Studies on 68Ga-Based Agents for PET Imaging of Cancer and Inflammation

Studies on ⁶⁸Ga-Based Agents for PET Imaging of Cancer and Inflammation Positron emission tomography (PET) is based on the use of radiolabeled agents and facilitates in vivo imaging of biological processes, such as cancer. Because the detection of cancer is demanding and is often obscured by inflammation, there is a demand for better PET imaging agents. The aim was to preliminarily evaluate new PET agents for imaging cancer and inflammation using experimental models. ⁶⁸Ga-chloride and peptides, ⁶⁸Ga-labeled through 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), targeting matrix metalloproteinase-9 (MMP-9) were tested for tumor imaging. In addition, a ⁶⁸Ga-DOTA-conjugated peptide targeting vascular adhesion protein-1 (VAP-1), was tested for inflammation imaging. The ⁶⁸Ga-based imaging agents described here showed potential features by passing the essential in vitro tests, proceeding further to preclinical in vivo evaluation and being able to visualize the target. The target uptake and target-to-background ratios of ⁶⁸Ga-based agents were, however, not optimal. ⁶⁸Ga-chloride showed slow clearance caused by its binding to blood transferrin. In the case of ⁶⁸Ga-DOTA-peptides low in vivo stability and/or low lipophilicity led to too rapid blood clearance and urinary excretion. The properties of ⁶⁸Ga-labeled peptides are modifiable, as shown with matrix metalloproteinase-9 targeting ligands. In the conclusion of this PhD thesis, ⁶⁸Ga-based agents for PET imaging of cancer and inflammation could be applied in the development of drugs, earlier diagnostics and following-up of the efficacy of therapies.

Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Bonding of Composite Resin to Alumina and Zirconia Ceramics with Special Emphasis on Surface Conditioning and Use of Coupling Agents

Dental oxide ceramics have been inspired by their biocompability and mechanical properties which have made durable all-ceramic structures possible. Clinical longevity of the prosthetic structures is dependent on effective bonding with luting cements. As the initial shear bond strength values can be comparable with several materials and procedures, long-term durability is affected by ageing. Aims of the current study were: to measure the shear bond strength of resin composite-to-ceramics and to evaluate the longevity of the bond; to analyze factors affecting the bond, with special emphasis on: the form of silicatization of the ceramic surface; form of silanization; type of resin primer and the effect of the type of the resin composite luting cement; the effect of ageing in water was studied regarding its effect to the endurance of the bond. Ceramic substrates were alumina and yttrium stabilized zirconia. Ceramic conditioning methods included tribochemical silicatization and use of two silane couplings agents. A commercial silane primer was used as a control silane. Various combinations of conditioning methods, primers and resin cements were tested. Bond strengths were measured by shear bond strength method. The longevity of the bond was generally studied by thermocycling the materials in water. Additionally, in one of the studies thermal cycling was compared with long-term water storaging. Results were analysed statistically with ANOVA and Weibull analysis. Tribochemical treatment utilizing air pressure of 150 kPa resulted shear bond strengths of 11.2 MPa to 18.4 MPa and air pressure of 450 kPa 18.2 MPa to 30.5 MPa, respectively. Thermocycling of 8000 cycles or four years water storaging both decreased shear bond strength values to a range of 3.8 MPa to 7.2 MPa whereas initial situation varied from 16.8. Mpa to 23.0 MPa. The silane used in studies had no statistical significance. The use of primers without 10-MDP resulted spontaneous debonding during thermocycling or shear bond strengths below 5 MPa. As conclusion, the results showed superior long-term bonding with primers containing 10-MDP. Silicatization with silanizing showed improved initial shear bond strength values which considerably decreased with ageing in water. Thermal cycling and water storing for up to four years played the major role in reduction of bond strength, which could be due to thermal fatigue of the bonding interface and hydrolytic degradation of the silane coupled interface.

Accountability and corruption : a study into political institutions as referees between principals and agents

Representativ demokrati innebär att medborgare istället för att själv göra beslut i frågor som angår dem, ofta delegerar dylikt beslutsfattande till representanter. Det här betyder att viktiga beslut görs av personer som medborgarna i allmänhet inte känner speciellt väl, och i vars ageranden medborgarna endast har lite insyn. Vanliga medborgare och deras representanter har därtill ofta mycket olika intressen, d.v.s. har olika syn på vad som är viktigt. Representanterna har följaktligen både möjligheter och incitament att missbruka den makt som anförtrotts dem, bl.a. genom korrupt verksamhet. Denna avhandling analyserar mekanismer genom vilka korruption bland representanter kan förebyggas, och (då korrupta handlingar redan ägt rum) upptäckas. Avhandlingen granskar mekanismer som a) ger medborgare och andra ansvarsutkrävare mer information om representanternas målsättningar och ageranden, b) som tvingar representanterna att rättfärdiga sina ageranden gentemot medborgare och andra ansvarsutkrävare, och c) som gör det möjligt för medborgare och andra ansvarsutkrävare att straffa representanter som agerat korrupt. Avhandlingen hävdar att tillämpandet av dylika mekanismer minskar lockelsen för och möjligheterna att engagera sig i korrupta handlingar. Avhandlingen studerar de mekanismer för ansvarsutkrävande som skapas genom politiskt institutionsbyggande. Bl.a. analyseras i vilken grad olika valsystem och typer av maktfördelning gör det möjligt att hålla representanter till svars, och därmed förhindra och upptäcka korruption. Sambandet mellan institutionsbyggande, möjligheter till ansvarsutkrävande och förekomst av korruption studeras på såväl makro- som mikronivå. Studien på makronivå inkluderar ett flertal länder och analyserar sambandet med hjälp av statistisk analys. Studien på mikronivå däremot består av två fallstudier (Österrike och Botswana) och utgör en djupdykning i dessa länders politiska institutioner, möjligheter till ansvarsutkrävande inom ramen för institutionerna, och följder i form av korruption.

Effects of obtained benefits on willingness to pay and word-of-mouth behavior in newspaper industry

The purpose of this master’s thesis was to investigate the effects which benefits obtained from reading a newspaper and using its website have on behavioral outcomes such as word-of-mouth behavior and willingness to pay. Several other antecedents of willingness to pay have been used as the control variables. However, their interrelations haven’t been hypothesized. The empirical part focused on a case company – Finnish regional newspaper. Empirical research has been conducted using a quantitative method and data was collected via online survey placed on newspaper’s website during 2010. 1001 responses have been collected. The results showed that benefits obtained both from traditional printed newspaper and from online one have positive effects on the word-of-mouth about this newspaper and its website. However, it has been revealed that benefits obtained from reading the newspaper don’t have effect on the willingness to pay for this newspaper. Additionally, only interpersonal and convenience benefits obtained from using the newspaper’s website influence on the willingness to pay for it. Finally, willingness to pay for the bundle of printed newspaper and its website access is affected positively only by the information/learning benefits obtained from reading the newspaper and by the interpersonal benefits obtained from using the newspaper’s website.

Launch communications best practices: Online newspaper paywall context

The goal of the thesis is to identify the best practices of marketing communications in the context of online newspaper paywall launch. Theoretical point of views emphasize the value for the customer as an antecedent for a workable value proposition and marketing communications. Value-based communications contribute to the customer loyalty. The empirical evidence for this benchmark study was collected in seven company interviews. These firms represented several kinds of Finnish newspaper companies which had recently gone through the paywall launch and launch communications process. The results imply that there are multiple factors influencing on launch communications choices. However, recommendations can be drawn based on the common practices. The main managerial results were that the companies should utilize the online newspaper content and usage value as the core of the launch message, target both new and current readers and use multiple online and offline communications channels to reach the target audience. The launch communications message should be started with the emotional appeal, complemented with the more informative message later.

Future of Newspaper Business Models in Finland

The purpose of this Master’s thesis was to study the business model development in Finnish newspaper industry during the next then years through scenario planning. The objective was to see how will the business models develop amidst the many changes in the industry, what factors are affecting the change, what are the implications of these changes for the players in the industry and how should the Finnish newspaper companies evolve in order to succeed in the future. In this thesis the business model change is studied based on all the elements of business models, as it was discovered that the industry is too often focusing on changes in only few of those elements and a more broader view can provide valuable information for the companies. The results revealed that the industry is affected by many changes during the next ten years. Scenario planning provides a good tool for analyzing this change and for developing valuable options for businesses. After conducting series of interviews and discovering forces affecting the change, four different scenarios were developed centered on the role that newspaper will take and the level at which they are providing the content in the future. These scenarios indicated that there are varieties of options in the way the business models may develop and that companies should start making decisions proactively in order to succeed. As the business model elements are interdepended, changes made in the other elements will affect the whole model, making these decisions about the role and level of content important for the companies. In the future, it is likely that the Finnish newspaper industry will include many different kinds of business models, some of which can be drastically different from the current ones and some of which can still be similar, but take better into account the new kind of media environment.