| 1. |
- Marchesi, Silvia, MD, 1985-
(författare)
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The effect of mechanical ventilation on abdominal organs : Analysing the role of PEEP and perfusion.
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The effect of mechanical ventilation on abdominal organs is not well understood and investigated yet. Previous studies, using an animal sepsis-like model, found an association between mechanical ventilation (MV) and abdominal edema and inflammation.The presented thesis was aimed to investigate the role of perfusion in edema formation and inflammation, and to study the abdomen during mechanical ventilation in an ARDS model to reduce the confounding effect of inflammation related to sepsis.Methods: In the first paper presented, inflammation and edema in the abdomen were investigated in an endotoxin model. The study subjects were divided into two groups with different mean arterial pressures (MAP), another small group of healthy controls were studied as well. MRI analyses were used to measure perfusion in the different abdominal organs. In the second paper presented, differences in abdominal edema and inflammation were assessed in two groups of subjects, one group underwent MV and one group had spontaneously breathing.Results: In the first study, MRI analyses confirm that the group with higher MAP had better perfusion than the low MAP group. In the liver, perfusion was lower in LowMAP group compared to HighMAP group, but the HighMAP group had lower perfusion than the healthy controls. However, in the other studied organs HighMAP group and healthy controls had similar perfusion.Edema did not differ between the groups. Inflammation was globally higher in LowMAP group and correlated with hemodynamics. TNFα in liver tissue and portal vein serum correlated with intra-abdominal pressure (IAP).In the second study, the cytokine concentration was higher in serum in the MV group. MV did not increase abdominal edema or inflammation, compared to spontaneous breathing. Discussion and conclusion: Abdominal edema and inflammation are multifactorial phenomena, and many elements have to be included in the analysis. Perfusion plays an important role in determining inflammation and IAP. MV per se was not found to be related to increased edema and inflammation. In a previous study, the role of different levels of PEEP and different respiratory rate between mechanically ventilated and spontaneously breathing animals were not analyzed, but could have contributed to the results. The efforts made in this study to maintain similar respiratory rate and PEEP in both groups, could have contributed to the presented results.It is important to underline that, even if MV was not related to inflammation in abdomen, it was related to an increase in systemic inflammation, most probably because of an enhanced lung production of inflammatory mediators.Further studies, focusing on the role of respiratory rate and PEEP on abdomen, as well as the analysis of the inter-relations among inflammation, perfusion and edema, are needed to increase the pathophysiological understanding of these phenomena.
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| 2. |
- Olsson, Karl Wilhelm, 1985-
(författare)
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Persistent ductus arteriosus in extremely preterm infants
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patent ductus arteriosus (PDA) is common in infants born <28 weeks gestational age (GA) and associated with significant morbidity. Despite extensive research efforts, the indications for PDA treatment remain controversial. The aims of these studies were to gain knowledge of factors affecting ductal closure during the early postnatal period and provide better means for identification of preterm infants that may benefit from PDA treatment.In Paper I, infants born <28 weeks GA and pharmacologically treated for PDA were retrospectively identified and their echocardiographic examinations were reviewed. Twenty-nine (52%) infants successfully closed and 27 (48%) infants failed to close PDA during treatment. High maximal ductal flow velocity (Vmax) was independently associated with closure (OR 3.04, p=0.049).Paper II prospectively included infants born <28 weeks GA and assessed early respiratory, circulatory and echocardiographic parameters. PDA was persistent in 18 (30%) and ultimately closed or insignificant in 42 (70%) infants. Echocardiographic criteria for hemodynamically significant PDA on days 2-7 did not predict persistent PDA (p=1.000). Mechanical ventilation (p=0.025), high mean airway pressure (p=0.020) and low Vmax (p=0.024) during day two were associated with future persistent PDA.Blood samples were obtained during the second day of life from 47 of the infants in Paper II and serum markers previously associated with PDA or factors affecting PDA were analyzed for Paper III. Inflammatory markers and erythropoietin (EPO) were elevated in infants with future persistent PDA. EPO levels were also higher in infants that did not close PDA during pharmacological treatment.In Paper IV, 44 infants born <28 weeks GA with surgically ligated PDA were retrospectively compared to non-surgically treated controls. Ligated infants had larger ductal diameter prior to, and lack of diameter decrease after pharmacological treatment for PDA (p=0.048 and p=0.022 respectively), and higher incidence of severe bronchopulmonary dysplasia (p=0.025). Longer periods with invasive ventilation was independently associated with ligation (OR 1.04, p=0.018).In conclusion, early hsPDA do not predict persistence of ductus arteriosus in extremely preterm infants, but Vmax and EPO are promising early markers for prediction of persistence and should be subjects of future studies.
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| 3. |
- Björnfot, Cecilia, et al.
(författare)
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Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
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Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
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| 4. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 5. |
- Larsson, Anders, 1977-
(författare)
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Test Optimization for Core-based System-on-Chip
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The semiconductor technology has enabled the fabrication of integrated circuits (ICs), which may include billions of transistors and can contain all necessary electronic circuitry for a complete system, so-called System-on-Chip (SOC). In order to handle design complexity and to meet short time-to-market requirements, it is increasingly common to make use of a modular design approach where an SOC is composed of pre-designed and pre-verified blocks of logic, called cores.Due to imperfections in the fabrication process, each IC must be individually tested. A major problem is that the cost of test is increasing and is becoming a dominating part of the overall manufacturing cost. The cost of test is strongly related to the increasing test-data volumes, which lead to longer test application times and larger tester memory requirement. For ICs designed in a modular fashion, the high test cost can be addressed by adequate test planning, which includes test-architecture design, test scheduling, test-data compression, and test sharing techniques.In this thesis, we analyze and explore several design and optimization problems related to core-based SOC test planning. We perform optimization of test sharing and test-data compression. We explore the impact of test compression techniques on test application time and compression ratio. We make use of analysis to explore the optimization of test sharing and test-data compression in conjunction with test-architecture design and test scheduling. Extensive experiments, based on benchmarks and industrial designs, have been performed to demonstrate the significance of our techniques.
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| 6. |
- Larsson, Jenny, 1990-
(författare)
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Population-based studies of higher-level gait disorders and hydrocephalus : focused on brain ventricular morphometry and patient outcomes following shunt surgery
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: To study gait is of great importance for the health of the aging population. Higher-level gait disorders (HLGD) are characterized by a slow, symmetrical, unsteady gait. Its cause is most often unknown. HLGD in combination with ventriculomegaly (i.e., large brain ventricles) is obligatory for the diagnosis of Idiopathic Normal pressure hydrocephalus (INPH), a syndrome that is sometimes treatable with insertion of a CSF shunt. It is therefore important to investigate the prevalence of HLGD in the population and brain morphometry in individuals with HLGD. Further, self-perceived confidence in gait and balance among patients with HLGD and INPH is unknown and important to study as slow gait velocity is associated with falls, injuries, and death. CSF shunts in INPH are associated with adverse events and little is known about epilepsy after surgery or minor and moderate adverse events such as headache and abdominal pain.Objective: In the older population investigate the prevalence of HLGD, and its association to ventriculomegaly. To investigate quality of life (QoL), depressive symptoms, and balance confidence in an HLGD population. In patients shunted for INPH, assess falls, fear of falling, balance confidence and prevalence of the possible adverse events headache, epilepsy, and abdominal pain after shunt surgery. Methods: Two population-based case-controlled cohorts were studied. In the first study, the "Ventriculomegaly and gait disturbance in the senior population in the region of Västerbotten" (VESPR) study, individuals (65-84 years) were recruited through a questionnaire (n=6467 dispatched). The final population consisted of 798 cases with gait disorders and 249 controls without gait disorders, age- and sex-matched to individuals with HLGD. All had been examined by a physician and were categorized: 1. "HLGD"; 2. "neurological gait disorder"; 3. "non-neurological gait disorder" or; 4. "no gait disorder". Participants were assessed with: the Swedish modification of the Falls-Efficacy Scale (FES(S)), the Modified Gait-Efficacy Scale (mGES), the Euro Quality of Life 5-Dimension 5-Level (EQ5D5L) instrument (EQ5D5L index and Euro Quality of life visual analogue scale (EQ VAS)) and the Geriatric depression scale 15 (GDS-15). Cases and controls had an MRI of the brain and ventricular size was measured. The second study, the "Comorbidities and vascular risk factors associated with idiopathic normal pressure hydrocephalus" (INPH-CRasH) study, consisted of 176 shunted INPH patients and 368 age- and sex-matched controls. Mean age was 74 years in INPH and 73 in controls. All had a visit to a healthcare facility. Information regarding adverse events, falls and fear of falling were gathered through a questionnaire. Additional information on diagnoses and prescribed drugs were obtained from the Swedish national patient- and drug registries. Data was compared between the groups, and before- and after surgery for INPH. Results: In the VESPR study, 87 individuals were categorized as HLGD, corresponding to a prevalence of 5.8% (95% confidence interval (CI) 4.6-7.0) in the older population. A definite cause was found in 13% (n=11) of individuals with HLGD, but ventriculomegaly was present in 63% (n=46/73, controls: 38%, n=70/184; OR 2.8 95% CI 1.6-4.9, p<0.001). HLGD had more depressive symptoms and lower quality of life (QoL), compared with individuals without gait disorder (GDS-15: 3.9±3.4 vs. 2.5±2.8, p=0.004; EQ VAS: 63±17 vs. 71±18; p<0.001; EQ5D5L index: 0.671±0.188 vs. 0.840±0.126, p<0.001). HLGD had low confidence in gait and to avoid falls compared to those without gait disorder (mGES: 60±22 vs. 74±21; p<0.001; FES(S): 93±32 vs. 111±25 p<0.001). The INPH-CRasH study revealed that patients with INPH feared falling more often (3.3±1.1) and had lower balance confidence (78±40) than controls (fear of falling: 1.6±0.9, balance confidence: 126±14; p<0.001 in both comparisons). After surgery, the proportions were reduced in INPH (p<0.001). More INPH than controls were fallers (before surgery: 67% vs. 11% OR 15.48 95% CI 9.85-24.32; after surgery: 35% vs 11% OR 4.15 95% CI 2.65-6.50, p<0.001). The proportion was reduced after surgery (p<0.001). In shunted INPH, epilepsy, antiepileptic drug (AED) treatment and headache was more common than in controls (epilepsy: 4.5% vs. 1.1% OR 4.3, 95% CI 1.3-14.6, p=0.023; AED treatment: 14.8% vs. 7.3% OR 0.5 95% CI 0.3-0.8, p=0.010; headache: 36.1% vs 11.6% OR 0.2 95% CI 0.2-0.4, p<0.001). Forty percent INPH (n=70) had abdominal pain after surgery. Conclusions: HLGD was common in the general older population and associated to ventriculomegaly. HLGD was also associated with low quality of life and depressive symptoms. Both individuals with HLGD and patients with INPH had low confidence in their balance but it was less common after surgery for INPH. However, patients shunted for INPH still had more problems with low balance confidence, falls, and fear of falling than controls. After shunt surgery for INPH, a significant portion of patients developed epilepsy, headache, and abdominal pain. The findings motivate investigations of causal relationships between HLGD and ventriculomegaly and if treatment options exist for HLGD. The observed adverse events in patients shunted for INPH should be considered in pre- and postoperative evaluations of shunt surgery, and in the development of new techniques for shunt placement. Additional interventions directed towards low balance confidence, falls and fear of falling should be considered for patients with INPH, and for individuals with HLGD.
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| 7. |
- Larsson, Magnus, 1983-
(författare)
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National environmental evaluation systems : guiding towards sustainability?
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dealing with environmental threats is one of the largest, if not the largest, challenge contemporary societies face. One way to better deal with this challenge would be to produce knowledge that can be used to improve environmental work and environmental policy and thus ultimately contribute to sustainable development. National environmental evaluations, which this thesis explores, could potentially fill this function because they are supposed to generate applicable and useful knowledge for improving environmental policy and practice for a sustainable transition. However, what different environmental actors view as useful knowledge varies, and needs to be empirically investigated. Against this background, the aim of this thesis is to investigate whether, and how, national environmental evaluation systems contribute to key actors’ environmental work and sustainable development. The thesis explores two national environmental evaluation systems in Sweden.Method: A mixed methods approach is applied that combines three methods. Firstly, a narrative synthesis is developed and applied to compile a list of sustainable development effects from national environmental evaluations. Secondly, a critical program theory is used to investigate the evaluation system’s underlying logic and to assess the likelihood of it achieving its intended effects. Thirdly, a directed content analysis is used to explore the usability and use of environmental evaluations and evaluation systems. The methods are applied to various documents, interviews with key actors, and observations at two environmental seminars.Results: The results show that, to contribute to sustainable development in the context of evaluation systems and network governance, environmental evaluations need to be of sufficient quality and meet different stakeholders’ knowledge needs. However, only some evaluations meet this demand. The main value of national environmental evaluations and evaluation systems is that they reinforce the national objectives, provide a recurrent report on achievement of objectives, and push actors to take responsibility to improve their environmental work.
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| 8. |
- Lindström, Elin
(författare)
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Evaluation of Regularized Image Reconstruction for Clinical Positron Emission Tomography
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Positron emission tomography (PET) combined with computed tomography (CT) is a widely used noninvasive molecular imaging modality with a broad range of clinical applications in oncology, neurology, and cardiology. Producing imperative image quality and accurate quantification are important driving forces behind the technological advances within PET image reconstruction and system development. To ensure clinical quality and to understand how the modern state-of-the-art PET/CT systems and image reconstruction methods compare with older systems and reconstruction methods they need to be evaluated and assessed in a clinical setting. This thesis summarizes six studies assessing the effect of state-of-the-art image reconstruction methods and the introduction of digital PET on image quality and quantitative outcomes of clinical PET scans in oncology, neurology, and cardiology. The overall aim was to evaluate, optimize, and compare quantitative results of regularized image reconstruction with the current standard reconstruction method used in routine clinical practice, ordered subsets expectation maximization (OSEM).The optimal setting of regularized image reconstruction by block-sequential regularized expectation maximization (BSREM) was found to be tracer dependent, and a potential clinical benefit in terms of image quality measures of BSREM over OSEM was found when applied for whole-body 18F-FDG, 68Ga-DOTATOC, 18F-fluorde, 11C-acetate, and 68Ga-PSMA-11 PET imaging. Software-aided assessment of neurodegenerative disease evaluated with 18F-FDG and 18F-flutemetamol was affected by image reconstruction methods and should be used with caution when employing other image reconstruction methods than those used for acquisition of the normal database. In contrast, changes in reconstruction settings were shown to not implicate myocardial blood flow (MBF) based on 15O-water PET analyzed using automated software. This shows that diagnostic MBF cutoff values can be consistently used for 15O-water. Also, large variations in image noise with three different image reconstruction methods did not impact quantitative cerebral blood flow (CBF) in white and gray matter volumes of interest with 15O-water brain PET to any large extent.BSREM image reconstruction shows a great potential clinical benefit providing improved image quality measures with a subsequent possibility of shortening image acquisition durations and/or lowering amount of radioactivity needed for each examination.
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| 9. |
- Retamal Montes, Jaime, 1978-
(författare)
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Aspects on ventilation induced stress and strain on regional and global inflammation in experimental acute respiratory distress syndrome
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanical ventilation (MV) is a life-saving therapy in acute respiratory distress syndrome (ARDS), a condition that affects 3000 patients/year in Sweden with a mortality rate of about 40%. However, MV may induce or worsen lung injury causing “ventilator-induced lung injury (VILI)”. From a mechanical perspective strain (deformation, or relative change in lung volume) and stress (tension) have been postulated as main determinants of VILI. High respiratory rate is potentially another factor that may exacerbate VILI by amplifying the total energy transmitted to the lungs during MV. In this thesis in animal ARDS models the hypotheses were that 1) lung parenchyma inhomogeneities concentrate stress and amplify lung damage and inflammation, 2) higher respiratory rates increase lung inflammation and lung edema in heterogeneous ARDS, and 3) local lung deformation is related to local inflammation.First, in a rat model the effect on inflammation and structural damage of regional lung collapse on the healthy surrounding lung tissue was assessed. Second, in porcine models the effect of respiratory rate on lung edema and inflammation was studied during two ventilatory modes; a) a permissive collapse mode and b) a homogenized lung parenchyma mode. Finally, lung deformation was correlated with lung inflammation assessed by positron emission tomography using 18F-FDG uptake.It was found that; 1) local inhomogeneities can act as stress amplifiers, increasing lung tissue inflammation and damage in the healthy surrounded lung. 2) high respiratory rate increases lung edema but decreases lung inflammation when permissive lung collapse is used and that these effects are prevented with lung parenchyma homogenization; 3) local lung deformation and inflammation are well correlated.In conclusion, lung inhomogeneities may aggravate VILI, respiratory rate may affect in different ways VILI progression depending on the ventilatory strategy, and finally, lung deformation is closely related to lung inflammation. With the caveat that the studies are performed in animal models, the results suggest that using ventilator strategies that homogenize the lungs, i.e., open collapsed lung regions and prevent re-collapse in ARDS will reduce VILI and in the end may decrease morbidity and the high mortality in this condition.
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| 10. |
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| 11. |
- Befekadu Wodajo, Rahel, 1968-
(författare)
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Analysis of new biomarkers and their kinetics in connection with ST-elevation myocardial infarction and percutaneous coronary intervention
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis studies different biomarkers in a cohort of patients suffering from ST-elevation myocardial infarction (STEMI) who underwent Percutaneous coronary intervention (PCI) in Örebro in 2011-2012. Blood samples were collected at three time points, at the arrival at the hospital, 1-3 days after PCI and for a smaller group of patients also 3 months after PCI. The study is a sub-study of the TASTE study, so half of the patients were also randomized to thrombus aspiration in conjunction with their PCI. For all patients, it was also recorded whether the culprit coronary vessel was totally occluded or partially patent. In total, there are samples from 165 patients, but not all markers have been measured in all patients, and 3-month samples are only available from those who had their follow-up in Örebro. The plasma levels of the biomarkers have also been measured in plasma from blood donors for comparison. In March 2019, a follow-up was made of the patients' survival, and the time of death was noted in cases where this had occurred.The markers studied are the lysosome protein Cathepsin S (Cat-S), the platelet granule protein thrombospondin 1 (TSP-1), the pentraxins C-reactive protein (CRP) and pentraxin 3 (PTX3), the endopeptidase neprilysin, the soluble forms of TNF-receptor 1 and 2 (sTNFR1 and sTNFR2), markers showing activation of the lectin pathway for complement activation (MASP-1/AT, MASP-1/C1-INH, MASP-2/C1-INH, MASP-2/AT) and common activation markers for complement activation (C3a and sC5b-9).In summary, the thesis shows that the plasma levels of all markers, except neprilysin and sC5b-9, are elevated at the time of arrival compared to healthy blood donors. Neprilysin is at the same level, and sC5b-9 is lower compared to blood donors. 1-3 days after PCI, the levels for CRP, sTNFR1 and sC5b-9 have risen strongly (>50%) compared to the levels at arrival. MASP-1/AT and MASP-2/AT have fallen moderately (about 50%), Cat-S and TSP-1 have decreased strongly, while the remaining markers are relatively similar to the levels at arrival (± 25%). The levels for CRP, PTX3, sTNFR1, sTNFR2 and neprilysin decreased even further between 1-3 days and 3 months, sC5b-9 rises slightly while the other markers remain at roughly the same levels. At 3 months, most markers still show higher levels compared to corresponding levels in blood donors, only MASP-2/C1-INH has the same level, while neprilysin is slightly lower and TSP-1 much lower compared to blood donors (the latter presumably an effect of ongoing medication with platelet inhibitors in the patients). No relevant differences were observed between patients with and without thrombus aspiration, and few differences were seen between patients with occluded or partially patent vessels. This may indicate that these factors were of minor importance for the levels of the analyzed markers. In contrast, analysis of survival showed that individuals with plasma levels above the median value for PTX3, sTNFR1 and sTNFR2 at admission and/or at 1-3 days had a significantly increased mortality compared to those with levels below the median value, which indicates that these markers could be interesting for further studies in a material where also analysis of possible interfering factors can be implemented.
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| 12. |
- Björnemo, Erik, 1974-
(författare)
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Energy Constrained Wireless Sensor Networks : Communication Principles and Sensing Aspects
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Wireless sensor networks are attractive largely because they need no wired infrastructure. But precisely this feature makes them energy constrained, and the consequences of this hard energy constraint are the overall topic of this thesis. We are in particular concerned with principles for energy efficient wireless communication and the energy-wise trade-off between sensing and radio communication.Radio transmission between sensors incurs both a fixed energy cost from radio circuit processing, and a variable energy cost related to the level of radiated energy. We here find that transmission techniques that are otherwise considered efficient consumes too much processing energy. Currently available sensor node radios typically have a maximum output power that is too limited to benefit from transmission-efficient, but processing-intensive, techniques. Our results provide new design guidelines for the radio output power. With increasing transmission energy -- with increasing distance -- the considered techniques should be applied in the following order: output power control, polarisation receiver diversity, error correcting codes, multi-hop communication, and cooperative multiple-input multiple-output transmissions.To assess the measurement capability of the network as a whole, and to facilitate a study of the sensing-communication trade-off, we devise a new metric: the network measurement capacity. It is based on the number of different measurement sequences that a network can provide, and is hence a measure of the network's readiness to meet a large number of possible events. Optimised multi-hop routing under this metric reveals that the energy consumed for sensing has decisive impact on the best multi-hop routes. We also find support for the use of hierarchical heterogeneous network structures.Model parameter uncertainties have large impact on our results and we use probability theory as logic to include them consistently. Our analysis shows that common assumptions can give misleading results, and our analysis of radio channel measurements confirms the inadequacy of the Rayleigh fading channel model.
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| 13. |
- Larsson, Anders
(författare)
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Systematics of Woodsia : Ferns, bioinformatics and more
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ferns are one of the three main clades of vascular plants. They have few easily studied morphological characters, reflected in a historically unstable classification. The fern genus Woodsia is known to have a complex evolutionary history including numerous polyploid taxa and hybrids. It is a cosmopolitan group of small rock loving ferns mainly found in montane areas.This thesis aims at analyzing the patterns of diploid and polyploid evolution in Woodsia and to resolve and classify the relationships of Woodsiaceae and the other families in the large fern clade Eupolypods II.The Eupolypods II family relationships were inferred with DNA sequences from 81 specimens representing all major lineages. This resulted in the first well supported phylogeny of this clade and revealed Woodsiaceae to be non-monophyletic. The genera previously placed in this family were reclassified into five new or resurrected families. Swedish fern genera that have changed family classification are Woodsia (hällebräknar), now in the monogeneric family Woodsiaceae, Athyrium (majbräknar), now in Athyriaceeae and Cystopteris (stenbräknar) and Gymnocarpium (ekbräknar) now in Cystopteridaceae.To analyze the evolution of Woodsia, phylogenies were produced from five plastid and two nuclear regions sequenced from 188 specimens. The results show that most taxa in Woodsia are polyploid. Polyploidization is the most common mode of speciation in the genus with an estimated polyploid speciation rate of 54%. The polyploids are mostly young and many of the polyploid taxa seem to have formed multiple times. The results also address several taxonomic and biogeographic questions.In the process of the work we made methodological advancements and developed 20 new low copy nuclear marker regions as well as a software pipeline for finding primers in transcriptome datasets. The alignment editor software AliView was developed for handling the increasing size datasets in a user friendly way.In conclusion this thesis provides new insights into the complexities of the evolution of a fern genus in which much of the diversity is accommodated in young species formed through polyploidization. It provides a framework of phylogenetic relationships at different levels that both answers long standing questions and generates new ones.
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| 14. |
- Larsson, Joakim, 1975-
(författare)
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Disciplin och motstånd : Pedagogisk-filosofiska perspektiv på samtida svensk skoldisciplin
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As Sweden approached its 2006 national election, issues on order and discipline in educational environments came to the forefront of educational interest, debate, and reform. This thesis aims at a critical discussion of the discourses in question, making use of educational, post-structural as well as political philosophy. In a series of articles, disciplinary policies are contextualized within current understandings of major trends in global educational politics; empirically investigated with a focus on resistance and political subjectivation; but also theoretically/ philosophically examined with the intention of bringing alternative conceptualizations of discipline to light.As a result, it is concluded that the political platform supporting contemporary school discipline is highly ambiguous, especially in terms of the different subjectification ideals that it embodies. In consequence, substantial possibilities for resistance, political influence and creative subjectification emerge in the breaks and ruptures between neoliberal and neoconservative territory. As for the disciplinary policies themselves, this thesis highlights the possibility that they amount to little more than a powerful simulation; a mode of perceptual management rather than a hands-on engagement with the real demands of contemporary education.An alternative route, the thesis suggests, would be to radically re-conceptualize the meaning and relevance of discipline – using, for instance, philosophers like Gilles Deleuze, Félix Guattari and Jacques Rancière – but also while taking notice of relevant discussions in the fields of complexity and chaos theory. Such a re-conceptualization would allow for an immanent form of discipline, one that affords a circular segmentation to emerge; contextualized and sensitized to the particular demands of each learning situation rather than pre-stratified, pre-territorialized according to the ideals of classical discipline.
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| 15. |
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| 16. |
- Larsson, Lars, 1969-
(författare)
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När EU kom till byn : LEADER II - ett sätt att styra landsbygdens utveckling
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to analyse changes in political and territorial organisation that followed the introduction and implementation of the EU initiative for rural development, LEADER II, in Sweden. Focusing on the actors involved, the LEADER process is analysed from three perspectives: local democracy; the construction of regions; and the political capacity to act. Governance is the conceptual framework that guides the analysis. The main empirical material consists of 85 interviews conducted with people who actively participated in LEADER II. The LEADER programme is aiming at transgressing existing boundaries between societal sectors. It is done through the creation of partnership organisations and new regions. Viewed from a governance standpoint, the inclusion of actors from the private and non-profit sectors promises higher efficiency in delivering political goods through added resources and increased local knowledge. However, even if governance indicates that new forms for political implementation can be experimented with there are limits to what can be achieved. In the LEADER case, it is clear that the public sector retained its power over resources, means and ends.
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| 17. |
- Lindehell, Henrik, 1984-
(författare)
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Jack of all trades, master of none : the multifaceted nature of H3K36 methylation
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Post-translational modifications of histones enable differential transcriptional control of the genome between cell types and developmental stages, and in response to environmental factors. The methylation of Histone 3 Lysine 36 (H3K36) is one the most complex and well-studied histone modifications and is known to be involved in a wide range of molecular processes. Commonly associated with active genes and transcriptional elongation, H3K36 methylation also plays a key role in DNA repair, repression of cryptic transcription, and guiding additional post-translational modifications to histones, genomic DNA, and RNA. In Drosophila melanogaster, trimethylated H3K36 has also been linked to dosage compensation of the single male X chromosome as a binding substrate for the Male-Specific Lethal (MSL) complex. However, this model has been challenged by structural and biochemical studies demonstrating higher MSL complex affinity for other methylated lysines. There is an additional system of chromosome-specific gene regulation in D. melanogaster where transcription from the small heterochromatic fourth chromosome is increased by Painting of fourth (POF), a protein specifically binding nascent RNA on the fourth chromosome. The fourth chromosome is thought to have been an ancestral X chromosome that reverted into an autosome. POF mediating high transcription levels from an autosome is believed to be a remnant of an ancient sex-chromosome dosage compensation mechanism. Proximity ligation assays revealed no interaction between MSL complex components and methylated H3K36. This finding was corroborated by RNA sequencing of H3K36 methylation impaired mutants: the transcriptional output of the male X chromosome was unaffected in mutants where Lysine 36 on Histone 3 was replaced by an Arginine, abolishing methylation of this site. However, we found that knocking out Set2, which encodes the methyltransferase responsible for H3K36 trimethylation, significantly reduced X-linked transcription relative to autosomal transcription. This strongly suggests the existence of previously unrecognized alternate Set2 substrates. Interestingly, we also found that Ash1- and NSD-mediated methylation of H3K36 was required to maintain high expression from chromosome four. Recent studies have also implicated H3K36 methylation in the silencing of transposon activity in somatic cells. By analyzing the transcription of transposable elements and Piwi-interacting RNAs (piRNAs), we identified dimethylation of H3K36 by Set2 as the main methylation mark involved in this process and showed that dual-stranded piRNA clusters are preferentially activated upon disturbing the methylation machinery. These findings extends the long list of processes dependent on functional H3K36 methylation.
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| 18. |
- Marchesi, Silvia, MD, 1985-
(författare)
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The effect of mechanical ventilation on the abdominal organs
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During mechanical ventilation (MV), the interplay between abdomen and thorax has been studied unilaterally focusing on the effect that an increased abdominal pressure would have on the thorax. Only a small cluster of studies offered a different perspective showing a lower inflammation and a better lymphatic clearance of edema in abdominal organs when spontaneous breathing was applied compared to MV. Apart from these insights, a deeper understanding of the effect of different MV features on the abdominal organs remains uninvestigated.The aims of the thesis were: to investigate how changes in perfusion and edema influence inflammation and affect each other, and to examine how the management of ARDS could affect abdominal organs by comparing MV with spontaneous breathing and prone with supine position. All the studies were conducted using a porcine model. In three studies, a septic-like status was generated with an infusion of endotoxin; while in one study, a VILI model was used to simulate ARDS.In the first two studies, perfusion and lymphatic drainage were modified in different groups of animals and the impact of the changes on the abdominal organs was assessed. In the other two studies the effect of different ventilation settings on the abdominal organs was investigated: in Paper III, spontaneous breathing(CPAP) was compared with MV (maintaining positive end expiratory pressure – PEEP – and respiratory rate similar in both groups), and, in Paper IV, MV in prone position was compared with MV in supine position. The main findings were that low perfusion increased inflammation in the abdominal organs, but the hemodynamic parameters could not affect intestinal perfusion or edema. Similarly, increased edema was not associated with a decreased perfusion, but it enhanced inflammation in duodenum. MV increased systemic inflammation compared to CPAP, but did not increased inflammation or edema in the abdominal organs. Prone position reduced renal perfusion and was associated to extensive renal micro-thrombosis. In conclusion, both perfusion and edema influence inflammation in the abdomen, even if they seem not to affect one another. Besides, spontaneous breathing develops less systemic inflammation compared to MV, but it was not associated to a lower edema or inflammation in the abdomen; on the other side, prone positioning resulted in a possibly dangerous decrease of renal perfusion.
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| 19. |
- Olausson, Johan, 1980-
(författare)
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Studies of recombinant forms of Aleuria aurantia lectin
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The presented work describes construction and analysis of recombinantly produced forms of Aleuria aurantia lectin (AAL). The binding properties of the produced AAL forms were studied using techniques such as tryptophan fluorescence, hemagglutination analysis, ELISA and surface plasmon resonance analysis.Lectins are proteins that are ubiquitous in nature with the ability to bind specifically to different types of carbohydrates. The physiological function of different lectins is not always known, but they are involved in many recognition events at molecular and cellular levels. In research, lectins are widely used for structural and functional studies of complex carbohydrates, and they are also used to detect changes in the carbohydrate pattern on glycoproteins in different diseases.With the use of recombinant technology it is now possible to refine properties of lectins such as decreasing the valency and alter specificity and affinity. This may be a way of constructing more suitable reagents for use in diagnostic glycosylation analysis assays.AAL has been extensively used in different types of research for its ability to bind the monosaccharide fucose and to fucose-containing oligosaccharides. It is composed of two identical subunits where each subunit contains five binding sites for fucose. AAL was expressed recombinantly (rAAL) and its properties was investigated. These studies reveled that one of the binding sites in rAAL had unusually high affinities towards fucose and fucosecontaining oligosaccharides with Kd-values in the nanomolar range. This binding site is not detected in AAL that have been exposed to fucose during its purification, and therefore we proposed that this site may be blocked with free fucose in commercial preparations of AAL.Normally lectin-oligosaccharide interactions are considered to be of weak affinity, so the finding of a high affinity site was interesting for the future study of recombinant forms of AAL. The next step was to produce recombinant AAL forms with decreased valency. This was done using site-directed mutagenesis. First a monomeric form of AAL (mAAL) was constructed and then a monovalent form of AAL, containing only one fucose-binding site (S2-AAL) was constructed. Both of these forms had retained ability to bind fucose. The binding characteristics of mAAL were similar to that of rAAL, but mAAL showed decreased hemagglutinating activity. S2-AAL showed a lower binding affinity to fucosylated oligosaccharides and did not bind to sialylated fuco-oligosaccharides such as sialyl-LewisX. This study shows that molecular engineering techniques could be important tools for development of reliable and specific diagnostic and biological assays for carbohydrate analysis.
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| 20. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 21. |
- Sütterlin, Robert, 1981-
(författare)
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Jet Ventilation for Airway Surgery : The Influence of Mode and Frequency on Ventilation Efficacy
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In surgery for airway obstruction, the anesthetist and the ear-nose-throat surgeon share the approach to the airway and jet ventilation (JV) is a mutually convenient ventilation technique for both parties. As a consequence of the open system jet ventilation is applied in, bedside measurements of lung volumes are cumbersome to perform and thus, there is a lack of studies comparing different modes of JV or investigating the influence of ventilator settings on lung volumes and gas exchange. In this thesis, single frequency jet ventilation and superimposed high frequency jet ventilation (SHFJV) at different frequencies are systematically compared with respect to lung volume changes, underlying airway pressure variations and the resulting gas exchange.We compared three single-frequency JV modalities with SHFJV in patients. Moreover, we performed a systematic investigation of single frequency JV and SHFJV in a porcine model. Single frequency JV and SHFJV were compared frequency-wise in intact airways and in a newly developed model of tracheal obstruction. This model was also used to assess the influence of variable airway diameter on ventilation effectiveness during SHFJV. We measured chest wall volume variations with opto-electronic plethysmography and obtained airway pressures as well as gas exchange parameters.In unobstructed airways, both single-frequency JV and SHFJV provided adequate oxygenation, despite differences in lung volumes. Carbon dioxide removal was most effective using single frequency JV at a frequency of 150 min-1. During SHFJV, for both intact and obstructed airways, the choice of frequency for the high frequency component had little influence on lung volumes, airway pressures and gas exchange. With decreasing airway diameter and SHFJV, we observed air trapping and lower tidal volumes and acceptable oxygenation. Carbon dioxide removal, however, was insufficient at the narrowest airway diameter. In single frequency JV, very high frequencies resulted in negligible tidal volume and inacceptable gas exchange. Airway obstruction potentiated this frequency dependence.In conclusion, in intact airways, single frequency JV at sufficiently low frequencies provided adequate oxygenation and better CO2 removal than SHFJV. With decreasing airway diameter, SHFJV provided better oxygenation and CO2 removal and may therefore be the mode of choice in more complicated cases.
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| 22. |
- Söderberg, Ewa
(författare)
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Experimental septic shock – Effects of endotoxemia with special reference to pathophysiological responses in the pig
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis and septic shock are conditions, with severe outcome or in many cases death. Sepsis is a systemic inflammatory response trigger by bacteraemia but systemic inflammatory response can also be triggered by major trauma, major surgery, pancreatitis, severe burns etc.The systemic inflammatory reaction initiating the evolvement of septic organ dysfunction can be modelled using endotoxin, a Gram-negative bacterial lipopolysaccharide. This thesis used a porcine experimental sepsis model to examine timing of the inflammatory response due to endotoxin infusion (Paper I) and the influence of steroid treatment on the inflammatory response in endotoxemic pigs (Paper II). Timing of steroid treatment and the role of neutrophil granulocyte activation was evaluated with pig specific NGAL assessing neutrophil activation (Paper III). A clinical observational study was performed with the aim to differentiate between sepsis and other inflammatory conditions (e.g. trauma due to major surgery) evaluated by calprotectin as a marker of neutrophil activation (Paper IV).There was a dose-dependency in endotoxin tolerance which was measured with TNF-a. Pre-exposure to endotoxin did not reduce the pulmonary response to endotoxemic challenge. In fact, both PaO2 / FiO2 and static pulmonary compliance were reduced in this group when pre-treated with endotoxin at low dose.Endotoxemic animals treated with hydrocortisone were more stable in circulatory variables than those without such treatment. This was not explained by an ability of steroids to modulate the production of NO (Nitric oxide), which has been suggested to be a mechanism of steroids in this aspect.Pre-treatment with hydrocortisone attenuated the neutrophil granulocyte response and consequently diminished the release of NGAL in plasma. Circulatory derangement was associated with high plasma NGAL levels. Urine NGAL levels did not differ among the four groups.Plasma calprotectin levels on ICU admission is a sensitive marker of systemic inflammation and are markedly increased in patients with sepsis and patients with systemic inflammatory response. Plasma Calprotectin performed better than any of the other inflammatory variables in predicting mortality at 30 days, except from the composite mortality prediction score, SAPS 3.
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| 23. |
- Tibblin, Petter, 1979-
(författare)
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Migratory behaviour and adaptive divergence in life-history traits of pike (Esox lucius)
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Population divergence shaped by natural selection is central to evolutionary ecology research and has been in focus since Darwin formulated “The origin of species”. Still, the process of adaptive divergence among sympatric populations is poorly understood. In this thesis I studied patterns of adaptive divergence among subpopulations of pike (Esox lucius) that are sympatric in the Baltic Sea but become short-term allopatric during spawning and initial juvenile growth in freshwater streams. I also examined causes and consequences of phenotypic variation among individuals within subpopulations to evaluate the contribution of natural selection to population divergence. I first investigated homing behaviour and population structures of pike to assess the potential for adaptive divergence among sympatric pike that migrate to spawn in different streams. Mark-recapture data suggested that migrating pike displayed homing behaviour and repeatedly returned to the same stream. Analyses of microsatellite data revealed partial reproductive isolation among subpopulations spawning in different streams. These subpopulations, however, were truly sympatric during the life-stage spent in the Baltic Sea. To address whether short-term allopatry has resulted in adaptive divergence among sympatric subpopulations I combined observational, experimental and molecular approaches. Observational data showed that subpopulations differed in morphological and life-history traits and common-garden experiments suggested that differences were, at least in part, genetically based. Moreover, QST-FST comparisons indicated that genetically based phenotypic differences has been driven by divergent selection, and a reciprocal translocation experiment showed that phenotypic variation represented local adaptations to spawning habitats. Finally, longitudinal and cross-sectional comparisons among individuals revealed associations between phenotypes, performance and fitness components. In conclusion, my thesis illustrates how short-term allopatry due to migratory behaviour can result in adaptive divergence among sympatric subpopulations. These findings advance the understanding of evolutionary processes at the finest spatiotemporal scale and illustrate that local adaptations can arise in environments with high connectivity. The results also emphasise that fine spatial scale population structures must be taken into consideration in management and conservation of biodiversity in the Baltic Sea.
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| 24. |
- Wigenstam, Elisabeth, 1980-
(författare)
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Pathogenesis and treatment of chemical-induced lung injury
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inhalation of chemical substances can cause irritation to airways and in high doses acute airway injury. When mice are exposed to the alkylating nitrogen mustard analogue melphalan they develop an acute airway inflammation with a rapid influx of neutrophils to the lungs. The acute phase is followed by long-term respiratory complications characterized by bronchitis, lung fibrosis, and airway hyperreactivity. In this thesis, a mouse model for chemical airway inflammation was established and the effects on the lungs in a time span from 6 hours up to 3 months were investigated in order to study both acute effects and possible chronic injury. We find that treatment with corticosteroids, e.g. dexamethasone, effectively blocks the inflammatory reaction in several ways: Neutrophil influx to the lungs is diminished, the expression of the proinflammatory cytokines interleukin (IL) -6 and IL-1b is decreased and edema formation as well as development of lung fibrosis is mitigated. In acute airway inflammation we show that the antioxidant vitamin E can be used as a possible complement to corticosteroids but not as a replacement since it causes insufficient downregulation of the inflammatory response. We show the importance of the T lymphocytes as they play a prominent role in the pathogenesis of long-term lung injuries caused by melphalan. Especially the minor gd T cell subset is of major importance orchestrating a number of responses including the acute cytokine and neutrophil response and late-phase lung fibrosis. In order to find the critical time for dexamethasone treatment, mice were exposed to melphalan, treated with dexamethasone at specific time points and lung physiology and airway reactivity was measured in anaesthetized, tracheostomized mice using a small animal ventilator. From these results we conclude that an early treatment, i.e. within one hour after exposure, with dexamethasone is needed to prevent chronic lung injury. This thesis was undertaken with the main goal to better understand the pathogenesis of melphalan-induced airway inflammation. We believe that our findings have shed new light in this area of research and hope that this increased knowledge may be of future clinical use.
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| 25. |
- Berglund, Jenny, 1968-
(författare)
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Teaching Islam : Islamic Religious Education at Three Muslim Schools in Sweden
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study concerns the formulation of Islamic religious education (IRE) at three Swedish Muslim schools which offered IRE as an extra curricular subject, one to three hours per week. The study contributes to the understanding of how IRE is formed as a confessional school subject within the framework and under the jurisdiction of the Swedish school system. The meaning of the studied IRE was construed as a way of building connectedness between pupils to both the common Islamic tradition and the Swedish society, but also highlighting and establishing connections between these two entities. The primary finding is that it is inaccurate to speak about IRE in homogeneous terms since the content varies distinctively between different schools. In addition, it has been found that the educational questions considered by the involved teachers are similar to those considered by many other types of teachers. Although classroom observations and teacher interviews showed that the general content of all three IRE classrooms included the teaching of the Quran, Islamic history through religious narratives and song, specific content variations were evident. Differences concerned approaches to the teaching of the Quran, ways of using religious narratives and genre of songs. Therefore pupils in each school received somewhat different answers to local and global questions that were raised in the classrooms, indicating somewhat different interpretations of Islam. These differences suggest that the depiction of IRE as a transmission of Islam to the younger generation is not accurate since it leads to the impression that religions are insulated entities that are capable of being passed from one generation to the next without any change taking place. Instead this study shows that the teachers translate the content of IRE according to their perception of what is vital for their pupils to know and suitable for them to comprehend since they constantly choose content and negote its meaning.
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| 26. |
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| 27. |
- Bolander, Åsa, 1977-
(författare)
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Prognostic Factors in Malignant Melanoma
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.None of the investigated markers in study III and IV correlated with disease free survival or overall survival.In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
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| 28. |
- Dubois, Louise
(författare)
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Prostasomes as Diagnostic, Prognostic and Therapeutic Vesicles
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores prostasomes and their ability to be used as a new diagnostic tool for prostate cancer. Alongside diagnosis, this thesis also suggests prostasomes as a tool for prognosis and therapeutic treatment in patients with prostate cancer. By further characterizing prostasomes we can identify a biomarker and also a method of visualizing and interpreting the information provided in order to conduct a correct and fast diagnosis for prostate cancer.In Paper I, we show that the prostasomal bilayered membrane consists of lipid rafts, clusters that holds cholesterol, sphingolipids and gives receptors a rigid platform upon which to work. We compare the proteomic content of prostasome lipid rafts with the entire prostasome membrane in the search for a specific biomarker. In Paper II, we show that purified lipid rafts from the prostasome membrane can re-vesiculate and create new bioengineered vesicles. These new vesicles can carry different agents inside them and we find that the method is also applicable to blood cells. This suggests a new method for cell-specific delivery of drugs and cancer therapy. In Paper III, we further characterize the prostasome membrane, this time mapping purinergic receptors. This could be used in the development of prostate cancer treatment and to gain better understanding of how prostasomes interact with surrounding cells in their ambient environment.In Paper IV, we investigate the difference in thymidine kinase 1 (TK1) enzyme activity between prostasomes and malignant exosomes. TK1 is considered to be a biomarker of cell proliferation and could therefore be used as a biomarker for prostate cancer diagnosis and progression.In summary, this thesis contributes to the puzzle of how to better diagnose, prognose and treat prostate cancer. Although it is mainly pre-clinical research it opens up new possibilities for the diagnosis and treatment of prostate cancer.
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| 29. |
- Falkeborn, Tina, 1981-
(författare)
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Nasal vaccination using novel mucosal adjuvants : with main focus on influenza A virus
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Influenza viruses have sporadically caused pandemics during the last century, with the most severe occurring in 1918 when the “Spanish flu”, an A/H1N1 influenza virus, passed around the globe killing about 20-100 million people. Today 250 000-500 000 deaths occur annually due to influenza virus or secondary infection after influenza, e.g. pneumonia. Influenza viruses cause severe infections in susceptible age groups like children and elderly and in individuals with impaired immune response due to other medical conditions. The best way to prevent an influenza epidemic is by vaccination. Since the 1950´s we have vaccines against seasonal flu, but vaccine efficacy is not 100 % and there is a need to develop better and more effective vaccines, especially for the risk groups. Since the virus enters the host through the nasal cavity, nasal vaccination is a good approach. By stimulating a mucosal immune response already in the nasal cavity, the goal with nasal vaccination is to stop the virus before it enters the host. Nasal vaccination also reduces the risk of transmission of blood-borne diseases, and is less painful and easier to administer, compared to injectable vaccines.In order to be able to use less immunogenic antigens, like split and subunit antigens, as nasal vaccine components, an adjuvant is needed to enhance the immune response. At the moment there is no licensed mucosal adjuvant for human use. Several studies are ongoing, but it is a complicated and long way to reach the market. In this thesis nasal vaccination with influenza antigen together with the mucosal adjuvant Endocine™ and other mucosal adjuvants has been evaluated. The Endocine™ adjuvant has been shown to be safe and well tolerated in clinical trials. Depending on the pathogen of interest, different approaches are necessary. For HIV, DNA-vaccination has been evaluated together with a plasmid encoding Salmonella typhimurium flagellin C and the mucosal adjuvant N3. The results found in paper I-IV show that by adding adjuvant to the antigen enhances the protective immune response towards the antigen. Enhanced systemic, mucosal and cell-mediated immunity were observed. Hopefully in the future these adjuvants evaluated in this thesis, will be used in vaccines for humans.
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| 30. |
- Höstman, Staffan, 1979-
(författare)
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Minimal volume ventilation in lung injury : With special reference to apnea and buffer treatment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A fairly large portion of patients receiving surgical or intensive care will need mechanical ventilation at some point. The potential ventilator-induced lung injury (VILI) is thus of interest. One of the main causal factors in VILI is the cyclic energy shifts, i.e. tidal volumes, in the lung during mechanical ventilation. The problem can be approached in two ways. Firstly, one can utilize apneic oxygenation and thus not cause any tidal injuries at all. Secondly, and more traditionally, one can simply lower the tidal volumes and respiratory rates used. The following describes a series of animal experiments exploring these options.In the first two papers, I explored and improved upon the methodology of apneic oxygenation. There is a generally held belief that it is only possible to perform apneic oxygenation by prior denitrogenation and by using 100% oxygen during the apnea. As 100% oxygen is toxic, this has prevented apneic oxygenation from more widespread use. The first paper proves that it is indeed possible to perform apneic oxygenation with less than 100% oxygen. I also calculated the alveolar nitrogen concentration which would conversely give the alveolar oxygen concentration. The second paper addresses the second large limitation of apneic oxygenation, i.e. hypercapnia. Using a high dose infusion of tris(hydroxymethyl)aminomethane (THAM) buffer, a pH > 7.2 could be maintained during apneic oxygenation for more than 4.5 hours.In the last two papers, THAM’s properties as a proton acceptor are explored during respiratory acidosis caused by very low volume ventilation. In paper III, I found that THAM does not, in the long term, affect pH in respiratory acidosis after stopping the THAM infusion. It does, however, lower PVR, even though the PaCO2 of THAM-treated animals had rebounded to levels higher than that of the controls. In the last experiment, I used volumetric capnography to confirm our hypothesis that carbon dioxide elimination through the lungs was lower during the THAM infusion. Again, the PaCO2 rebounded after the THAM infusion had stopped and I concluded that renal elimination of protonated THAM was not sufficient.
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| 31. |
- Iakovleva, Irina, 1977-
(författare)
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Selection of transthyretin amyloid inhibitors
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyloidosis is a group of clinical disorders caused by the aggregation of specific proteins into abnormal extracellular deposits. Today, 31 different proteins have been linked to amyloid diseases including transthyretin-related amyloidosis (ATTR). ATTR occurs through the aggregation of either wild-type plasma protein transthyretin (TTR) or a mutated form. TTR is a homotetramer that under normal circumstances functions as a carrier of thyroxine and retinol binding protein. The aggregation cascade requires dissociation of the tetramer into monomers, and preventing this dissociation represents a potential mode of intervention. Interestingly, small molecules, referred as kinetic stabilizers, can bind to TTR’s thyroxine-binding site (TBS) and such molecules are currently being used as a therapeutic approach to impair tetramer dissociation.The efficacy of TTR stabilization is directly correlated to the binding affinity of the ligand to TBS. However, the binding of the ligand to TTR in vivo can be affected by other plasma components resulting in poor efficacy. Thus, the selectivity of ligands is an important parameter. We have designed an assay where the ability to stabilize TTR can be directly evaluated in plasma and we have investigated the stabilizing effect of nine potential TTR binders (Paper I). The results, surprisingly, revealed that the binding affinity of molecules has a poor correlation to its selectivity. However, the nature of protein-ligand complex formation can also be described by enthalpic (∆H) and entropic (∆S) energy contributions. ∆H represents the change in chemical bonds and frequently requires a higher order of orientation compared to the ∆S component, which mainly represents the hydrophobic effect via the exclusion of water. We hypothesized that ligands possessing high ΔH in binding to their co-partner would also be more specific in a complex environment such as plasma. By applying a thermodynamic analysis using isothermal titration calorimetry, we found that the selectivity in plasma correlates well with the ∆H contribution and might, therefore, be a better predictor for selectivity.Luteolin was found to be a highly selective stabilizer of TTR and was investigated further (Paper II). The ligand displayed a significant rescuing effect in both cell culture and animal models. However, luteolin undergoes rapid enzymatic degradation in the liver and this impairs its use as a potential therapeutic drug. To attempt to circumvent this issue, we modified the most exposed hydroxyl group thus rendering the molecule inert towards glucuronidation (Paper III). The substitutions resulted in higher stability in the face of hepatic degradation molecules, but they also affected the selectivity in a negative manner.The screening for new TTR stabilizers resulted in the discovery of tetrabromobisphenol A, which displayed a very high selectivity (Paper IV). This study also included a comparison with the drug Vyndaqel™ which currently is in clinically use, and showed how the dosage could be altered to acquire a better level of saturation and possibly also a better clinical effect.Taken together we present new molecules with the ability to stabilize TTR, and these can serve as scaffolds for the design of new drugs. We present a method to measure the efficacy of a TTR-stabilizing drugs in a complex matrix and as well as a way to adjust the dosage of existing drugs. We also show that the selectivity of a drug is affected by the relative proportion of ∆H and ∆S, and this is of interest for drug design in general.
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| 32. |
- Knudsen, Kati
(författare)
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Airway management in anaesthesia care : – professional and patient perspectives
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Careful airway management, including tracheal intubation, is important when performing anaesthesia in order to achieve safe tracheal intubation. Aim: To study airway management in anaesthesia care from both the professional and patient perspectives. Methods: 11 RNAs performed three airway tests in 87 patients, monitored in a study-specific questionnaire. The tests usefulness for predicting an easy intubation was analysed (Study I). 68 of 74 anaesthesia departments in Sweden answered a self-reported questionnaire about the presence of airway guidelines (Study II). 20 anaesthesiologists were interviewed; a phenomenographic analysis was performed to describe how anaesthesiologists' understand algorithms for management of the difficult airway (Study III). 13 patients were interviewed; content analysis was performed to describe patients' experiences of being awake fiberoptic intubated (Study IV). Results: The Mallampati classification is a good screening test for predicting easy intubation and intubation can be safely performed by RNAs (Study I). The presence of airway guidelines in Swedish anaesthesia departments is poorly implemented (Study II). Algorithms can be understood as law-like rules, a succinct plan to follow in difficult airway situations, an action plan kept in the back of one's mind while creating flexible and versatile personal algorithms, or as consensus guidelines based on expert opinion in order to be followed in clinical practice (Study III). One theme emerged describing experiences of being awake intubated; feelings of being in a vulnerable situation but cared for in safe hands, described in five categories: a need for tailored information, distress and fear of the intubation, acceptance and trust of the staff's competence, professional caring and support, and no hesitation about new awake intubation (Study IV). Conclusions: The Mallampati classification is a good screening test for predicting easy intubation, when the airway assessment is performed in a structured manner by RNAs. The presence of airway guidelines in Swedish anaesthesia departments was poorly implemented and should receive higher priority. Algorithms need to be simple and easy to follow and based on the best available scientific evidence. Tailored information about what to expect, ensuring eye contact, and giving breathing instructions during the procedure may reduce patients' feeling distress.
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| 33. |
- Kretzschmar, Moritz Andreas
(författare)
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Ventilation/Perfusion Matching and its Effect on Volatile Pharmacokinetics
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mismatching of alveolar ventilation and perfusion (VA/Q) is the major determinant of impaired gas exchange. The gold standard for analyzing VA/Q distribution is the multiple inert gas elimination technique (MIGET), conventionally based on gas chromatography (GC), and, although simple in principle, a technically demanding procedure limiting its use. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) combined MIGET with mass spectrometry, simplifying the sample handling process, and potentially providing VA/Q distributions for a general clinical approach.The kinetics of volatile anesthetics are well known in patients with healthy lungs. The uptake and distribution of inhaled anesthetics have usually been modeled by physiologic models. However, these models have limitations, and they do not consider ventilation/perfusion matching. Respiratory diseases account for a large part of morbidity and mortality and are associated with pulmonary VA/Q mismatch that may affect uptake and elimination of volatile anesthetics.The objectives of the studies were firstly to investigate assessment of VA/Q mismatch by MMIMS and secondly to investigate the effects of asthma-like VA/Q mismatch on the kinetics of volatile anesthetics in an experimental porcine model.Anesthetized and mechanically ventilated piglets were studied.In study I, a direct comparison of MIGET by MMIMS with the conventional MIGET by GC in three animal models that covered a wide range of VA/Q distributions was preformed. The two methods agreed well, and parameters derived from both methods showed good agreement with externally measured references.In studies II–IV, a stable method of inducing and maintaining asthma-like VA/Q mismatch with methacholine (MCh) administration was established, and the effect of VA/Q mismatch on the pharmacokinetics of desflurane and isoflurane was investigated. The present model of bronchoconstriction demonstrates a delay in volatile anesthetic uptake and elimination, related to the heterogeneity of MCh-inhalation induced ventilation. The difference in solubility of volatile anesthetics has a significant influence on their uptake and elimination under VA/Q mismatch. The higher blood soluble isoflurane is affected to a lesser degree than the fairly insoluble desflurane.
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| 34. |
- Larsson, Anders, 1954-
(författare)
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Att vara – tillsammans : Människosyn och medborgarskapsideal i den politiska idéhistorien
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on two phenomena: normative citizenship ideals and onto-logical notions of man. The study is an inductive search for different attributes to describe a variation of these phenomena. The search is conducted from several different perspectives: Current research within citizenship theory, history in a material sense, the history of political ideas, the philosophy of science and thematic analyses of important aspects of the two phenomena.Throughout the thesis attributes are collected and sorted in order to build typologies that can define the variation.In the end the attributes of normative citizenship ideals are sorted into three groups. The ideals are explained in three ways: why they came in to existence, how the transition from one ideal to another took place and how the idealistic content of the ideals were transformed.The attributes of ontological notions of man are sorted into sex types and four of them are defined to have relevance for an existing variation today.Finally the relations between the two typologies are analyzed and ten combinations are found to be possibly useful in studies of contemporary societal contexts.Together, the results are contributing to theories of citizenship.Apart from the results of the study it is argued for a broader definition of politics in political science, for more specific ways to handle egalitarian questions in the field rights of man / citizenship rights and finally against the possibility of a neutral order, for example a neutral state.
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| 35. |
- Larsson, Anders Olof, 1979-
(författare)
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Doing Things in Relation to Machines : Studies on Online Interactivity
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Internet is often discussed in conjunction with various notions of interactivity. Recently, conceptualizations of a “Web 2.0″, mainly focusing on harnessing user-generated content, have grown increasingly common in both public discourse and among researchers interested in the continued growth and transformation of the Internet.This thesis approaches the use and non-use of online interactive features by societal institutions. Specifically, the thesis focuses on online newspapers and online political actors, studying the practitioners working within those institutions and on their respective audiences. Consisting of four empirical studies, the thesis is informed theoretically by the application of conceptual tools pertaining to structuration theory. In Anthony Giddens’ original conception, structuration theory posits that social structure is recursively shaped (and possibly altered) as human agents choose to re-enact certain modalities of specific structures. By changing their uses of the rules and resources made available to them by structure, humans are given agency in relation to overarching, macro-level structures. Giddens’ writings have also been contextualized to the study of information technology use by Wanda Orlikowski, who has mostly focused on organizational research.Combining insights from Giddens and Orlikowski, the thesis suggests that most Internet users are enacting a “structure of audiencehood”, entailing somewhat traditional consumer behavior, rather than a “structure of prosumerism”, which would entail extensive uses of the interactive features made available online. Similar traditional use patterns are discerned for practitioners. The thesis suggests that we should not be surprised at relatively low levels of use of interactive features by practitioners and audiences in these contexts. While the chosen areas of study are often surrounded by expectations and “hype” regarding the consequences of online interactivity, institutionalized news and politics can be said to represent stable structures – structures that have functioned in similar ways for extended periods of time, and, thus, are not so easily amended.
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| 36. |
- Larsson, Anders, 1977-
(författare)
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System-on-Chip Test Scheduling and Test Infrastructure Design
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are several challenges that have to be considered in order to reduce the cost of System-on-Chip (SoC) testing, such as test application time, chip area overhead due to hardware introduced to enhance the testing, and the price of the test equipment. In this thesis the test application time and the test infrastructure hardware overhead of multiple-core SoCs are considered and two different problems are addressed. First, a technique that makes use of the existing bus structure on the chip for transporting test data is proposed. Additional buffers are inserted at each core to allow test application to the cores and test data transportation over the bus to be performed asynchronously. The non-synchronization of test data transportation and test application makes it possible to perform concurrent testing of cores while test data is transported in a sequence. A test controller is introduced, which is responsible for the invocation of test transportations on the bus. The hardware cost, introduced by the buffers and test controller, is minimized under a designer-specified test time constraint. This problem has been solved optimally by using a Constraint Logic Programming formulation, and a tabu search based heuristic has also been implemented to generate quickly near-optimal solutions. Second, a technique to broadcast tests to several cores is proposed, and the possibility to use overlapping test vectors from different tests in a SoC is explored. The overlapping tests serve as alternatives to the original, dedicated, tests for the individual cores and, if selected, they are broadcasted to the cores so that several cores are tested concurrently. This technique allows the existing bus structure to be reused; however, dedicated test buses can also be introduced in order to reduce the test time. Our objective is to minimize the test application time while a designer-specified hardware constraint is satisfied. Again Constraint Logic Programming has been used to solve the problem optimally. Experiments using benchmark designs have been carried out to demonstrate the usefulness and efficiency of the proposed techniques.
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| 37. |
- Larsson, Hedvig, 1963-
(författare)
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Jews and Gentiles in Early Jewish Novels
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation deals with Jewish novels from the late Persian, Hellenistic and early Roman periods. The five texts chosen for this study are the Books of Ruth, Judith, Esther, Daniel and Joseph & Aseneth. Focus is on how the Jewish narrators describe non-Jews and non-Jewish religion, and on the relations between Jews and non-Jews.The study analyses the five texts and shows how they are intertextually related to each other and to other texts from the same or earlier periods. It also shows how the texts are situated in specific historical, sociological and religious contexts. The image of “the other” was from the Jewish point of view to a great extent depending of where this “other” should be located in the world made up of ethnic groups seen as descendants of various eponym fathers. This was often crucial especially if there was a case of close relations or even acceptance and integration into the Jewish community.For the shaping of the image of this “other” the historical and sociological development was important. The emergence of the Hellenistic empires and the Hellenistic culture was welcomed by some groups, but not by all. In the novels the authors expressed a strong aversion toward many of the novelties they encountered. Still they were strongly affected by the Hellenistic culture, and all of the novels were written in or translated into the Greek language.With the help of typescenes the authors could convey messages about Jews and non-Jews. The images of the non-Jews are often, but not always, negative, and there is a frequent use of irony and parody so that many of the non-Jewish characters are ridiculed and laughed at.
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| 38. |
- Larsson, Ida, 1979-
(författare)
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Measurement of Self-Heating of Biomass Pellets using Isothermal Calorimetry
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Self-heating in storage facilities of biomass pellet can lead to spontaneous combustion. This has resulted in many fires over the years, causing both financial and environmental losses.In order to assess the risk for spontaneous combustion of biomass pellets during storage, it is important to know how prone the fuel is to self-heating, i.e. to determine its reactivity. This thesis presents experimental work performed to develop a sensitive screening test procedure for biomass pellets, using isothermal calorimetry for direct measurement of the heat production rate. This method can be used to compare the reactivity of different biomass pellets. This could be useful for e.g. facility owners to gain better knowledge of their fuels propensity for self-heating and thereby facilitate safer storage.The screening test procedure can also be used for research purposes. Experiments have been performed with 31 different biomass pellet batches to investigate how the pellet composition, origin, etc. influence the reactivity of the pellets. The results from these experiments clearly show a significant difference in reactivity between different types of pellets. The results indicate that pine/spruce mix pellets are significantly more reactive than all other types of pellets tested, and that pellets consisting of 100 % pine are more reactive than pellets consisting of 100 % spruce. Pellets produced from winery wastes, straw, or eucalyptus, have low reactivity compared to pellets consisting of pine and/or spruce. The reactivity of the pellets was shown to be reduced by either introducing certain types of anti-oxidants into the pellets or by extracting lipids from the raw material of pellets.The screening test procedure is already being used today by some facility owners for assessing their fuels propensity for self-heating. The procedure is also one of the suggested test methods in “ISO/CD 20049 Solid biofuels — Determination of self-heating of pelletized biofuels”.
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| 39. |
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| 40. |
- Larsson, Jennie K, 1972-
(författare)
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Integrationen och arbetets marknad : Hur jämställdhet, arbete och annat "svenskt" görs av arbetsförmedlare och privata aktörer
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Avhandlingen belyser vad som hänt i svensk integrationspolitik sedan etableringsreformen genomfördes 2010 och ansvaret för flyktingmottagandet överfördes till Arbetsförmedlingen. Utöver förändringen som Arbetsförmedlingens ansvar innebar medförde reformen också ökad marknadsorientering, införande av valfrihetssystem, villkorad aktiveringspolitik samt andra genomgripande organisatoriska förändringar.I fokus står aktörer som på olika sätt har makt att påverka hur integrationspolitiken görs i praktiken. Studien analyserar vad som händer när privata företag bedriver arbetsförmedlande verksamheter där ersättningen kopplas till uppnådda resultat. Vidare analyseras betydelsen av ”svenskhet” i görandet av integrationspolitik.Avhandlingen är etnografisk och det empiriska materialet består av intervjuer och observationer med individer som arbetar på arbetsförmedlingskontor, som etableringslotsar samt samhällskommunikatörer på utbildningsföretag.Genom att syntetisera teorier om gatubyråkratier med en intersektionell ansats visar avhandlingen att görandet av integrationspolitik också är ett görande av ojämlikheter som grundas i stereotypa bilder av ”svenskhet” och ”invandrarskap”. Studien visar vidare hur föreställningen om Sverige som jämställd nation påverkar hur politiken görs. I analysen framkommer att de strategier som arbetsförmedlarna utvecklar för att hantera de krav som ställs på dem, i form av aktivering och resultat, inte leder till att de nyanlända kommer närmare arbetsmarknaden. Studien visar även att privata företag prioriterar resultat, lönsamhet och satsar på de nyanlända som de lättast kan nå resultat med.
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| 41. |
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| 42. |
- Larsson, Pontus, 1977-
(författare)
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Computational Approaches to the Identification and Characterization of Non-Coding RNA Genes
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-coding RNAs (ncRNAs) have emerged as highly diverse and powerful key players in the cell, the range of capabilities spanning from catalyzing essential processes in all living organisms, e.g. protein synthesis, to being highly specific regulators of gene expression. To fully understand the functional significance of ncRNAs, it is of critical importance to identify and characterize the repertoire of ncRNAs in the cell. Practically every genome-wide screen to identify ncRNAs has revealed large numbers of expressed ncRNAs and often identified species-specific ncRNA families of unknown function. Recent years' advancement in high-throughput sequencing techniques necessitates efficient and reliable methods for computational identification and annotation of genes. A major aim in the work underlying this thesis has been to develop and use computational tools for the identification and characterization of ncRNA genes.We used computational approaches in combination with experimental methods to study the ncRNA repertoire of the model organism Dictyostelium discoideum. We report ncRNA genes belonging to well-characterized gene families as well as previously unknown and potentially species-specific ncRNA families. The complicated task of de novo ncRNA gene prediction was successfully addressed by developing a method for nucleotide composition-based gene prediction using maximal-scoring partial sums and considering overlapping dinucleotides.We also report a substantial heterogeneity among human spliceosomal snRNAs. Northern blot analysis and cDNA cloning, as well as bioinformatical analysis of publicly available microarray data, revealed a large number of expressed snRNAs. In particular, U1 snRNA variants with several nucleotide substitutions that could potentially have dramatic effects on splice site recognition were identified.In conclusion, we have by using computational approaches combined with experimental analysis identified a rich and diverse ncRNA repertoire in the eukaryotes D. discoideum and Homo sapiens. The surprising diversity among the snRNAs in H. sapiens suggests a functional involvement in recognition of non-canonical introns and regulation of messenger RNA splicing.
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| 43. |
- Larsson Taghizadeh, Jonas, 1986-
(författare)
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Power from Below? : The Impact of Protests and Lobbying on School Closures in Sweden
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent decades, there has been a considerable expansion of citizen participation in protests and voluntary advocacy groups. To analyze this development, the social movement literature and the interest group literature have emerged. Yet these two bodies of literature have not communicated with each other and have rarely incorporated knowledge from other fields in political science. As a result, critical questions remain unanswered regarding the political influence of advocacy groups. How do they affect politicians? To what degree do informal groups use lobbying tactics? Are socioeconomically advantaged groups more influential? This thesis endeavors to address the above shortcomings by bridging the literature on social movements, interest groups and political parties. The purpose of the thesis is to explain if and how advocacy groups affect public policy and to analyze which resources that are required to influence political decisions. The focus is on informal and loosely organized social movement organizations (informal SMOs): parental networks, staff networks, and village networks. To test my arguments, I use a unique database on protests and lobbying against school closures in Sweden. Closures of public schools have been one of the most important drivers of political activism in Sweden. The results are presented in three essays.Essay I tests new electoral mechanisms that could condition the political influence of advocacy groups. The results suggest that the political influence of informal SMOs on school closure decisions varies according to the type of voter they mobilize: swing voters or core voters.Essay II demonstrates how informal SMOs use lobbying tactics, such as presenting policy-relevant information, to influence politicians. Social movement scholars often focus on protests and ignore lobbying tactics. However, the results show that SMOs that present policy-relevant information are more likely to stop school closures than SMOs that mobilize large protests.Essay III analyzes which informal SMOs exchange policy-relevant information with politicians. Previous studies on the use of lobbying tactics have ignored activist resources. My results suggest that SMOs mobilizing high-income activists and activists with analytical and civic skills are more likely to present policy-relevant information. This is problematic given normative ideals of equal access to decision-making by all members of society.
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| 44. |
- Larsson, Viveca, 1974-
(författare)
-
"A suffering heart". On the health of women living with violence in Vietnam.
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study addresses abused Vietnamese women’s experience of health, as well as other health problems and family conflicts, while also taking into consideration professional dealings with family violence. Women’s health in everyday life is largely affected when they are exposed to violence by their male partners. Such violence exists in most societies around the world, also in the Vietnamese context, where the official policies focus on gender equality, together with a strong family concept. Thus, the present study aims to contribute to an empirical understanding of the relation between women’s health and violence against women within the family, from three perspectives: That of the society (organisations and professionals), the neighbourhood community (family members and neighbours), and the individuals (the abused women).The thesis is based on three qualitative interview studies. To reach the official Vietnamese society, national organisations working against violence were invited to participate and eleven professionals of different positions were interviewed. The semi-structured interviews were analysed with content analysis. To include the neighbourhood community perspectives on health and conflicts in family life, twenty-two men and women of different ages and backgrounds, but without any known history of abuse, participated in sixteen semi-structured interviews. For the third study twelve abused women presented life-stories through indepth interviews. The interviews of study two and three were analysed using narrative approach.On a professional level, the discussion on violence focus on the abusive men’s violent acts, on how to promote good social relations and how to make people in general recognise violence as a public health problem and value gender equality. In family everyday life, the informants consider women as the main responsible for the family well-being, but find cooperative support necessary in daily life. To adjust family life to social change, and to make everyone feel important, means to avoid boredom or distress are strategies used, since such conditions are considered to cause troubled relations, abuse and suffering. Violence within the family is seen as interpersonal problems where both partners are to blame for family dysfunction. Empathic sentiments, mutual support and communication are means to handle problems, and a harmonious and happy family is seen as protecting health.The abused women experience vulnerability, which they see as the foremost threat to their health. Injuries as well as worries cause harm. The abused women blame their husbands, for the violence, but they rarely confront them. Instead they use a number of strategies to handle their situation; through enduring, making their husband’s face others judgements, or divorce. They see violence as part of an everyday life of hardship, and consider that bearing too many troubles harms their health.A coherent approach between the different perspectives is needed if the abused women and their families will have a possibility to experience health. The professionals need to consider both public equality policies and the individuals’ experience of vulnerability. The abused women, and abusive men, would benefit from a neighbourhood community that is open to individual failure but still supportive and encouraging. To experience health this study found that it matters what position a person has, what expectations and judgement a person face, how well a person can manage her obligations, and what room for action she possesses.
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| 45. |
- Nersäter, Anders
(författare)
-
Att konstruera historiska förklaringar : Vad elever kan behöva lära för att kunna resonera om orsak samt tolka och använda källor inom gymnasieämnet historia
- 2014
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this study was to gain knowledge concerning what up-per secondary students need to learn to be able to construct historical explanations while working with historical sources. The study also explored how teaching could be designed to enhance student’s capabilities. The history didactical framework took its departure in the British Historical Thinking-tradition and the methodology was based on Learning Study, an iterative research method for analysis and enhancement of teaching and learning. Empirical data originates from one Learning Study undertaken in an upper secondary school performed in cooperation with three teachers teaching three different classes. The bulk of data consists of student interviews, video recordings from research lessons and essay texts performed by the students before and after research lessons. Variation Theory was used to analyse teaching and learning with the purpose to identify critical aspects of what characterizes the capabilities and what the students needed to learn to reason about causation, interpret and use historical sources. The historical content was framed on the late 19th century phenomenon known as The Scramble for Africa where the students were supposed to reason on the causes for thescramble while working with a variety of primary sources. The methodological design of the research-lessons was based on a combination of principles from Variation Theory and Learning Activity with the ambition to form an educational practice that would allow students to discern the critical aspects and advance their learning. The results show that the students who participated in this study needed to distinguish the following critical aspects to be able to construct Historical Explanations when working with sources:CauseTo distinguish temporal aspects of historical change not to confuse causes and consequences.To distinguish that historical change are caused by societal structures and intervention by historical actors and do not occur by itself.To distinguish that historical change predominantly have their origin in several causes and cannot be reduced to single causes.To distinguish that historical explanations need support from evidence.Interpret and Use Historical SourcesTo asses sources critically rather than view them as neutral information.To contextualize sources to avoid presentism and literal interpretations.To corroborate sources to be able to validate claims and present different perspectives in a historical explanation.To see that values and limitations of sources depend on the historical questions we seek an answer to.To distinguish the difference between authentic sources and reliable claims.
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| 46. |
- Nilsson, Elin, 1979-
(författare)
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Characterization of IgY for Oral Immunotherapy and Prevention of Pseudomonas aeruginosa Infections in Cystic Fibrosis Patients
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chicken antibodies, commonly referred to as IgY, have several properties that make them suitable for oral treatment of infections and there is essentially no risk for development of resistance. The overall aims of this thesis were to investigate Anti-Pseudomonas IgY as prophylaxis against infections with Pseudomonas aeruginosa for cystic fibrosis (CF) patients and to characterize the antibody treatment. We found that Anti-Pseudomonas IgY has affinity for P. aeruginosa flagellin, the major component of the flagellum. This is important since the flagellum is required for host invasion and establishment of infection. Flagellin induces inflammation. The main cause of morbidity and mortality among CF patients is chronic colonization of the airways with P. aeruginosa. We have studied prophylactic treatment of 17 Swedish CF patients with Anti-Pseudomonas IgY for up to twelve years. The results were compared with a control group of 23 Danish CF patients. Patients treated with IgY had 2.3 P. aeruginosa positive cultures/100 treatment months vs. 7.0 cultures/100 treatment months in the control group (p=0.028), and the time from inclusion to the first recolonization was significantly longer in the IgY-treated group (p=0.012). Lung function was preserved and patients treated with IgY had good nutritional status at the end of the study. Furthermore, other bacteria have not emerged instead of P. aeruginosa. Freeze-drying of IgY and the content of IgY preparations for oral use was investigated. Besides IgY, 26 egg yolk proteins were identified. Some of the proteins are known to have antimicrobial and immunostimulatory effects, and could have a positive additive effect to IgY treatment. Cholesterol levels were low. Conclusion: Anti-Pseudomonas IgY is a promising complement in the prevention of Pseudomonas aeruginosa infections in CF patients, partly explained by the fact that IgY binds to flagellin.
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| 47. |
- Nordahl, Oscar
(författare)
-
Intraspecific diversity of pike (Esox lucius) in the Baltic Sea and new insights on thermoregulation in fish
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fish display a fascinating variation in behavior, morphology and physiology among species, among individuals within species, and within individuals over time. A central quest in ecology and evolution is to understand causes and consequences of such variation. This thesis aims to contribute to this knowledge by: (1) investigating the evolutionary processes that shape intraspecific variation among sympatric subpopulations of pike in coastal areas of the Baltic Sea; and (2) exploring whether fish can utilize sun-basking to regulate body temperature and whether this has any consequences for fitness.Identifying barriers that delineate populations is a first step towards evaluating the evolutionary origin of intraspecific variation. This thesis reports on genetic population structures among co-existing pike in the coastal Baltic Sea separated by homing behavior, different spawning strategies and geographic barriers. Field studies revealed that these subpopulations also show phenotypic divergence in reproductive and meristic traits. Experimental studies suggested that differentiation among subpopulations likely was a result of divergent selection and local adaptations to spawning grounds. These adaptations that may further reinforce barriers among subpopulations due to a reduced success of immigrant genotypes.For the second aim of the thesis, we first studied seasonal and diel patterns of activity and vertical migration among the Baltic Sea pike. The results suggested that pike exposed themselves to sunlight during spring and summer, and that body temperatures were positively correlated with sun exposure during these basking events. This was followed by experimental studies on inanimate physical models and a field study on carp which demonstrated that fish can become warmer than ambient water when exposed to sun light, a previously overlooked mechanism for fish thermoregulation, and that the heat gain was positively correlated with growth.This thesis contributes to our understanding of the origin and maintenance of intraspecific variation among coexisting populations with direct implications for management of pike. It also establishes sun-basking as a novel mechanism for fish to obtain body temperatures in excess of ambient water which could motivate adaptations, both evolutionary and plastic, that optimize heat gain, affect spatiotemporal distributions and biotic interaction within and among species.
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| 48. |
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| 49. |
- Pettersson-Pablo, Paul, 1986-
(författare)
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Biomarkers of vascular function and structure in young healthy adults
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a disease affecting the blood vessels in the body. Its pathophysiologic mechanisms involve infiltration of the vessel walls by fatty matter and immune cells. This process is slow, starting in childhood but typically not manifesting as symptomatic disease until late adulthood (after 60 years of age). The identification of younger individuals with a high risk for early intervention has a higher potential of preventing morbidity and mortality.In this thesis, part of the Lifestyle, Biomarkers and Atherosclerosis study (LBA), the earliest stages of vascular dysfunction have been examined in a population of young, healthy, non-smoking subjects. Vascularfunction and structure measurements predict a future risk of cardiovascular disease (CVD). The measurements were analyzed in relation to clinical chemistry analyses of various biomarkers in serum and plasma that have been associated with inflammation or cardiovascular risk. A secondary aim was to examine estrogen containing contraceptive use and its relation to the CVD biomarkers.In Paper I and Paper II of the thesis, the association between inflammatory biomarkers, body fat percentage and vascular function and structure measurements was examined in multivariable linear regression models. A higher body fat percentage predicted an increased serum concentration of C-reactive protein (CRP) and orosomucoid. In Paper II, a higher body fat percentage and a higher CRP were associated with a more unfavorable vascular function and structure.In Paper III and Paper IV, we employed two multiplex proteomics panels to analyze inflammatory proteins and proteins previously implicated in CVD. In multivariable linear regression models, proteins implicated in hemostasis, inflammatory signaling and chemoattraction correlated with different vascular function and structure measurements. InPaper IV, insulin-like growth factor-binding protein 1 (IGFBP1) and IGFBP2 were independently predictive of an increased vascular stiffness.In conclusion, even in young, healthy individuals, altered concentrations of serum biomarkers can be detected in subjects with increased body fat and unfavorable vascular function and structure.
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| 50. |
- Prästings, Anders, 1984-
(författare)
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Aspects on probabilistic approach to design : From uncertainties in pre-investigation to final design
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Geotechnical engineering is strongly associated with large uncertainties. Exploring a medium (soil) that is almost entirely and completely hidden from us is no easy task. Investigations can be made only at discrete points, and the majority of a specific soil volume is never tested. All soils experience inherent spatial variability, which contributes to some uncertainty in the design process of a geotechnical structure. Furthermore, uncertainties also arise during testing and when design properties are inferred from these tests. To master the art of making decisions in the presence of uncertainties, probabilistic description of soil properties and reliability-based design play vital roles. Historically, the observational method (sometimes referred to as the “learn-as-you-go-approach”), sprung from ideas by Karl Terzaghi and later formulated by Ralph Peck, has been used in projects where the uncertainties are large and difficult to assess. The design approach is still highly suitable for numerous situations and is defined in Eurocode 7 for geotechnical design. In paper I, the Eurocode definition of the observational method is discussed. This paper concluded that further work in the probabilistic description of soil properties is highly needed, and, by extension, reliability-based design should be used in conjunction with the observational method. Although great progress has been made in the field of reliability-based design during the past decade, few geotechnical engineers are familiar with probabilistic approaches to design. In papers II and III, aspects of probabilistic descriptions of soil properties and reliability-based design are discussed. The connection between performing qualitative investigations and potential design savings is discussed in paper III. In the paper, uncertainties are assessed for two sets of investigations, one consisting of more qualitative investigations and hence with less uncertainty. A simplified Bayesian updating technique, referred to as “the multivariate approach”, is used to cross-validate data to reduce the evaluated total uncertainty. Furthermore, reliability-based design was used to compare the two sets of investigations with the calculated penetration depth for a sheet-pile wall. The study is a great example of how a small amount of both time and money (in the pre-investigation phase) can potentially lead to greater savings in the final design.
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