| 1. |
- Essner, Ann, 1971-
(författare)
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On assessment methods related to pain in dogs with osteoarthritis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a need of valid and reliable assessment methods that are clinically applicable in canine rehabilitation practice. The aim of this thesis was to psychometrically evaluate measurement properties in assessment methods related to pain in naturally occurring canine osteoarthritis. Assessment methods developed for heart rate variability analysis, i.e. Polar heart rate monitor, and owner-reported perceptions of pain severity and pain interference with functionality, i.e. Canine Brief Pain Inventory, were tested.Methods: Four observational studies were conducted. Study I was a cross-sectional study consisting of two groups of consecutively recruited dogs. The Canine Brief Pain Inventory was administered to owners of dogs with naturally occurring osteoarthritis (n=61) and clinically sound dogs (n=21). Study II was a descriptive and correlative cross-sectional study based on the same sample of dogs with osteoarthritis (n=71), assessing chronic pain behavior and associations between explanatory variables and chronic pain behavior. Study III and IV were correlative studies, assessing Polar heart rate monitor measuring interbeat intervals and time- and frequency-based heart rate variability parameters, compared to simultaneously recorded electrocardiogram in dogs (n=11).Results: High internal consistencies and ability to discriminate sound dogs from osteoarthritis dogs were found. The hypothesis of the presented two-factor structure of the Canine Brief Pain Inventory was rejected. Owners reported higher proportions of chronic pain behavior in items targeting physical activities, e.g. getting up, moving after rest and moving after major exercise. A minor proportion of dogs with osteoarthritis showed no owner-perceived behavioural signs of chronic pain. Owner observations were not associated with ongoing antiinflammatory medications. In Study III and IV, 595 errors (12.3%) were identified in Polar data. The number of errors were unequally distributed among the dogs. Interbeat intervals and heart rate variability parameters from electrocardiogram and Polar were strongly associated. Standard error of measurements were high among some heart rate variability parameters in Polar and electrocardiogram.In conclusion, this thesis contributes to our knowledge about assessment methods related to diverse components of pain in dogs with osteoarthritis, allowing improved pain management in clinical practice.
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| 2. |
- Morell Miranda, Pedro
(författare)
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Following the herd : Population genetics of European sheep in time and space
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sheep, which were domesticated in the Fertile Crescent about 10,000-12,000 years ago, have been a key resource for human populations ever since. We, however, know little about how they were domesticated, and what happened to them after their initial expansion from their domestication area into all corners of Eurasia and later Africa and the Americas. In this thesis I use state-of-the-art methods in population genetics and archaeogenetics to try to elucidate how sheep have evolved into the big diversity of modern breeds we see today and what demographic events shaped modern sheep genetic landscape in Europe. We were able to characterize the demographic history of three key locations in Europe for sheep: Iberia, the Baltic region and the Mediterranean islands. Our results confirm that the initial Neolithic expansion into Europe followed two independent routes, through the Danube-Rhine axis in Central Europe and sailing through the Mediterranean, and that mouflons from Corsica and Sardinia descend from this last early domestic sheep. We were also able to identify two independent expansions into Europe of Eastern ancestry, one related with archaic long wool, a phenotype retained by primitive European sheep breeds, and a later one associated with more modern woolly phenotypes. This last expansion, that occurred slightly before or during the Roman period in Iberia, didn’t reached the Baltic region, whose breeds are still to this day displaying primitive phenotypes. Lastly, we were able to describe the phylogeny of modern wild and feral mouflons from the Mediterranean and the Middle East. My thesis highlight the dynamic nature of the demographic history of sheep, and how responsive it has been to human demographic and cultural changes.
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| 3. |
- Sharma, Garima, 1990-
(författare)
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The risk of antimicrobial resistance and zoonotic diseases in India's dairy value chain, and how we can mitigate the public health threat through interventions
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- India is the world's largest producer of milk and milk products with small-scale farms dominating the dairy industry. The infrastructure is inadequate, and quality control is minimal. India has a high burden of infectious and zoonotic diseases due to a lack of awareness, poor hygiene practices, poverty, and limited access to medical services. There is however unrestricted access to medicines. Antibiotics are widely used in dairy animals for therapeutic and prophylactic purposes and are sometimes given in large quantities to prevent diseases.This thesis assessed knowledge, attitude, and practices (KAP) regarding antibiotics, antimicrobial resistance (AMR), milk safety, and zoonotic diseases. Surveys among dairy farmers and milk vendors were conducted to assess their knowledge and practices regarding milk safety, antibiotics, and milk handling. Milk samples from dairy farms were analyzed for antibiotic residues and milk samples from vendors were analyzed for antibiotic-resistant bacteria. Veterinary practitioners were interviewed to understand their knowledge and perceptions. Interventions were carried out to raise awareness and a follow-up survey was conducted to assess knowledge change.The knowledge of dairy farmers related to antibiotics, AMR, and zoonotic diseases was quite low. There were 5.9% positive samples with antibiotic residue levels over the maximum residue limit. Farmers admitted using antibiotics without a veterinarian's approval and reported a lack of veterinarians. Milk vendors were unaware of antibiotics and AMR. They knew very little about milk hygiene and sold raw milk. Most (64.5%) vendor milk samples had antibiotic-resistant bacteria. Due to a lack of diagnostic facilities, veterinarians gave antibiotics based on their knowledge of diseases and symptoms without testing. A follow-up study found that farmers who attended intervention training showed an improvement in their knowledge level. This thesis offers a glimpse of the many factors that are contributing to the inappropriate use of antibiotics in the livestock industry of India. The level of knowledge can be improved with regular discussions. In addition to improving veterinary facilities, stakeholders in the informal dairy value chain should get frequent training.
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| 4. |
- Almqvist, Annika, 1949-
(författare)
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Drömmen om det egna huset : Från bostadsförsörjning till livsprojekt
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Swedish housing research has disproportionately concentrated on the study of apartment blocks and on how to create functioning neighbourhoods and neighbourliness, as part of a national housing policy that aimed at building apartment blocks for ordinary families. Yet at the same time, most Swedish families with children have been choosing to live in an owner occupied house. How can this paradox be explainedThe starting point for Swedish housing policy - and therefore for Swedish housing research - has consequently been to foster equality and social justice in and through housing and town planning. In part this has aimed at providing better housing for working class people. But it has also aimed at easing the burden of work in the home, and it has done so by providing rationally planned housing and neighbourhoods, as well as well-developed public transport and other collective facilities. Alva Myrdal was a leading light in working for gender equility and has been an important source of inspiration for this approach to housing and town planning. Yet at the same time as this focus on equality was being pursued there were also strong currents favouring an approach that built on the strengths of gender differences and in particularly a view of women as housewives and home-oriented experts.Yet why have so many families taken the opportunity and chosen to move to an owner occupied house? In order to explain this, the positivistic tradition of housing research is indaquate. It is necessary to turn to the hermeneutic tradition of research on the meaning and significance of housing in a social and cultural context to look for answers.The social and cultural context can in turn be related to developments and issues in modernity. I argue that the continuing appeal of the owner occupied house even when most women are in paid employment needs to be understood against a background of increasing intimisation. This in turn can be seen as a reaction against the built-in tendency towards the development of individualisation. When people become increasingly home-oriented and inward- looking, the home as part of their lives increases in significance. The home in our time has become a free zone and a love project and so the owner occupied house appears to provide a better type of housing than an apartment in a multi-family building. This goes for men as well as women, despite the risk that traditional gender roles in the household can thereby be strengthened.
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| 5. |
- Andersson, Jenny, 1972-
(författare)
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Older Women and Food : Dietary Intake and Meals in Self-Managing and Disabled Swedish Females Living at Home
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the present thesis was to study elderly self-managing and disabled women’s dietary intake and meals in relation to age, household structure (single-living or cohabitant), disability and cooking ability. The women were aged 64-88 years and living at home, in the mid-eastern part of Sweden. The self-managing women were randomly selected. The disabled women – suffering from Parkinson's disease, rheumatoid arthritis or stroke – were selected from patient records. A total of 139 self-managing and 63 disabled women participated. Two dietary assessment methods were used: a repeated 24-h recall and a three-day estimated food diary, providing dietary intake for five non-consecutive days. The results indicate that elderly women still living in their homes seem to manage a sufficient dietary intake despite disability and high age. The reported energy intakes in all groups of women were low, which might be explained by an actual low intake and/or under-reporting. The portion sizes seemed to be smaller in the highest age group, leading to lower intakes of some nutrients. Thus also the nutrient density of the food should be given greater consideration. The meal pattern was shown to be regular and the distribution of main meals and snacks was found to be satisfactory. Meals and snacks that were defined as such by the women themselves thus seem to be more significant from an energy and nutritional perspective. Perceived cooking ability co-varied with energy and nutrient intake as well as with meal pattern.Further, a qualitative dietary assessment method, FBCE, was analysed. It was concluded that it must be supplemented with a dietary assessment method providing energy intake figures to ensure a sufficient intake, especially when studying groups at risk for low energy intake.Furthermore, the aim was to perform a dropout analysis. When studying older women and food, a low participation rate might be expected since the most active, the very ill as well as the disabled tend to decline participation, but also since food is a gender issue. Food could, especially for women, be a sensitive area of discussion, even though older women seem to choose "healthy foods" and eat "proper meals".
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| 6. |
- Berglund, Johan, 1983-
(författare)
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Separation of Water and Fat Signal in Magnetic Resonance Imaging : Advances in Methods Based on Chemical Shift
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue. Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality. In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners. A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers. The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated. Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers. Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer. The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.
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| 7. |
- Börjesson, Andreas, 1976-
(författare)
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Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is a chronic autoimmune disease targeted against the pancreatic β-cells. Proinflammatory cytokines are considered to play a major role in the destruction of the insulin-producing β-cells. This thesis studied strategies to counteract proinflammatory cytokines in experimental T1D. Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined.In the first study we observed that cytokine treatment of mouse pancreatic islets lacking inducible nitric oxide synthase (iNOS) induced a prolongation of the early stimulatory phase of glucose stimulated insulin secretion. Various experiments led to the conclusion that this prolonged stimulatory effect may involve the DAG/PLD/PKC pathway.Next, we transplanted mouse islets deficient in iNOS to spontaneously diabetic NOD mice. We observed a normalization of hyperglycemia but not a delayed allograft rejection compared to transplanted wild type islets. Thus, absence of iNOS in the graft was not sufficient to prolong allograft survival.In paper III we found that sustained glucose stimulation of rat pancreatic islets was coupled to a decreased conversion of proinsulin to insulin. Islet treatment with IL-1β was also coupled to a decreased proinsulin conversion. Islet proconvertase activity may be a target in islet damage.In paper IV prolactin (PRL) was administered to mice in the multiple low dose streptozotocin model and we observed that PRL enhanced a Th2 response. This may contribute to the protective action by PRL in this model of autoimmune T1D.Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 transgenic islets were protected in an allogeneic transplantation model.
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| 8. |
- Cristea, Alexander, 1966-
(författare)
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Effects of Ageing and Physical Activity on Regulation of Muscle Contraction
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.
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| 9. |
- Enberg, Cecilia, 1976-
(författare)
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Knowledge Integration in Product Development Projects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Denna avhandling handlar om kunskapsintegration i produktutvecklingsprojekt. Med kunskapsintegration avses processer av mål-orienterad interrelatering med syfte att dra fördel av de kunskapskomplementariteter som finns mellan individer som har differentierade kunskapsbaser. Förmågan att integrera specialiserad och distribuerad kunskap är betydelsefull för många företag då den bidrar till att förklara skillnader i produktutvecklingsframgång. Dock saknas det detaljerade, empiriska, studier av kunskapsintegration. Mot denna bakgrund är syftet med denna avhandling att undersöka vilka kunskapsintegrationsmekanismer som är lämpliga att använda i olika projektkontexter.Avhandlingen är baserad på två longitudinella realtidsstudier av produktutvecklingsprojekt. En detaljerad redogörelse av projektarbetet, tillsammans med en analys, presenteras för respektive projekt. Därefter görs en komparativ analys, i vilken såväl likheter som olikheter mellan de två fallen och deras respektive projektkontext diskuteras. En iterativ modell för kunskapsintegration förslås som ett resultat av studierna. Den iterativa modellen har ett flertal egenskaper som kan bidra till att öka vår förståelse för kunskapsintegration i empiriska projektkontexter. För det första visar den på vikten av att förstå i vilken utsträckning som kunskapsproblematiken i ett specifikt projekt medför behov av såväl ”aktion” som ”interaktion” och hur dessa kompletterar varandra i en iterativ process. För det andra indikerar den betydelsen av artefakter och hur dessa kan bidra till såväl aktion som interaktion. För det tredje tar den hänsyn till det faktum att aktion och interaktion medför olika kostnader för kunskapsintegration.
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| 10. |
- Fuchs, Dieter, 1979-
(författare)
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Novel Treatment Modalities for High-Risk Neuroblastoma : Studies in Animal Models
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroblastoma, the most common extracranial solid tumor of childhood, is a heterogeneous tumor. In some patients, the tumor can go into spontaneous regression and disappear whereas other patients have rapidly growing tumors with a poor prognosis. The overall long-term survival rate in patients with high-risk neuroblastoma is less than 30%, indicating the need for new treatment strategies. Angiogenesis inhibition hampers the formation of new blood vessels, thereby limiting the tumors’ metabolic exchange. Neuroblastoma is rapidly growing and high tumor angiogenesis has been associated with poor outcome. Therefore, the aim of this thesis was to investigate the effect of novel treatment modalities for angiogenesis inhibition on high-risk neuroblastoma xenografts. For that purpose, we used subcutaneous mouse models and characterized orthotopic mouse models for high-risk neuroblastoma. We found that xenotransplantation of neuroblastoma cells into the adrenal gland of SCID and SCID beige mice resulted in orthotopic tumors resembling clinical neuroblastoma in respect to tumor site, growth and spread. Using contrast-enhanced ultrasound, we observed that the receptor tyrosine kinase inhibitor SU11248 reduced orthotopic neuroblastoma growth and spread by reducing tumor angiogenesis.In subcutaneous xenografts for high-risk neuroblastoma, valuable for studies requiring continuous assessment of tumor volume, we demonstrated that immune-neutralizing VEGF with the anti-VEGF antibody bevacizumab significantly reduced neuroblastoma growth. Finally, we found that formulations of the chemotherapeutic drug GMX1778 inhibited angiogenesis and induced tumor regression in a dose dependent manner without host toxicity. We showed that relapsing tumors remained responsive to GMX-therapy without accelerated growth or induced drug resistance.In conclusion, SU11248, bevacizumab, and formulations of the active compound GMX1778 may become useful for treating high-risk neuroblastoma.
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