| 41. |
- Aas, Wenche
(författare)
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Constitution, dynamics and structure of binary and ternary actinide complexes
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stoichiometry, ligand exchange reactions, coordinationgeometry and stability of complexes of type UO2LpFq(H2O)3-n(p= 1–2,q= 1-3), where L is one of the bidentate ligandspicolinate, oxalate, carbonate or acetate have beeninvestigated using single crystal X-ray diffraction, an arrayof19F-,13C-,17O- and1H-NMR techniques and potentiometric titration usingboth F-and H+selective electrodes. The experiments wereperformed in a 1.00 M NaClO4medium. The equilibrium constants were determinedat 25°C while most of the kinetic experiments were done at- 5°C. The equilibrium constants for the stepwise additionof F-to UO2L and UO2L2indicates that the prior coordination of L toU(VI) has a fairly small effect on the subsequent bonding offluoride, except for a statistical effect determined by thenumber of available coordination sites. This indicates thatternary complexes might be important for the speciation andtransport of hexavalent actinides in ground and surface watersystems. A single crystal structure of UO2(picolinate)F32-has been determined showing the same pentagonalbipyramidal symmetry as in aqueous solution studied by NMR. Theexchangeable donor atoms are situated in a plane perpendicularto the linear uranyl group. The complexes show a variety ofdifferent exchange reactions depending on the ligand used. Ithas been possible to quantify external fluoride and the otherligands exchange reactions as well asintra-molecular reactions. This type of detailedinformation has not been observed in aqueous solution before.Water takes a critical part in the exchange mechanism, and whenit is eliminated from the inner coordination sphere a muchslower kinetics can be observed.19F-NMR has showed to be a powerful technique tostudy these reactions, both because of the sensitivity of thisNMR nucleus and also the possibility to observe reactions wherefluoride is not directly involved in the mechanism. TernaryTh(edta)F1-2and (UO2)2(edta)2F1-4have been investigated using1H and19F-NMR. The fluoride complexation to Cm(III) wasstudied using time resolved fluorescence spectroscopy (TRLFS)and the stability constant for the CmF2+complex was determined at 25°C in 1.0 mNaCl.Keywords. Ternary complexes, actinides,dioxouranium(VI), curium(III), thorium(IV), ligand exchange,isomers, NMR, potentiometric titrations, aqueous solution,oxalate, picolinate, acetate, EDTA.
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| 42. |
- Aasa, Annika, 1963
(författare)
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User Defined Syntax
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes two examples of user defined syntax. The first, and most thoroughly investigated, is a new datatype construction, the conctype, the elements of which have a very flexible syntax. An embedded language can easily be introduced into a programming language using conctypes and computations are easily expressed using the concrete syntax and a special pattern matching form. The second example is user defined distfix operators which give a user possibility to extend the syntax for expressions in a programming language. We describe both a user's view and the implementation of these two examples. In both cases, context-free grammars serve as a basis for the definition of the new syntax. A problem that is investigated is how to disambiguate grammars with precedences. To see how this should be done we investigate which language a grammar together with precedence rules defines. For a sub-class of context-free grammars we give a predicate that defines the precedence correct syntax trees according to some precedence rules. We also give an algorithm that transforms such a grammar to an ordinary unambiguous context-free grammar and prove the correctness of the algorithm. We use the algorithm in our implementation of distfix operators. For more general grammars, we isolate one kind of ambiguity which is suitable to resolve with precedence rules. We define the generated language for such a grammar by an attribute grammar. This approach of resolving ambiguity is used in the implementation of conctypes.
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| 43. |
- Aasa, Jenny, 1978-
(författare)
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Cancer Risk Assessment of Glycidol : Evaluation of a Multiplicative Risk Model for Genotoxic Compounds
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Humans are exposed to chemical compounds in everyday life, both from the environment and from endogenous processes. Some compounds constitute a risk for cancer development. One such compound is glycidol, which is genotoxic and an animal carcinogen. It is the model compound of this work, partly due to its presence in food. Glycidol, often together with 3-monochloropropane-1,2-diol (3-MCPD), occurs in the form of esters particularly in refined cooking oils, which are used in a variety of food products. The esters are hydrolyzed in the gastrointestinal tract to form glycidol (and 3-MCPD).The aim of the thesis has been to evaluate an approach for cancer risk estimation of genotoxic carcinogens based on a multiplicative (relative) risk model and genotoxic potency. Further, the aim was to estimate the cancer risk for exposure to glycidol via food. Measurement of the internal doses (concentration × time) of glycidol in the studied biological systems, including humans, has been crucial. Glycidol is electrophilic and forms adducts with nucleophilic sites in proteins and DNA. The doses of glycidol were quantified by mass spectrometry: in vivo from adduct levels to hemoglobin (Hb); in vitro from adducts to cob(I)alamin.The first part of the thesis concerns the genotoxic potency (genotoxic response per internal dose) of glycidol, measured in vitro by mutation studies and in vivo by micronuclei as a biomarker for genotoxicity (short-term studies in mice). The results were compared to that of ionizing radiation, used as a standard, to estimate the relative genotoxic potency of glycidol: 10 and 15 rad-equ./mMh from mutations and micronuclei, respectively. No induction of micronuclei was observed for the related compound 3-MCPD.Tumor incidence from published carcinogenicity studies of glycidol in mice and rats, together with the measured in vivo doses, was evaluated with the relative cancer risk model. A good agreement between predicted and observed tumor incidence was shown, and no significant difference of the obtained cancer risk coefficients (risk per dose) between mice (5.1 % per mMh) and rats (5.4 % per mMh) was observed. The overall results support that the relative risk coefficient (β) is independent of sex, tumor site, and species, and indicated that it can be transferred also to humans. The doubling dose, expressed as 1/β, is the dose that is required to double the background tumor incidence. The mean of the doubling doses from mice and rats (19 mMh) was assumed valid for risk estimation for humans. Transfer of β of glycidol to rad-equ. via its relative genotoxic potency showed a risk coefficient in agreement with the relative cancer risk coefficient of ionizing radiation.In the final work, the lifetime (70 years) in vivo doses of glycidol were calculated from measured Hb adduct levels in blood from 50 children and 12 adults, and compared to the doubling dose. A fivefold variation was observed in the in vivo doses. The estimated lifetime excess cancer risk from glycidol exceeds 1/1000. This is much higher than what is considered as an acceptable risk.To conclude, the multiplicative (relative) risk model together with relative genotoxic potency is promising to use in an approach for cancer risk estimation and in line with 3R (reduce-refine-replace) initiatives.
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| 44. |
- Aasa, Mikael
(författare)
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Reperfusion therapy in acute ST-elevation myocardial infarction : a comparison between primary percutaneous intervention and thrombolysis in a short- and long-term perspective
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Approximately 35,000 people suffer from a heart attack in Sweden annually. Among them, approximately 8000 are diagnosed with a ST-elevation myocardial infarction (STEMI) where timely reperfusion has been shown to save lives. Previous studies that have compared the existing reperfusion strategies, thrombolysis (TL) and primary PCI (PPCI), made use of treatment regimens that since have been improved with the use of mechanical and medical adjunctives. The objective of this thesis was to compare both of these strategies employing updated regimens in accordance to current guidelines with respect to; 1) efficacy in restoring blood flow and myocardial perfusion, 2) clinical outcome and 3) cost-effectiveness. Methods and results: Between November 2001 and May 2003, 205 patients with STEMI were randomized to PPCI with adjunctive abciximab or TL. The low molecular weight heparin enoxaparin was used as anticoagulant in both groups. In 42% treatment was initiated in the pre-hospital phase. The primary end points were the rate of STsegment resolution (STRES) ≥ 50% 120 minutes after inclusion and the rate of normalized (TIMI 3) flow in the infarct related vessel 5-7 days after treatment, serving as surrogates for a beneficial outcome. Secondary end points were the ability to restore myocardial perfusion evaluated angiographically by TIMI Myocardial Perfusion Grade (TMPG) 5-7 days after inclusion in the study, clinical events at 30 days and one year cost-effectiveness. The patients were followed prospectively for one year and, in addition, information on survival status and major clinical events was collected from national registries for an extended follow up period of a median of 5.3 years. STRES≥ 50% was achieved in 68% following PPCI and 64% after TL (n.s.). However, the TIMI 3 rate was higher after PPCI compared to TL (71% vs. 54%, p=0.04). TMPG tended to be better in the PPCI group than in the TL group. An analysis of the evolution of TMPG in the PPCI cohort revealed that there was a significant improvement of myocardial perfusion in the week following PPCI. Thirty day mortality rates were low and similar in the groups. At one year PPCI was tended to be less costly ($-2,505) than TL ($-2,505; n.s.), mainly due to higher costs for re-hospitalizations in the TL group. Primary PCI also lead to an insignificant gain in quality-adjusted survival (0.031 QALYs). A bootstrap analysis indicated that PPCI has a high probability of being cost-effective when a threshold value of $50,000 is employed. A survival analysis at 5.3 years showed a significant benefit from PPCI in terms of the combination of all-cause death and recurrent infarction (p=0.03) as well as for cardiac mortality alone (p=0.02). Conclusion: Primary PCI is more efficient than thrombolysis in re-establishing antegrade flow in the infarct- related artery and offers a better long term clinical outcome with respect to major cardiac events without an increase in societal costs. Thus, based on the conditions under which this study was performed, primary PCI is a more efficient alternative than thrombolysis for the treatment of ST-elevation myocardial infarction.
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| 45. |
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| 46. |
- Aasa, Ulrika
(författare)
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Ambulance Work : Relationships between occupational demands, individual characteristics and health-related outcomes
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although musculoskeletal disorders (MSDs) and other health complaints are an occupational problem for ambulance personnel, there is a lack of knowledge regarding work-related factors associated with MSDs and other health complaints. The overall aim of this thesis was to investigate the relationships between occupational demands, individual characteristics and health-related outcomes among ambulance personnel. A random sample of 234 female and 953 male ambulance personnel participated in a national questionnaire survey on work-related factors, and musculoskeletal and other health complaints. Physical demands was associated with activity limitation due to neck-shoulder and low-back complaints among the female personnel. Among the male personnel, physical demands was associated with low-back complaints and activity limitation due to low-back complaints. Psychological demands was significantly associated with neck-shoulder complaints, sleeping problems, headache and stomach symptoms among both female and male ambulance personnel. Worry about work conditions was associated with musculoskeletal disorders and sleeping problems, headache and stomach symptoms. A local sample of 26 ambulance personnel was followed during a 24-hour work shift and for the next two work-free days. Subjective stress- and energy levels, and cortisol levels were measured at regular intervals, and heart rate was registered continuously by electrocardiogram (ECG). Autonomic reactivity to standardized tests before (pre-work) and at the end of the work shift (post-work) was also investigated. For the whole group, baseline values of heart rate were higher pre-work than post-work, but autonomic reactivity did not differ. Increased reactivity to the mental test, modest deviation in heart rate variability (HRV) pattern during the late night hours at work and higher morning cortisol values during work than during leisure time were observed in personnel with many health complaints, but not among their co-workers without or with few complaints. Ambulance personnel with many health complaints also reported higher psychological demands and tended to be more worried about work conditions. Heart rate (HR), lactate level (LL) and perceived exertion (RPE) were investigated in 17 female and 48 male ambulance personnel during a simulated standardized work task “carry a loaded stretcher”. The ambulance personnel had to carry the loaded stretcher (920 N) up and down three flights of stairs twice. The high physiological strain (HR, LL, RPE) for the male, and near or at maximal strain for the female ambulance personnel, implied the importance to identify what kind of physical capacity is most important for ambulance personnel. Therefore, the explained variance of developed fatigue by tests of cardiorespiratory capacity, muscular strength and endurance, and coordination was investigated. The results showed that VO2max and isometric back endurance were important predictors for development of fatigue when carrying a loaded stretcher. The influence of body size on the relationships between maximal strength and functional performance was investigated in a methodological study. The results confirm that the assessment of physical performance could be confounded by the body weight. Therefore, the models for explaining development of fatigue when carrying the loaded stretcher were adjusted for height and weight. Including height in the models significantly increased the explained variance of accumulated lactate among female, but not among male personnel. Lactate levels were higher among short compared to tall female personnel. Weight had no effect on any of the models. In conclusion, the national survey showed that self-reported physical demands was a risk factor of having MSDs, and that self-reported psychological demands and worry about work were important risk factors of having MSDs and other health complaints. Stress monitoring of ambulance personnel during work and leisure time showed that physiological and subjective stress markers did not show any differences between the 24-hour ambulance work shift and leisure time afterwards. However, ambulance personnel with many health complaints had certain physiological changes during the work shift in comparison with the next two work-free days. The physiological and subjective responses during carrying a loaded stretcher, especially among the female ambulance personnel, showed that female and male ambulance personnel could be exposed to internal exposures at different levels when performing the same work task. A better understanding of the relationships between occupational demands and health-related outcomes require further studies on age- and gender matched groups in long-term perspective studies.
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| 47. |
- Aase, Karin
(författare)
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On vascular endothelial growth factor B and platelet-derived growth factor C : two members of the VEGF/PDGF family of growth factors
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular endothelial growth factors (VEGFs), platelet-derived growth factors (PDGFs) and their receptors are important for normal development. They have also been implicated in many pathological conditions. VEGFs have been shown to play an important role in the development of both blood and lymphatic vessels. PDGFs on the other hand, are important regulators of the connective tissue cells of both the vascular network and other organs systems. The focus of the work presented in this thesis has been to elucidate the role of two members of the VEGF/PDGF family of growth factors, namely VEGF-B and PDGF-C. Embryonic analysis at the mRNA and protein level showed that VEGF-B was expressed in several organs, with highest expression in the developing muscles. VEGF-B was not detected in endothelial cells, where its receptor VEGFR-1 is expressed, which suggested that VEGF-B acts in a paracrine way. The expression of the two isoforms, VEGF-B167 and VEGF-B186 were investigated using techniques that can distinguish the two isoforms. The results showed that the VEGF-B167 isoform is predominantly expressed in most tissues. The VEGF-B186 isoform is expressed at lower levels and only in a limited numbers of organs. Moreover, the VEGF-B186 isoform is upregulated in mouse and human tumour cell lines and primary tumours compared with their corresponding normal tissues. These data suggest a fine genetic control of the expression of the two isoforms of VEGF-B, implying tissue- and cell-specific roles for the two VEGF-B isoforms. To elucidate the function in vivo, a VEGF-B knockout mouse strain was generated. The results showed that VEGF-B is not required for normal development of the cardiovascular system or for angiogenesis in adults. However, adult VEGF-B deficient mice have an atrial conduction abnormality characterised by a prolonged PQ interval in the electrocardiogram; thus VEGF-B appears to be required for normal heart function in adult animals. The second growth factor, PDGF-C contains a domain structure not present in other members of the VEGF/PDGF family. Following the signal sequence, PDGF-C contains an N-terminal CUB-domain and, in the C-terminus, the VEGF/PDGF homology domain. PDGF-C is synthesised as an inactive precursor protein that has to be proteolytically processed in the N-terminus before it can bind and activate its receptor, PDGFR-a. Expression analysis during mouse development suggests that PDGF-C acts in both paracrine and autocrine ways.
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| 48. |
- Aasheim, Vigdis
(författare)
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Becoming a mother at an advanced age : pregnancy, outcomes, psychological distress, experience of childbirth and satisfaction with life
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objectives of this thesis were to investigate adverse pregnancy outcomes, and pregnancy and psychological experiences in women who become mothers in the later phase of the reproductive period. The age of first-time mothers has increased in most high-income countries in recent decades. Research into the postponement of childbirth phenomenon has predominantly focused on pregnancy and infant outcomes, and only to a lesser degree on psychological aspects of postponement. Study I is a population-based register study including 955 804 primiparous women from the Swedish and Norwegian Medical Birth Registers who gave birth between 1990-2010. It investigates the risk for preterm birth, infants small for gestation age, low Apgar score, stillbirth and neonatal death in women aged 30-34 years, 35-39 years and ≥40 years compared with women aged 25-29 years. Study I also compares risks associated with advanced maternal age with those associated with smoking and being overweight or obese. The adjusted Odds Ratios (aOR) of all outcomes increased with maternal age in a similar way in Sweden and Norway and the risk of fetal death already at age 30-35 years (Sweden OR 1.24; 95% CI 1.13-1.37, Norway aOR 1.26; 95% CI 1.12-1.41). The Swedish data showed that a maternal age of ≥30 years was associated with the same number of additional cases of fetal deaths as being overweight/obesity (251) and a larger number than smoking (67) compared with normal weight, nonsmokers aged 25-29 years, and estimated over the entire time period. Studies II-IV are longitudinal prospective population-based cohort studies based on data from the National Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Study II investigated psychological distress in 19 291nulliparous women from mid pregnancy to 18 months after the birth, comparing women of ≥32 years with those of 25-31 years. It was found that women in the oldest group had a slightly increased risk of psychological distress during pregnancy and the first 18 months of motherhood. Study III investigated 30 065 women’s experience of childbirth at six months postpartum in relation to antenatal expectations, using the same age categories as in Study II. The oldest women had a marginally higher risk of experiencing childbirth as worse than expected. Older women seemed to manage better than younger women when having an operative delivery. Study IV investigated 18 565 women’s satisfaction with life during pregnancy and the first three years of motherhood, comparing women of 32-37 years and ≥38 years respectively with the same reference groups as above. Women in the two oldest age groups reported a slightly lower degree of satisfaction with life, and the age effect was greatest three years after the birth. In conclusion, this thesis shows that the postponement of childbirth in high-income countries may increase the risk of adverse pregnancy outcomes at an earlier age than has previously been reported, and that it may have marginal negative effects on women’s emotional wellbeing and satisfaction with life. These findings should be included when giving reproductive health information to young people.
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| 49. |
- Aasi, Parisa, 1986-
(författare)
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Information Technology Governance: The Role of Organizational Culture and Structure
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Information Technology Governance (ITG) is among the most important challenges for the managers today. IT is not anymore just a supportive tool but also a strategic driver for the businesses. In the dynamic and competitive world of today, it is crucial for organizations to know how to govern IT rather than just to use it. IT governance deals with specifying responsibilities and decision rights to encourage the desirable behaviour from IT and generate value from IT investments. IT governance can impact the overall performance of organizations, however there are still difficulties in understanding IT governance and the factors that may influence it.Organizational culture and structure are among the factors that have significant influence on many issues in an organization. According to previous research, organizational culture and structure need to be considered when implementing IT governance. However, there is a lack of research focusing on how organizational culture and structure can influence IT governance performance and implementation. Thus, the main research question addressed in this thesis is: How are organizational culture and structure related to IT governance? To address this question, this research has performed literature reviews and conducted case studies to investigate the role of organizational culture and structure on IT governance. As the first step, the previous literature was reviewed to find the gaps in the research on culture and IT governance. As the next step, four case studies were conducted to explore the influence of organizational culture and structure on IT governance. Two case studies have investigated the relation between organizational structure and IT governance implementation and performance in large organizations; and two other case studies investigated on how different types of organizational culture influence IT governance performance outcomes.The results of this research respond to the research question by specifying the role of culture in IT governance through a categorization of prior research both from research and practice perspectives; specifying the influence of different organizational culture types on IT governance performance outcomes in different organizations; and by specifying IT organizational structure relationship with IT governance performance outcomes and IT governance implementation.The research presented in this thesis provides both theoretical and empirical contributions to the IT governance research and practice.
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| 50. |
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