| 1. |
- Gustafsson Bragde, Hanna, 1979-
(författare)
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Biomarkers of Inflammation and Intestinal Mucosa Pathology in Celiac Disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy triggered by gluten. The only currently available treatment is complying with a lifelong gluten-free diet, which should not be commenced before a CD diagnosis has been established by diagnostic test results (including histopathologic assessment of small intestinal biopsies and CD-specific antibody levels). This makes diagnostic swiftness and accuracy important. In cases with low CD-specific antibody levels and/or low-grade intestinal injuries the diagnosis can be difficult to establish. The main objective of this thesis was to complement and improve CD diagnostics by identifying and implementing new biomarkers, mainly based on gene expression, in small intestinal biopsies and blood. In paper I, genes were selected to reflect villous height, crypt elongation, immune response, and epithelial integrity. The results showed that a subset of those genes could discriminate active CD mucosa from mucosa without CD-related changes and grade the intestinal injury. In paper III, an unbiased investigation of gene expression in CD mucosa was performed using transcriptome analysis. Active CD and non-CD mucosa showed differential expression in a subset of genes, and some were differentially expressed in CD mucosa before histopathologic assessment could confirm intestinal alterations compatible with a CD diagnosis. Gene set analysis revealed that there are many biological processes affected in CD mucosa, including those associated with immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation.In parallel, gene expression was investigated in stabilised whole blood. Blood is a more accessible sampling material than intestinal biopsies, and stabilised blood is suitable for routine diagnostics since transcript levels are preserved at sampling. In paper II, expressions from a selection of genes were quantified in stabilised whole blood (RNA) and/or plasma (protein). Three genes with differential expression in CD were identified. Compared to the CD-specific autoantibodies against tissue transglutaminase (anti-TG2) alone, the addition of the information from the new potential markers resulted in a nonsignificant contribution to the diagnostic capacity of anti-TG2. An unbiased investigation using transcriptome analysis (paper IV) showed that gene level expression differences in stabilised whole blood were small between CD and non-CD. However, expression differences on a gene set level could potentially be used in CD diagnostics. CD-associated biological processes suggested by the results included a pro-inflammatory response, negative regulation of viral replication, proliferation, differentiation, cell migration, cell survival, translation, and haemostasis.Expression analysis using real-time polymerase chain reaction (PCR) is easy to perform, with instrumentation available at most clinical laboratories. Although select solitary biomarkers could be very useful in the diagnosis of CD, basing gene expression profiles on pathway information instead of single genes might also disclose disease heterogeneity between patients and add stability to a diagnostic method based on gene expressions. In conclusion, the results of this work demonstrate that analysing the expression of a few small intestinal genes can complement CD diagnostics. The application of gene expression analysis in cases with minor small intestine histopathological changes shows promising results, but needs further investigations. Additionally, gene expressions in other inflammatory diseases of the small intestine need to be investigated and compared with CD to complete the picture. Moreover, the findings from this work give clues about the biological contexts in which CD resides, and the potential of gene expression in blood at a gene set level is of interest for further investigations.
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| 2. |
- Nilsson, Per, 1969-
(författare)
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Brukade bilder : Södra Skandinaviens hällristningar ur ett historiebruksperspektiv
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The timeframe of the south Scandinavian rock art tradition extends from c.1700/1600 to 300 /200 BC. The chronological boundaries of the rock art phenomenon thereby coincide roughly with the timeframe of the Nordic Bronze Age, and rock art figures have come to be understood and interpreted as a Bronze Age phenomenon. It is argued that a dominant Bronze Age narrative has come to direct the discourse and fieldwork alike towards a focus on the origin , rather than the use, of rock art. The rock carver’s intention with the image, explicitly or implicitly, has come to equate with its meaning. The aim of the thesis is to approach rock art figures from a different perspective, with the aim of understanding how south Scandinavian rock art has been used and interpreted over time. The question of what archaeological evidence the use of rock art may have left behind is taken up, and the archaeological excavations carried out at rock art sites in southern Scandinavia are summarized and discussed. The survey shows that finds and features date to some extent from the Bronze Age, yet most of the dateable evidence comes from periods after the tradition of creating new images had ended, especially the Early Iron Age. This phenomenon is of particular interest given the explicit uses of the past-perspective of the thesis. It is argued that some of the rock art sites were still being used during later prehistoric periods. Other examples of later period´s uses of rock art sites are presented and discussed, such as runic inscriptions on rock art panels as well as the use of rock art and cup-mark sites during historic times. A study of the chronological development of the rock art tradition in the Himmelstalund-region in the county of Östergötland is also presented, based on recently developed ship chronologies of rock art. The study shows that the earliest ship figures, which are found in the Himmelstalund area, were probably made in the Bronze Age period I/II. Yet the majority of the dateable ship figures date from the Bronze Age period II–III, after which the number of dateable ships declines in period IV, a development becoming even more prominent in period V-VI. Another theme discussed in the thesis is archaeology’s own uses of rock art and how this has affected the interpretations of the material. The thesis shows it is feasible to combine a discussion on the prehistoric use of rock art sites and images with a critical view of interactions between archaeological and antiquarian practice and the source material. It has also shown the potential for a broadened discussion, where we regard the use of rock art, during the Bronze Age as well as during later periods, as integral and essential to rock art research.
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| 3. |
- Abbasi, Saeed
(författare)
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Characterisation of airborne particles from rail traffic
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since the investigation of wear particles in rail transport started in late-1910s, the high mass concentration of these particles has raised worries among researchers concerned with air quality. However, effective action has yet to be taken because of lack of relevant knowledge. This thesis provides applicable information for the airborne wear particles in rail transport. Some aspects of their characteristics such as diameter size, mass concentration, number concentration, and morphology of particles were investigated in field tests and laboratory tests.The effects on particle characterisations from different operational conditions in the field tests, and applying different braking materials, conducting tests in different applied loads or sliding velocities in the laboratory tests were studied. The main advantage of conducting laboratory tests was to focus on studying particles from one source. The possibility of repetition, using high sensitive instruments and conducting tests at low costs are the other advantages of laboratory studies. Paper A describes how a pin-on-disc machine was used to reproduce similar real operational conditions during mechanical braking in a train. The results were validated by comparing the field tests results with the laboratory studies. The particles morphology and size distribution were also studied.Paper B presents a summary of field tests results. The effects of curve negotiating and applying braking in different real conditions were investigated with an on-board measurement.The element composition of the particles and their potential sources were also investigated outside of the particles morphologies.Paper C presents comprehensive results from laboratory studies on airborne particles from different braking materials. The differences in the particle characteristics in similar test conditions were attributable to different material compositions and dominant wear mechanisms. A new index was introduced in this paper and is suggested to be used as a qualitative factor with regard to the airborne wear particle emission rate.Paper D is a review of the recent studies of exhaust emission and non-exhaust emission from rail vehicles. A summary of results, measurements, adverse health effects, and proposed or applied solutions are reviewed in this paper.
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| 4. |
- Abenius, Erik, 1971-
(författare)
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Direct and Inverse Methods for Waveguides and Scattering Problems in the Time Domain
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Numerical simulation is an important tool in understanding the electromagnetic field and how it interacts with the environment. Different topics for time-domain finite-difference (FDTD) and finite-element (FETD) methods for Maxwell's equations are treated in this thesis. Subcell models are of vital importance for the efficient modeling of small objects that are not resolved by the grid. A novel model for thin sheets using shell elements is proposed. This approach has the advantage of taking into account discontinuities in the normal component of the electric field, unlike previous models based on impedance boundary conditions (IBCs). Several results are presented to illustrate the capabilities of the shell element approach. Waveguides are of fundamental importance in many microwave applications, for example in antenna feeds. The key issues of excitation and truncation of waveguides are addressed. A complex frequency shifted form of the uniaxial perfectly matched layer (UPML) absorbing boundary condition (ABC) in FETD is developed. Prism elements are used to promote automatic grid generation and enhance the performance. Results are presented where reflection errors below -70dB are obtained for different types of waveguides, including inhomogeneous cases. Excitation and analysis via the scattering parameters are achieved using waveguide modes computed by a general frequency-domain mode solver for the vector Helmholtz equation. Huygens surfaces are used in both FDTD and FETD for excitation in waveguide ports. Inverse problems have received an increased interest due to the availability of powerful computers. An important application is non-destructive evaluation of material. A time-domain, minimization approach is presented where exact gradients are computed using the adjoint problem. The approach is applied to a general form of Maxwell's equations including dispersive media and UPML. Successful reconstruction examples are presented both using synthetic and experimental measurement data. Parameter reduction of complex geometries using simplified models is an interesting topic that leads to an inverse problem. Gradients for subcell parameters are derived and a successful reconstruction example is presented for a combined dielectric sheet and slot geometry.
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| 5. |
- Coello Midence Balthasar, Zairis Aida
(författare)
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Insufficient water supply in an urban area - case study : Tegucigalpa, Honduras
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tegucigalpa, the capital of Honduras, has experienced an unsatisfied water demand during the last three decades. The state owned water utility in charge of the water supply of the country, SANAA, has faced this deficit by providing an intermittent water supply. The intermittent water supply has increased the gap between the rich and the poor, who cannot afford water storage facilities. Theories explain water scarcity either by low precipitation or by lack of investment in water structures. This thesis investigates the applicability of both explanations by quantifying the annual precipitation in the sub catchments with water supply potential for Tegucigalpa, and identifying the problems which caused the lack of investment into the water infrastructure. The analysis concluded that even if the annual precipitation is abundant, it is not evenly distributed in time and in space. Furthermore, it is argued that the financial limitations which hindered the lack of investment in water structures originated in the low tariffs imposed, and to the practices of the patronage system.
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| 6. |
- Falk, Erik, 1962-
(författare)
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Verbala förolämpningar i 1630-talets Uppsala : En historisk talaktsanalys
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates verbal insults recorded in judicial protocols in the Swedish university townUppsaladuring the 1630s. The aim of the study is to analyze insults as linguistic formulations and social acts in Early Modern Swedish society. The methodology of the study is guided by speech act theory and ethnography of communication in order to examine the lexical realizations of insults and verbal action in different speech communities.From a total of 652 protocols in two series of records from the city court and the university council inUppsalain the 1630s, sections of text were excerpted that registered insults. The material under investigation comprises 179 cases that contained 276 insults. The descriptive meta-linguistic expressions for insults are rich as well as varied, and the performed insults are reported with or without invectives and as direct or indirect speech.Clear patterns emerged in the investigation by performing various semantic-, pragmatic-, and discourse-level analyses of the judicial records. Insults among city people were commonly interpreted as truth-conditional representative speech acts and thereby were viewed as false accusations of various kinds. In the academic world, however, the truth value of the insult was of minor importance. The speech act was regarded mainly as an expressive utterance of anger and frustration.Through a comparison of the city and university judicial records, it is shown that the patterns of insults reveal a general semantic process in which primarily concrete, objective meanings come to fulfill increasingly interpersonal and pragmatic speech functions.
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| 7. |
- Gustafsson Bragde, Hanna, 1979-, et al.
(författare)
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Characterisation of gene and pathway expression in stabilised blood from children with coeliac disease
- 2020
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Ingår i: BMJ open gastroenterology. - : BMJ. - 2054-4774. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A coeliac disease (CD) diagnosis is likely in children with levels of tissue transglutaminase autoantibodies (anti-TG2) >10 times the upper reference value, whereas children with lower anti-TG2 levels need an intestinal biopsy to confirm or rule out CD. A blood sample is easier to obtain than an intestinal biopsy sample, and stabilised blood is suitable for routine diagnostics because transcript levels are preserved at sampling. Therefore, we investigated gene expression in stabilised whole blood to explore the possibility of gene expression-based diagnostics for the diagnosis and follow-up of CD.DESIGN: We performed RNA sequencing of stabilised whole blood from active CD cases (n=10), non-CD cases (n=10), and treated CD cases on a gluten-free diet (n=10) to identify diagnostic CD biomarkers and pathways involved in CD pathogenesis.RESULTS: No single gene was differentially expressed between the sample groups. However, by using gene set enrichment analysis (GSEA), significantly differentially expressed pathways were identified in active CD, and these pathways involved the inflammatory response, negative regulation of viral replication, translation, as well as cell proliferation, differentiation, migration, and survival. The results indicate that there are differences in pathway regulation in CD, which could be used for diagnostic purposes. Comparison between GSEA results based on stabilised blood with GSEA results based on small intestinal biopsies revealed that type I interferon response, defence response to virus, and negative regulation of viral replication were identified as pathways common to both tissues.CONCLUSIONS: Stabilised whole blood is not a suitable sample for clinical diagnostics of CD based on single genes. However, diagnostics based on a pathway-focused gene expression panel may be feasible, but requires further investigation.
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| 8. |
- Gustafsson, Nina-Katri, 1976-
(författare)
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Bridging the world : Alcohol Policy in Transition and Diverging Alcohol Patterns in Sweden
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present dissertation aims at analysing the effects of recent alcohol policy changes. The traditional strict policy in Sweden had focused on high pricing and limited availability to control levels of alcohol consumed and thus alcohol-related harms. However, increased travellers’ allowances meant larger availability of cheaper alcohol when importing from Denmark and Germany, which are the countries from which Swedes obtain most of their private imports; the tax decrease in Denmark further decreased the price. As the economic literature links demand to price of a commodity and the early (smaller) quota changes had resulted in higher consumption in southern Sweden, it was expected that these latest changes would mean higher consumption and more alcohol-related problems in this area in particular. Some groups were additionally expected to be more affected than others.The present compilation thesis comprises four related articles and an introductory chapter that ties them together. Article I focuses on private imports in relation to quota changes 2002 – 2004 and relate this to purchase at the alcohol monopoly stores. Self-reported consumption and alcohol-related problems are studied in Article II and IV. In Article III, register data on alcohol-related harms, i.e. hospitalizations and police-recorded crimes, are analysed.The results of the dissertation were puzzling, since there was no large increase in consumption or alcohol-related problems in the south, but increases in the north during the period. However, private imports and cases of hospitalization due to alcohol poisoning were found to have increased in the south. Thus, the results imply that these policy changes had an effect on private imports, but that this effect was not large enough to increase total consumption as well. Additionally, increased alcohol poisoning cases implied that there had been an impact among high consumers. The increases found in consumption and problems in the north may instead have other explanations.
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| 9. |
- Israelsson, Axel
(författare)
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Chewing gum and human hair as retrospective dosimeters
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Retrospective dosimeters are sometimes needed after radiological/nuclear (RN) exposures to determine the doses to individuals. Conventional dosimeters may not be at hand or may not be applicable calling for alternative materials.The possible exposure situations can be divided into external and internal; the radiation field stems either from outside the body or from a source within. This thesis investigates the possibility to use chewing gum and hair as retrospective dosimeters. The chewing gum would be used after an unexpected radiation event of external type whereas human hair is examined after chronic intake of uranium. Chewing gum containing xylitol and sorbitol was analyzed using electron paramagnetic resonance (EPR) and the hair was analyzed by alphaspectrometry following radiochemistry and by synchrotron radiation microbeam x-ray fluorescence (SR μ-XRF).Xylitol and chewing gum (in this particular case, V6) are in the present work found to be valuable dosimeters after unexpected radiation events. The xylitol signal linearity with dose in the interval 0-10 Gy was confirmed (r2=1.00). The doses to the coating of the chewing gums were determined 4-6 days after irradiation with an uncertainty of less than 0.2 Gy (1 SD). Spectral dependence with time after exposure was found, but was, however, minimal between 4-8 days.Hair was evaluated and compared with urine as biodosimeter after ingestion and inhalation intake of uranium. Concentrations of 234U and 238U and their activity ratios were measured in the hair, urine and drinking water sampled from 24 drilled bedrock well water users in Östergötland, Sweden, as well as among 8 workers at a nuclear fuel fabrication factory, Westinghouse Electric Sweden. The results show that there is a stronger correlation between the uranium concentrations in the drinking water of the well water and the users’ hair (r2 = 0.50) than with their urine (r2 = 0.21). There is also a stronger correlation between the 234U/238U activity ratios of water and hair (r2 = 0.91) than between water and urine (r2 = 0.56). The individual absorbed fraction of uranium, the ƒ value, calculated as the ratio between the excreted amount of uranium in urine and hair per day and the daily drinking water intake of uranium stretched from 0.002 to 0.10 with a median of 0.023. The uranium concentrations of the fuel factory workers’ hair and urine were also obtained as well as that of personal air sampler (PAS) filters for the determination of inhaled uranium activity. A large day-to-day variation (7-70 Bq d-1) of the inhaled 234U activity was seen over a 6 week period. Over a 12 week period the 234U activity concentration in urine was similarly seen to vary from 2 to 50 mBq kg-1. Four hair samples from the same subject and period showed less variation (100-240 mBq g-1). The uranium inhalation to urine and hair factors finh,u and finh,h were found to be 0.0014 and 0.0002 respectively given by calculations based on the measured PAS, urine and hair data from two individuals. The SR μ-XRF measurements showed that uranium is present in an outer layer of the hair shaft, about 10-15 μm wide. The measurements also revealed particles containing uranium being present on the surface of unwashed hair shafts. However, the washed hair shafts showed few, if any, particles.This thesis concludes that chewing gum and hair can be used as retrospective dosimeters after external radiation and after intake of uranium respectively.
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| 10. |
- Karling, Mats, 1944-
(författare)
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Child behaviour and pain after hospitalization, surgery and anaesthesia
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hospitalization, surgery and anaesthesia are for some children associated with anxiety and could be a frightful experience which may result in later problematic behaviour. Pain is associated with the fears of hospitalization. The first aim was to investigate how pain in children is treated in Swedish hospitals as well as to assess the results of this treatment. Behaviour after hospitalization has been measured by the Post Hospital Behaviour Questionnaire (PHBQ). A second aim was to translate this instrument into Swedish and to validate it. The third aim was to analyze which factors (sociodemographic back¬ground; earlier experience; events at the hospital) that might be associated with changes in behaviour. Methods: A questionnaire regarding acute pain, its treatment methods and results of treatments as well as contributing factors to inadequate results, was sent to all departments in hospitals that might treat children. One form was answered by phy¬sicians and another form by nurses. In the second part of the study, a cohort of 340 children ages 2-13 were followed from two weeks before hospitalization until two weeks after. Data regarding socio¬demography and earlier health care experience were collected. The Child Behav¬iour Checklist was issued before and after hospitalization, the PHBQ was issued after. During hospitalization staff and parents assessed anxiety, pain and nausea mainly by VAS and Likert scales, (parents assessed own and child emotions). Children, older than 4-5 years of age, assessed their own pain using a faces scale. Results: Despite treatment, moderate to severe pain occurred postoperatively in 23% of patients and in 31% of patients with pain of other origin. Postoperative pain seemed to be a greater problem in units where children were treated together with adults and in departments where fewer children were treated. Pain could often or always be treated more efficiently according to 45% of physi¬cians and nurses. Of all departments, pain assessments were performed regularly in 43%, but pain measurement was less frequent. Opioids were never or infrequently used by 15 %. A five factor model fitted data better than the original 6 factor model when confir¬mative factor analyse was performed. Cronbach’s alpha was adequate for factors and excellent for the total score (0.92). Risk factors for increased problematic be¬haviour included the following: age less than 5 years of age, living in a one adult family, anxiety at anaesthesia induction, nausea at hospital and pain at home. Liv¬ing in a rural area and midazolam in premedication seem to be protective. Conclusions: Acute pain in children is still a problem. Inadequate pain treatment is mainly associated with organisational factors (missing prescriptions; a low rate of pain assessments). The PHBQ in Swedish translation is a reliable instrument and its relation to CBCL warrants its further use in research and quality control espe¬cially in younger children. Hospital-induced stress in older children needs further investigation. One third of the children who have been hospitalized and exposed to anaesthesia will have in¬creased problematic behaviour when returning home. Pro¬active interventions are suggested to prevent this by improving pain treatment at home.
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