| 1. |
- Tengdelius, Mattias, 1984-
(författare)
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Fucoidan-Mimetic Glycopolymers : Synthesis and Biomedical Applications
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The marine polysaccharide fucoidan has demonstrated several interesting biological properties, for instance being antiviral, anticoagulant, anti-inflammatory, anticancer, and platelet activating. Many of these properties are desirable for various biomedical applications. Yet, there are few reports on fucoidan being used in such applications. The reasons for this are primarily the heterogeneity and low structural reproducibility of fucoidan.This thesis describes the synthesis of polymers with pendant saccharides bearing the key structural features of fucoidan. These glycopolymers were synthesized via different radical polymerization techniques yielding polymers of different chain lengths and dispersity. These glycopolymers showed antiviral and platelet activating properties similar to those of natural fucoidan, thus making them fucoidan-mimetic glycopolymers. However, compared to fucoidan from natural sources, the fucoidan-mimetic glycopolymers had homogeneous and reproducible structures making them suitable for biomedical applications.Further studies demonstrated that platelet activation, caused by these glycopolymers, showed dose-response curves almost identical to fucoidan. The platelet activation was induced via intracellular signaling and caused platelet surface changes similar to those of fucoidan. Fucoidan-mimetic glycopolymers can therefore be used as unique biomolecular tools for studying the molecular and cellular responses of human platelets.Fucoidan-mimetic glycopolymers generally assert their antiviral activity by blocking viral entry to host cells, thus inhibiting spreading of the viral infection but not acting virucidal, i.e. not killing the viruses. Introduction of hydrophobic groups to the polymer’s chain ends improved the antiviral properties significantly and is an important step towards yielding glycopolymers with virucidal properties.The fucoidan-mimetic glycopolymers were also applied as capping agents when synthesizing gold nanoparticles. These fucoidan-mimetic glycopolymer coated gold nanoparticles showed improved colloidal stability compared to uncapped gold nanoparticles. Furthermore, the nanoparticles also demonstrated selective cytotoxicity against a human colon cancer cell line over fibroblast cells.
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| 2. |
- Holmberg, Susan, 1957-
(författare)
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Confronting Value Strain : Press Coverage of Health Care Reform in Sweden and the United States
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation examines the journalistic discourse surrounding health care reform debates in Sweden and the US in the early 1990's. It found that in both countries, the challenging value (i.e. collectivism in US, individualism in Sweden) was treated less favorably than the dominant value both in the journalistic text and in the choice of actors allowed to speak through the media. Journalists in both countries protected their own dominant value and helped to resist core value change, although they tended to allow actors to express challenging values more loudly than they themselves would do. Study based on qualitative and quantitative content analysis of New York Times, USA Today, Dagens Nyheter and Expressen 1992-1995.
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| 3. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 4. |
- Hällmark, Robert, 1981-
(författare)
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Composite Bridges : Innovative ways of achieving composite action
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The topic of this thesis is steel-concrete composite bridges and innovative ways of achieving composite action. The typical superstructure consists of three main components: the steel girders, the concrete deck slab and the shear connectors. The latter connects the steel and the concrete parts to each other, which enables a design where the parts are assumed to act as one structural member, the composite beam.The research presented in this thesis is primarily focused on different construction- and strengthening-methods, developed to reduce the impact on the road users, mainly by reducing the time spent on the construction site and the need of traffic restrictions.The prefabricated steel girders give composite bridges some advantages in the construction stage, in comparison to the more common in-situ cast concrete bridges, since the girders can be launched or lifted into their final positions. Such an installation procedure is often favourable in case of crossings over roads, railways, rivers etc., since it minimizes the impact on the citizens using the infrastructure below the bridges and the need of temporary supports. In order to shorten the time spent on the construction site and to reduce the impact on the road users even more, prefabrication of the concrete deck can also be considered.In this thesis, a review of different prefabrication techniques for composite bridges is presented, along with a study of one specific prefabrication concept that reduces the need of in-situ cast deck joints. This concept, with prefabricated concrete deck elements with dry joints, utilizes concrete shear keys to transfer shear forces over the transverse deck joints, while in-situ cast joints are used for the longitudinal connection between the steel girders and the concrete deck slab.The structural behaviour of composite bridges with dry deck joints has been investigated by large scale beam tests, along with field measurements on a composite bridge built with this prefabrication concept. The load capacity of the shear keys has also been investigated by laboratory tests. The test results have been compared to numerical analyses and different design models, with the aim of developing design recommendations.The results indicate that this type of bridges do not behave as conventional composite bridges with in-situ cast deck slabs. For single span bridges, which only experience positive bending moments, the structural behaviour in the ultimate limit state is close to the structural behaviour of conventional composite bridges. However, the degree of composite action is strongly reduced at lower load levels. This should be taken into account in the design in the fatigue- and the serviceability-limit states. Sections under negative bending moments behave in general as non-composite sections, which was expected due to the dry deck joints.Based on the evaluation of the test results and the state -of-the-art review, design recommendations and design criteria are presented, along with production and execution recommendations for this type of prefabricated bridges.Strengthening of existing bridges is another activity that often leads to traffic restrictions, which causes costs and troubles for the road users and the society. One method for strengthening non-composite steel-concrete bridges is post-installation of shear connectors, to create composite action. The composite cross-section has a larger stiffness and bending capacity, implying that a larger traffic load often can be allowed. It must however also be assured that other structural parts do not limit the load capacity of the structure.There are several different types of shear connectors that can be used for post-installation, and some are more suitable than others. This thesis presents a state-of-the-art review on post-installed shear connectors in general and Coiled Spring Pins in particular. The latter is an interference fit connector that can be installed from below the bridge, with no or minor impact on the traffic on the bridge.The behaviour of Coiled Spring Pins, used as shear connectors in composite bridges, has been investigated by experimental methods. Push-out tests have been used to study the static strength and the fatigue lifetime, while field monitoring of a real bridge structure has been used to study the behaviour on a structural level. The tests results have been evaluated and design criteria and design recommendations have been suggested.The static tests and the following analysis show that Coiled Spring Pins are a very ductile type of shear connector, with a slightly different load-deformation behaviour than headed shear studs. The static strength of the shear connection shows a quite small spread even when different parameters are varied quite a lot. The performed fatigue tests in dicate a fatigue strength that are somewhat lower than headed studs, in terms of detail category, while previous test series by other researchers indicate a higher fatigue strength than headed studs. It can be noted that there is a large scatter between the results from different test series, performed by different researchers. The reasons to this scatter are discussed in the thesis and a conservative fatigue design criterion is presented.The results from the field monitoring indicate that a bridge strengthened with Coiled Spring Pins behaves as a composite structure and that the Coiled Spring Pins reduce the slip significantly. The analysis of the test results shows that a design assuming full composite action, with rigid shear connection, describes the measured behaviour in a good way.Based on the state-of-the-art review and the different tests performed, design recommendations and criteria are presented, along with production and execution recommendations for post-installation of Coiled Spring Pins.
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| 5. |
- Pupkaite, Justina, 1988-
(författare)
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Collagen Hydrogels for Regenerative Medicine
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The need for regenerative therapies to repair damaged or deteriorated organs and tissues, such as heart, skin, and cornea, is rising due to donor shortage and aging of the world’s population. Many proposed regenerative therapeutic approaches include a combination of cells, bioactive compounds, and hydrogels. Although collagen hydrogels have shown a lot of promise in regenerative medicine research, there are still challenges in their design and application strategies. Therefore, this thesis describes the development of novel collagen hydrogel designs for improved use in tissue bonding, cell delivery, and myocardial infarction therapy applications.Firstly, a visible-light crosslinked collagen hydrogel for tissue photobonding was developed. Methacrylated collagen hydrogel was crosslinked using the photoinitiator rose Bengal and visible light. The properties of the resulting hydrogel were tunable by changing the hydrogel composition. Biomimetic and ex vivo skin models were used to demonstrate the ability of the hydrogel to bond tissues whose edges are separated. Additionally, using the hydrogel led to less scarring compared to traditional sutures in a mouse skin incision model.Secondly, collagen was modified with thiol groups to design a hydrogel crosslinked using the thiol-Michael addition click reaction for cell encapsulation and delivery. The hydrogels demonstrated excellent shear-thinning and self-healing properties, allowing for injection after the crosslinking was complete. Additionally, the hydrogels showed minimal swelling and maintained their shape in an aqueous buffer for a prolonged period. Cell encapsulation and delivery using the hydrogels was demonstrated in vitro with mesenchymal stromal cells and endothelial cells.Thirdly, recombinant human collagen III hydrogels were prepared by crosslinking the collagen with EDC and NHS. The hydrogels contained either 1% or 2% collagen. Therapeutic strategies for these hydrogels were investigated, including the timing and dosage of the treatment, in a mouse MI model. Comparing 1% hydrogel injection at a single early time point (3 h) and three time points (3 h, 7 and 14 days) post-MI revealed improved cardiac function, reduced scar size and inflammation, and increased vascularization in the single injection group. Additionally, increasing the collagen III dose to 2% in the hydrogel at a single early time point (3 h) injection did not confer any additional functional improvement compared to 1% and resulted in scar size and vascular density comparable to control (PBS injection). In summary, this work contributes to the development of collagen hydrogel therapies for regenerative medicine by presenting a visible-light crosslinked collagen hydrogel for tissue bonding, a novel click-crosslinked collagen hydrogel with excellent shear-thinning properties for cell delivery, and the use of a recombinant human collagen III hydrogel in post-MI therapy, highlighting the importance of optimizing the timing and dosage of biomaterial therapies.
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| 6. |
- Sorensen, Julie, 1968-
(författare)
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Social marketing for injury prevention : changing risk perceptions and safety-related behaviors among New York farmers
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the U.S., work-related death is an all too familiar occurrence on farms. Tractor overturns continue to be the most frequent cause of these fatalities. Efforts to alter farming’s ranking as one of the most deadly occupations in the country must provide proven strategies for the elimination of these preventable deaths. In the past, efforts to decrease the rate of overturn fatalities and injuries have largely focused onincreasing the proportion of tractors with a rollover protective structure (ROPS). These devices, in combination with seatbelts, are 99% effective in protecting the tractor operator from death or injury. Unfortunately, only 59% of U.S. tractors are currently equipped with ROPS. Due to the relative lack of political willpower to legislate ROPS installation and the less than encouraging response to education and awareness programs to date, it appeared necessary to explore alternative intervention strategies. The over-arching purpose of this thesis project has been to assess the utility of social marketing as a framework for developing effective health and safety interventions in the farm community. However, our specific objectives included; a more thorough understanding of the perceived barriers and motivators that influence farmer’s safety decisions, the design and evaluation of social marketing incentives developed to encourage safe behaviors and the evaluation of a social marketing campaign designed to positively impact farmer’s intentions and readiness to retrofit unsafe tractors. The research was by and large conducted in New York State and supported by grants from the National Institutes of Occupational Safety and Health (NIOSH). Previous research conducted in the New York farm community had indicated that small crop and livestock farmers would be an ideal intervention target for a social marketing tractor overturn intervention as their farms accounted for close to 85% of New York farms which lack or have only one ROPS protected tractor. A qualitative assessment of perceived barriers and motivators regarding retrofitting behaviors was performed with representatives of the small crop and livestock community. Grounded theory analysis of these in-depth interviews revealed several key categories which include: 1) risk becomes “normal”, 2) risk becomes part of a “farming identity”, and 3) risk becomes “cost-effective”. This information was used to design potential intervention incentives, such as toll-free assistance finding and purchasing ROPS, financial rebates, and campaign messages designed to address farmer’s stated concerns. Subsequent research included testing and revising messages and evaluating the effect of the different campaign incentives in a prospective quasirandomized controlled trial conducted in different regions of New York and Pennsylvania. The results indicate that social marketing offers a promising framework for the development of injury or fatality prevention programs in farm communities. Farmers in the social marketing region demonstrated the most significant changes in both behavioral intention and readiness to retrofit compared to farmers from other regions. Data also indicated that social norms strongly influence farmer’s decisions to work safely, as demonstrated by the strong correlations between behavioral intention measures and measures of social norms. As well as providing an assessment of the utility of social marketing as an intervention framework, the thesis provides a cogent example of how behavioral theories can be used in the design and evaluation of intervention programs. Both stages of change theory and the theory of planned behavior proved to be valuable for measuring dispositional and behavioral changes and for finetuning future interventions.
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