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- Grahn, Tonje, 1976-
(författare)
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Risk assessment of natural hazards : Data availability and applicability for loss quantification
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Quantitative risk assessments are a fundamental part of economic analysis and natural hazard risk management models. It increases the objectivity and the transparency of risk assessments and guides policymakers in making efficient decisions when spending public resources on risk reduction. Managing hazard risks calls for an understanding of the relationships between hazard exposure and vulnerability of humans and assets. The purpose of this thesis is to identify and estimate causal relationships between hazards, exposure and vulnerability, and to evaluate the applicability of systematically collected data sets to produce reliable and generalizable quantitative information for decision support. Several causal relationships have been established. For example, the extent of lake flood damage to residential buildings depends on the duration of floods, distance to waterfront, the age of the house and in some cases the water level. Results also show that homeowners private initiative to reduce risk, prior to or during a flood, reduced their probability of suffering building damage with as much as 40 percent. Further, a causal relationship has been established between the number of people exposed to quick clay landslides and landslide fatalities. Even though several relationships were identified between flood exposure and vulnerability, the effects can only explain small parts of the total variation in damages, especially at object level. The availability of damage data in Sweden is generally low. The most comprehensive damage data sets in Sweden are held by private insurance companies and are not publicly available. Data scarcity is a barrier to quantitative natural hazard risk assessment in Sweden. More efforts should therefore be made to collect data systematically for modelling and validating standardized approaches to quantitative damage estimation.
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| 2. |
- Tydén, Jonas, 1973-
(författare)
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Heparin-binding protein and organ failure in critical illness
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: For patients severely ill enough to require care in an intensive care unit (ICU), both the disease itself (e.g. bacteria in the blood in sepsis or fractures after trauma) and effects of the immune system can cause circulatory, pulmonary, or renal dysfunction. Leukocytes play a dominant role in the immune system. When activated they release a range of small proteins with different properties Heparin-binding protein (HBP) being one of these proteins, has many functions, including to increase vascular permeability. Heparin-binding protein causes plasma leakage from blood vessels into surrounding tissue (oedema), which can lead to organ dysfunction depending on the site and degree of oedema formation. Increased concentration of HBP in plasma is associated with failing circulation and lung function in subgroups of critically ill patients.Aims: We investigated the possibility of using concentration of HBP in plasma for predicting circulatory, respiratory or renal failure in an ICU population with mixed diagnosis. We assessed concentration of HBP in alveoli in ventilator induced lung injury (VILI), and finally assessed elimination of HBP in urine and effluent fluid from continuous dialysis.Methods: In Papers I and II, HBP concentration in plasma was measured in 278 patients on admission to ICU. Sequential organ failure assessment (SOFA) scores and acute kidney injury (AKI) stage were recorded daily. In Paper III HBP concentration in bronco-alveolar fluid was measured in a pig model of ventilatory induced lung injury, in 16 healthy volunteers and in 10 intubated ICU patients. In Paper IV plasma and urine concentration of HBP was measured in 8 healthy volunteers and 20 burn ICU patients. In addition, HBP was sampled in plasma and effluent fluid in 32 ICU patients on continuous renal replacement therapy (CRRT).Results: In Paper I, patients developing circulatory failure (circulatory sub-score of SOFA = 4) had higher plasma concentration of HBP compared to those who did not (median(IQR)ng/ml) (63.5(32–105) vs 36.4(24–59)) p<0.01), and patients developing respiratory failure (P:F ratio < 27) had higher HBP concentration than those who did not (44.4(30-109) vs 35.2(23-57) p<0.01). Discriminatory capacity was (ROC AUC (95%CI)) (0.65 (0.54–0.76)) for circulatory failure and (0.61(0.54–0.69)) for respiratory failure. In Paper II, patients developing renal failure (AKI stage 2-3) had higher plasma concentration of HBP compared to those who did not (72.1 (13.0–131.2) vs 34.5 (19.7–49.3) p<0.01). Discriminatory capacity for AKI stage 3 was 0.68(0.54-0.83) (ROC AUC (95%CI)). In the subgroup with severe sepsis, it was 0.93 (0.85–1.00). In Paper III, HBP concentration in bronchoalveolar lavage was higher in pigs subjected to injurious ventilation over 6 hours ventilation compared to controls (1144(359–1636) vs 89(33–191) p=0.02) (median(IQR)ng/ml). The median HBP concentration in bronchoalveolar lavage from healthy volunteers was 0.90(0.79– 1.01) compared to 1959(612–3306) from intubated ICU patients (p < 0.01).In Paper IV, renal clearance of HBP was 0.19 (0.08-0.33) in healthy individuals and 0.30 (0.01-1.04) (median, IQR, ml/min) in burn ICU patients. Clearance of HBP was higher in burn patients with increased cystatin C (0.45(0.15-2.81) vs. 0.28(0.14-0.55) p=0.04). Starting CRRT did not alter plasma concentration of HBP (p=0.14). Median HBP concentration in effluent fluid on CRRT was 9.1 ng/ml (7.8-14.4).Conclusions: Papers I and II:There is an association between high concentration of HBP in plasma on ICU admission and circulatory, respiratory and renal failure. For the individual patient, the predictive value of a high HBP concentration is low, with the possible exception of renal failure in septic patients. Paper III:HBP concentration in alveoli increases in pigs subjected to injurious ventilation. HBP concentration in alveoli of intubated ICU patients ventilated protectively is elevated to similar levels, a factor of approximately 1000 times higher than the concentration seen in healthy controls. Paper IV:In healthy study participants, renal clearance of HBP is low. In critically ill burn patients with impaired renal function, clearance of HBP is increased. Starting CRRT in critically ill patients does not alter plasma concentration of HBP. Still, HBP is found in the CRRT effluent fluid, and concentration does not appear to be dependent on plasma concentration.
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| 3. |
- Aguirre Rivera, Javier, 1989-
(författare)
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Tracking single molecules in uncharted territory : A single-molecule method to study kinetics in live bacteria
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The synthesis of proteins, also known as translation, is a fundamental process in every living organism. The steps in the translation of genetic information to functional proteins have been meticulously studied, mostly using in vitro techniques, yielding a detailed model of their mechanisms. However, the use of minimal cell-free systems allows for the possibility to miss interactions from absent components or that reactions are affected by the buffer composition. The work presented in this thesis opens a way to study the kinetics of complex molecular processes, like protein synthesis, directly inside live bacterial cells in real time. We developed and optimized a method to deliver dye-labeled macromolecules inside live cells and generate a kinetic model of the particle’s interactions based on its diffusion inside the cell.This method facilitated the study of translation elongation and initiation directly in live cells. Our measurements of reaction times of tRNA in the ribosome, agree with previous reports from in vitro techniques. We further applied the method to examine the effects of three aminoglycoside antibiotics and erythromycin directly in live cells. The aminoglycoside antibiotics slowed-down protein synthesis 2- to 4-fold, while the number of elongation cycles per initiation event decreased significantly. In the case of erythromycin, cells showed a 4-fold slower protein synthesis. Additionally, we measured the kinetics of sequence-specific effects of erythromycin: translational arrest, and peptidyl-tRNA drop-off; these in vivo measurements revealed a complex mechanism of action of the drug, in agreement with models suggested by previous experiments. Additionally, we applied the method to measure the effects, on the kinetics of protein synthesis, caused by modifications in the C-terminal tail of the S13 ribosomal protein. Our measurements showed that specific mutations led to different changes in the occupancy and dwell-time of labeled-tRNA in the ribosome.To summarize, the present work will guide the reader through the development of a method to study the kinetics of protein synthesis directly in live bacterial cells, as well as its application to characterize the effects of different antibiotics within the complex environment of a living organism.
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| 4. |
- Johansson, Magnus, 1975-
(författare)
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Do Non Player Characters dream of electric sheep? : A thesis about Players, NPCs, Immersion and Believability
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This is a thesis that deals with the norms and rules of players playing online games together. It is also a thesis about believability, the current capabilities of non-player characters (NPCs) and the attitudes amongst game developers towards dynamic and systemic games AI.The primary theme of this thesis considers which means of communication and coordination in terms of norms and rules are present in groups of players and particularly in guilds and clans playing Massively Multi Online Games (MMOGs) and First Person Shooters (FPSs) respectively. The presence of norms in these types of groups has been overlooked in previous research even though guilds have been addressed to some extent. When rules have been discussed in games research, the actual use, meaning and interpretation behind these rules from a player perspective has been omitted. In this thesis rules and norms are interpreted from a guild and clan perspective as important means for coordination, used in order to keep the group together. The implicit rules are further seen as implicit rules made explicit through guild and clan forums where these groups of players express how to preserve the shared game experience. The absence of rituals, norms and rules has also been studied in temporary groups of one MMOG, with the explanation that existing relations with other players are maintained in these game sessions, but new relations are usually seen as too costly to invest in.The second theme is directed at believability and the state of current NPCs, how immersion is influenced by NPCs that do not act in believable ways. The second theme is also influenced by the first theme, whereby rules and norms are seen as valuable tools for creating believability in NPCs, directly targeting the social layer, a slightly overlooked area of research.The last section is directed at applying the results from the first section, how players play by the rules and norms of the group, and how this could foster believability in NPCs.
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| 5. |
- Melik, Wessam, 1973-
(författare)
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Molecular characterization of the Tick-borne encephalitis virus : Environments and replication
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The flavivirus genus is of major concern for world morbidity and mortality and includes viruses causing both encephalitic as well as hemorrhagic diseases. The incidence of Tick-borne encephalitis is increasing in many European countries and several reports have emphasized the expansion of the main vector, Ixodes ricinus. The pattern of vector distribution is also changing in Sweden, which makes it important to set up solid and successful strategies for detection and genetic characterization of novel Swedish TBEV strains.In this study we have generated strategies for detection of broad types of tick-borne flaviviruses in pools of I. ricinus sampled in Sweden.The positive collection on the island of Torö was used to generate a sequence of a complete TBEV genome straight from the arthropod reservoir. This cloned virus was used to construct a self-replicating DNA based sub-genomic TBEV replicon capable of expressing reporter genes. The replicon was used to study the effect of TBEV on neurite outgrowth, which revealed that the MTase domain of NS5 block the formation of the Scribble/Rac1/βPIX protein complex, impairing neurite outgrowth in neuronal growth factor induced PC12 cells.We also demonstrate that TBEV replication is affected by two PDZ binding motifs within NS5 and reveal putative PDZ binding proteins. These interactions might affect cellular pathways and might have a role in flavivirus replication.We also characterize the variable 3´ non-coding region (V3’-NCR) by in silico studies on TBEV. Analysis brings new evidence that V3’-NCR region carries an enhancer element important for different replication/translation dynamics during the viral lifecycle in mammalian and tick cells. We also propose a temperature-sensitive trans-acting riboswitch mechanism; altering the secondary RNA structures of a closed form at lower temperatures and a form open for translation at higher temperatures. This mechanism may explain the low TBEV level observed in sampled ticks.
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