Liquid Chromatography-Mass Spectrometry in Studies of Drug Metabolism and Permeability

Poor pharmacokinetics is one of the reasons for the withdrawal of drug candidates from clinical trials. There is an urgent need for investigating in vitro ADME (absorption, distribution, metabolism and excretion) properties and recognising unsuitable drug candidates as early as possible in the drug development process. Current throughput of in vitro ADME profiling is insufficient because effective new synthesis techniques, such as drug design in silico and combinatorial synthesis, have vastly increased the number of drug candidates. Assay technologies for larger sets of compounds than are currently feasible are critically needed. The first part of this work focused on the evaluation of cocktail strategy in studies of drug permeability and metabolic stability. N-in-one liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the multiple component analysis of samples in cocktail experiments. Together, cocktail dosing and LC/MS/MS were found to form an effective tool for increasing throughput. First, cocktail dosing, i.e. the use of a mixture of many test compounds, was applied in permeability experiments with Caco-2 cell culture, which is a widely used in vitro model for small intestinal absorption. A cocktail of 7-10 reference compounds was successfully evaluated for standardization and routine testing of the performance of Caco-2 cell cultures. Secondly, cocktail strategy was used in metabolic stability studies of drugs with UGT isoenzymes, which are one of the most important phase II drug metabolizing enzymes. The study confirmed that the determination of intrinsic clearance (Clint) as a cocktail of seven substrates is possible. The LC/MS/MS methods that were developed were fast and reliable for the quantitative analysis of a heterogenous set of drugs from Caco-2 permeability experiments and the set of glucuronides from in vitro stability experiments. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), was evaluated through comparison with electrospray ionization (ESI), where both techniques were used for the analysis of Caco-2 samples. Like ESI, also APPI proved to be a reliable technique for the analysis of Caco-2 samples and even more flexible than ESI because of the wider dynamic linear range. The second part of the experimental study focused on metabolite profiling. Different mass spectrometric instruments and commercially available software tools were investigated for profiling metabolites in urine and hepatocyte samples. All the instruments tested (triple quadrupole, quadrupole time-of-flight, ion trap) exhibited some good and some bad features in searching for and identifying of expected and non-expected metabolites. Although, current profiling software is helpful, it is still insufficient. Thus a time-consuming largely manual approach is still required for metabolite profiling from complex biological matrices.

Socioeconomic Status, Occupational Factors and Lifestyle as Predictors of Hospitalisation for Back Disorders

The aim of this dissertation was to examine the determinants of severe back disorders leading to hospital admission in Finland. First, back-related hospitalisations were considered from the perspective of socioeconomic status, occupation, and industry. Secondly, the significance of psychosocial factors at work, sleep disturbances, and such lifestyle factors as smoking and overweight was studied as predictors of hospitalisation due to back disorders. Two sets of data were used: 1) the population-based data comprised all occupationally active Finns aged 25-64, and included hospitalisations due to back disorders in 1996 and 2) a cohort of employees followed up from 1973 to 2000 having been hospitalised due to back disorders. The results of the population-based study showed that people in physically strenuous industries and occupations, such as agriculture and manufacturing, were at an increased risk of being hospitalised for back disorders. The lowest hospitalisation rates were found in sedentary occupations. Occupational class and the level of formal education were independently associated with hospitalisation for back disorders. This stratification was fairly consistent across age-groups and genders. Men had a slightly higher risk of becoming hospitalised compared with women, and the risk increased with age among both genders. The results of the prospective cohort study showed that psychosocial factors at work such as low job control and low supervisor support predicted subsequent hospitalisation for back disorders even when adjustments were made for occupational class and physical workload history. However, psychosocial factors did not predict hospital admissions due to intervertebral disc disorders; only admissions due to other back disorders. Smoking and overweight predicted, instead, only hospitalisation for intervertebral disc disorders. These results suggest that the etiological factors of disc disorders and other back disorders differ from each other. The study concerning the association of sleep disturbances and other distress symptoms with hospitalisation for back disorders revealed that sleep disturbances predicted subsequent hospitalisation for all back disorders after adjustment for chronic back disorders and recurrent back symptoms at baseline, as well as for work-related load and lifestyle factors. Other distress symptoms were not predictive of hospitalisation.

Biological Control of Oilseed Rape Pests with Entomopathogenic Nematodes

Biological control techniques attract increasing attention as one of the sustainable alternatives to pesticide use in integrated pest management programs. In order to develop sustainable pest management methods for arable crops based on entomopathogenic nematodes (EPN), their efficacy and persistence needed to be investigated, and an economically feasible delivery system had to be developed. In this study, first a survey of entomopathogens was conducted, and a system approach was tested, using the oilseed Brassica (OSB) growing system (OSB, spring wheat, and red clover) as a model. The system approach aimed at determining the potential of Steinernema feltiae (Filipjev) for the control of OSB pests, developing OSB rotation schemes that support EPN persistence, and investigating the impact of the selected biotic and abiotic factors on efficacy and persistence of EPN. This study employed abductive logic (which employs constant interplay between the theory and empirical observation), quantitative methods, and a case study on OSB. Laboratory and field experiments were carried out, and two types of pathogen surveys. A horizontal survey included OSB fields across Estonia, Germany, Poland, Sweden and the UK, while a vertical survey included sampling from two sets of differently managed experimental fields during three years. A new approach was introduced for measuring occurrence, where the prevalence and relative intensity of entomopathogens, biotic agents, and unidentified insect antagonists were determined. The effect of dose, timing, and the application method on S. feltiae in the control of pests in OSB, and the potential of a controlled release delivery system (CRS) were evaluated in the field. Studies on the impact of selected biotic and abiotc factors (Brassica plant, bait insects, developmental stages of Meligethes aeneus Fab., Isaria fumosorosea Wize (Ifr), and organic and synthetic fertilizers) on the efficacy of S. feltiae were conducted in the laboratory. Persistence of S. feltiae in the OSB growing system, and the effect of dose, timing, and the application method, was assessed in the field as part of the efficacy experiments. The impact of selected biotic and abiotic factors on S. feltiae persistence was assessed in laboratory experiments. The pathogen survey showed that the occurrence of entomopathogens is low in the OSB growing system, and that a management system causing less disturbance (ICM) to the soil increases the relative intensity of insect parasitic nematodes and other insect antagonists. A longer study period is required to show any possible impact of ICM on the relative intensity of entomopathogenic fungi, or on the prevalence of entomopathogens. Two different measures of the occurrence yielded different results: the relative intensity revealed the difference between the two different crop management methods, while prevalence did not. The highest efficacy of S. feltiae was achieved by using a low dose and targeting all stages of M. aeneus. When only the larval stage was targeted, the application method and dose had no significant effect. The CRS decreased the pest abundance significantly more than the surface application method. S. feltiae persisted in the OSB fields in Finland for several months, but did not survive the winter. The strain survived for 7 months when it was applied in autumn in Germany, but its populations declined rapidly after winter. The examined biotic and abiotic factors had variable impacts on S. feltiae efficacy and persistence. The two measures, prevalence and relative intensity of entomopathogens, gave valuable information for their use in biocontrol programs. The recommended biocontrol strategy for OSB growing in Finland is inundation and seasonal inoculation of EPN. The impact of some biotic and abiotic factors on S. feltiae efficacy and persistence is significant, and can be used to improve the efficacy of EPN. The CRS is a novel alternative for EPN application, and should also be considered for use on other crops. Keywords: Biological control, inundation, inoculation, conservation, formulation, slow release method, crop rotation, Entomopathogenic nematodes, Steinernema feltiae, oilseed rape pests, Meligethes aeneus, Phyllotreta spp., occurrence, prevalence, intensity, efficacy, persistence, field, Isaria fumosorosea, biotic factors, abiotic factors, interaction, impact, insect stages, integrated crop management, standard (conventional) crop management

On Orlicz-Sobolev capacities

This thesis consists of three articles on Orlicz-Sobolev capacities. Capacity is a set function which gives information of the size of sets. Capacity is useful concept in the study of partial differential equations, and generalizations of exponential-type inequalities and Lebesgue point theory, and other topics related to weakly differentiable functions such as functions belonging to some Sobolev space or Orlicz-Sobolev space. In this thesis it is assumed that the defining function of the Orlicz-Sobolev space, the Young function, satisfies certain growth conditions. In the first article, the null sets of two different versions of Orlicz-Sobolev capacity are studied. Sufficient conditions are given so that these two versions of capacity have the same null sets. The importance of having information about null sets lies in the fact that the sets of capacity zero play similar role in the Orlicz-Sobolev space setting as the sets of measure zero do in the Lebesgue space and Orlicz space setting. The second article continues the work of the first article. In this article, it is shown that if a Young function satisfies certain conditions, then two versions of Orlicz-Sobolev capacity have the same null sets for its complementary Young function. In the third article the metric properties of Orlicz-Sobolev capacities are studied. It is usually difficult or impossible to calculate a capacity of a set. In applications it is often useful to have estimates for the Orlicz-Sobolev capacities of balls. Such estimates are obtained in this paper, when the Young function satisfies some growth conditions.

Computational Identification of Recessive Mutations in Cancers using High Throughput SNP-arrays

This thesis presents a highly sensitive genome wide search method for recessive mutations. The method is suitable for distantly related samples that are divided into phenotype positives and negatives. High throughput genotype arrays are used to identify and compare homozygous regions between the cohorts. The method is demonstrated by comparing colorectal cancer patients against unaffected references. The objective is to find homozygous regions and alleles that are more common in cancer patients. We have designed and implemented software tools to automate the data analysis from genotypes to lists of candidate genes and to their properties. The programs have been designed in respect to a pipeline architecture that allows their integration to other programs such as biological databases and copy number analysis tools. The integration of the tools is crucial as the genome wide analysis of the cohort differences produces many candidate regions not related to the studied phenotype. CohortComparator is a genotype comparison tool that detects homozygous regions and compares their loci and allele constitutions between two sets of samples. The data is visualised in chromosome specific graphs illustrating the homozygous regions and alleles of each sample. The genomic regions that may harbour recessive mutations are emphasised with different colours and a scoring scheme is given for these regions. The detection of homozygous regions, cohort comparisons and result annotations are all subjected to presumptions many of which have been parameterized in our programs. The effect of these parameters and the suitable scope of the methods have been evaluated. Samples with different resolutions can be balanced with the genotype estimates of their haplotypes and they can be used within the same study.

Where and how to conserve: Extending the scope of spatial reserve network design

Ongoing habitat loss and fragmentation threaten much of the biodiversity that we know today. As such, conservation efforts are required if we want to protect biodiversity. Conservation budgets are typically tight, making the cost-effective selection of protected areas difficult. Therefore, reserve design methods have been developed to identify sets of sites, that together represent the species of conservation interest in a cost-effective manner. To be able to select reserve networks, data on species distributions is needed. Such data is often incomplete, but species habitat distribution models (SHDMs) can be used to link the occurrence of the species at the surveyed sites to the environmental conditions at these locations (e.g. climatic, vegetation and soil conditions). The probability of the species occurring at unvisited location is next predicted by the model, based on the environmental conditions of those sites. The spatial configuration of reserve networks is important, because habitat loss around reserves can influence the persistence of species inside the network. Since species differ in their requirements for network configuration, the spatial cohesion of networks needs to be species-specific. A way to account for species-specific requirements is to use spatial variables in SHDMs. Spatial SHDMs allow the evaluation of the effect of reserve network configuration on the probability of occurrence of the species inside the network. Even though reserves are important for conservation, they are not the only option available to conservation planners. To enhance or maintain habitat quality, restoration or maintenance measures are sometimes required. As a result, the number of conservation options per site increases. Currently available reserve selection tools do however not offer the ability to handle multiple, alternative options per site. This thesis extends the existing methodology for reserve design, by offering methods to identify cost-effective conservation planning solutions when multiple, alternative conservation options are available per site. Although restoration and maintenance measures are beneficial to certain species, they can be harmful to other species with different requirements. This introduces trade-offs between species when identifying which conservation action is best applied to which site. The thesis describes how the strength of such trade-offs can be identified, which is useful for assessing consequences of conservation decisions regarding species priorities and budget. Furthermore, the results of the thesis indicate that spatial SHDMs can be successfully used to account for species-specific requirements for spatial cohesion - in the reserve selection (single-option) context as well as in the multi-option context. Accounting for the spatial requirements of multiple species and allowing for several conservation options is however complicated, due to trade-offs in species requirements. It is also shown that spatial SHDMs can be successfully used for gaining information on factors that drive a species spatial distribution. Such information is valuable to conservation planning, as better knowledge on species requirements facilitates the design of networks for species persistence. This methods and results described in this thesis aim to improve species probabilities of persistence, by taking better account of species habitat and spatial requirements. Many real-world conservation planning problems are characterised by a variety of conservation options related to protection, restoration and maintenance of habitat. Planning tools therefore need to be able to incorporate multiple conservation options per site, in order to continue the search for cost-effective conservation planning solutions. Simultaneously, the spatial requirements of species need to be considered. The methods described in this thesis offer a starting point for combining these two relevant aspects of conservation planning.

Slogans of Change : Three Outlooks on Finnish Television

The study Slogans of Change. Three Outlooks on Finnish Television Contents is concerned with alleged changes of television contents during the 1990s and 2000s, such as dumbing down, tabloidisation, entertainisation , and the like. Specifically, the focus is on the ways these changes might manifest in Finnish television. The aim of the study has been threefold: 1. To operationalise public and academic discussions about changes via specific slogans emerging from the debates; 2. Consequently, to study the slogans empirically and reflect on the findings with earlier research, including studies on institutional and audience-related aspects; 3. Finally, to suggest what the findings might mean regarding discussions about television s role, and what kinds of slogans or concepts might best serve future discussions and research. The empirical outlooks presented in this study offer analyses with three different sets of opposing slogans of change. The outlooks also follow three different traditions of the study of television. The first outlook focuses on quantity, as it gives a longitudinal (1993-2004), macro-level view on programme structures. The methodological approach is derived from media economic and policy studies. The claims that frame the analysis are convergence versus diversification of programme structures. The second outlook provides quantitative and qualitative views on the characteristics and quality  the term signifying essence as well as worth  of Finnish television journalism during sample weeks from the years 2002 and 2003. This outlook follows the traditions of quantitative content analysis found in journalism studies coupled with descriptive qualitative content analyses. The slogans reflected in this section are the lightening or widening of journalism. The third outlook narrows down the material and focuses at a micro-level on form; that is, communicative conventions in a small array of selected programmes in 1993, 2000 and during 2002-2004. The analyses have been inspired by the method of conversation analysis of verbal interaction, and coupled with qualitative close readings, with the focus of different communicative situations in the programmes. The catchphrases employed in this part are emotainment versus democratainment, coupled with more specific claims of discursive hybridisation and conversationalisation. The findings depict that, empirically, changes in Finnish television contents are not clear linear trends and cannot easily be moulded into neat slogans. The quantitative outlook on programme output during 1993-2004 depicts a tendency towards differentiation of channels, paving the way for the multi-channel digital system. The change in programme structures, however, is not dramatic on the level of total output. The second outlook suggests that the dualistic concepts, such as the pair information-entertainment, are not sufficient in understanding the array and changes of programmes that could be called journalism. The outlook on communicative conventions highlights hybridisation in the manner of television talk and its relation to broader debates on contents. Despite the three dissimilar empirical approaches, unifying aspects emerge. The outlooks suggest, albeit in different ways, tendencies toward distinction and polarisation. This study proposes that in order to facilitate a more nuanced understanding of the changes in television contents, dualistic slogans should be replaced with a multi-dimensional understanding of the concept of diversity.

Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.

Growing up in Affiliation with a Religious Community : A Case Study of Seventh-day Adventist Youth in Finland

This study investigates how the religious community as a socialization context affects the development of young people's religious identity and values, using Finnish Seventh-day Adventism as a context for the case study. The research problem is investigated through the following questions: (1) What aspects support the intergenerational transmission of values and tradition in religious home education? (2) What is the role of social capital and the social networks of the religious community in the religious socialization process? (3) How does the religious composition of the peer group at school (e.g., a denominational school in comparison to a mainstream school) affect these young people s social relations and choices and their religious identity (as challenged versus as reinforced by values at school)? And (4) How do the young people studied negotiate their religious values and religious membership in the diverse social contexts of the society at large? The mixed method study includes both quantitative and qualitative data sets (3 surveys: n=106 young adults, n=100 teenagers, n=55 parents; 2 sets of interviews: n=10 young adults and n=10 teenagers; and fieldwork data from youth summer camps). The results indicate that, in religious home education, the relationship between parents and children, the parental example of a personally meaningful way of life, and encouraging critical thinking in order for young people to make personalized value choices were important factors in socialization. Overall, positive experiences of the religion and the religious community were crucial in providing direction for later choices of values and affiliations. Education that was experienced as either too severe or too permissive was not regarded as a positive influence for accepting similar values and lifestyle choices to those of the parents. Furthermore, the religious community had an important influence on these young people s religious socialization in terms of the commitment to denominational values and lifestyle and in providing them with religious identity and rooting them in the social network of the denomination. The network of the religious community generated important social resources, or social capital, for both the youth and their families, involving both tangible and intangible benefits, and bridging and bonding effects. However, the study also illustrates the sometimes difficult negotiations the youth face in navigating between differentiation and belonging when there is a tension between the values of a minority group and the larger society, and one wants to and does belong to both. It also demonstrates the variety within both the majority and the minority communities in society, as well as the many different ways one can find a personally meaningful way of being an Adventist. In the light of the previous literature about socialization-in-context in an increasingly pluralistic society, the findings were examined at four levels: individual, family, community and societal. These were seen as both a nested structure and as constructing a funnel in which each broader level directs the influences that reach the narrower ones. The societal setting directs the position and operation of religious communities, families and individuals, and the influences that reach the developing children and young people are in many ways directed by societal, communal and family characteristics. These levels are by nature constantly changing, as well as being constructed of different parts, like the pieces of a jigsaw puzzle, each of which alters in significance: for some negotiations on values and memberships the parental influence may be greater, whereas for others the peer group influences are. Although agency does remain somewhat connected to others, the growing youth are gradually able to take more responsibility for their own choices and their agency plays a crucial role in the process of choosing values and group memberships. Keywords: youth, community, Adventism, socialization, values, identity negotiations

The Value of Being on the Net- the effects of Web sites of companies on consumer decision making

The unique characteristics of marketspace in combination with the fast growing number of consumers interested in e-commerce have created new research areas of interest to both marketing and consumer behaviour researchers. Consumer behaviour researchers interested in the decision making processes of consumers have two new sets of questions to answer. The first set of questions is related to how useful theories developed for a marketplace are in a marketspace context. Cyber auctions, Internet communities and the possibilities for consumers to establish dialogues not only with companies but also with other consumers make marketspace unique. The effects of these distinctive characteristics on the behaviour of consumers have not been systematically analysed and therefore constitute the second set of questions which have to be studied. Most companies feel that they have to be online even though the effects of being on the Net are not unambiguously positive. The relevance of the relationship marketing paradigm in a marketspace context have to be studied. The relationship enhancement effects of websites from the customers’ point of view are therefore emphasized in this research paper. Representatives of the Net-generation were analysed and the results show that companies should develop marketspace strategies while Net presence has a value-added effect on consumers. The results indicate that the decision making processes of the consumers are also changing as a result of the progress of marketspace

Forest governance and climate change adaptation : Case studies of four African countries

Africa is threatened by climate change. The adaptive capacity of local communities continues to be weakened by ineffective and inefficient livelihood strategies and inappropriate development interventions. One of the greatest challenges for climate change adaptation in Africa is related to the governance of natural resources used by vulnerable poor groups as assets for adaptation. Practical and good governance activities for adaptation in Africa is urgently and much needed to support adaptation actions, interventions and planning. The adaptation role of forests has not been as prominent in the international discourse and actions as their mitigation role. This study therefore focused on the forest as one of the natural resources used for adaptation. The general objective of this research was to assess the extent to which cases of current forest governance practices in four African countries Burkina Faso, The Democratic Republic of Congo (DRC), Ghana and Sudan are supportive to the adaptation of vulnerable societies and ecosystems to impacts of climate change. Qualitative and quantitative analyses from surveys, expert consultations and group discussions were used in analysing the case studies. The entire research was guided by three conceptual sets of thinking forest governance, climate change vulnerability and ecosystem services. Data for the research were collected from selected ongoing forestry activities and programmes. The study mainly dealt with forest management policies and practices that can improve the adaptation of forest ecosystems (Study I) and the adaptive capacity through the management of forest resources by vulnerable farmers (Studies II, III, IV and V). It was found that adaptation is not part of current forest policies, but, instead, policies contain elements of risk management practices, which are also relevant to the adaptation of forest ecosystems. These practices include, among others, the management of forest fires, forest genetic resources, non-timber resources and silvicultural practices. Better livelihood opportunities emerged as the priority for the farmers. These vulnerable farmers had different forms of forest management. They have a wide range of experience and practical knowledge relevant to ensure and achieve livelihood improvement alongside sustainable management and good governance of natural resources. The contributions of traded non-timber forest products to climate change adaptation appear limited for local communities, based on their distribution among the stakeholders in the market chain. Plantation (agro)forestry, if well implemented and managed by communities, has a high potential in reducing socio-ecological vulnerability by increasing the food production and restocking degraded forest lands. Integration of legal arrangements with continuous monitoring, evaluation and improvement may drive this activity to support short, medium and long term expectations related to adaptation processes. The study concludes that effective forest governance initiatives led by vulnerable poor groups represent one practical way to improve the adaptive capacities of socio-ecological systems against the impacts of climate change in Africa.

Theorizing the Nature of Reflection

For the past decades reflection has been the buzzword of adult and higher education. Reflection is facilitated in many practices and there is abundant research on the issue. Despite the popularity of the concept, the reasons why bringing about reflection in educational practices is difficult remain unclear. The prevailing theories inform of the process in its ideal form. However, to a great extent, they fail to offer conceptual tools for understanding and working with the actualities of reflection. The aim of the doctoral thesis was to explore the challenges and prerequisites of reflection in order to theorize the nature of reflection. By the term reflection it is here referred to becoming aware of and questioning the assumptions that orient our thinking, feelings and actions. The doctoral thesis consists of five studies that approach these questions from different viewpoints and within different contexts. The methods involve both a philosophical and an empirical approach. This multifaceted approach embodies the aim of both gaining a more thorough grasp of the phenomenon and to develop the methodology of researching reflection. The theory building is based on conceptual analysis and rational reconstruction (see Davia 1998; Habermas 1979; Rorty1984) of Mezirow s (1981; 1991; 2000; 2009) theory of transformative learning. In order to explore the aspects which, based on the analysis, appeared insufficiently considered within Mezirow s theory, Damasio s (1994; 1999; 2003; 2010) theory on emotions and consciousness as well as Clausewitz s (1985) view on friction are used as complementary theories. Empirical analyses are used in dialogue with the theoretical, in order to challenge and refine the emerging theorization. Reflection is examined in three different contexts; regarding university teachers pedagogical growth, involuntarily childless women recovering from a life-event crisis, and soldiers preparing to act in chaotic situations of the battlefield as well as recovering from it. The choice of these contexts is based on Mezirow s notion of disorienting dilemma as a trigger for reflection. This notion indicates that reflection may more naturally emerge in association to life-event crises or other cumulative sets of instances, which bring our worldview and beliefs under question. Nevertheless, reflection is often being promoted in educational contexts in which the trigger conditions may not readily prevail. These contextual issues as well as the differences between the facilitated and non-facilitated contexts have not, however, been considered in detail within the research on reflection (or transformative learning). The doctoral thesis offers a new perspective into reflection which, as a further development on Mezirow s transformative learning theory, theorizes the nature of reflection. The developed theory explicates the prerequisites and challenges to reflection. The theory suggests that the challenges of reflection are fundamentally connected to the way the biological life-support system affects our thinking through emotions. While depicting the mechanisms that function as a counterforce to reflection, the developed theory also opens a perspective for considering possibilities for carrying out reflection, and suggests ways to locate and deal with the assumptions to be reflected on. The basic dynamic of the challenges to reflection was explicated by conceptually bridging the gap between Mezirow s and Damasio s theories, through exploring the connections between the meaning perspective and the biological functions of emotions. The concepts of comfort zone and edge-emotions were formed so as to depict the emotional orientation of our thinking, as part of the explanation of the nature of reflection.

Systems between information and knowledge : In a memory management model of an extended enterprise

The research question of this thesis was how knowledge can be managed with information systems. Information systems can support but not replace knowledge management. Systems can mainly store epistemic organisational knowledge included in content, and process data and information. Certain value can be achieved by adding communication technology to systems. All communication, however, can not be managed. A new layer between communication and manageable information was named as knowformation. Knowledge management literature was surveyed, together with information species from philosophy, physics, communication theory, and information system science. Positivism, post-positivism, and critical theory were studied, but knowformation in extended organisational memory seemed to be socially constructed. A memory management model of an extended enterprise (M3.exe) and knowformation concept were findings from iterative case studies, covering data, information and knowledge management systems. The cases varied from groups towards extended organisation. Systems were investigated, and administrators, users (knowledge workers) and managers interviewed. The model building required alternative sets of data, information and knowledge, instead of using the traditional pyramid. Also the explicit-tacit dichotomy was reconsidered. As human knowledge is the final aim of all data and information in the systems, the distinction between management of information vs. management of people was harmonised. Information systems were classified as the core of organisational memory. The content of the systems is in practice between communication and presentation. Firstly, the epistemic criterion of knowledge is not required neither in the knowledge management literature, nor from the content of the systems. Secondly, systems deal mostly with containers, and the knowledge management literature with applied knowledge. Also the construction of reality based on the system content and communication supports the knowformation concept. Knowformation belongs to memory management model of an extended enterprise (M3.exe) that is divided into horizontal and vertical key dimensions. Vertically, processes deal with content that can be managed, whereas communication can be supported, mainly by infrastructure. Horizontally, the right hand side of the model contains systems, and the left hand side content, which should be independent from each other. A strategy based on the model was defined.

Geometric Characterizations for Patterson-Sullivan Measures of Geometrically Finite Kleinian Groups

The main results of this thesis show that a Patterson-Sullivan measure of a non-elementary geometrically finite Kleinian group can always be characterized using geometric covering and packing constructions. This means that if the standard covering and packing constructions are modified in a suitable way, one can use either one of them to construct a geometric measure which is identical to the Patterson-Sullivan measure. The main results generalize and modify results of D. Sullivan which show that one can sometimes use the standard covering construction to construct a suitable geometric measure and sometimes the standard packing construction. Sullivan has shown also that neither or both of the standard constructions can be used to construct the geometric measure in some situations. The main modifications of the standard constructions are based on certain geometric properties of limit sets of Kleinian groups studied first by P. Tukia. These geometric properties describe how closely the limit set of a given Kleinian group resembles euclidean planes or spheres of varying dimension on small scales. The main idea is to express these geometric properties in a quantitative form which can be incorporated into the gauge functions used in the modified covering and packing constructions. Certain estimation results for general conformal measures of Kleinian groups play a crucial role in the proofs of the main results. These estimation results are generalizations and modifications of similar results considered, among others, by B. Stratmann, D. Sullivan, P. Tukia and S. Velani. The modified constructions are in general defined without reference to Kleinian groups, so they or their variants may prove useful in some other contexts in addition to that of Kleinian groups.