Experimental Studies on Non-Metallic Composite Bone Implants With a Special Reference to Staphylococcal Biofilm Infection

Non-metallic implants made of bioresorbable or biostable synthetic polymers are attractive options in many surgical procedures, ranging from bioresorbable suture anchors of arthroscopic surgery to reconstructive skull implants made of biostable fiber-reinforced composites. Among other benefits, non-metallic implants produce less interference in imaging. Bioresorbable polymer implants may be true multifunctional, serving as osteoconductive scaffolds and as matrices for simultaneous delivery of bone enhancement agents. As a major advantage for loading conditions, mechanical properties of biostable fiber-reinforced composites can be matched with those of the bone. Unsolved problems of these biomaterials are related to the risk of staphylococcal biofilm infections and to the low osteoconductivity of contemporary bioresorbable composite implants. This thesis was focused on the research and development of a multifunctional implant model with enhanced osteoconductivity and low susceptibility to infection. In addition, the experimental models for assessment, diagnostics and prophylaxis of biomaterial-related infections were established. The first experiment (Study I) established an in vitro method for simultaneous evaluation of calcium phosphate and biofilm formation on bisphenol-Aglycidyldimethacrylate and triethylenglycoldimethacrylate (BisGMA-TEGDMA) thermosets with different content of bioactive glass 45S5. The second experiment (Study II) showed no significant difference in osteointegration of nanostructured and microsized polylactide-co-glycolide/β-tricalcium phosphate (PLGA /β-TCP) composites in a minipig model. The third experiment (Study III) demonstrated that positron emission tomography (PET) imaging with the novel 68Ga labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) CD33 related sialic-acid immunoglobulin like lectins (Siglec-9) tracer was able to detect inflammatory response to S. epidermidis and S. aureus peri-implant infections in an intraosseous polytetrafluoroethylene catheter model. In the fourth experiment (Study IV), BisGMATEGDMA thermosets coated with lactose-modified chitosan (Chitlac) and silver nanoparticles exhibited antibacterial activity against S. aureus and P. aeruginosa strains in an in vitro biofilm model and showed in vivo biocompatibility in a minipig model. In the last experiment (Study V), a selective androgen modulator (SARM) released from a poly(lactide)-co-ε-caprolactone (PLCL) polymer matrix failed to produce a dose-dependent enhancement of peri-implant osteogenesis in a bone marrow ablation model.

Determinants of Bone Strength and Predictors of Hip Fracture among Finnish Adults. Results from the Health 2000 Survey and the Mini-Finland Health Survey

The objective of this thesis was to identify the determinants of bone strength and predictors of hip fracture in representative samples of Finnish adults. A secondary objective was to construct a simple multifactorial model for hip fracture prediction over a 10-year follow-up period. The study was based on the Health 2000 Survey conducted during 2000 to 2001 (men and women aged 30 years or over, n=6 035) and the Mini-Finland Health Survey conducted during 1978 to 1980 (women aged 45 years or over, n=2 039). Study subjects participated in health interviews and comprehensive health examination. In the Health 2000 Survey, bone strength was assessed by means of calcaneal quantitative ultrasound (QUS). The follow-up information about hip fractures was drawn from the National Hospital Discharge Register. In this study, age, weight, height, serum 25-hydroxyvitamin D (S-25(OH)D), physical activity, smoking and alcohol consumption as well as menopause and eventual HRT in women were found to be associated with calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS). Parity was associated with a decreased risk of hip fracture in postmenopausal women. Age, height, weight or waist circumference, quantitative ultrasound index (QUI), S-25(OH)D and fall-related factors, such as maximal walking speed, Parkinson’s disease, and the number of prescribed CNS active medication were significant independent predictors of hip fracture. At the population level, the incremental value of QUS appeared to be minor in hip fracture prediction when the fall-related risk factors were taken into account. A simple multifactorial model for hip fracture prediction presented in this study was based on readily available factors (age, gender, height, waist circumference, and fallrelated factors). Prospective studies are needed to test this model in patient-based study populations.

The Impact of the 2007-2009 Financial Crisis on the Relationship between Central Bank Rates and the Corresponding Interbank Interest Rates in 2002-2014

The role of central banks throughout the global financial system has become even more important during and after the events of the financial crisis. In order to stabilize the market conditions and provide solid ground for future development, the central banks use discount rate as their primary monetary policy tool in many developed and emerging economies. The purpose of this thesis is to examine how the relationship between central bank rates and corresponding interbank rates has developed before, during and after the crisis period of 2007-2009 in five developed countries and five emerging market countries. The results indicate that during the before-crisis period the interest rate markets reacted diversely but the joint recovery attempts of global economies seem to have stabilized the reactions during and especially after the crisis. The crisis also seems to have highlighted the characteristics of each country’s survival strategy as the role of other policy instruments arose.

Reconstruction of cranial bone defects with fiber-reinforced composite–bioactive glass implants

A cranial bone defect may result after an operative treatment of trauma, infection, vascular insult, or tumor. New biomaterials for cranial bone defect reconstructions are needed for example to mimic the biomechanical properties and structure of cranial bone. A novel glass fiber-reinforced composite implant with bioactive glass particulates (FRC–BG, fiber-reinforced composite–bioactive glass) has osteointegrative potential in a preclinical setting. The aim of the first and second study was to investigate the functionality of a FRC–BG implant in the reconstruction of cranial bone defects. During the years 2007–2014, a prospective clinical trial was conducted in two tertiary level academic institutions (Turku University Hospital and Oulu University Hospital) to evaluate the treatment outcome in 35 patients that underwent a FRC–BG cranioplasty. The treatment outcome was good both in adult and pediatric patients. A number of conventional complications related to cranioplasty were observed. In the third study, a retrospective outcome evaluation of 100 cranioplasty procedures performed in Turku University Hospital between years 2002–2012 was conducted. The experimental fourth study was conducted to test the load-bearing capacity and fracture behavior of FRC–BG implants under static loading. The interconnective bars in the implant structure markedly increased the load-bearing capacity of the implant. A loading test did not demonstrate any protrusions of glass fibers or fiber cut. The fracture type was buckling and delamination. In this study, a postoperative complication requiring a reoperation or removal of the cranioplasty material was observed in one out of five cranioplasty patients. The treatment outcomes of cranioplasty performed with different synthetic materials did not show significant difference when compared with autograft. The FRC–BG implant was demonstrated to be safe and biocompatible biomaterial for large cranial bone defect reconstructions in adult and pediatric patients.

Development of 3D super-resolution tomographic STED microscopy and its application to studies on bone resorption

In this doctoral thesis, a tomographic STED microscopy technique for 3D super-resolution imaging was developed and utilized to observebone remodeling processes. To improve upon existing methods, wehave used a tomographic approach using a commercially available stimulated emission depletion (STED) microscope. A certain region of interest (ROI) was observed at two oblique angles: one at a standard inverted configuration from below (bottom view) and another from the side (side view) via a micro-mirror positioned close to the ROI. The two viewing angles were reconstructed into a final tomogram. The technique, named as tomographic STED microscopy, was able to achieve an axial resolution of approximately 70 nm on microtubule structures in a fixed biological specimen. High resolution imaging of osteoclasts (OCs) that are actively resorbing bone was achieved by creating an optically transparent coating on a microscope coverglass that imitates a fractured bone surface. 2D super-resolution STED microscopy on the bone layer showed approximately 60 nm of lateral resolution on a resorption associated organelle allowing these structures to be imaged with super-resolution microscopy for the first time. The developed tomographic STED microscopy technique was further applied to study resorption mechanisms of OCs cultured on the bone coating. The technique revealed actin cytoskeleton with specific structures, comet-tails, some of which were facing upwards and some others were facing downwards. This, in our opinion, indicated that during bone resorption, an involvement of the actin cytoskeleton in vesicular exocytosis and endocytosis is present. The application of tomographic STED microscopy in bone biology demonstrated that 3D super-resolution techniques can provide new insights into biological 3D nano-structures that are beyond the diffraction-limit when the optical constraints of super-resolution imaging are carefully taken into account.

“Who is steering the ship and which constellation guides the way? Exploring transparency in the European Central Bank during the time of crisis”

This paper explores transparency in the decision-making of the European Central Bank (ECB). According to ECB´s definition, transparency means that the central bank provides the general public with all relevant information on its strategy, assessments and policy decisions as well as its procedures in an open, clear and timely manner. In this paper, however, the interpretation of transparency is somewhat broader: Information is freely available and directly accessible to those who will be affected by the decisions. Moreover, the individuals shall be able to master this material. ECB´s negative attitude towards publication of documents has demonstrated central bank´s reluctance to strive towards more extensive transparency. By virtue of the definition adopted by the ECB the bank itself is responsible for determining what is considered as relevant information. On the grounds of EU treaties, this paper assesses ECB`s accountability concentrating especially on transparency by employing principal-agent theory and constitutional approach. Traditionally, the definite mandate and the tenet of central bank independence have been used to justify the limited accountability. The de facto competence of the ECB has, however, considerably expanded as the central bank has decisively resorted to non-standard measures in order to combat the economic turbulences facing Europe. It is alleged that non-standard monetary policy constitutes a grey zone occasionally resembling economic policy or fiscal policy. Notwithstanding, the European Court of Justice has repeatedly approved these measures. This dynamic interpretation of the treaties seems to allow temporarily exceptions from the central bank´s primary objective during extraordinary times. Regardless, the paper suggests that the accountability nexus defined in the treaties is not sufficient in order to guarantee the accountability of the ECB after the adoption of the new, more active role. Enhanced transparency would help the ECB to maintain its credibility. Investing in the quality of monetary dialogue between the Parliament and the ECB appears to constitute the most adequate and practicable method to accomplish this intention. As a result of upgraded transparency the legitimacy of the central bank would not solely rest on its policy outputs.

On site measurements of DC link electrolytic capacitor bank of frequency converter using constant DC magnetization of the motor

Preventive maintenance of frequency converters has been based on pre-planned replace-ment of wearing or ageing components. Exchange intervals follow component life-time expectations which are based on empirical knowledge or schedules defined by manufac-turer. However, the lifetime of a component can vary significantly, because drives are used in very different operating environments and applications. The main objective of the research was to provide information on methods, i.e. how in-verter's operating condition can be measured reliably under field conditions. At first, the research focused on critical components such as current transducers, IGBTs and DC link capacitor bank, because these aging have already been identified. Of these, the DC link capacitor measurement method was selected for closer examination. With this method, the total capacitance and its total series resistance can be measured. The suitability of the measuring procedure was estimated on the basis of practical measurements. The research was made by using so called triangulation method, including a literature review, simulations and practical measurements. Based on the results, the new measu-rement method seems suitable with some reservations to practical measurements. How-ever, the measuring method should be further developed in order to improve its reliability.

Bank Income Diversification and its Impact on Profitability and Risk: Evidence from Nordic Markets

Financial industry has recently encountered many changes in the business environment. Increased regulation together with growing competition is forcing commercial banks to rethink their business models. In order to maintain profitability in the new environment, banks are focusing more into activities that yield noninterest income. This is a shift away from the traditional intermediation function of banks. This study aims to answer the question if the shift from traditional income yielding activities to more innovative noninterest activities is logical in terms of profitability and risk in Nordics. This study also aims to answer the question if diversification within the noninterest income categories has impact on profitability and risk and if there are certain categories of noninterest income that are better than others in terms of profitability and risk in Nordics. Results show that diversification between interest and noninterest activities and increase in the share of noninterest income have a negative impact on the risk adjusted returns and risk profile. Results also show that further diversification within the noninterest income categories has negative impact on risk adjusted profitability and risk while an increase of the share of commission and fee income category of total noninterest income has a positive impact on risk adjusted profitability and risk. Results are logical and in line with previous research (De Young & Roland, 2001; Stiroh, 2004). Results provide useful information to banks and help them better evaluate outcomes of different income diversification strategies.