The cost of a road construction over its service life is a function of the design, quality of construction, maintenance strategies and maintenance operations. Unfortunately, designers often neglect a very important aspect which is the possibility to perform future maintenance activities. The focus is mainly on other aspects such as investment costs, traffic safety, aesthetic appearance, regional development and environmental effects. This licentiate thesis is a part of a Ph.D. project entitled “Road Design for lower maintenance costs” that aims to examine how the life-cycle costs can be optimized by selection of appropriate geometrical designs for the roads and their components. The result is expected to give a basis for a new method used in the road planning and design process using life-cycle cost analysis with particular emphasis on road maintenance. The project started with a review of literature with the intention to study conditions causing increased needs for road maintenance, the efforts made by the road authorities to satisfy those needs and the improvement potential by consideration of maintenance aspects during planning and design. An investigation was carried out to identify the problems which obstruct due consideration of maintenance aspects during the road planning and design process. This investigation focused mainly on the road planning and design process at the Swedish Road Administration. However, the road planning and design process in Denmark, Finland and Norway were also roughly evaluated to gain a broader knowledge about the research subject. The investigation was carried out in two phases: data collection and data analysis. Data was collected by semi-structured interviews with expert actors involved in planning, design and maintenance and by a review of design-related documents. Data analyses were carried out using a method called “Change Analysis”. This investigation revealed a complex combination of problems which result in inadequate consideration of maintenance aspects. Several urgent needs for changes to eliminate these problems were identified. Another study was carried out to develop a model for calculation of the repair costs for damages of different road barrier types and to analyse how factors such as road type, speed limits, barrier types, barrier placement, type of road section, alignment and seasonal effects affect the barrier damages and the associated repair costs. This study was carried out using a method called the “Case Study Research Method”. Data was collected from 1087 barrier repairs in two regional offices of the Swedish Road Administration, the Central Region and the Western Region. A table was established for both regions containing the repair cost per vehicle kilometre for different combinations of barrier types, road types and speed limits. This table can be used by the designers in the calculation of the life-cycle costs for different road barrier types. / QC 20101112

Epilepsy affects 3.4 million patients in the USA and is characterized by recurring seizures. The blood-brain barrier is leaky in epilepsy and may contribute to seizure progression but the mechanisms which cause this leakage are not fully understood. We hypothesized that seizures trigger LOX- and COX-mediated blood-brain barrier leakage and that dual LOX/COX inhibition prevents barrier leakage in vivo. To test this hypothesis, we administered either the dual LOX/COX inhibitor licofelone or a combination of the 5-LOX inhibitor zileuton and the COX-2 inhibitor celecoxib to rats that experienced status epilepticus (SE). Serum and brain capillaries were isolated 48 hours after SE and serum S100β levels were measured and Texas Red™ leakage rates were determined. Dual inhibition of 5-LOX and COX prevented serum S100β elevations observed in SE rats in a dose-dependent manner with licofelone. Inhibition of 5-LOX and COX-2 with zileuton and celecoxib completely prevented serum S100β elevation. Texas Red™ leakage rates for SE rats were also reduced in a dose-depended manner with licofelone and reduced to control rates with zileuton and celecoxib. These data support our hypothesis that seizure-induced blood-brain barrier leakage is mediated by LOX and COX, and inhibition of these enzymes prevents barrier leakage.

published_or_final_version / abstract / toc / Physics / Master / Master of Philosophy

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Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease in premature babies. Despite significant morbidity and mortality, the cause of this disease remains unclear and there are no preventative treatments available. Prematurity and enteral feeding of infant formula are considered to be the primary risk factors for development of NEC. Interestingly, the incidence of NEC is six to ten times lower in breast-fed babies compared to those that were formula-fed. The factors responsible for the protective effect of breast milk against NEC have not been identified, but epidermal growth factor (EGF) is one of the most promising candidates. EGF is found at high concentrations in human milk, but is not present in any commercial formula. Mothers with extremely premature babies have 50-80% higher levels of EGF in their breast milk compared to mothers with full term infants. This suggests that EGF plays an important role in the development of premature infants. Our studies have shown that supplementation of EGF into formula significantly reduces the incidence of NEC in a neonatal rat model. However, the mechanisms underlying this EGF-mediated reduction of NEC are not understood. The overall hypothesis of this dissertation is that the protective effect of EGF in NEC pathogenesis is mediated via increased expression of pro-survival genes and strengthening of the mucosal barrier. The results of the studies within this dissertation demonstrate that treatment with EGF significantly decreases intestinal epithelial cell apoptosis at the site of NEC injury by up-regulating anti-apoptotic genes and down-regulating pro-apoptotic genes. Furthermore, supplementation of formula with EGF strengthens the mucosal barrier by inducing accelerated maturation of ileal goblet cells and mucin-2 production. In addition, EGF treatment normalizes expression of crucial tight junction proteins in the ileum. Consequently, EGF treatment results in a significant decrease in intestinal paracellular permeability and improved barrier function. Results from these studies will provide significant contributions to the understanding of EGF-mediated reduction of NEC, which may lead to development of therapeutic strategies for the treatment of human NEC.

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