Understanding solid-state transformations during dehydration: new insights using vibrational spectroscopy and multivariate modelling

Many active pharmaceutical ingredients (APIs) have both anhydrate and hydrate forms. Due to the different physicochemical properties of solid forms, the changes in solid-state may result in therapeutic, pharmaceutical, legal and commercial problems. In order to obtain good solid dosage form quality and performance, there is a constant need to understand and control these phase transitions during manufacturing and storage. Thus it is important to detect and also quantify the possible transitions between the different forms. In recent years, vibrational spectroscopy has become an increasingly popular tool to characterise the solid-state forms and their phase transitions. It offers several advantages over other characterisation techniques including an ability to obtain molecular level information, minimal sample preparation, and the possibility of monitoring changes non-destructively in-line. Dehydration is the phase transition of hydrates which is frequently encountered during the dosage form production and storage. The aim of the present thesis was to investigate the dehydration behaviour of diverse pharmaceutical hydrates by near infrared (NIR), Raman and terahertz pulsed spectroscopic (TPS) monitoring together with multivariate data analysis. The goal was to reveal new perspectives for investigation of the dehydration at the molecular level. Solid-state transformations were monitored during dehydration of diverse hydrates on hot-stage. The results obtained from qualitative experiments were used to develop a method and perform the quantification of the solid-state forms during process induced dehydration in a fluidised bed dryer. Both in situ and in-line process monitoring and quantification was performed. This thesis demonstrated the utility of vibrational spectroscopy techniques and multivariate modelling to monitor and investigate dehydration behaviour in situ and during fluidised bed drying. All three spectroscopic methods proved complementary in the study of dehydration. NIR spectroscopy models could quantify the solid-state forms in the binary system, but were unable to quantify all the forms in the quaternary system. Raman spectroscopy models on the other hand could quantify all four solid-state forms that appeared upon isothermal dehydration. The speed of spectroscopic methods makes them applicable for monitoring dehydration and the quantification of multiple forms was performed during phase transition. Thus the solid-state structure information at the molecular level was directly obtained. TPS detected the intermolecular phonon modes and Raman spectroscopy detected mostly the changes in intramolecular vibrations. Both techniques revealed information about the crystal structure changes. NIR spectroscopy, on the other hand was more sensitive to water content and hydrogen bonding environment of water molecules. This study provides a basis for real time process monitoring using vibrational spectroscopy during pharmaceutical manufacturing.

Towards real-time understanding of processes in pharmaceutical powder technology

There is a need for better understanding of the processes and new ideas to develop traditional pharmaceutical powder manufacturing procedures. Process analytical technology (PAT) has been developed to improve understanding of the processes and establish methods to monitor and control processes. The interest is in maintaining and even improving the whole manufacturing process and the final products at real-time. Process understanding can be a foundation for innovation and continuous improvement in pharmaceutical development and manufacturing. New methods are craved for to increase the quality and safety of the final products faster and more efficiently than ever before. The real-time process monitoring demands tools, which enable fast and noninvasive measurements with sufficient accuracy. Traditional quality control methods have been laborious and time consuming and they are performed off line i.e. the analysis has been removed from process area. Vibrational spectroscopic methods are responding this challenge and their utilisation have increased a lot during the past few years. In addition, other methods such as colour analysis can be utilised in noninvasive real-time process monitoring. In this study three pharmaceutical processes were investigated: drying, mixing and tabletting. In addition tablet properties were evaluated. Real-time monitoring was performed with NIR and Raman spectroscopies, colour analysis, particle size analysis and compression data during tabletting was evaluated using mathematical modelling. These methods were suitable for real-time monitoring of pharmaceutical unit operations and increase the knowledge of the critical parameters in the processes and the phenomena occurring during operations. They can improve our process understanding and therefore, finally, enhance the quality of final products.

Investigating physical properties of solid dosage forms during pharmaceutical processing : Process analytical applications of vibrational spectroscopy

In order to improve and continuously develop the quality of pharmaceutical products, the process analytical technology (PAT) framework has been adopted by the US Food and Drug Administration. One of the aims of PAT is to identify critical process parameters and their effect on the quality of the final product. Real time analysis of the process data enables better control of the processes to obtain a high quality product. The main purpose of this work was to monitor crucial pharmaceutical unit operations (from blending to coating) and to examine the effect of processing on solid-state transformations and physical properties. The tools used were near-infrared (NIR) and Raman spectroscopy combined with multivariate data analysis, as well as X-ray powder diffraction (XRPD) and terahertz pulsed imaging (TPI). To detect process-induced transformations in active pharmaceutical ingredients (APIs), samples were taken after blending, granulation, extrusion, spheronisation, and drying. These samples were monitored by XRPD, Raman, and NIR spectroscopy showing hydrate formation in the case of theophylline and nitrofurantoin. For erythromycin dihydrate formation of the isomorphic dehydrate was critical. Thus, the main focus was on the drying process. NIR spectroscopy was applied in-line during a fluid-bed drying process. Multivariate data analysis (principal component analysis) enabled detection of the dehydrate formation at temperatures above 45°C. Furthermore, a small-scale rotating plate device was tested to provide an insight into film coating. The process was monitored using NIR spectroscopy. A calibration model, using partial least squares regression, was set up and applied to data obtained by in-line NIR measurements of a coating drum process. The predicted coating thickness agreed with the measured coating thickness. For investigating the quality of film coatings TPI was used to create a 3-D image of a coated tablet. With this technique it was possible to determine coating layer thickness, distribution, reproducibility, and uniformity. In addition, it was possible to localise defects of either the coating or the tablet. It can be concluded from this work that the applied techniques increased the understanding of physico-chemical properties of drugs and drug products during and after processing. They additionally provided useful information to improve and verify the quality of pharmaceutical dosage forms

Onnistuneen ikääntymisen ymmärrystä rakentamassa : Fysioterapeuttiopiskelijoiden oppiminen kestävää kehitystä edistävän kasvatuksen kehyksessä

The purpose of the present study was to investigate the possibilities and interconnec-tions that exist concerning the relationship between the University of Applied Sci-ences and the Learning by Developing action model (LbD), on the one hand, and education for sustainable development and high-quality learning as a part of profes-sional competence development on the other. The research and learning environment was the Coping at Home research project and its Caring TV project, which provided the context of the Physiotherapy for Elderly People professional study unit. The re-searcher was a teacher and an evaluator of her own students learning. The aims of the study were to monitor and evaluate learning at the individual and group level using tools of high-quality learning − improved concept maps − related to understanding the projects core concept of successful ageing. Conceptions were evaluated through aspects of sustainable development and a conceptual basis of physiotherapy. As edu-cational research this was a multi-method case study design experiment. The three research questions were as follows. 1. What kind of individual conceptions and conceptual structures do students build concerning the concept of successful ageing? How many and what kind of concepts and propositions do they have a) before the study unit, b) after the study unit, c) after the social-knowledge building? 2. What kind of social-knowledge building exists? a) What kind of social learn-ing process exists? b) What kind of socially created concepts, propositions and conceptual structures do the students possess after the project? c) What kind of meaning does the social-knowledge building have at an individual level? 3. How do physiotherapy competences develop according to the results of the first and second research questions? The subjects were 22 female, third-year Bachelor of Physiotherapy students in Laurea University of Applied Sciences in Finland. Individual learning was evaluated in 12 of the 22 students. The data was collected as a part of the learning exercises of the Physiotherapy for Elderly People study unit, with improved concept maps both at individual and group levels. The students were divided into two social-knowledge building groups: the first group had 15 members and second 7 members. Each group created a group-level concept map on the theme of successful ageing. These face-to-face interactions were recorded with CMapTools and videotaped. The data consists of both individually produced concept maps and group-produced concept maps of the two groups and the videotaped material of these processes. The data analysis was carried out at the intersection of various research traditions. Individually produced data was analysed based on content analysis. Group-produced data was analysed based on content analysis and dialogue analysis. The data was also analysed by simple statistical analysis. In the individually produced improved concept maps the students conceptions were comprehensive, and the first concept maps were found to have many concepts unrelated to each other. The conceptual structures were between spoke structures and chain structures. Only a few professional concepts were evident. In the second indi-vidual improved concept maps the conception was more professional than earlier, particulary from the functional point of view. The conceptual structures mostly re-sembled spoke structures. After the second individual concept mapping social map-ping interventions were made in the two groups. After this, multidisciplinary concrete links were established between all concepts in almost all individual concept maps, and the interconnectedness of the concepts in different subject areas was thus understood. The conceptual structures were mainly net structures. The concepts in these individual concept maps were also found to be more professional and concrete than in the previ-ous concept maps of these subjects. In addition, the wider context dependency of the concepts was recognized in many individual concept maps. This implies a conceptual framework for specialists. The social-knowledge building was similar to a social learning process. Both socio-cultural processes and cognitive processes were found to develop students conceptual awareness and the ability to engage in intentional learning. In the knowl-edge-building process two aspects were found: knowledge creation and pedagogical action. The discussion during the concept-mapping process was similar to a shared thinking process. In visualising the process with CMapTools, students easily comple-mented each others thoughts and words, as if mutually telepathic . Synthesizing, supporting, asking and answering, peer teaching and counselling, tutoring, evaluating and arguing took place, and students were very active, self-directed and creative. It took hundreds of conversations before a common understanding could be found. The use of concept mapping in particular was very effective. The concepts in these group-produced concept maps were found to be professional, and values of sustainable development were observed. The results show the importance of developing the contents and objectives of the European Qualification Framework as well as education for sustainable development, especially in terms of the need for knowledge creation, global responsibility and systemic, holistic and critical thinking in order to develop clinical practice. Keywords: education for sustainable development, learning, knowledge building, improved concept map, conceptual structure, competence, successful ageing

Physical activity, fitness, abdominal obesity, and cardiovascular risk factors in Finnish men and women : The National FINRISK 2002 Study

Physical inactivity, low cardiorespiratory fitness, and abdominal obesity are direct and mediating risk factors for cardiovascular disease (CVD). The results of recent studies suggest that individuals with higher levels of physical activity or cardiorespiratory fitness have lower CVD and all-cause mortality than those with lower activity or fitness levels regardless of their level of obesity. The interrelationships of physical activity, fitness, and abdominal obesity with cardiovascular risk factors have not been studied in detail. The aim of this study was to investigate the associations of different types of leisure time physical activity and aerobic fitness with cardiovascular risk factors in a large population of Finnish adults. In addition, a novel aerobic fitness test was implemented and the distribution of aerobic fitness was explored in men and women across age groups. The interrelationships of physical activity, aerobic fitness and abdominal obesity were examined in relation to cardiovascular risk factors. This study was part of the National FINRISK Study 2002, which monitors cardiovascular risk factors in a Finnish adult population. The sample comprised 13 437 men and women aged 25 to 74 years and was drawn from the Population Register as a stratified random sample according to 10-year age groups, gender and area. A separate physical activity study included 9179 subjects, of whom 5 980 participated (65%) in the study. At the study site, weight, height, waist and hip circumferences, and blood pressure were measured, a blood sample was drawn, and an aerobic fitness test was performed. The fitness test estimated maximal oxygen uptake (VO2max) and was based on a non-exercise method by using a heart rate monitor at rest. Waist-to-hip ratio (WHR) was calculated by dividing waist circumference with hip circumference and was used as a measure of abdominal obesity. Participants filled in a questionnaire on health behavior, a history of diseases, and current health status, and a detailed 12-month leisure time physical activity recall. Based on the recall data, relative energy expenditure was calculated using metabolic equivalents, and physical activity was divided into conditioning, non-conditioning, and commuting physical activity. Participants aged 45 to 74 years were later invited to take part in a 2-hour oral glucose tolerance test with fasting insulin and glucose measurements. Based on the oral glucose tolerance test, undiagnosed impaired glucose tolerance and type 2 diabetes were defined. The estimated aerobic fitness was lower among women and decreased with age. A higher estimated aerobic fitness and a lower WHR were independently associated with lower systolic and diastolic blood pressure, lower total cholesterol and triglyceride levels, and with higher high-density lipoprotein (HDL) cholesterol and HDL to total cholesterol ratio. The associations of the estimated aerobic fitness with diastolic blood pressure, triglycerides, and HDL to total cholesterol ratio were stronger in men with a higher WHR. High levels of conditioning and non-conditioning physical activity were associated with lower high-sensitivity C-reactive protein (CRP) levels. High levels of conditioning and overall physical activities were associated with lower insulin and glucose levels. The associations were stronger among women than men. A better self-rated physical fitness was associated with a higher estimated aerobic fitness, lower CRP levels, and lower insulin and glucose levels in men and women. In each WHR third, the risk of impaired glucose tolerance and type 2 diabetes was higher among physically inactive individuals who did not undertake at least 30 minutes of moderate-intensity physical activity on five days per week. These cross-sectional data show that higher levels of estimated aerobic fitness and regular leisure time physical activity are associated with a favorable cardiovascular risk factor profile and that these associations are present at all levels of abdominal obesity. Most of the associations followed a dose-response manner, suggesting that already low levels of physical activity or fitness are beneficial to health and that larger improvements in risk factor levels may be gained from higher activity and fitness levels. The present findings support the recommendation to engage regularly in leisure time physical activity, to pursue a high level of aerobic fitness, and to prevent abdominal obesity.

The social patterning of health, smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004

The Baltic countries share public health problems typical of most Eastern European transition economies: morbidity and mortality from non-communicable diseases is higher than in Western European countries. This situation has many similarities compared to a neighbouring country, Finland during the late 1960s. There are reasons to expect that health disadvantage may be increasing among the less advantaged population groups in the Baltic countries. The evidence on social differences in health in the Baltic countries is, however, scattered to studies using different methodologies making comparisons difficult. This study aims to bridge the evidence gap by providing comparable standardized cross-sectional and time trend analyses to the social patterning of variation in health and two key health behaviours i.e. smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004 representing Eastern European transition countries and a stable Western European country. The data consisted of similar cross-sectional postal surveys conducted in 1994, 1996, 1998, 2000, 2002 and 2004 on adult populations (aged 20 64 years) in Estonia (n=9049), Latvia (n=7685), Lithuania (n=11634) and Finland (n=18821) in connection with the Finbalt Health Monitor project. The main statistical method was logistic regression analysis. Perceived health was found to be worse among both men and women in the Baltic countries than in Finland. Poor health was associated with older age and lower education in all countries studied. Urbanization and marital status were not consistently related to health. The existing educational inequalities in health remained generally stable over time from 1994 to 2004. In the Baltic countries, however, improvement in perceived health was mainly found among the better educated men and women. Daily smoking was associated with young age, lower education and psychological distress in all countries. Among women smoking was also associated with urbanisation in all countries except Estonia. Among Lithuanian women, the educational gradient in smoking was weakest, and the overall prevalence of smoking increased over time. Drinking was generally associated with young age among men and women, and with education among women. Better educated women were more often frequent drinkers and less educated binge drinkers. The exception was that in Latvian men and women both frequent drinking and binge drinking were associated with low education. In conclusion, the Baltic countries are likely to resemble Western European countries rather than other transition societies. While health inequalities did not markedly change, substantial inequalities do remain, and there were indications of favourable developments mainly among the better educated. Pressures towards increasing health inequalities may therefore be visible in the future, which would be in accordance with the results on smoking and drinking in this study.

Devolution of forest-related rights: Comparative analyses of six developing countries

The study focused on the different ways that forest-related rights can be devolved to the local level according to the current legal frameworks in Laos, Nepal, Vietnam, Kenya, Mozambique and Tanzania. The eleven case studies represented the main ways in which forest-related rights can be devolved to communities or households in these countries. The objectives of this study were to 1) analyse the contents and extent of forest-related rights that can be devolved to the local level, 2) develop an empirical typology that represents the main types of devolution, and 3) compare the cases against a theoretical ideal type to assess in what way and to what extent the cases are similar to or differ from the theoretical construct. Fuzzy set theory, Qualitative Comparative Analysis and ideal type analysis were used in analysing the case studies and in developing an empirical typology. The theoretical framework, which guided data collection and analyses, was based on institutional economics and theories on property rights, common pool resources and collective action. On the basis of the theoretical and empirical knowledge, the most important attributes of rights were defined as use rights, management rights, exclusion rights, transfer rights and the duration and security of the rights. The ideal type was defined as one where local actors have been devolved comprehensive use rights, extensive management rights, rights to exclude others from the resource and rights to transfer these rights. In addition, the rights are to be secure and held perpetually. The ideal type was used to structure the analysis and as a tool against which the cases were analysed. The contents, extent and duration of the devolved rights varied greatly. In general, the results show that devolution has mainly meant the transfer of use rights to the local level, and has not really changed the overall state control over forest resources. In most cases the right holders participate, or have a limited role in the decision making regarding the harvesting and management of the resource. There was a clear tendency to devolve the rights to enforce rules and to monitor resource use and condition more extensively than the powers to decide on the management and development of the resource. The empirical typology of the cases differentiated between five different types of devolution. The types can be characterised by the devolution of 1) restricted use and control rights, 2) extensive use rights but restricted control rights, 3) extensive rights, 4) insecure, short term use and restricted control rights, and 5) insecure extensive rights. Overall, the case studies conformity to the ideal type was very low: only two cases were similar to the ideal type, all other cases differed considerably from the ideal type. The restricted management rights were the most common reason for the low conformity to the ideal type (eight cases). In three cases, the short term of the rights, restricted transfer rights, restricted use rights or restricted exclusion rights were the reason or one of the reasons for the low conformity to the ideal type. In two cases the rights were not secure.

Automatic Lameness Detection in a Milking Robot : Instrumentation, measurement software, algorithms for data analysis and a neural network model

The aim of this thesis is to develop a fully automatic lameness detection system that operates in a milking robot. The instrumentation, measurement software, algorithms for data analysis and a neural network model for lameness detection were developed. Automatic milking has become a common practice in dairy husbandry, and in the year 2006 about 4000 farms worldwide used over 6000 milking robots. There is a worldwide movement with the objective of fully automating every process from feeding to milking. Increase in automation is a consequence of increasing farm sizes, the demand for more efficient production and the growth of labour costs. As the level of automation increases, the time that the cattle keeper uses for monitoring animals often decreases. This has created a need for systems for automatically monitoring the health of farm animals. The popularity of milking robots also offers a new and unique possibility to monitor animals in a single confined space up to four times daily. Lameness is a crucial welfare issue in the modern dairy industry. Limb disorders cause serious welfare, health and economic problems especially in loose housing of cattle. Lameness causes losses in milk production and leads to early culling of animals. These costs could be reduced with early identification and treatment. At present, only a few methods for automatically detecting lameness have been developed, and the most common methods used for lameness detection and assessment are various visual locomotion scoring systems. The problem with locomotion scoring is that it needs experience to be conducted properly, it is labour intensive as an on-farm method and the results are subjective. A four balance system for measuring the leg load distribution of dairy cows during milking in order to detect lameness was developed and set up in the University of Helsinki Research farm Suitia. The leg weights of 73 cows were successfully recorded during almost 10,000 robotic milkings over a period of 5 months. The cows were locomotion scored weekly, and the lame cows were inspected clinically for hoof lesions. Unsuccessful measurements, caused by cows standing outside the balances, were removed from the data with a special algorithm, and the mean leg loads and the number of kicks during milking was calculated. In order to develop an expert system to automatically detect lameness cases, a model was needed. A probabilistic neural network (PNN) classifier model was chosen for the task. The data was divided in two parts and 5,074 measurements from 37 cows were used to train the model. The operation of the model was evaluated for its ability to detect lameness in the validating dataset, which had 4,868 measurements from 36 cows. The model was able to classify 96% of the measurements correctly as sound or lame cows, and 100% of the lameness cases in the validation data were identified. The number of measurements causing false alarms was 1.1%. The developed model has the potential to be used for on-farm decision support and can be used in a real-time lameness monitoring system.

Environmental factors affecting the occurrence of periglacial landforms in Finnish Lapland: a numerical approach

Determination of the environmental factors controlling earth surface processes and landform patterns is one of the central themes in physical geography. However, the identification of the main drivers of the geomorphological phenomena is often challenging. Novel spatial analysis and modelling methods could provide new insights into the process-environment relationships. The objective of this research was to map and quantitatively analyse the occurrence of cryogenic phenomena in subarctic Finland. More precisely, utilising a grid-based approach the distribution and abundance of periglacial landforms were modelled to identify important landscape scale environmental factors. The study was performed using a comprehensive empirical data set of periglacial landforms from an area of 600 km2 at a 25-ha resolution. The utilised statistical methods were generalized linear modelling (GLM) and hierarchical partitioning (HP). GLMs were used to produce distribution and abundance models and HP to reveal independently the most likely causal variables. The GLM models were assessed utilising statistical evaluation measures, prediction maps, field observations and the results of HP analyses. A total of 40 different landform types and subtypes were identified. Topographical, soil property and vegetation variables were the primary correlates for the occurrence and cover of active periglacial landforms on the landscape scale. In the model evaluation, most of the GLMs were shown to be robust although the explanation power, prediction ability as well as the selected explanatory variables varied between the models. The great potential of the combination of a spatial grid system, terrain data and novel statistical techniques to map the occurrence of periglacial landforms was demonstrated in this study. GLM proved to be a useful modelling framework for testing the shapes of the response functions and significances of the environmental variables and the HP method helped to make better deductions of the important factors of earth surface processes. Hence, the numerical approach presented in this study can be a useful addition to the current range of techniques available to researchers to map and monitor different geographical phenomena.

Middleware for Mobile Sensing Applications in Urban Environments

Sensor networks represent an attractive tool to observe the physical world. Networks of tiny sensors can be used to detect a fire in a forest, to monitor the level of pollution in a river, or to check on the structural integrity of a bridge. Application-specific deployments of static-sensor networks have been widely investigated. Commonly, these networks involve a centralized data-collection point and no sharing of data outside the organization that owns it. Although this approach can accommodate many application scenarios, it significantly deviates from the pervasive computing vision of ubiquitous sensing where user applications seamlessly access anytime, anywhere data produced by sensors embedded in the surroundings. With the ubiquity and ever-increasing capabilities of mobile devices, urban environments can help give substance to the ubiquitous sensing vision through Urbanets, spontaneously created urban networks. Urbanets consist of mobile multi-sensor devices, such as smart phones and vehicular systems, public sensor networks deployed by municipalities, and individual sensors incorporated in buildings, roads, or daily artifacts. My thesis is that "multi-sensor mobile devices can be successfully programmed to become the underpinning elements of an open, infrastructure-less, distributed sensing platform that can bring sensor data out of their traditional close-loop networks into everyday urban applications". Urbanets can support a variety of services ranging from emergency and surveillance to tourist guidance and entertainment. For instance, cars can be used to provide traffic information services to alert drivers to upcoming traffic jams, and phones to provide shopping recommender services to inform users of special offers at the mall. Urbanets cannot be programmed using traditional distributed computing models, which assume underlying networks with functionally homogeneous nodes, stable configurations, and known delays. Conversely, Urbanets have functionally heterogeneous nodes, volatile configurations, and unknown delays. Instead, solutions developed for sensor networks and mobile ad hoc networks can be leveraged to provide novel architectures that address Urbanet-specific requirements, while providing useful abstractions that hide the network complexity from the programmer. This dissertation presents two middleware architectures that can support mobile sensing applications in Urbanets. Contory offers a declarative programming model that views Urbanets as a distributed sensor database and exposes an SQL-like interface to developers. Context-aware Migratory Services provides a client-server paradigm, where services are capable of migrating to different nodes in the network in order to maintain a continuous and semantically correct interaction with clients. Compared to previous approaches to supporting mobile sensing urban applications, our architectures are entirely distributed and do not assume constant availability of Internet connectivity. In addition, they allow on-demand collection of sensor data with the accuracy and at the frequency required by every application. These architectures have been implemented in Java and tested on smart phones. They have proved successful in supporting several prototype applications and experimental results obtained in ad hoc networks of phones have demonstrated their feasibility with reasonable performance in terms of latency, memory, and energy consumption.

Essays on corporate governance, stakeholders, and restructuring

This dissertation consists of an introductory section and three theoretical essays analyzing the interaction of corporate governance and restructuring. The essays adopt an incomplete contracts approach and analyze the role of different institutional designs to facilitate the alignment of the objectives of shareholders and management (or employees) over the magnitude of corporate restructuring. The first essay analyzes how a firm's choice of production technology affects the employees' human capital investment. In the essay, the owners of the firm can choose between a specific and a general technology that both require a costly human capital investment by the employees. The specific technology is initially superior in using the human capital of employees but, in contrast to the general technology, it is not compatible with future innovations. As a result, anticipated changes in the specific technology diminish the ex ante incentives of the employees to invest in human capital unless the shareholders grant the employees specific governance mechanisms (a right of veto, severance pay) so as to protect their investments. The results of the first essay indicate that the level of protection that the shareholders are willing to offer falls short of the socially desirable one. Furthermore, when restructuring opportunities become more abundant, it becomes more attractive both socially and from the viewpoint of the shareholders to initially adopt the general technology. The second essay analyzes how the allocation of authority within the firm interacts with the owners' choice of business strategy when the ability of the owners to monitor the project proposals of the management is biased in favor of the status quo strategy. The essay shows that a bias in the monitoring ability will affect not only the allocation of authority within the firm but also the choice of business strategy. Especially, when delegation has positive managerial incentive effects, delegation turns out to be more attractive under the new business strategy because the improved managerial incentives are a way for the owners to compensate their own reduced information gathering ability. This effect, however, simultaneously makes the owners hesitant to switch the strategy since it would involve a more frequent loss of control over the project choice. Consequently, the owners' lack of knowledge of the new business strategy may lead to a suboptimal choice of strategy. The third essay analyzes the implications of CEO succession process for the ideal board structure. In this essay, the presence of the departing CEO on the board facilitates the ability of the board to find a matching successor and to counsel him. However, the ex-CEO's presence may simultaneously also weaken the ability of the board to restructure since the predecessor may use the opportunity to distort the successor's project choice. The results of the essay suggest that the extent of restructuring gains, the firm's ability to hire good outside directors and the importance of board's advisory role affect at which point and for how long the shareholders may want to nominate the predecessor to the board.

Essays on Illegal Activities, Institutions and Economic Growth

In public economics, two extremist views on the functions of a government compete: one emphasizes government working for the public interest to provide value for the citizens, while another regards government mainly as a workhorse for private interests. Moreover, as the sole legitimate authority, the government has the right to define the rules and laws as well as to enforce them. With respect to regulation, two extremes arise: from too little regulation to too much of it. If the government does not function or ceases to exist, the state falls into anarchy or chaos (Somalia). If it regulates too much, it will completely suffocate private activities, which might be considered extralegal (the former Soviet Union). In this thesis I scrutinize the government s interventionist policies and evaluate the question of how to best promote economic well-being. The first two essays assume that the government s policies promote illegal activity. The first paper evaluates the interaction between the government and the mafia, and pays attention to the law enforcement of underground production. We show that the revenue-maximizing government will always monitor the shadow economy, as monitoring contributes to the government s revenue. In general, both legal and illegal firms are hurt by the entry of the mafia. It is, however, plausible that legal firms might benefit by the entry of the mafia if it competes with the government. The second paper tackles the issue of the measurement of the size of the shadow economy. To formulate policies it is essential to know what drives illegal economic activity; is it the tax burden, excess regulation, corruption or a weak legal environment? In this paper we propose an additional explanation for tax evasion and shadow production, namely cultural factors as manifested by religion as determinants of tax morality. According to our findings, Catholic and Protestant countries do not differ in their tax morale. The third paper contributes to the literature discussing the role of the government in promoting economic and productivity growth. Our main result is that, given the complex relationship between economic growth and economic freedom, marketization has not necessarily been beneficial in terms of growth. The last paper builds on traditional growth literature and revisits the debate on convergence clubs arising from demographic transition. We provide new evidence against the idea that countries within a club would converge over time. Instead, we propose that since the demographic transition is a dynamic process, one can expect countries to enter the last regime of stable, modern growth in stages.

Essays on Microcredit in Rural Bangladesh

This thesis is a collection of three essays on Bangladeshi microcredit. One of the essays examines the effect of microcredit on the cost of crime. The other two analyze the functioning mechanism of microcredit programs, i.e. credit allocation rules and credit recovery policy. In Essay 1, the demand for microcredit and its allocation rules is studied. Microcredit is claimed to be the most effective means of supplying credit to the poorest of the poor in rural Bangladesh. This fact has not yet been examined among households who demand microcredit. The results of this essay show that educated households are more likely to demand microcredit and its demand does not differ by sex. The results also show that microcredit programs follow different credit allocation rules for male and female applicants. Education is an essential characteristic for both sexes that credit programs consider in allocating credit. In Essay 2, the focus is to establish a link between microcredit and the incidence of rural crime in Bangladesh. The basic hypothesis is that microcredit programs jointly hold the group responsibility which provides an incentive for group members to protect each other from criminal gang in order to safeguard their own economic interests. The key finding of this essay is that the average cost of crime for non-borrowers is higher than that for borrowers. In particular, 10% increase in the credit reduces the costs of crime by 4.2%. The third essay analyzes the reasons of high repayment rate amid Bangladeshi microcredit programs. The existing literature argues that credit applicants are able to screen out the high risk applicants in the group formulation stage using their superior local information. In addition, due to the joint liability mechanism of the programs, group members monitor each others economic activities to ensure the minimal misuse of credit. The arguments in the literature are based on the assumption that once the credit is provided, credit programs have no further role in ensuring that repayments are honored by the group. In contrast, using survey data this essay documents that credit programs use in addition organizational pressures such as humiliation and harassment the non-payer to recover the unpaid installments. The results also show that the group mechanisms do not have a significant effect in recovering default dues.

Country-scale carbon accounting of the vegetation and mineral soils of Finland

The increase in global temperature has been attributed to increased atmospheric concentrations of greenhouse gases (GHG), mainly that of CO2. The threat of severe and complex socio-economic and ecological implications of climate change have initiated an international process that aims to reduce emissions, to increase C sinks, and to protect existing C reservoirs. The famous Kyoto protocol is an offspring of this process. The Kyoto protocol and its accords state that signatory countries need to monitor their forest C pools, and to follow the guidelines set by the IPCC in the preparation, reporting and quality assessment of the C pool change estimates. The aims of this thesis were i) to estimate the changes in carbon stocks vegetation and soil in the forests in Finnish forests from 1922 to 2004, ii) to evaluate the applied methodology by using empirical data, iii) to assess the reliability of the estimates by means of uncertainty analysis, iv) to assess the effect of forest C sinks on the reliability of the entire national GHG inventory, and finally, v) to present an application of model-based stratification to a large-scale sampling design of soil C stock changes. The applied methodology builds on the forest inventory measured data (or modelled stand data), and uses statistical modelling to predict biomasses and litter productions, as well as a dynamic soil C model to predict the decomposition of litter. The mean vegetation C sink of Finnish forests from 1922 to 2004 was 3.3 Tg C a-1, and in soil was 0.7 Tg C a-1. Soil is slowly accumulating C as a consequence of increased growing stock and unsaturated soil C stocks in relation to current detritus input to soil that is higher than in the beginning of the period. Annual estimates of vegetation and soil C stock changes fluctuated considerably during the period, were frequently opposite (e.g. vegetation was a sink but soil was a source). The inclusion of vegetation sinks into the national GHG inventory of 2003 increased its uncertainty from between -4% and 9% to ± 19% (95% CI), and further inclusion of upland mineral soils increased it to ± 24%. The uncertainties of annual sinks can be reduced most efficiently by concentrating on the quality of the model input data. Despite the decreased precision of the national GHG inventory, the inclusion of uncertain sinks improves its accuracy due to the larger sectoral coverage of the inventory. If the national soil sink estimates were prepared by repeated soil sampling of model-stratified sample plots, the uncertainties would be accounted for in the stratum formation and sample allocation. Otherwise, the increases of sampling efficiency by stratification remain smaller. The highly variable and frequently opposite annual changes in ecosystem C pools imply the importance of full ecosystem C accounting. If forest C sink estimates will be used in practice average sink estimates seem a more reasonable basis than the annual estimates. This is due to the fact that annual forest sinks vary considerably and annual estimates are uncertain, and they have severe consequences for the reliability of the total national GHG balance. The estimation of average sinks should still be based on annual or even more frequent data due to the non-linear decomposition process that is influenced by the annual climate. The methodology used in this study to predict forest C sinks can be transferred to other countries with some modifications. The ultimate verification of sink estimates should be based on comparison to empirical data, in which case the model-based stratification presented in this study can serve to improve the efficiency of the sampling design.

Microbe-induced activation of inflammatory cytokine response in human cells

Human body is in continuous contact with microbes. Although many microbes are harmless or beneficial for humans, pathogenic microbes possess a threat to wellbeing. Antimicrobial protection is provided by the immune system, which can be functionally divided into two parts, namely innate and adaptive immunity. The key players of the innate immunity are phagocytic white blood cells such as neutrophils, monocytes, macrophages and dendritic cells (DCs), which constantly monitor the blood and peripheral tissues. These cells are armed for rapid activation upon microbial contact since they express a variety of microbe-recognizing receptors. Macrophages and DCs also act as antigen presenting cells (APCs) and play an important role in the development of adaptive immunity. The development of adaptive immunity requires intimate cooperation between APCs and T lymphocytes and results in microbe-specific immune responses. Moreover, adaptive immunity generates immunological memory, which rapidly and efficiently protects the host from reinfection. Properly functioning immune system requires efficient communication between cells. Cytokines are proteins, which mediate intercellular communication together with direct cell-cell contacts. Immune cells produce inflammatory cytokines rapidly following microbial contact. Inflammatory cytokines modulate the development of local immune response by binding to cell surface receptors, which results in the activation of intracellular signalling and modulates target cell gene expression. One class of inflammatory cytokines chemokines has a major role in regulating cellular traffic. Locally produced inflammatory chemokines guide the recruitment of effector cells to the site of inflammation during microbial infection. In this study two key questions were addressed. First, the ability of pathogenic and non-pathogenic Gram-positive bacteria to activate inflammatory cytokine and chemokine production in different human APCs was compared. In these studies macrophages and DCs were stimulated with pathogenic Steptococcus pyogenes or non-pathogenic Lactobacillus rhamnosus. The second aim of this thesis work was to analyze the role of pro-inflammatory cytokines in the regulation of microbe-induced chemokine production. In these studies bacteria-stimulated macrophages and influenza A virus-infected lung epithelial cells were used as model systems. The results of this study show that although macrophages and DCs share several common antimicrobial functions, these cells have significantly distinct responses against pathogenic and non-pathogenic Gram-positive bacteria. Macrophages were activated in a nearly similar fashion by pathogenic S. pyogenes and non-pathogenic L. rhamnosus. Both bacteria induced the production of similar core set of inflammatory chemokines consisting of several CC-class chemokines and CXCL8. These chemokines attract monocytes, neutrophils, dendritic cells and T cells. Thus, the results suggest that bacteria-activated macrophages efficiently recruit other effector cells to the site of inflammation. Moreover, macrophages seem to be activated by all bacteria irrespective of their pathogenicity. DCs, in contrast, were efficiently activated only by pathogenic S. pyogenes, which induced DC maturation and production of several inflammatory cytokines and chemokines. In contrast, L. rhamnosus-stimulated DCs matured only partially and, most importantly, these cells did not produce inflammatory cytokines or chemokines. L. rhamnosus-stimulated DCs had a phenotype of "semi-mature" DCs and this type of DCs have been suggested to enhance tolerogenic adaptive immune responses. Since DCs have an essential role in the development of adaptive immune response the results suggest that, in contrast to macrophages, DCs may be able to discriminate between pathogenic and non-pathogenic bacteria and thus mount appropriate inflammatory or tolerogenic adaptive immune response depending on the microbe in question. The results of this study also show that pro-inflammatory cytokines can contribute to microbe-induced chemokine production at multiple levels. S. pyogenes-induced type I interferon (IFN) was found to enhance the production of certain inflammatory chemokines in macrophages during bacterial stimulation. Thus, bacteria-induced chemokine production is regulated by direct (microbe-induced) and indirect (pro-inflammatory cytokine-induced) mechanisms during inflammation. In epithelial cells IFN- and tumor necrosis factor- (TNF-) were found to enhance the expression of PRRs and components of cellular signal transduction machinery. Pre-treatment of epithelial cells with these cytokines prior to virus infection resulted in markedly enhanced chemokine response compared to untreated cells. In conclusion, the results obtained from this study show that pro-inflammatory cytokines can enhance microbe-induced chemokine production during microbial infection by providing a positive feedback loop. In addition, pro-inflammatory cytokines can render normally low-responding cells to high chemokine producers via enhancement of microbial detection and signal transduction.