascular endothelial growth factor and basic fibroblast growth factor mRNA levels remained essentially unaltered, whereas insulin-like growth factor-1 increased later in the healing process, suggesting potential beneficial effects of exogenous addition, increasing tendon strength through stimulating tenocyte proliferation and collagen synthesis. Matrix metalloproteinase-13 mRNA levels increased and remained high in both tendon and sheath, whereas there was only a transient increase of matrix metalloproteinase-3 mRNA in tendon. We could also demonstrate a significant increase of the proportion of myofibroblasts, mast cells and neuropeptide containing nerve fibers in the healing tendon tissue, all components of the profibrotic myofibroblast-mast cell-neuropeptide pathway.
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| 8. |
- Berglund, Mats, 1970-
(författare)
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Massans röst : Upplopp och gatubråk i Stockholm 1719–1848
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis examines riots and street violence in Stockholm between 1719 and 1848. By studying open conflicts, the thesis explores changes in societal power structures which otherwise are hidden. The study shows how these levels of power and conflict structures interacted with one another and thereby contributed to the social development during the period; from a patriarchal society of privilege to a society based on a democratic view of the world. The thesis focuses on three collective actors; the people, the authorities and the press.The investigation of the people in the crowds shows that the military element, as well as the lower strata of labourers and servants, was significant in the early events. However, in later phases, middle class groupings such as burghers and civil servants, dominated the masses. These changes in the social composition of the crowds are tightly connected to a similar change in the aims of the riots; from local issues to national policy matters.Tactics of the authorities in their encounter with street disturbances also changed during the period, from passive observation by the police in the 18th century to an active military confrontational approach in the 19th century. The legal base was however strong throughout the period. The parties attached great importance to court proceedings, and knowledge of the legal system was surprisingly good among the common people.During the second half of the period, the press became firmly established. At the turn of the century 1800, there were two short glimpses of free press in connection to the political turbulence in 1792 and 1809. But it was mainly from the 1830's that the newspaper editors became significant actors in the riots. The popular demands for international news and politics gradually grew stronger during the period. A bottom-up perspective thus shows that popular political involvement in a significant way helped to pave the way for the coming breakthrough of democracy.
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| 9. |
- Bergman, Ingrid-Maria, 1961-
(författare)
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Polymorphism in pattern recognition receptor genes in pigs
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mammalian immune defense consists of two systems, which are interconnected and co-operate to provide host defense. The innate immune system is always active and detects and responds to non-self without delay. The adaptive immune system has a lag phase, but is more specific and has got a memory.The innate immune system relies on pattern recognition receptors (PRRs) to detect molecular patterns signaling microbial presence. This thesis focuses on a centrally placed family of PRRs, namely the Toll-like receptors (TLRs), and on mannan-binding lectin (MBL), a PRR which initiates the lectin activation pathway of complement. TLRs are expressed on the cell surface and in intracellular compartments, while MBL is a soluble protein present in most body fluids.Polymorphism – literally ’many forms’ – refers to variation between individuals, at DNA level as well as in traits. A single nucleotide polymorphism (SNP) implicates that alternative nucleotides are present at a particular position in the genome. Mutations, together with phenomena like gene duplication and whole genome duplication, are the ultimate source of variation in nature and the fuel for evolution. Through natural selection and breeding, i.e. artificial selection, species are shaped and change over time.Domestic animals are well suited for genetic studies, since they enable comparisons of populations exposed to different selection criteria and environmental challenges. Also, in the case of pigs, comparisons to the wild ancestor – i.e. the wild boar – can shed light on the evolutionary process. Moreover, pigs are large animal models for humans.Paper I reports the refinement of previously identified quantitative trait loci for immune-related traits on pig chromosome 8.Papers II and III report differences in polymorphic patterns between wild boars and domestic pigs in the TLR1, TLR2, TLR6, and TLR10 genes. In TLR1 and TLR2, more SNPs were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNPs were present in the domestic pigs, and a higher number of non-synonymous SNPs was detected in TLR10 compared to the other genes. This might suggest redundancy for TLR10 in pigs.Paper IV reports the presence of an SNP, previously detected in domestic pigs and assumed to affect MBL concentrations in serum, in European wild boars. Also, the connection between the presumed low-producing allele and low MBL concentration in serum was confirmed. Moreover, a novel SNP, with potential to be functionally important, was detected.Owing to the domestication process and differences in selection pressure, differences in polymorphic patterns between wild boars and domestic pigs are not surprising. However, since breeding means choosing among genotypes, the opposite pattern – more SNPs in wild boars than in domestic pigs – would have been expected. However, the result confirms other studies, which have shown that European wild boars went through a bottle neck before domestication started. The higher number of SNPs in domestic pigs may be due to relaxed purifying selection during the domestication process.
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| 10. |
- Bojsen-Møller, Emil, 1989-
(författare)
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Movement Behaviors and Cognitive Health for Office Workers
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The lifetime trajectories of movement behavior and cognitive functioning depend on complex interactions between genetic and environmental factors. There is substantial evidence suggesting that physical activity benefits cognitive functions. However, how sedentary behavior and the composition of movement behaviors (i.e., sleep, physical activity, and sedentary behavior) influences cognitive functions remains to be elucidated. Observational studies suggest that sedentary time is unfavorably related to cognitive functions in older adults, but the majority of evidence comes from self-reported estimates of movement behavior, which are rather weakly related to device-based measures. Furthermore, while evidence suggests that structured exercise can have protective effects on cognition in inactive older adults, much less is known about how midlife movement behavior is related to cognitive functions. Thus, knowledge of how midlife movement behavior relates to and possibly affects cognitive functions and its underlying mechanisms is much needed. This thesis is part of a larger research project investigating how movement behaviors relate to and influence cognitive function, mental health, and neurophysiological mechanisms underpinning these. The project specifically targets healthy office workers and is co-produced with employers of office workers and health-promoting companies. This thesis aimed to investigate how movement behaviors relate to and influence cognitive functions and neuroplasticity among office workers.The first study investigated cross-sectional relationships between device-measured movement behavior and cognitive functions among 334 office workers. The results revealed no association between total time spent in moderate to vigorous physical activity or sedentary behavior and cognitive functions, suggesting that this association may not be as robust as previously suggested in older populations or as inferred from self-report. The second study investigated the extent to which corticospinal excitability is influenced by different movement behaviors. Sixteen sedentary office workers participated in a cross-over randomized controlled trial. We contrasted 3 hours of prolonged sitting with 3 hours of interrupted sitting and 2.5 hours sitting followed by a 25-minute bout of exercise. Acute changes in corticospinal excitability and long-term potentiation-like neuroplasticity were investigated using transcranial magnetic stimulation and paired associative stimulation. Changes in corticospinal excitability over time did not differ between conditions, suggesting that in inactive middle-aged office workers, a physical activity bout or frequently breaking up prolonged sitting does not induce immediate changes in corticospinal excitability or long-term potentiation-like neuroplasticity. The third and fourth studies are based on a 6-month cluster-randomized intervention conducted in 263 healthy office workers. An ecological model for behavior change was used to design two interventions aiming at reducing sedentary behavior or increasing physical activity relative to a passive control group, with the ultimate aim of improving cognitive functions and mental health. The third study investigated how effective each intervention was at changing the 24-hour movement behavior, and the fourth study examined intervention effects on cognitive functions. The results showed that the interventions were ineffective in reducing sedentary behavior and increasing physical activity, respectively, with no detected beneficial effects on cardiorespiratory fitness or cognitive functions relative to the control group. Changes in cognition from baseline to follow-up were not associated with changes in the composition of movement behaviors or cardiorespiratory fitness, but some associations between changes in movement behaviors and cognition were moderated by sex, age, and cardiorespiratory fitness. Thus, the third and fourth studies of the thesis have highlighted the challenges involved in successfully achieving movement behavior change to address the possible effects on cognitive improvements in an ecological setting.In summary, the results presented in this thesis did not provide support for an association between movement behaviors and cognitive functions in healthy physically active office workers, demonstrated no acute effect of a single session of physical activity or breaking up prolonged sitting on corticospinal excitability in sedentary office workers, and revealed no evidence for successful movement behavior change or benefits for cognition in an ecological cluster-randomized intervention in healthy physically active office workers. The findings suggest that among physically active office workers, sedentary behavior may not be as detrimental for cognition and neuroplasticity as previously suggested and shows that changing movement behavior in office workers at the workplace represents a challenging endeavor. Still, these findings do not exclude the possibility that changes in movement behaviors might benefit cognitive functions in physically inactive office workers at higher cardiovascular risk, with lower cardiorespiratory fitness and/or lower daily cognitive stimulation.
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