Characterization of local and systemic immune-modulation in melanoma patients

Le mélanome cutané est un des cancers les plus agressifs et dont l'incidence augmente le plus en Suisse. Une fois métastatique, le pronostic de survie moyenne avec les thérapies actuelles est d'environ huit mois, avec moins de 5% de survie à cinq ans. Les récents progrès effectués dans la compréhension de la biologie de la cellule tumorale mais surtout dans l'importance du système immunitaire dans le contrôle de ce cancer ont permis le développement de nouveaux traitements novateurs et prometteurs. Ces thérapies, appelées immunothérapies, reposent sur la stimulation et l'augmentation de la réponse immunitaire à la tumeur. Alors que les derniers essais cliniques ont démontré l'efficacité de ces traitements chez les patients avec des stades avancés de la maladie, le contrôle de la maladie à long- terme est seulement atteint chez une minorité des patients. La suppression locale et systémique de la réponse immunitaire spécifique anti-tumorale apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Des études sur les souris ont montré que les vaisseaux lymphatiques joueraient un rôle primordial dans ce processus en induisant une tolérance immune, ce qui permettrait à la tumeur d'échapper au contrôle du système immunitaire et métastatiser plus facilement. Ces excitantes découvertes n'ont pas encore été établi et prouvé chez l'homme. Dans cette thèse, nous montrons pour la première fois que les vaisseaux lymphatiques sont directement impliqués dans la modulation de la réponse immunitaire au niveau local et systémique dans le mélanome chez l'homme. Ces récentes découvertes montrent le potentiel de combiner des thérapies visant le système lymphatique avec les immunothérapies actuellement utilisées afin d'améliorer le pronostic des patients atteint du mélanome. -- Cutaneous melanoma is one of the most invasive and metastatic human cancers and causes 75% of skin cancer mortality. Current therapies such as surgery and chemotherapy fail to control metastatic disease, and relapse occurs frequently due to microscopic residual lesions. It is, thus, essential to develop and optimize novel therapeutic strategies to improve curative responses in these patients. In recent decades, tumor immunologists have revealed the development of spontaneous adaptive immune responses in melanoma patients, leading to the accumulation of highly differentiated tumor-specific T cells at the tumor site. This remains one of the most powerful prognostic markers to date. Immunotherapies that augment the natural function of these tumor-specific T cells have since emerged as highly attractive therapeutic approaches to eliminate melanoma cells. While recent clinical trials have demonstrated great progress in the treatment of advanced stage melanoma, long-term disease control is still only achieved in a minority of patients. Local and systemic immune suppression by the tumor appears to be responsible, in part, for this poor clinical evolution. These facts underscore the need for a better analysis and characterization of immune- related pathways within the tumor microenvironment (TME), as well as at the systemic level. The overall goal of this thesis is, thus, to obtain greater insight into the complexity and heterogeneity of the TME in human melanoma, as well as to investigate immune modulation beyond the TME, which ultimately influences the immune system throughout the whole body. To achieve this, we established two main objectives: to precisely characterize local and systemic immune modulation (i) in untreated melanoma patients and (ii) in patients undergoing peptide vaccination or checkpoint blockade therapy with anti-cytotoxic T- lymphocyte-asisctaed protein-4 (CTLA-4) antibody. In the first and main part of this thesis, we analyzed lymphatic vessels in relation to anti-tumor immune responses in tissues from vaccinated patients using a combination of immunohistochemistry (IHC) techniques, whole slide scanning/analysis, and an automatic quantification system. Strikingly, we found that increased lymphatic vessel density was associated with high expression of immune suppressive molecules, low functionality of tumor-infiltrating CD8+ T cells and decreased cytokine production by tumor-antigen specific CD8+ T cells in the blood. These data revealed a previously unappreciated local and systemic role of lymphangiogenesis in modulating T cell responses in human cancer and support the use of therapies that target lymphatic vessels combined with existing and future T cell based therapies. In the second objective, we describe a metastatic melanoma patient who developed pulmonary sarcoid-like granulomatosis following repetitive vaccination with peptides and CpG. We demonstrated that the onset of this pulmonary autoimmune adverse event was related to the development of a strong and long-lasting tumor-specific CD8+ T cell response. This constitutes the first demonstration that a new generation tumor vaccine can induce the development of autoimmune adverse events. In the third objective, we assessed the use of Fourier Transform Infrared (FTIR) imaging to identify melanoma cells and lymphocyte subpopulations in lymph node (LN) metastasis tissues, thanks to a fruitful collaboration with researchers in Brussels. We demonstrated that the different cell types in metastatic LNs have different infrared spectral features allowing automated identification of these cells. This technic is therefore capable of distinguishing known and novel biological features in human tissues and has, therefore, significant potential as a tool for histopathological diagnosis and biomarker assessment. Finally, in the fourth objective, we investigated the role of colony- stimulating factor-1 (CSF-1) in modulating the anti-tumor response in ipilimumab-treated patients using IHC and in vitro co-cultures, revealing that melanoma cells produce CSF-1 via CTL-derived cytokines when attacked by cytotoxic T lymphocytes (CTLs), resulting in the recruitment of immunosuppressive monocytes. These findings support the combined use of CSF-1R blockade with T cell based immunotherapy for melanoma patients. Taken together, our results reveal the existence of novel mechanisms of immune modulation and thus promote the optimization of combination immunotherapies against melanoma. -- Le mélanome cutané est un des cancers humains les plus invasifs et métastatiques et est responsable de 75% de la mortalité liée aux cancers de la peau. Les thérapies comme la chirurgie et la chimiothérapie ont échoué à contrôler le mélanome métastatique, par ailleurs les rechutes sous ces traitements ont été montrées fréquentes. Il est donc essentiel de développer et d'optimiser de nouvelles stratégies thérapeutiques pour améliorer les réponses thérapeutiques de ces patients. Durant les dernières décennies, les immunologistes spécialisés dans les tumeurs ont démontré qu'un patient atteint du mélanome pouvait développer spontanément une réponse immune adaptative à sa tumeur et que l'accumulation de cellules T spécifiques tumorales au sein même de la tumeur était un des plus puissants facteurs pronostiques. Les immunothérapies qui ont pour but d'augmenter les fonctions naturelles de ces cellules T spécifiques tumorales ont donc émergé comme des approches thérapeutiques très attractives pour éliminer les cellules du mélanome. Alors que les derniers essais cliniques ont démontré un progrès important dans le traitement des formes avancées du mélanome, le contrôle de la maladie à long-terme est seulement atteint chez une minorité des patients. La suppression immune locale et systémique apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Ces considérations soulignent la nécessité de mieux analyser et caractériser les voies immunitaires non seulement au niveau local dans le microenvironement tumoral mais aussi au niveau systémique dans le sang des patients. Le but de cette thèse est d'obtenir une plus grande connaissance de la complexité et de l'hétérogénéité du microenvironement tumoral dans les mélanomes mais aussi d'investiguer la modulation immunitaire au delà du microenvironement tumoral au niveau systémique. Afin d'atteindre ce but, nous avons établi deux objectifs principaux : caractériser précisément la modulation locale et systémique du système immunitaire (i) chez les patients atteints du mélanome qui n'ont pas reçu de traitement et (ii) chez les patients qui ont été traités soit par des vaccins soit par des thérapies qui bloquent les points de contrôles. Dans la première et majeure partie de cette thèse, nous avons analysé les vaisseaux lymphatiques en relation avec la réponse immunitaire anti-tumorale dans les tissus des patients vaccinés grâce à des techniques d'immunohistochimie et de quantification informatisé et automatique des marquages. Nous avons trouvé qu'une densité élevée de vaisseaux lymphatiques dans la tumeur était associée à une plus grande expression de molécules immunosuppressives ainsi qu'à une diminution de la fonctionnalité des cellules T spécifiques tumoral dans la tumeur et dans le sang des patients. Ces résultats révèlent un rôle jusqu'à là inconnu des vaisseaux lymphatiques dans la modulation directe du système immunitaire au niveau local et systémique dans les cancers de l'homme. Cette recherche apporte finalement des preuves du potentiel de combiner des thérapies visant le système lymphatique avec des autres immunothérapies déjà utilisées en clinique. Dans le second objectif, nous rapportons le cas d'un patient atteint d'un mélanome avec de multiples métastases qui a développé à la suite de plusieurs vaccinations répétées et consécutives avec des peptides et du CpG, un évènement indésirable sous la forme d'une granulomatose pulmonaire sarcoid-like. Nous avons démontré que l'apparition de cet évènement était intimement liée au développement d'une réponse immunitaire durable et spécifique contre les antigènes de la tumeur. Par là- même, nous prouvons pour la première fois que la nouvelle génération de vaccins est aussi capable d'induire des effets indésirables auto-immuns. Pour le troisième objectif, nous avons voulu savoir si l'utilisation de la spectroscopie infrarouge à transformée de Fourier (IRTF) était capable d'identifier les cellules du mélanome ainsi que les différents sous-types cellulaires dans les ganglions métastatiques. Grâce à nos collaborateurs de Bruxelles, nous avons pu établir que les diverses composantes cellulaires des ganglions atteints par des métastases du mélanome présentaient des spectres infrarouges différents et qu'elles pouvaient être identifiées d'une façon automatique. Cette nouvelle technique permettrait donc de distinguer des caractéristiques biologiques connues ou nouvelles dans les tissus humains qui auraient des retombées pratiques importantes dans le diagnostic histopathologique et dans l'évaluation des biomarqueurs. Finalement dans le dernier objectif, nous avons investigué le rôle du facteur de stimulation des colonies (CSF-1) dans la modulation de la réponse immunitaire anti-tumorale chez les patients qui ont été traités par l'Ipilimumab. Nos expériences in vivo au niveau des tissus tumoraux et nos co-cultures in vitro nous ont permis de démontrer que les cytokines secrétées par les cellules T spécifiques anti-tumorales induisaient la sécrétion de CSF-1 dans les cellules du mélanome ce qui résultait en un recrutement de monocytes immunosuppresseurs. Dans son ensemble, cette thèse révèle donc l'existence de nouveaux mécanismes de modulation de la réponse immunitaire anti-tumorale et propose de nouvelles optimisations de combinaison d'immunothérapies contre le mélanome.

Technology roadmap for new sales support and management system for crane manufacturing company

Sales configurators are essential tools for companies that offer complicated case specifically crafted products for customers. Most sophisticated of them are able to design an entire end product on the fly according to given constraints, calculate price for the offer and move the order into production. This thesis covers a sales configurator acquisition project in a large industrial company that offers cranes for its customers. The study spans the preliminary stages of a large-scale software purchase project starting from the specification of problem domain and ending up presenting the most viable software solution that fulfils the requirements for the new system. The project consists of mapping usage environment, use cases, and collecting requirements that are expected from the new system. The collected requirements involve fitting the new sales system into enterprise application infrastructure, mitigating the risks involved in the project and specifying new features to the application whilst preserving all of the admired features of the old sales system currently used in the company. The collected requirements were presented to a number of different sales software vendors who were asked to provide solution suggestions that would fulfil all the demands. All of the received solution proposals were exposed to an evaluation to determine the most feasible solutions, and the construction of evaluation criteria itself was a part of the study. The final outcome of this study is a short-list of the most feasible sales configurator solutions together with a description of how software purchase process in large enterprises work, and which aspects should be paid attention in large projects of similar kind.

Evolutionary Ecology of Mountain Birch in Subarctic Stress Gradients: Interplay of Biotic and Abiotic Factors in Plant-Plant Interactions and Evolutionary Processes

In nature, variation for example in herbivory, wind exposure, moisture and pollution impact often creates variation in physiological stress and plant productivity. This variation is seldom clear-cut, but rather results in clines of decreasing growth and productivity towards the high-stress end. These clines of unidirectionally changing stress are generally known as ‘stress gradients’. Through its effect on plant performance, stress has the capacity to fundamentally alter the ecological relationships between individuals, and through variation in survival and reproduction it also causes evolutionary change, i.e. local adaptations to stress and eventually speciation. In certain conditions local adaptations to environmental stress have been documented in a matter of just a few generations. In plant-plant interactions, intensities of both negative interactions (competition) and positive ones (facilitation) are expected to vary along stress gradients. The stress-gradient hypothesis (SGH) suggests that net facilitation will be strongest in conditions of high biotic and abiotic stress, while a more recent ‘humpback’ model predicts strongest net facilitation at intermediate levels of stress. Plant interactions on stress gradients, however, are affected by a multitude of confounding factors, making studies of facilitation-related theories challenging. Among these factors are plant ontogeny, spatial scale, and local adaptation to stress. The last of these has very rarely been included in facilitation studies, despite the potential co-occurrence of local adaptations and changes in net facilitation in stress gradients. Current theory would predict both competitive effects and facilitative responses to be weakest in populations locally adapted to withstand high abiotic stress. This thesis is based on six experiments, conducted both in greenhouses and in the field in Russia, Norway and Finland, with mountain birch (Betula pubescens subsp. czerepanovii) as the model species. The aims were to study potential local adaptations in multiple stress gradients (both natural and anthropogenic), changes in plant-plant interactions under conditions of varying stress (as predicted by SGH), potential mechanisms behind intraspecific facilitation, and factors confounding plant-plant facilitation, such as spatiotemporal, ontogenetic, and genetic differences. I found rapid evolutionary adaptations (occurring within a time-span of 60 to 70 years) towards heavy-metal resistance around two copper-nickel smelters, a phenomenon that has resulted in a trade-off of decreased performance in pristine conditions. Heavy-metal-adapted individuals had lowered nickel uptake, indicating a possible mechanism behind the detected resistance. Seedlings adapted to heavy-metal toxicity were not co-resistant to others forms of abiotic stress, but showed co-resistance to biotic stress by being consumed to a lesser extent by insect herbivores. Conversely, populations from conditions of high natural stress (wind, drought etc.) showed no local adaptations, despite much longer evolutionary time scales. Due to decreasing emissions, I was unable to test SGH in the pollution gradients. In natural stress gradients, however, plant performance was in accordance with SGH, with the strongest host-seedling facilitation found at the high-stress sites in two different stress gradients. Factors confounding this pattern included (1) plant size / ontogenetic status, with seedling-seedling interactions being competition dominated and host-seedling interactions potentially switching towards competition with seedling growth, and (2) spatial distance, with competition dominating at very short planting distances, and facilitation being strongest at a distance of circa ¼ benefactor height. I found no evidence for changes in facilitation with respect to the evolutionary histories of plant populations. Despite the support for SGH, it may be that the ‘humpback’ model is more relevant when the main stressor is resource-related, while what I studied were the effects of ‘non-resource’ stressors (i.e. heavy-metal pollution and wind). The results have potential practical applications: the utilisation of locally adapted seedlings and plant facilitation may increase the success of future restoration efforts in industrial barrens as well as in other wind-exposed sites. The findings also have implications with regard to the effects of global change in subarctic environments: the documented potential by mountain birch for rapid evolutionary change, together with the general lack of evolutionary ‘dead ends’, due to not (over)specialising to current natural conditions, increase the chances of this crucial forest-forming tree persisting even under the anticipated climate change.

Investigating the impact of small versus large firms on economic performance of countries and industries

Following earlier work by Audretsch et al. (2002), we assume that an optimal size-class structure exists, in terms of achieving maximal economic growth rates. Such an optimal structure is likely to exist as economies need a balance between the core competences of large firms (such as exploitation of economies of scale) and those of smaller firms (such as flexibility and exploration of new ideas). Accordingly, changes in size-class structure (i.e., changes in the relative shares in economic activity accounted for by micro, small, medium-sized and large firms) may affect macro-economic growth. Using a unique data base of the EU-27 countries for the period 2002-2008 for five broad sectors of economic activity and four size-classes, we find empirical support which suggests that, on average for these countries over this period, the share of micro and large firms may have been ‘above optimum’ (particularly in lower income EU countries) whereas the share of medium-sized firms may have been ‘below optimum’ (particularly in higher income EU countries). This evidence suggests that the transition from a ‘managed’ to an ‘entrepreneurial’ economy (Audretsch and Thurik, 2001) has not been completed yet in all countries of the EU-27. Keywords: small firms, large firms, size-classes, macro-economic performance

Profiles of Second Language Learners in Bilingual Education: A Comparative Study of the Characteristics of Finnish and American Students

The purpose of this comparative study is to profile second language learners by exploring the factors which have an impact on their learning. The subjects come from two different countries: one group comes from Milwaukee, US, and the other from Turku, Finland. The subjects have attended bilingual classes from elementary school to senior high school in their respective countries. In the United States, the subjects (N = 57) started in one elementary school from where they moved on to two high schools in the district. The Finnish subjects (N = 39) attended the same school from elementary to high school. The longitudinal study was conducted during 1994-2004 and combines both qualitative and quantitative research methods. A Pilot Study carried out in 1990-1991 preceded the two subsequent studies that form the core material of this research. The theoretical part of the study focuses first on language policies in the United States and Finland: special emphasis is given to the history, development and current state of bilingual education, and the factors that have affected policy-making in the provision of language instruction. Current language learning theories and models form the theoretical foundation of the research, and underpin the empirical studies. Cognitively-labeled theories are at the forefront, but sociocultural theory and the ecological approach are also accounted for. The research methods consist of questionnaires, compositions and interviews. A combination of statistical methods as well as content analysis were used in the analysis. The attitude of the bilingual learners toward L1 and L2 was generally positive: the subjects enjoyed learning through two languages and were motivated to learn both. The knowledge of L1 and parental support, along with early literacy in L1, facilitated the learning of L2. This was particularly evident in the American subject group. The American subjects’ L2 learning was affected by the attitudes of the learners to the L1 culture and its speakers. Furthermore, the negative attitudes taken by L1 speakers toward L2 speakers and the lack of opportunities to engage in activities in the L1 culture affected the American subjects’ learning of L2, English. The research showed that many American L2 learners were isolated from the L1 culture and were even afraid to use English in everyday communication situations. In light of the research results, a politically neutral linguistic environment, which the Finnish subjects inhabited, was seen to be more favorable for learning. The Finnish subjects were learning L2, English, in a neutral zone where their own attitudes and motivation dictated their learning. The role of L2 as a means of international communication in Finland, as opposed to a means of exercising linguistic power, provided a neutral atmosphere for learning English. In both the American and Finnish groups, the learning of other languages was facilitated when the learner had a good foundation in their L1, and the learning of L1 and L2 were in balance. Learning was also fostered when the learners drew positive experiences from their surroundings and were provided with opportunities to engage in activities where L2 was used.

Essays on pricing of risk and international linkage of Russian stock market

Last two decades have seen a rapid change in the global economic and financial situation; the economic conditions in many small and large underdeveloped countries started to improve and they became recognized as emerging markets. This led to growth in the amounts of global investments in these countries, partly spurred by expectations of higher returns, favorable risk-return opportunities, and better diversification alternatives to global investors. This process, however, has not been without problems and it has emphasized the need for more information on these markets. In particular, the liberalization of financial markets around the world, globalization of trade and companies, recent formation of economic and regional blocks, and the rapid development of underdeveloped countries during the last two decades have brought a major challenge to the financial world and researchers alike. This doctoral dissertation studies one of the largest emerging markets, namely Russia. The motivation why the Russian equity market is worth investigating includes, among other factors, its sheer size, rapid and robust economic growth since the turn of the millennium, future prospect for international investors, and a number of important major financial reforms implemented since the early 1990s. Another interesting feature of the Russian economy, which gives motivation to study Russian market, is Russia’s 1998 financial crisis, considered as one of the worst crisis in recent times, affecting both developed and developing economies. Therefore, special attention has been paid to Russia’s 1998 financial crisis throughout this dissertation. This thesis covers the period from the birth of the modern Russian financial markets to the present day, Special attention is given to the international linkage and the 1998 financial crisis. This study first identifies the risks associated with Russian market and then deals with their pricing issues. Finally some insights about portfolio construction within Russian market are presented. The first research paper of this dissertation considers the linkage of the Russian equity market to the world equity market by examining the international transmission of the Russia’s 1998 financial crisis utilizing the GARCH-BEKK model proposed by Engle and Kroner. Empirical results shows evidence of direct linkage between the Russian equity market and the world market both in regards of returns and volatility. However, the weakness of the linkage suggests that the Russian equity market was only partially integrated into the world market, even though the contagion can be clearly seen during the time of the crisis period. The second and the third paper, co-authored with Mika Vaihekoski, investigate whether global, local and currency risks are priced in the Russian stock market from a US investors’ point of view. Furthermore, the dynamics of these sources of risk are studied, i.e., whether the prices of the global and local risk factors are constant or time-varying over time. We utilize the multivariate GARCH-M framework of De Santis and Gérard (1998). Similar to them we find price of global market risk to be time-varying. Currency risk also found to be priced and highly time varying in the Russian market. Moreover, our results suggest that the Russian market is partially segmented and local risk is also priced in the market. The model also implies that the biggest impact on the US market risk premium is coming from the world risk component whereas the Russian risk premium is on average caused mostly by the local and currency components. The purpose of the fourth paper is to look at the relationship between the stock and the bond market of Russia. The objective is to examine whether the correlations between two classes of assets are time varying by using multivariate conditional volatility models. The Constant Conditional Correlation model by Bollerslev (1990), the Dynamic Conditional Correlation model by Engle (2002), and an asymmetric version of the Dynamic Conditional Correlation model by Cappiello et al. (2006) are used in the analysis. The empirical results do not support the assumption of constant conditional correlation and there was clear evidence of time varying correlations between the Russian stocks and bond market and both asset markets exhibit positive asymmetries. The implications of the results in this dissertation are useful for both companies and international investors who are interested in investing in Russia. Our results give useful insights to those involved in minimising or managing financial risk exposures, such as, portfolio managers, international investors, risk analysts and financial researchers. When portfolio managers aim to optimize the risk-return relationship, the results indicate that at least in the case of Russia, one should account for the local market as well as currency risk when calculating the key inputs for the optimization. In addition, the pricing of exchange rate risk implies that exchange rate exposure is partly non-diversifiable and investors are compensated for bearing the risk. Likewise, international transmission of stock market volatility can profoundly influence corporate capital budgeting decisions, investors’ investment decisions, and other business cycle variables. Finally, the weak integration of the Russian market and low correlations between Russian stock and bond market offers good opportunities to the international investors to diversify their portfolios.

Relaxation and derelaxation of pure and hydrogenated amorphous silicon during thermal annealing experiments

The structural relaxation of pure amorphous silicon (a-Si) and hydrogenated amorphous silicon (a-Si:H) materials, that occurs during thermal annealing experiments, has been analyzed by Raman spectroscopy and differential scanning calorimetry. Unlike a-Si, the heat evolved from a-Si:H cannot be explained by relaxation of the Si-Si network strain but it reveals a derelaxation of the bond angle strain. Since the state of relaxation after annealing is very similar for pure and hydrogenated materials, our results give strong experimental support to the predicted configurational gap between a-Si and crystalline silicon

Traffic flow development at North European company level with respect of China and Russia

The aim of the thesis is to analyze traffic flows and its development from North European companies` point of view to China and Russia using data from logistics questionnaire. Selected North European companies are large Finnish and Swedish companies. The questionnaire was sent via email to the target group. The study is based on the answers got from respondent companies from years 2006, 2009 and 2010. In the thesis Finnish Talouselämä newspaper and Swedish Affärsdata are used as a database to find the target companies for the survey. Respondents were most often logistics managers in companies. In the beginning of the thesis concepts of transportation logistics is presented, including container types, trade terms, axel loads in roads and in railways. Also there is information about warehousing types and terminals. After that, general information of Chinese and Russian transportation logistics is presented. Chinese and Russian issues are discussed in two sections. In both of them it is analyzed economic development, freight transport and trade balance. Some practical examples of factory inaugurations in China and Russia are presented that Finnish and Swedish companies have completed. In freight transport section different transportation modes, logistics outsourcing and problems of transportation logistics is discussed. The results of the thesis show that transportation flows between Europe and China is changing. Freight traffic from China to European countries will strengthen even more from the current base. When it comes to Russia and Europe, traffic flows seem to be changing from eastbound traffic to westbound traffic. It means that in the future it is expected more freight traffic from Russia to Europe. Some probable reasons for that are recent factory establishments in Russia and company interviews support also this observation. Effects of the economic recession are mainly seen in the lower transportation amounts in 2009.

Group mentoring for junior medical students: perceptions of mentees and mentors

Entering medical school can be associated with a number of difficulties that can hinder students' performance. Mentoring programs are designed to help students circumvent difficulties and improve their learning and personal development. The current study aimed to evaluate the perceptions of both students and mentors regarding a recently introduced, group-based mentoring program designed to support first-year students. After one year of regular meetings, students and mentors' perceptions of the program were assessed by means of structured questionnaires. Response content categories were identified through multiple readings. Both regular attendees and non-participating students had positive opinions about the program. Mentors were highly satisfied at having participated and acknowledged that the program has been useful not only for assisting students, but also for fostering their own personal and professional development. In conclusion, the group-based mentoring program is feasible and can elicit positive views from both mentors and students. In addition, faculty members' participation as mentors can also be beneficial, since the program appears to contribute to their own personal and professional development

Identifying first graders at risk of reading and writing difficulties : creating a group-based screening tool in kiswahili in Tanzania

Early identification of beginning readers at risk of developing reading and writing difficulties plays an important role in the prevention and provision of appropriate intervention. In Tanzania, as in other countries, there are children in schools who are at risk of developing reading and writing difficulties. Many of these children complete school without being identified and without proper and relevant support. The main language in Tanzania is Kiswahili, a transparent language. Contextually relevant, reliable and valid instruments of identification are needed in Tanzanian schools. This study aimed at the construction and validation of a group-based screening instrument in the Kiswahili language for identifying beginning readers at risk of reading and writing difficulties. In studying the function of the test there was special interest in analyzing the explanatory power of certain contextual factors related to the home and school. Halfway through grade one, 337 children from four purposively selected primary schools in Morogoro municipality were screened with a group test consisting of 7 subscales measuring phonological awareness, word and letter knowledge and spelling. A questionnaire about background factors and the home and school environments related to literacy was also used. The schools were chosen based on performance status (i.e. high, good, average and low performing schools) in order to include variation. For validation, 64 children were chosen from the original sample to take an individual test measuring nonsense word reading, word reading, actual text reading, one-minute reading and writing. School marks from grade one and a follow-up test half way through grade two were also used for validation. The correlations between the results from the group test and the three measures used for validation were very high (.83-.95). Content validity of the group test was established by using items drawn from authorized text books for reading in grade one. Construct validity was analyzed through item analysis and principal component analysis. The difficulty level of most items in both the group test and the follow-up test was good. The items also discriminated well. Principal component analysis revealed one powerful latent dimension (initial literacy factor), accounting for 93% of the variance. This implies that it could be possible to use any set of the subtests of the group test for screening and prediction. The K-Means cluster analysis revealed four clusters: at-risk children, strugglers, readers and good readers. The main concern in this study was with the groups of at-risk children (24%) and strugglers (22%), who need the most assistance. The predictive validity of the group test was analyzed by correlating the measures from the two school years and by cross tabulating grade one and grade two clusters. All the correlations were positive and very high, and 94% of the at-risk children in grade two were already identified in the group test in grade one. The explanatory power of some of the home and school factors was very strong. The number of books at home accounted for 38% of the variance in reading and writing ability measured by the group test. Parents´ reading ability and the support children received at home for schoolwork were also influential factors. Among the studied school factors school attendance had the strongest explanatory power, accounting for 21% of the variance in reading and writing ability. Having been in nursery school was also of importance. Based on the findings in the study a short version of the group test was created. It is suggested for use in the screening processes in grade one aiming at identifying children at risk of reading and writing difficulties in the Tanzanian context. Suggestions for further research as well as for actions for improving the literacy skills of Tanzanian children are presented.

Professional development among educators pursuing a B.Ed. program in special education in Tanzania : a study of motives and perceived outcomes

Implementation of different policies and plans aiming at providing education for all is a challenge in Tanzania. The need for educators and professionals with relevant knowledge and qualifications in special education is substantial. Teacher education does not equip educators with sufficient knowledge and skills in special education and professional development programs in special education are few in number. Up to 2005 no degree programs in special education at university level were available in Tanzania. The B.Ed. Special Education program offered by the Open University of Tanzania in collaboration with Åbo Akademi University in Finland was one of the efforts aimed at addressing the big national need for teachers and other professionals with degree qualifications in special education. This pilot program offered unique possibilities to study professional development in Tanzania. The research group in this study consisted of the group of students who participated in the degree program 2005-2007. The study is guided by three theoretical perspectives: individual, social and societal. The individual perspective emphasizes psychological factors as motives, motivation, achievement, self-directed behavior and personal growth. Within social perspective, professional development is viewed as situated within the social and cultural context. The third perspective, the societal, focuses on change, reforms, innovations and transformation of school systems and societies. Accordingly, professional development is viewed as an individual, social and societal phenomenon. The overall aim of the study is to explore the participants’ motives for participating in a B.Ed. Special Education program and the perceived outcomes of the program in terms of professional development. In order to achieve the objectives of the study, a case study approach was adopted. Questionnaires and semi-structured interviews were administered in three waves between January 2007 and February 2009 to the 35 educators participating in the B.Ed. Special Education program. The findings of the study reveal that the participants expressed motives which were related to job performance, knowledge, skills, academic degree and career. Also altruistic motives were expressed by the participants in terms of helping and supporting students with special needs and their communities. The perceived outcomes of the program were in line with the expressed motives. However, the results indicate that the participants also learned new skills, as interaction skills and guidance and counseling skills. Increased self-confidence was also mentioned as an outcome. The participants also got deepened understanding of disability issues. In addition, they learned strategies for creating awareness of persons with disability in the communities. Thus the findings of the study indicate positive outcomes of the program in terms of professional development. The conclusion of the study is that individual, social and societal factors interact when it comes to explaining why Tanzanian educators in special education choose to pursue a degree program in special education. The individual motives, as increased knowledge and better prospects of career development interact with the social and societal motives to help and support vulnerable student groups. The study contributes to increased understanding of the complexity of professional development and of the realities educators meet when educational reforms are implemented in a developing country.

Internationalization of small and medium-sized enterprises and impact of institutions on international entrepreneurship in emerging economies: the case of Russia

The doctoral study presents a comprehensive analysis of the impact of the institutional environment on the internationalization-based growth strategic choices of small and mediumsized enterprises (SMEs) in emerging economies. In responding to the calls for more research on institutions and international entrepreneurship, this dissertation extends the linkages between the two to the context of emerging economies. The study presents a comprehensive analysis of institutional challenges and their impact on the internationalization of SMEs in emerging economies, particularly in Russia. The research contributes to the adoption of the institution-based view in international entrepreneurship. The dissertation is presented through five research papers. Based on primary and secondary data, the study categorizes the possible sources of institutional influences on internationalization and empirically tests their impact by applying a method triangulation research design. The result of the conducted research is a proposed theoretical model of the institutional impact on the internationalization of SMEs in emerging economies. The model is specifically focused on the growth stage of the entrepreneurial process and considers only its internationalization facet. The research identifies and provides empirical support for the existence of a positive influence of a transparent and supportive regulatory environment, an institutionalized pool of general business knowledge, and collectivistic value orientation on the proclivity of SMEs to internationalize. A level of appreciation of entrepreneurial initiatives in home country and a greater positive institutional gap provide a positive impact on the international performance of SMEs. The research provides contextualized knowledge of the institutional impact on the internationalization of SMEs in Russia. The obtained results present theoretical value in terms of showing how the environmental conditions effect the entrepreneurial internationalization-based growth in emerging economies, providing the methodological insights into the measurement of the institutional effects, and empirically contextualizing the linkage between institutions and internationalization in the Russian business environment. The research also provides value for the business and policy making stakeholders by identifying ways of utilizing the conditions in the external institutional environment.

Accounting for competition, governance and accountability during institutional change in not-for-profit and public sector organisations

Purpose The aim of this thesis1 is to analyse theoretically how institutionalisation of competitive tendering2, governance and budgetary policies cannot be taken for granted to lead to accountability among institutional actors3. The nature of an institutionalised management accounting policy, its relevance as a source of power in organisational decision making, and in negotiating inter-organisational relationships, are also analysed. Practical motivation The practical motivation of the thesis is to show how practitioners and policy makers can institutionalise changes which improve the power of management accounting and control systems4 as a mechanism of accountability among institutional actors and in negotiating relationships with other organisations. Theoretical motivation and conceptual approach The theoretical motivation of the thesis is to extend the institutional framework of management accounting change proposed by Burns and Scapens (2000) by using the theories of critical realism, communicative action, negotiated order and the framework of circuits of power. The Burns and Scapens framework needs further theorisation to analyse the relationship between the institutionalisation of management accounting and accountability; and the relevance of management accounting information in negotiating in inter-organisational relationships. Methodology and field studies Field research took place in public and not-for-profit health care organisations and a municipality in Finland from 2008 to 2013. Data were gathered by document analysis, interviews, participation in meetings and observations. Findings The findings are explained in four different essays that show that institutionalisation of competitive tendering, governance and budgetary policies cannot be taken for granted to lead to accountability among institutional actors. The ways by which institutional actors think and act can be influenced by other institutional mechanisms, such as inter-organisational circuits of power and intraorganisational governance policies, independent of the institutional change process. The relevance of institutionalised management accounting policies in negotiating relationships between two or more organisations depends on processes and contexts through which institutional actors use management accounting information as a tool of communication, mutual understanding and power. Research limitations / implications The theoretical framework used can be applied validly in other studies. The empirical findings cannot be generalised directly to other organisations than the organisations analysed. Practical implications Competitive tendering and budgetary policies can be institutionalised to shape actions of institutional actors within an organisation. To lead to accountability, practitioners and policy makers should implement governance policies that increase the use of management accounting information in institutional actors’ thinking, actions and responsibility for their actions. To reach a negotiated order between organisations, institutionalised management accounting policies should be used as one of the tools of communication aiming to reach mutual agreement among institutional actors.

Estimation of weed dry biomass and grain yield as a function of growth and yield traits under allelopathic weed management in maize

Growing concerns about toxicity and development of resistance against synthetic herbicides have demanded looking for alternative weed management approaches. Allelopathy has gained sufficient support and potential for sustainable weed management. Aqueous extracts of six plant species (sunflower, rice, mulberry, maize, brassica and sorghum) in different combinations alone or in mixture with 75% reduced dose of herbicides were evaluated for two consecutive years under field conditions. A weedy check and S-metolachlor with atrazine (pre emergence) and atrazine alone (post emergence) at recommended rates was included for comparison. Weed dynamics, maize growth indices and yield estimation were done by following standard procedures. All aqueous plant extract combinations suppressed weed growth and biomass. Moreover, the suppressive effect was more pronounced when aqueous plant extracts were supplemented with reduced doses of herbicides. Brassica-sunflower-sorghum combination suppressed weeds by 74-80, 78-70, 65-68% during both years of study that was similar with S-metolachlor along half dose of atrazine and full dose of atrazine alone. Crop growth rate and dry matter accumulation attained peak values of 32.68 and 1,502 g m-2 d-1 for brassica-sunflower-sorghum combination at 60 and 75 days after sowing. Curve fitting regression for growth and yield traits predicted strong positive correlation to grain yield and negative correlation to weed dry biomass under allelopathic weed management in maize crop.

ORCIDs in the Wild: Implementing ORCIDs into Research Support and Repository Systems

Panel at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014