| 1. |
- Hulsart Billström, Gry, 1982-
(författare)
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Bone Regeneration with Cell-free Injectable Scaffolds
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.
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| 2. |
- Waldau, Susanne, 1954-
(författare)
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Creating organisational capacity for priority setting in health care : using a bottom-up approach to implement a top-down policy decision
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, priority setting to the form of the Swedish parliamental decision on priority setting, 1997, is considered an innovation for implementation in health care. The features of this innovation are investigated. The practical implications of implementation are identified by investigating the user organisation, ie, Swedish health care organisations and management systems. Also, a case of a three-stage process for macro-level priority setting that engaged the entire organisation in the Västerbotten County Council (VCC) is presented. This is done against a background of preceding implementation efforts in the VCC. Four specific research efforts and papers are presented. In Paper I, priority setting is operationalised into a multi-dimensional resource allocation task. On that basis, with the help of interviews (1998) and surveys (2002 and 2005) primarily of VCC health care managers, the impact of implementation is measured by prioritisation structures, processes and decisions. Survey response rates were low. Results were used as qualitative data, internally compared, and interpreted as: a) responses reflected mainly “early adopters’” opinions; b) priority setting is an ambiguous concept; c) indicating limited overall implementation; d) reinterpretation of the prioritisation task occurred over time among respondents; and, e) this group took increasingly personal responsibility as stakeholders in priority setting. Paper II reports a case study intervention of explicit, departmental level priority setting with the aim of improving cost-effectiveness in in vitro fertilization resource use and a rationing of services perceived legitimate by all stakeholders. The intervention combined priority setting and structured quality improvement techniques. Results were: a) improved operational efficiency of diagnostic procedures that allowed resources to be reallocated to treatment; and b) patients were prioritized and treatment resources were rationed based on evidence of treatment effect among subgroups. Evaluation showed that the procedure met stated criteria for legitimacy. In Paper III, a full-format test of the macro level prioritisation process is described and evaluated by participants with the help of surveys after each completed stage. Participants report the need for improvement of elements in the overall process and of procedural specifics. However, overall there was a strong commitment to the initiative and satisfaction with the process and the resulting decisions. In Paper IV, procedural specifics of the prioritisation process are evaluated. They are also compared to the Program Budgeting and Marginal Analysis (PBMA) framework when used for macro level purposes. Procedures provided intended results such as vertical and horizontal priority setting and a consistent process. However, economic targets were not fully achieved in any of the stages. Conclusions include that health care management systems are not prepared for priority setting and need profound restructuring and that the prioritisation process described in Papers III and IV was successful because: a) the process satisfied politicians’ directives; b) participants were satisfied with the procedures and perceived the subsequent reallocation decisions as legitimate; and, c) methods resulted in the intended outcome. Factors suggested as the basis of success include: long-term overall preparations; broad and deep participation; a readiness for change among participants; a stage for horizontal priority setting that added to the quality, feasibility and perceived validity of the knowledge base; a strong process leadership; and politicians determined to protect the process from opportunistic disturbances.
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| 3. |
- Ottosson, Niklas, 1981-
(författare)
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Aqueous Solutions as seen through an Electron Spectrometer : Surface Structure, Hydration Motifs and Ultrafast Charge Delocalization Dynamics
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In spite of their high abundance and importance, aqueous systems are enigmatic on the microscopic scale. In order to obtain information about their geometrical and electronic structure, simple aqueous solutions have been studied experimentally by photo- and Auger electron spectroscopy using the novel liquid micro-jet technique in conjunction with synchrotron radiation. The thesis is thematically divided into three parts. In the first part we utilize the surface sensitivity of photoelectron spectroscopy to probe the distributions of solutes near the water surface. In agreement with recent theoretical predictions we find that large polarizable anions, such as I- and ClO4-, display enhanced surface propensities compared to smaller rigid ions. Surface effects arising from ion-ion interactions at higher electrolyte concentrations and as function of pH are investigated. Studies of linear mono-carboxylic acids and benzoic acid show that the neutral molecular forms of such weak acids are better stabilized at the water surface than their respective conjugate base forms. The second part examines what type of information core-electron spectra can yield about the chemical state and hydration structure of small organic molecules in water. We demonstrate that the method is sensitive to the protonation state of titratable functional groups and that core-level lineshapes are dependent on local water hydration configurations. Using a combination of photoelectron and X-ray absorption spectroscopy we also show that the electronic re-arrangement upon hydrolysis of aldehydes yields characteristic fingerprints in core-level spectra. In the last part of this thesis we study ultrafast charge delocalization dynamics in aqueous solutions using resonant and off-resonant Auger spectroscopy. Intermolecular Coulombic decay (ICD) is found to occur in a number of core-excited solutions where excess energy is transferred between the solvent and the solute. The rate of ultrafast electron delocalization between hydrogen bonded water molecules upon oxygen 1s resonant core-excitation is found to decrease upon solvation of inorganic ions. The presented work is illustrative of how core-level photoelectron spectroscopy can be valuable in the study of fundamental phenomena in aqueous solutions.
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| 4. |
- Röding, Fredrik, 1969-
(författare)
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Injuries are not accidents! : an emergency-department population-based epidemiological study of injuries with special reference to trauma recidivism hip fractures and geriatric falls
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Injury is a major public health problem. In rich countries fall injures now kill more people than all other injury mechanisms together, because of global ageing and large-scale sustainable injury prevention programs for all other injury mechanisms but falls. Injuries from falls in the young are often trivial, but in old people falls may have devastating consequences.We used the Umeå Injury Database, 1993 – 2014, 220,014 injury events attended to by the emergency department: e.g., type of injury, localization, mechanism, activity and severity. Logistic regression was used to evaluate injury trends, Cox regression for associations between injury type, severity and recidivism.Fractures were responsible for 1⁄4 of all injuries and for 3⁄4 of trauma inpatient days. Fractures and contusions became more common with increasing age while sprains and wounds decreased with age. Injuries due to fall increased during the study period.Recurrent injuries accounted for some 40%, mostly in young men and in old women. Prior fractures and sprains were strongest predictors for recurrent serious injuries.The hip fracture incidence fell for the most important age/sex groups during the 22-year period, but the total number increased with 3,5%, due to an increasing elderly population. 40% of all hip fracture patients had sustained a previous injury. Multiple previous injuries also increase the risk of future hip fracture. No less than 12% hip fracture patients suffered a new one. With age, injury pattern changed, with more lower extremity fractures that also were more proximally located. Soft tissue injuries to the head/face also increased, also indicating that the ability to reduce and spread the impact of the kinetic energy is a key factor in geriatric trauma, in addition to tissue strengthThe most common, expensive and devastating injury mechanism, falls, are still outrageously neglected, especially concerning injury prevention, which has been so successful in reducing road traffic- and workplace-related deaths. Why? A common misconception is the primitive belief is that fall injuries are fated and therefore inevitable. There are also few economic and legal drivers to prevent falls, especially recurrent ones. Another reason is that GDPR has prohibited the injury database. Statistics on fall injuries are necessary for targeting preventive interventions. Without spying, no clue. On-line feedback of official statistics should be used to monitor the results. There are no technical, just legal hurdles. The Swedish parliament has since 1997 flagged a zero vision for road traffic injuries; in 2015 the government also launched a more modest goal for a 50% reduction of falls in the elderly. So far, nothing has happened...
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| 5. |
- Schilcher, Jörg, 1978-
(författare)
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Epidemiology, Radiology and Histology of Atypical Femoral Fractures : Development of understanding
- 2013
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Ingår i: Acta Orthopaedica. - Linköping : Linköping University Electronic Press. - 1745-3674 .- 1745-3682. ; 84:S352, s. 1-26
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bisphosphonates have been used successfully in the prevention of osteoporosis-related fractures for over two decades. Only recently an association between bisphosphonate use and femoral insufficiency fractures – atypical femoral fractures – has been found.Bone remodeling is necessary to maintain a healthy skeleton. With age this process can get out of balance and bone resorption can outweigh formation of new bone. This can lead to osteoporosis and fractures that occur after minor trauma. Almost half of all women 50 years of age or older will suffer an osteoporosis related fracture during their remaining life. Bisphosphonates inhibit bone resorption, and after some years of treatment an increase in bone mass can be noted. This increase in bone mass can reduce fracture risk by as much as half. However, bisphosphonate use seems associated with the development of femoral insufficiency fractures, so called atypical femoral fractures. This thesis aimed to estimate the risk of atypical femoral fractures in the population and its association with bisphosphonate use. It also describes the radiographic and histologic features of these fractures in order to improve our understanding of the pathophysiological background.Study 1) All women 55 years of age and older, who had sustained a femoral shaft fracture during 2008, were identified through the Swedish National Patient Register. Radiographs of 1234 women were reviewed, and 59 patients with atypical fractures and 263 control patients with common femoral shaft fractures were identified. Atypical femoral fractures were defined by their stress fracture-like appearance. In a cohort analysis, we estimated an age-adjusted relative risk of 47 for bisphosphonate users to suffer an atypical femoral fracture compared to non-users. A total of 78% of the patients with an atypical fracture and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33. The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. These results indicate that bisphosphonate use is strongly associated with atypical femoral fractures. The absolute risk is low and benefits of treatment will outweigh the risks.Study 2) A transverse fracture line and a small but visible callus reaction are well established radiographic features of stress fractures. Radiographs from 59 atypical fracture patients and 218 control patients from Study 1 were re-reviewed to measure fracture angles and to detect callus reactions. The majority of the patients with a transverse fracture angle used bisphosphonates. Fracture angle and callus reaction had a high specificity to detect bisphosphonate treatment. When an oblique fracture line was chosen to define atypical femoral fractures in the cohort from Study 1, the association of atypical femoral fractures to bisphosphonate use became attenuated. Therefore, a correct case definition of atypical femoral fractures is necessary for adequate risk calculations.Study 3) Bone biopsies from 8 patients with atypical femoral fractures were obtained during surgical fixation. The histological analysis of the fracture site itself showed a thin fracture line running perpendicular to the long axis of the femur. Despite ongoing remodeling in the bone adjacent to the fracture gap, no healing occurred within the gap itself. Necrotic material in the gap suggests that strains within the gap might prohibit ingrowth of cells necessary for healing. This mechanism of inhibited healing might share similarities with that of stress fractures in athletes. Although it is highly likely that bisphosphonates play a causative role, the pathogenesis of these fractures is still unclear. It may involve a reduced capacity for targeted remodeling.
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| 6. |
- Zhang, Chaofan
(författare)
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Multicomponent Clusters/Nanoparticles : An Investigation of Electronic and Geometric Properties by Photoelectron Spectroscopy
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clusters/nanoparticles are aggregates of a “small” number of building blocks, atoms or molecules, ranging from two up to millions of atoms. Two main groups of clusters have been studied using photoelectron spectroscopy based on synchrotron radiation. They are dry/wet alkali-halide clusters, including pure water clusters, and metal-based nanoparticles.For the dry alkali halide clusters, analysis of the data and theoretical modeling has allowed us insights into the local electronic properties at nanoscale: a change of polarizability of ions in the alkali-halide clusters due to the varying environment has been suggested. The study of the wet salt clusters shows that the alkali-halides are already solvated at the nanoscale reached by water clusters doped with salt vapor.The photoelectron angular distribution of water cluster shows lower anisotropy parameters as compared to the separate monomers. A model based on intracluster scattering has been built to partly explain the reduction.In the last part of the thesis, metal-based multi-component nanoparticles have been produced by self-assembly processes using reactive magnetron sputtering. Depending on the specific metal element, oxidation processes have been applied before or after the aggregation. Clearly radial distributions such as core-shell and “sandwich-like” structures have unambiguously determined by photoelectron spectroscopy.
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| 7. |
- Hallberg, Inger, 1956-
(författare)
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Health-Related Quality of Life in Postmenopausal Women with Osteoporotic Fractures
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The global burden of osteoporosis includes considerable numbers of fractures, morbidity, mortality and expenses, due mainly to vertebral, hip and forearm fractures. Underdiagnosis and undertreatment are common. Several studies have shown decreased health-related quality of life (HRQOL) after osteoporotic fracture, but there is a lack of data from long-term follow-up studies, particularly regarding vertebral fractures, which are often overlooked despite patients reporting symptoms.Aim: The overall aim of this thesis was to evaluate the usefulness of a recent low-energy fracture as index event in a case-finding strategy for osteoporosis and to describe and analyse long-term HRQOL in postmenopausal women with osteoporotic fracture. The specific aims were to describe bone mineral density and risk factors in women 55-75 years of age with a recent low-energy fracture (I), estimate the impact of osteoporotic fractures on HRQOL in women three months and two years after a forearm, proximal humerus, vertebral or hip fracture (II), investigate the changes and long-term impact of vertebral or hip fracture on HRQOL in women prospectively between two and seven years after the inclusion fracture (III), and describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis (IV).Design and methods: Data were collected from southern Sweden between 1998 and 2008. A total of 303 women were included in Study I, and this group served as the basis for Studies II (n=303), III (n=67), and IV (n=10). A cross-sectional observational, case-control design (I), and a prospective longitudinal observational design (II-III) were used. In Study IV a qualitative inductive approach with interviews was used and data were analysed using a qualitative conventional content analysis.Results: The type of recent fracture and number of previous fractures are important information for finding the most osteoporotic women in terms of severity (I). Hip and vertebral fractures in particular have a significantly larger impact on HRQOL evaluated using the SF-36 than do humerus and forearm fractures, both during the three months after fracture and two years later, compared between the different fracture groups and the reference population (II). Women who had a vertebral fracture as inclusion fracture had remaining pronounced reduction of HRQOL at seven years. At the mean age of 75.5 years (±4.6 SD), the prevalence of vertebral fracture suggests more negative long-term impact on HRQOL, more severe osteoporosis and a poorer prognosis than a hip fracture does, and this effect may have been underestimated in the past (III). Study IV demonstrates that the women’s HRQOL and daily life have been strongly affected by the long-term impact of the vertebral fracture several years after diagnosis. The women strive to maintain their independence by trying to manage different types of symptoms and consequences in different ways.Conclusions and implications: Type and number of fractures should be taken into account in the case-finding strategy for osteoporosis in postmenopausal women between 55 and 75 years of age. The long-term reduction of HRQOL in postmenopausal women (age span 55-75 yr) with vertebral fracture emerged clearly, compared to women with other types of osteoporotic fractures and references in this thesis. The results ought to be taken into consideration when developing guidelines for more effective fracture prevention and treatment, including non-pharmacological intervention for women with osteoporotic fractures, with highest priority placed on vertebral fractures and multiple fractures, to increase or maintain HRQOL.
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| 8. |
- Olofsson, Birgitta, 1963-
(författare)
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Old people with femoral neck fracture : delirium, malnutrition and surgical methods - an intervention program
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hip fracture is a global and a growing public health problem. More women than men sustain hip fractures, the incidence increases exponentially with age and mean age is above 80. About one third of hip-fracture patients suffer from dementia and are prone to develop acute confusional state (delirium). Delirium is one of the most common complications after hip-fracture surgery, and seriously impacts on morbidity and mortality. Malnutrition is also common in hip-fracture patients and is associated with postoperative complications, such as delayed healing of the wound, infections and decubitus ulcers. Arthroplasty is usually preferred procedure in displaced femoral neck fractures but is, however, controversial in patients with dementia due to the fear of dislocation of the prosthesis. The aims of this thesis are to identify risk factors for delirium and the impact of delirium on rehabilitation outcome, to evaluate whether a postoperative multi-factorial intervention program could reduce delirium, to investigate the effect of a nutritional intervention and to evaluate complications, functional outcome and mortality regarding two surgical methods, hemiarthroplasty (HAP) and internal fixation (IF), in old patients with femoral neck fracture. Thirty-eight out of 61 consecutive patients (62%) were delirious on admission to hospital or developed postoperative delirium. An increased risk of postoperative delirium was found among hip-fracture patients with dementia and/or depression. Delirious patients were hospitalized longer, were more dependent in their activities of daily living, had poorer psychological well-being and suffered more complications than non-delirious patients. A postoperative multi-factorial and multidisciplinary intervention program reduced the incidence, at 55% vs 75% (p=0.003), and number of days with delirium, 5 vs 10 days (p=0.009). Postoperative complications were also reduced; decubitus ulcers 9% vs 22% (p= 0.010), urinary tract infections 31% vs 51% (p=0.005), falls 12% vs 27% (p=0.007), and the mean hospitalization period was 10 days shorter in the intervention group (p=0.030). Malnutrition was common among all these patients (53 %) and associated with postoperative complications such as decubitus ulcers and delirium. However, the nutritional intervention had no effect on nutritional parameters at four months, nevertheless men had better nutritional outcomes than women. A higher proportion of patients with dementia operated on using HAP had regained their pre-fracture ability to walk independently at the one-year follow up compared with those operated on using IF. Six of 83 patients dislocated their HAP during hospitalization and during an episode of delirium, none had dementia. No difference in mortality between the surgical methods was seen. Dementia per se should not be a reason to disqualify patients from being treated with the most appropriate surgical method. It is clinically important to discriminate between dementia and delirium, since delirium can be prevented and treated even in patients with dementia. Old patients undergoing surgery have special needs that are not always catered for in ordinary orthopaedic or surgical wards. The special care for these patients should include: a combined nursing and medical care based on comprehensive geriatric assessments, systematic prevention, detection and treatment of postoperative complications such as delirium, hypoxemia, urinary tract infections, pain, malnutrition and an active rehabilitation. It is obvious that improved quality of care reduces patient suffering and seemingly the costs for society.
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| 9. |
- Svensson, Olle, 1967-
(författare)
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Experimental results from the Lysekil Wave Power Research Site
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents how experimental results, from wave power research performed offshore at the Lysekil research site, were obtained. The data were used to verify theoretical models as well as evaluate the feasibility of wave power as a future sustainable energy source.The first experiments carried out at the research site was the measurement of the force in a line where one end was connected to a buoy with a diameter of 3 m and the other end to a set of springs with limited stroke length. The system is exposed to high peak forces compared to average forces. The maximum measured force in the line, when the buoy motion is limited by a stiff stopper rope is ten times the average force in that particular sea state.The experiment performed on the first wave energy converter tested at the Lysekil Research Site is described. The infrastructure of the site is presented where the central connection point is the measuring station. The key finding is that it is possible to transform the motions of ocean waves into electrical energy and distribute it to land.Many wave energy converters must be interconnected if large amounts of energy are to be harvested from the waves. The first submerged substation intended for aggregation of energy from wave power converters is described, with focus on the measurement and control system placed inside the substation. During this experiment period the generators were equipped with many different sensors; these measurements are explained in the thesis.The system that aggregates power from the studied wave energy converter is regularly exposed to peak power of up to 20 times the maximum average output from the converter.Vertical and horizontal movement of the buoy has been measured in different ways. The result is that the vertical displacement of the buoy can be measured with a simple accelerometer circuit but it is much more complicated to measure the horizontal displacement. A special method for measuring the horizontal displacement has been implemented by measuring the strain in the enclosure and the force in the line.
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| 10. |
- Hellström, Hans-Olov, 1962-
(författare)
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Bone and Aluminium
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis is a major health care problem, by reason of its devastating consequences, in particular hip fractures. Worldwide it has been estimated that the incidence of hip fracture will increase to more than 6 million per year by 2050 compared to 1.7 million per year in 1990. Osteoporosis can be caused by various factors namely, genetic, lifestyle and environmental factors, and since the rising incidence of its consequences is not fully explained by the growing age of the population, there is an urgent need to identify individual causal factors of this condition. The present research has focused on aluminium, one potential environmental factor of importance for bone disease, and its possible relation to osteoporosis, since it is known to cause osteoporosis-like bone disease and has been associated with induction of progressive central nervous system diseases.Aluminium is the third most common element in the earth’s crust and the most abundant metal (8%). It is widely utilized industrially and it is also naturally present in many foods. Although aluminium is ubiquitous in the human environment, evolution has not given it an essential biological function.The aluminium content of bone was measured by inductively coupled mass spectrometry in a large group of patients suffering from hip fractures, high energy fractures and osteoarthrosis. An exponential increase in aluminium content of bone with age was found (p=0.0004). However, no significant association of aluminium in bone with occurrence of hip fracture or dementia could be found, and no indirect evidence was obtained, e.g. through bone mineral density or biomechanical properties, that aluminium is involved in the pathogenesis of osteoporosis. Although we accumulate aluminium in bone throughout our lives, and there are experimental suggestions that aluminium induces premature cell death, the body content of this metal does not seem to influence the overall mortality risk.
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