| 1. |
- Bergstrand, Sara, 1978-
(författare)
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Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces.This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals < 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH).The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures.This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.
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| 2. |
- Lowén, Mats, 1977-
(författare)
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Irritable Bowel Syndrome : Studies of central pathophysiological mechanisms and effects of treatment
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aimsIrritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. The societal costs of the disorder are significant, as are its negative effects on quality of life. Medical treatment options are limited, but psychological treatments such as hypnotherapy have proven to be effective. Important pathophysiological mechanisms include disturbances in brain processing of visceral sensation and expectation of visceral sensation. Increased sensation of stimuli (hypersensitivity) is present in a subset of IBS patients to distensions in the lower part of the gastrointestinal tract, indicating a probable important pathophysiological mechanism in IBS. The overall aim of the thesis was to further study the central pathophysiological mechanisms involved in IBS. Specifically, we aimed to identify differences in brain response to standardized repeated rectal distensions and expectation of these stimuli between IBS patients (with or without perceptual rectal hypersensitivity), and healthy controls. Furthermore, we aimed to investigate IBS patients´ brain responses to standardized rectal distensions and expectation of these stimuli after either a successful course hypnotherapy or educational intervention.MethodsFunctional magnetic resonance imaging (fMRI) data were acquired and analyzed from 15 IBS patients with visceral hypersensitivity, and 18 IBS patients with normal visceral sensitivity (papers I and II). In paper III, fMRI data were analyzed from IBS patients who reported significant symptom reduction after either a course of hypnotherapy, or an educational intervention. FMRI data from IBS patients and healthy controls were also compared.ResultsThe findings reported in papers I and II suggest, that the differences in brain response between IBS patients with and without rectal hypersensitivity, can be explained by changes in brain response during the course of the experiment. Even though the brain responses were similar between groups during the early phase of the experiment, they became substantially different during the late phase. The IBS patients with rectal hypersensitivity demonstrated increased brain response in several brain regions and networks involved in visceral sensation and processing. In contrast, IBS patients with normal rectal sensitivity exhibited reduced brain response during the late phase of the experiment. As reported in paper III, similar symptom reduction was achieved for both treatments. The symptomatic improvement was associated with a reduction of response in the anterior insula, indicating an attenuated awareness of the stimuli. The hypnotherapy group had a reduction of response in the posterior insula, indicating less input to the brain, possibly due to changed activity in endogenous pain modulatory systems. In patients who reported significant symptom reduction following treatment, the brain response to rectal distension got more similar to that observed in healthy controls.ConclusionsThe results from papers I and II indicate that a subpopulation of IBS patients lacks the ability to habituate to repeated rectal distensions and expectation of these stimuli. Results from paper III indicate that the abnormal processing of visceral stimuli in IBS can be altered, and that the treatments probably had a normalizing effect on the central processing abnormality of visceral signals in IBS.
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| 3. |
- Bednarska, Olga, 1973-
(författare)
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Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.
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| 4. |
- Engström, Annika
(författare)
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Lärande samspel för effektivitet : En studie av arbetsgrupper i ett mindre industriföretag
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- En viktig arena för samspel kring känsliga gränssnitt (marknad – konstruktion – produktion) i industrin är olika möten där arbetsgrupper kommer samman kring uppgifter. Syftet med avhandlingen är att bidra med kunskap om samspel som sker inom och mellan arbetsgrupper i deras hantering av uppgifter i mindre industriföretag (SME) och vilken betydelse samspelet har för lärande och effektivitet i verksamheten. Studien har närmare bestämt fokus på följande frågeställningar: 1. Vad karaktäriserar samspelet inom och mellan arbetsgrupper som det kommer till uttryck i olika möten? 2. Vilka faktorer underlättar respektive försvårar samspelet inom och mellan arbetsgrupper? 3. Vilka konsekvenser får olika typer av samspel för lärande och effektivitet i arbetsgrupper och i organisationer? Studien utgår från ett kritiskt realistiskt perspektiv på lärande i organisationer samt tidigare forskning om lärande, kommunikation och effektivitet i grupper och organisationer. Studien genomfördes under perioden 2008-2010 och var upplagd utifrån en kvalitativ och interaktiv forskningsansats. Datainsamlingen baserades på intervjuer, observationer av videofilmade möten samt frågeformulär. Analysen rör sig mellan två nivåer: samspel inom grupper samt mellan grupper på organisationsnivå. Samspelet inom och mellan grupper analyserades utifrån kontextuella faktorer och med fokus på i vad mån olika kommunikationsmönster kunde kopplas till olika typer av lärande och effektivitet i verksamheten. Ett rationalistiskt effektivitetsperspektiv utmanas till förmån för ett humanistiskt perspektiv där lärandet är en viktig aspekt. Tre slutsatser dras: Effektivitet grundar sig i att kommunikationsmönster och ledning anpassas efter det behov uppgiften för stunden kräver - utförande eller utveckling. Återkoppling och personliga länkar mellan grupper behöver översyn och ledningsrutiner för att underlätta samspelet. Diskrepanser (motsättningar, konflikter och störningar) som synliggörs i organisationen leder till utveckling. De som förblir i det dolda stör utförandet.
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| 5. |
- Hedlund, Anna, 1973-
(författare)
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MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.
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| 6. |
- Källman, Ulrika, 1968-
(författare)
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Evaluation of Repositioning in Pressure Ulcer Prevention
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: To reduce the risk for pressure ulcers, repositioning of immobile patients is an important standard nursing practice. However, knowledge on how this preventive intervention is carried out among elderly immobile patients is limited and to what extent patients perform minor movements between nursing staff-induced repositionings is largely unknown, but these movements might have implications for the repositioning intervention. Different lying positions are used in repositioning schedules, but there is lack of evidence to recommend specific positions.Aim: The overall aim of this thesis was to describe and evaluate how repositioning procedures work in practice in the care of elderly immobile patients. The aim was also to compare the effects of different positions with regard to interface pressure, skin temperature, and tissue blood flow in elderly patients lying on a pressure-redistribution mattress.Methods: This thesis consists of four quantitative studies. In Study I, 62 elderly immobile patients were included. All movements the patients made, either with help from the nursing staff or spontaneously, were registered continuously over the course of three days. Study II served to pilot the procedure for Study III. Tissue blood flow and skin temperature were measured in hospital patients (n = 20) for 5 minutes in two supine, two semi-Fowler, and two lateral positions. In Study III, a new sample was recruited (n = 25) from three nursing homes. Measurement of interface pressure was added, and the measurements were extended from 5 minutes to 1 hour. The six positions were reduced to four by excluding the two semi-Fowler positions. Blood flow was measured using photopletysmography (Study II-IV) and laser Doppler flowmetry (Studies III and IV). In Study IV a deeper analysis of the individual pressure-induced vasodilation (PIV) responses was performed on the sample from Study III. An age of 65 years or older was an inclusion criterion in all studies.Results: Study I showed that there was a large variation in the extent to which the elderly immobile patients made spontaneous movements, and these movements were positively related to taking analgesics and negatively related to taking psycholeptics. Patients scored as high risk for pressure ulcer development were repositioned more frequently than patients scored as low risk. However, the spontaneous movement frequency was not associated with any risk scores. Study II showed that the different lying positions influenced the blood flow in different ways. In Study III, it was found that the overall blood flow response during one hour of loading was significantly higher in the 30° supine tilt position than in the 0° supine, 30° lateral, and 90° lateral positions. The overall blood flow in the 90° lateral position did not differ compared to the 30° lateral position, although the interface pressure was significant higher in the 90° lateral position. In patients lacking a PIV response (Study IV), the blood flow decreased immediately and remained below baseline during the one hour of loading.Conclusions: Although elderly and immobilized, some patients frequently perform minor movements while others do not. Patients who cannot perform minor movements are important for the nursing staff to identify because they very likely need more intensive repositioning interventions. The spontaneous movement frequency was not associated with the risk assessment score, and this implies that some immobile patients assessed as low risk might need to be repositioned as often as patients assessed as high risk. Of the positions evaluated, the 30° supine tilt position was concluded to be most beneficial. There was no great difference in how the blood flow was affected in the 90° lateral position compared to the 30° lateral position, which question the appropriateness of the recommendation to avoid the 90° lateral position. The patients with lacking a PIV response might be particularly vulnerable to pressure, which also implies that these patients might need to be repositioned more frequently.
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| 7. |
- Ragnehed, Mattias, 1976-
(författare)
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Functional Magnetic Resonance Imaging for Clinical Diagnosis : Exploring and Improving the Examination Chain
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Functional Magnetic Resonance Imaging (fMRI) is a relatively new imaging technique, first reported in 1992, which enables mapping of brain functions with high spatial resolution. Functionally active areas are distinguished by a small signal increase mediated by changes in local blood oxygenation in response to neural activity. The ability to non-invasively map brain function and the large number of MRI scanners quickly made the method very popular, and fMRI have had a huge impact on the study of brain function, both in healthy and diseased subjects.The most common clinical application of fMRI is pre-surgical mapping of brain functions in order to optimise surgical interventions. The clinical fMRI examination procedure can be divided into four integrated parts: (1) patient preparation, (2) image acquisition, (3) image analysis and (4) clinical decision. In this thesis, important aspects of all parts of the fMRI examination procedure are explored with the aim to provide recommendations and methods for prosperous clinical usage of the technique.The most important results of the thesis were: (I) administration of low doses of diazepam to reduce anxiety did not invalidate fMRI mapping results of primary motor and language areas, (II) the choice of visual stimuli equipment can have severe impact on the mapping of visual areas, (III) three-dimensional fMRI imaging sequences did not perform better than two-dimensional imaging sequences, (IV) adaptive spatial filtering can improve the fMRI data analysis, (V) clinical decisions should not be based on activation results from a single statistical threshold.
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| 8. |
- Roos, Charlotte
(författare)
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Promoting living in dignity and with a sense of well-being among older people living in residential facilities – older people’s perspective
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish national fundamental values state that care of older people who are living in residential facilities should ensure that they live in dignity and with a sense of well-being. The overall aim of this licentiate thesis was to study, from older residents’ perspective, the effects of a caregiver intervention intended to put the Swedish national fundamental values into practice and to describe residents’ perceptions of what promotes the values: living in dignity and having a sense of well-being. The licentiate thesis is based on two studies, one using a descriptive design (Study I) and the other a cluster-randomized controlled trial with a pre- and one post-test design (Study II). Data were collected using interviews and questionnaires. The results showed that to promote dignity and well-being, it was important for residents to maintain their independence despite reduced abilities; to feel secure about care/services and certain about receiving assistance when it was needed; to maintain and create social relationships and to have a feeling of being at home (Study I). The intervention, aimed at putting the Swedish national fundamental values into practice, increased the self-reported empowerment, person-centered climate and life satisfaction regarding everyday activities of residents in the intervention group. There were significant interaction effects (differences in change over time between the intervention and control group) for empowerment, person-centered climate and life satisfaction regarding the factor everyday activities (Study II). Several conclusions can be drawn from the studies: In order to experience dignity and a sense of well-being, it was important for residents to maintain their independence, social relationships and their feeling of being at home. A caregiver intervention aimed at putting the Swedish national fundamental values into practice can improve everyday life among older residents. It is important that staff work alongside residents and that staff be given appropriate structural conditions, in the form of time, when putting the Swedish national fundamental values into practice.
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