| 1. |
- Sandstedt, Mårten, 1972-
(författare)
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Computed Tomography of the Coronary Arteries : Developmental and Prognostic Investigations
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Computed tomography (CT) is an increasingly used modality for investigations of patients with suspected coronary artery disease (CAD). Technical advances could improve diagnostic accuracy and lead to clinical workflow improvements. Also, more prognostic information can optimize clinical follow-up strategies and treatments.The general aim of this thesis was to explore the use of CT for CAD investigations. Three studies aimed to examine new technologies, including the evaluation of an on-site, computed tomography-based fractional flow reserve (CT-FFR) software (study I), the evaluation of an AI-based, calcium scoring computed tomography (CSCT) software (study III), and the evaluation of an photon-counting detector (PCD)-CT (study IV). One study aimed to evaluate the long-term prognostic value of coronary computed tomography angiography (CCTA) in symptomatic patients with no history of CAD (study II).The software evaluation studies (study I and III) and the prognostic study (study II) utilized CT data from clinical patients, while the PCD-CT evaluation study (study IV) used CT data from cadaveric specimens. The performances of both software programs were compared with standard references, being represented by fractional flow reserve (FFR) measurements (study I), and coronary artery calcification (CAC) scores from a semi-automatic software (study III), respectively. The PCD-CT performance on CAC quantification was compared with corresponding results from an energy integrating detector (EID)-CT, using micro-CT as the standard reference (study IV). The prognostic study merged registries to identify major adverse cardiac events (MACE), having a follow-up time of up to 7.5 years (study II).The CT-FFR and CSCT software correlation and agreement to corresponding standard references were good and excellent, respectively. Also, both software programs had time-saving potential (study I and III). The CAC quantification was more accurate using PCD-CT than EID-CT (study IV). The prognosis was excellent in patients with normal coronary arteries, and progressively impaired in non-obstructive and obstructive CAD (study II).The results in this thesis convey developmental, technical CT technology advances for CAD investigations. In addition, prognostic follow-up data is communicated. The results may benefit patients by an increased accuracy in the CT evaluation of CAD and can contribute to improve clinical follow-up strategies. Furthermore, the results suggest possibilities to improve the workflow in clinical radiology, which potentially could impact health care costs.
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| 2. |
- 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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| 3. |
- Kentson, Magnus
(författare)
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Fatigue and Peripheral Muscle Dysfunction: Studies on Vitamin D Status, Muscle Metabolism and Systemic Inflammation in Patients with COPD : Aspects of COPD severity beyond FEV1 and exacerbations
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe severity of Chronic Obstructive Pulmonary Disease (COPD) is usually described in terms of forced expiratory volume in one second (FEV1) and number of exacerbations. However, COPD is a complex disease with different ways of expression, involving pulmonary symptoms, extra pulmonal manifestations and comorbidities, which altogether affect the patient by contributing to reduced functional capacity, increased shortness of breath, reduced health-related quality of life and increased mortality. Systemic inflammation is common in COPD and can potentially constitute a link between the lungs and other organs. The aim of this thesis was to broaden the aspects of COPD severity beyond FEV1 and exacerbations by studying fatigue, the role of vitamin D, nutritional factors, systemic inflammation and peripheral muscle function in patients with COPD. Methods and ResultsIn paper I, we included 101 patients with COPD, and 34 control subjects. Assessment of experience of fatigue, functional limitation due to fatigue, and the relationships to physiological, psychological and situational variables and quality of life (QoL) were evaluated. We found that experience of fatigue was highly prevalent (72% versus 56% in control subjects) and a troublesome symptom in COPD. Patients with COPD and fatigue had lower lung function, shorter walking distance, more dyspnoea, anxiety and depressive symptoms and poorer health status compared to patients without fatigue (all p < 0.01). Several contributing factors were identified to experience of fatigue and functional limitations of fatigue with dyspnoea, depressive symptoms and insomnia as the most prominent factors. No clear association with systemic inflammation was found. Paper II evaluated vitamin D status in 66 patients with advanced COPD (28 with long-term oxygen therapy (LTOT)) and 47 control subjects. 25-hydroxyvitamin 25(OH)D were deter-mined in early fall in a short period of seven weeks. Questionnaires about COPD symptoms, general health, lifestyle, dietary habits and QoL were answered. Lung function tests and blood sampling including systemic inflammatory markers, carotenoids and protein carbonylation (PC) were assessed. The peak annual 25(OH)D of COPD patients was significantly lower than in the control subjects, but there was no significant difference between COPD patients with and without LTOT. Among vitamin D-deficient COPD patients, 25(OH)D correlated positively with lung function, blood oxygenation, food portion size, Mediterranean Diet Score and Ultra-violet Score and negatively with dyspnoea and DOSE-index, a composite index for COPD se-verity. Ongoing vitamin D supplementation was the single most important intervention to maintain 25(OH)D levels <50 nmol/L. In paper III, we evaluated in the same cohort as paper II oxidative damage and levels of carotenoids. Patients with COPD (±LTOT) did not demonstrate increased oxidative damage. Com-pared with the control group, levels of several carotenoids were significantly lower in COPD, and the diet contained significantly less fruit and vegetables. Lycopene correlated positively with saturation and lutein correlated positively with some inflammatory markers but negatively with IL-6, an important marker for systemic inflammation. The study highlights the importance of dietary factors in COPD. In paper IV, 32 patients with COPD answered questionnaires, and were subjected to lung function tests and blood analysis including systemic inflammatory markers. Magnetic resonance imaging (MRI) for analysis of whole-body and thigh muscle composition was performed. Bioenergetics in the resting thigh muscle, (PCr/Pi ratio), were analysed using 31phosphorus magnetic resonance spectroscopy (31P-MRS). We found that adverse muscle composition was common in the COPD group. Clinical characteristics reflecting COPD severity were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa correlated positively to systemic inflammatory markers, negative to physical activity and PCr/Pi ratio. We compared the COPD group with a virtual control group from UK Biobank (n= 3200). ConclusionsSevere COPD is much more than airway obstruction and exacerbations. The presence of fatigue is associated, as well as vitamin D status and nutritional factors, with important clinical out-comes reflecting COPD severity. Adverse muscle composition is common in COPD and there seems to be a link between systemic inflammation, muscle fat infiltration and bioenergetics.
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| 4. |
- Nahlen Bose, Catarina
(författare)
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Coping and emotional well-being in patients with chronic heart failure
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Chronic heart failure (CHF) is a serious illness, with a profound impact on the patient. Poor health-related quality of life (HRQoL) as well as anxiety and depression are prevalent in CHF and predict mortality and rehospitalization, yet, psychosocial factors are infrequently treated and cared for.Aim: To gather scientific evidence on illness perception and coping strategies to predict emotional well-being in patients with CHF and to establish a measurement model of coping strategies. Furthermore, to evaluate a nurse-led psychoeducational intervention, Coping Effectiveness Training (CET) adapted for patients with CHF.Methods: Studies I-III were cross sectional. Study IV was a randomized controlled trial aimed to improve emotional well-being (one-year follow-up). All studies used patient reported outcome measures and clinical data via medical journals.Results: Younger age and male gender were associated with higher levels of alcohol usage and/or drugs to cope, p < 0.01. Poor sense of coherence was associated with maladaptive coping (I). A four factorial model of Brief COPE displayed the best psychometric properties (II). Avoidant coping influenced negative affect (NA) (I), worse HRQoL (II) and greater anxiety and depression (III). CET (IV) improved personal control in the intervention group (IG) compared to the control group (CG), p = 0.036. Improved scores for the IG were detected in emotional well-being and HRQoL, p = ns. The IG demonstrated reduced NA, p = 0.022, excluding cases with clinical anxiety and depression. Time to cardiovascular readmission or death was non-significantly lower in the IG vs the CG (Hazard ratio 0.58 [0.29-1.18]) adjusted p = 0.135.Conclusions: Personal resources seemed to influence the coping strategies used by patients with CHF. Avoidant coping had an adverse influence on emotional wellbeing and illness perception in CHF. The perceived sense of control and illness burden were of importance for emotional well-being. A CET intervention for patients with CHF increased sense of control over the illness. CET also reduced NA in patients with no or mild symptoms of anxiety and depression.
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| 5. |
- Borsgård, Gustav, 1984-
(författare)
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Litteraturens mått : politiska implikationer av litteraturundervisning som demokrati- och värdegrundsarbete
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Avhandlingens syfte är att undersöka politiska implikationer av idén om litteraturundervisning som demokrati- och värdegrundsarbete i förhållande till det ideal om mätbar kunskap som präglar samtidens utbildningspolicydiskurser. Det som står i fokus är 2011 års gymnasiereform, som tolkas mot bakgrund av en genomgripande förändring av den globala och europeiska utbildningspolicydiskursen från och med millennieskiftet. Avhandlingen undersöker hur subjekt, samhälle och relationen däremellan förstås av aktörer inom policy, forskning och av lärare. Analysen är uppdelad i en transnationell nivå, en nationell nivå och en didaktisk nivå. Avhandlingen visar också hur policydiskurser rekontextualiseras mellan de olika nivåerna.Vad gäller den transnationella nivån visar avhandlingen hur EU:s utbildningspolicy lägger stor vikt vid utbildningens samhällsekonomiska funktion samtidigt som demokratiska aspekter av utbildning tonas ned. EU framhäver även värdet av entreprenörskap och kopplar kreativitetsfrämjande aspekter av konst och humaniora till arbetsmarknaden och ekonomisk tillväxt. I ramverket till OECD:s PISA-studier lyfts reading literacy fram som viktigt för såväl kritiskt tänkande som ekonomisk utveckling. Läsningen av skönlitteratur specifikt definieras dock som en individuell angelägenhet och fritidsaktivitet. Genom att anlägga ett psykologiskt perspektiv på skönlitteraturen och lyfta fram den som en individuell – snarare än samhällelig eller strukturell – angelägenhet sker en av avpolitisering av litteraturläsningens emancipatoriska värde.Vad gäller den nationella nivån visar avhandlingen hur skolans syn på demokrati och litteratur har genomgått förändringar sedan 1940-talet. Framför allt har demokratin gradvis kommit att förstås som ett ”fullbordat” projekt, snarare än som någonting som kan utvecklas eller fördjupas. Med hjälp av Gert Biestas tre dimensioner av medborgarfostran gör avhandlingen en kritisk genomgång av tongivande teorier om litteraturundervisning som demokrati- och värdegrundsarbete, och argumenterar för att merparten av teorierna fokuserar på medborgarfostran som socialisering snarare än subjektivering. Med andra ord innebär demokratiarbetet en anpassning till, snarare än en kritik av, det omgivande samhället. Avhandlingen använder sig också av Peter Dahler-Larsens begrepp konstitutiva effekter för att visa hur 2011 års gymnasiereform tonade ned demokratiska aspekter av litteraturundervisning i förhållande till den föregående läroplanen.Vad gäller den didaktiska nivån använder sig avhandlingen av kvalitativa lärarintervjuer som visar hur lärares didaktiska val ramas in av styrdokumenten och olika administrativa uppgifter. Avhandlingen argumenterar för att lärarnas tolkning av styrdokumenten innebär ett rekontextualiseringsfält inom vilket lärarna förhandlar med läroplanens bestämmelser. I flera fall väljer lärarna att bortse från aspekter av styrdokumenten för att i stället grunda sina didaktiska val på den egna lärarerfarenheten. Det avslutande kapitlet argumenterar för att en viktig politisk implikation av idén om litteraturundervisning som demokrati- och värdegrundsarbete – i synnerhet när den kombineras med strävan efter mätbarhet – är att utbildningens subjektiveringsdimension marginaliseras. Avhandlingen argumenterar för att utbildning skulle kunna handla mindre om fastslagna värden och mätbara kompetenser, och mer om elevers behov av att lära sig hantera icke-vetande.
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| 6. |
- Klasson, Maria, 1977-
(författare)
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Cobalt in the hard metal production industry : exposure via inhalation and skin and the inflammatory response in human keratinocytes
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cobalt is a strong sensitizer and can cause contact allergy upon both direct contact or from airborne exposure on the skin. In the skin, keratinocytes are the first cells to come in contact with the metal and will react and respond to the danger by triggering an alarm system resulting in an inflammatory response in the skin. Keratinocytes have been shown to produce IL-1β, which is one of the most potent inflammatory agents in our body and is associated with a variety of diseases.The aims of this thesis was to investigate cobalt air concentrations for different particle fractions for possible use as proxies for other article measures and to examine if cobalt skin and inhalable air exposure contributes to uptake. Also, to investigate the effect of cobalt on cultured human keratinocyte cell viability, pro-inflammatory cytokine/chemokine release and NLRP3 inflammasome activation using cells cultured at low or high calcium (the latter yielding a more differentiated cell type).Air exposure to cobalt was found in all departments and for all work tasks in the hard metal production facility and exposures were in general below the Swedish OEL for inhalable cobalt. The highest exposure levels were found in the powder production department and for laboratory and furnace work. Good correlations for the mass based measures enable us to use the findings for future references. When personal inhalable air levels of cobalt, cobalt skin levels skin and biological monitoring of cobalt in blood were analysed, the skin exposure was determined to be import as a route of uptake. Skin exposure to cobalt in the hard metal industry, could further affect the total uptake in the same order of magnitude as air exposure. In vitro investigations of cobalt using the human keratinocyte cell line HaCaT, showed that CoCl2 triggered an alarm system in cells where the proinflammatory cytokines/chemokines IL-6, CXCL8 and CCL2, known to be involved in skin inflammation, were secreted in a time- and dosedependent manner. Comparing HaCaT cells of high- and low differentiation stages indicated that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis. CoCl2 exposure also resulted in secretion of the proinflammatory cytokines IL-1β and IL-18, and caspase-1, which indicates activation of the NLRP3 inflammasome in the cells. CoCl2 regulates the inflammasome both as primer and as an activator. Our mRNA results indicates a negative feedback mechanism in the inflamamsome due to the exposure. The inflammatory response in general is more dose than time dependent, which be important for understanding the mechanisms of allergic sensitization.
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| 7. |
- Lundgren, Linda, 1973-
(författare)
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Incidental Gallbladder Cancer : Incidence, predictors, management and outcome in a Swedish population
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cholecystectomy is a common surgical procedure and incidental gallbladder cancer is a rare and unexpected finding at a cholecystectomy performed upon benign indications. Whether to perform routine or selective histopathology of the gallbladder specimen is still a subject for discussion. The prognosis of gallbladder cancer is largely affected by tumour stage and treatment.Aims: The overall aim was to study whether routine histological examination of the gallbladder specimen is of clinical and health economic value; determine if there are any predictive factors of incidental gallbladder cancer at benign cholecystectomy and compare the management and outcome of incidental gallbladder cancer patients in Sweden.Methods: All studies were based on registry data from GallRiks (The Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography) between 2007 and 2016, with some modifications between studies. Complemental cross-linkage was made to national registries, and medical records were reviewed. Papers I, II and III were population-based observational studies with prospectively and retrospectively collected data. Paper IV was a health economic evaluation based on the results from papers I and III.Results and conclusions: Hospitals submitting >75 per cent of gallbladder specimens diagnosed a higher proportion of incidental gallbladder cancer than did hospitals submitting ≤25 per cent of samples (paper I). Incidental gallbladder cancer was more prevalent in older patients, women and patients with acute or previous cholecystitis, as well as ongoing jaundice. The risk model based on predictive preoperative factors was further improved by adding a macroscopic assessment of the gallbladder (paper II). Predictive factors for gallbladder cancer appeared to have an impact on which specimens were submitted in hospitals with a selective approach of histopathology (paper I). For pT2 and pT3 patients, re-resection improved diseasespecific survival, although these groups differed in terms of age and comorbidity (paper III). Residual disease was an independent factor for impaired survival. A change to routine histopathology of gallbladder specimens in Sweden would lead to increased costs with little improved health outcomes. Instead, a more standardized approach to selective histology would be needed (paper IV).
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| 8. |
- Wärnheim, Alexander
(författare)
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Holistic evaluation and testing of coil coatings
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Coil coatings are durable organic coatings used to protect metal sheets from corrosion and improve their aesthetic properties. Because of their extensive use, coil coatings have long been of interest for industrial and academic researchers. This interest has recently been furthered by a societal push towards the replacement of fossil-based raw materials with alternatives that are biobased and renewable.The aim of this licentiate thesis is to demonstrate how analyses on the macro-, micro-, and nanoscale can be used to better understand the degradation process of polyester-based coil coatings. The included manuscripts showcase methods for evaluating and comparing different coil coating formulations and for verifying accelerated weathering techniques.Multiple techniques, focusing on infrared (IR) spectroscopy and atomic force microscopy (AFM), were used to analyze coating systems before and after different types of weathering. IR data acquired from techniques without spatial resolution, such as attenuated total reflection (ATR) and photoacoustic spectroscopy (PAS) have been expanded upon with spatially resolved focal plane array (FPA) and s-SNOM (scattering-type scanning near-field optical microscopy) measurements. Spatially resolved chemical data of coating cross sections were acquired and used to assess how the degradation at the surface and in the bulk was related. Additionally, differences between the degradation behavior of a standard fossil-based coating and a similar coating with biobased components as well as differences between the degradation caused by artificial and natural weathering was discussed.Nanoscale mechanical measurements of simplified coating surfaces showed that weathering increased nanomechanical stiffness and led to homogenization of mechanical properties on the local level. In addition, measurements with nanoscale FTIR correlated with macroscale FTIR. Even relatively minor changes in band intensities could be tracked on a local scale. Although the simplified samples were chemically homogeneous, nanoscale FTIR shows great promise for the assessment of local degradation of full systems.
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| 9. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 10. |
- Damian Risberg, Emiliana, 1978-
(författare)
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Structure and bonding of sulfur-containing molecules and complexes
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Synchrotron-based spectroscopic techniques enable investigations of the many important biological and environmental functions of the ubiquitous element sulfur. In this thesis the methods for interpreting sulfur K-edge X-ray absorption near edge structure (XANES) spectra are developed and applied for analyses of functional sulfur groups. The influence of coordination, pH, hydrogen bonding, etc., on the sulfur 1s electronic excitations is evaluated by transition potential density functional theory. Analyses have been performed of reduced sulfur compounds in marine-archaeological wood from historical shipwrecks, including the Vasa, Stockholm, Sweden and the Mary Rose, Portsmouth, U.K.. The accumulation of sulfur as thiols in lignin-rich parts of the wood on the seabed is also a probable pathway in the natural sulfur cycle for how reduced sulfur enters fossil fuels via humic matter in anaerobic marine sediments. Sulfur K-edge XANES spectra for several biochemical model compounds and for coexisting isomeric sulfur species in cysteine and sulfite(IV) aqueous solutions have been analyzed with the aid of theoretical calculations. Cysteine derivatives are important for biochemical detoxification, and mercury(II) cysteine complexes in solution have been structurally characterized by means of Extended X-ray Absorption Fine Structure (EXAFS), Raman and 199Hg NMR spectroscopy. Lanthanoid(III) ions were found to coordinate eight dimethyl sulfoxide oxygen atoms in a distorted square antiprism in the solid state and in solution, by combining crystallography, EXAFS, XANES and vibrational spectroscopy. The mean M-O bond distances for the disordered crystal structures are in good agreement with those from the lattice-independent EXAFS studies. The different sulfur K-edge XANES spectra for the dimethyl sulfoxide ligands in the hexasolvated complexes of the trivalent group 13 metal ions, Tl(III), In(III), Ga(III) and Al(III), were interpreted by theoretical calculations.
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