NORDEK : A Plan for Increased Nordic Economic Co-operation and Integration 1968-1970

For the first time the attempt of Denmark, Finland, Norway and Sweden to increase Nordic economic co-operation and integration (NORDEK 1968-1970) is analysed by using records from the four governments archives and interviews with central actors participating. A dominating argument has until now been that dynamics in Nordic economic integration is different from dynamics in European integration. This archive based study disproves the myth however of ideological Nordism and of short term political developments outside Norden as most important for the NORDEK initiative. The NORDEK initiative was actually more a consequence of a long term socioeconomic and socio-political path dependant process. The study also disproves the myth that the NORDEK plan was a political and ideological symbol without socioeconomic substance. The purpose with NORDEK was to create a better basis for generating economic growth and social welfare. The proposed NORDEK institutions were therefore developed to promote economic progress. The study finally shows that the NORDEK failure in 1970 was not a result of lacking economic rationale or incompatible economic interests. The failure was a result of a power struggle in Finnish domestic policy and lacking political will in the other Nordic countries to continue without Finland.

Studying the diurnal and seasonal acclimation of photosystem Ii using chlorophyll-a fluorescence

A small fraction of the energy absorbed in the light reactions of photosynthesis is re-emitted as chlorophyll-a fluorescence. Chlorophyll-a fluorescence and photochemistry compete for excitation energy in photosystem II (PSII). Therefore, changes in the photochemical capacity can be detected through analysis of chlorophyll fluorescence. Chlorophyll fluorescence techniques have been widely used to follow the diurnal (fast), and the seasonal (slow) acclimation in the energy partitioning between photochemical and non-photochemical processes in PSII. Energy partitioning in PSII estimated through chlorophyll fluorescence can be used as a proxy of the plant physiological status, and measured at different spatial and temporal scales. However, a number of technical and theoretical limitations still limit the use of chlorophyll fluorescence data for the study of the acclimation of PSII. The aim of this Thesis was to study the diurnal and seasonal acclimation of PSII in field conditions through the development and testing of new chlorophyll fluorescence-based tools, overcoming these limitations. A new model capable of following the fast acclimation of PSII to rapid fluctuations in light intensity was developed. The model was used to study the rapid acclimation in the electron transport rate under fluctuating light. Additionally, new chlorophyll fluorescence parameters were developed for estimating the seasonal acclimation in the sustained rate constant of thermal energy dissipation and photochemistry. The parameters were used to quantitatively evaluate the effect of light and temperature on the seasonal acclimation of PSII. The results indicated that light environment not only affected the degree but also the kinetics of response of the acclimation to temperature, which was attributed to differences in the structural organization of PSII during seasonal acclimation. Furthermore, zeaxanthin-facilitated thermal dissipation appeared to be the main mechanisms modulating the fraction of absorbed energy being dissipated thermally during winter in field Scots pine. Finally, the integration between diurnal and seasonal acclimation mechanisms was studied using a recently developed instrument MONI-PAM (Walz GmbH, Germany) capable of continuously monitoring the energy partitioning in PSII.

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context. The purpose of this thesis is to enhance cross-fertilization between three different approaches to network research. The business network approach may contribute in terms of how relationships are created, developed and how tie content changes within ties, not only between them. The social network approach adds to the discussion by offering concepts of structural change on a network level. The network approach in entrepreneurship contributes by emphasizing network content, governance and structure as a way of understanding and capturing networks. This is discussed in the conceptual articles, Articles 2 and 3. The ultimate purpose of this thesis is to develop a theoretical and empirical understanding of network development processes. This is fulfilled by presenting a theoretical framework, which offers multiple views on process as a developmental outcome. The framework implies that change ought to be captured both within and among relationships over time in the firm as well as in the network. Consequently, changes in structure and interaction taking place simultaneously need to be included when doing research on network development. The connection between micro and macro levels is also stressed. Therefore, the entrepreneur or firm level needs to be implemented together with the network level. The surrounding environment impacts firm and network development and vice versa and hence needs to be integrated. Further, it is necessary to view network development not only as a way forward but to include both progression and regression as inevitable parts of the process. Finally, both stability and change should be taken into account as part of network development. Empirical results in Article 1 show support for a positive impact of networks on SME internationalization. Article 4 compares networks of novice, serial and portfolio entrepreneurs but the empirical results show little support for differences in the networks by type of entrepreneur. The results demonstrate that network interaction and structure is not directly impacted by type of entrepreneur involved. It indicates instead that network structure and interaction is more impacted by the development phase of the firm. This in turn is in line with the theoretical implications, stating that the development of the network and the firm impacts each other, as they co-evolve.

Inarinsaamen käsitemetaforat

This study discusses the conceptual metaphors of Inari Saami, an endangered, indigenous, Finno-Ugrian language spoken in northern Finland. The research focuses on systematical mappings between source and target domains in conventional Inari Saami metaphors and metonymies. The research material consists of the Inarinsaamen idiomisanakirja [Inari Saami idiom dictionary] which has been compiled by the author in collaboration with an Inari Saami co-author; the Inarilappisches Wörterbuch; Inarinsaamelaista kansantietoutta [Inari Saami folk knowledge]; and Aanaarkiela čájttuzeh [Inari Saami sample texts]. The metaphors and metonymies found in these literary sources are divided into categories on the basis of the target domains and according to the classic model of Lakoff ja Johnson (1980). This method reveals the systematical recurrence of source domains inside each category and thus discovers the systematical patterns of metaphoric mapping, the conceptual metaphors . As a result 44 conceptual metaphors and 16 conceptual metonymies are presented through approximately 500 glossed examples. These findings are discussed against the background of what is known about the cognitive and neural processing of metaphors on the one hand, and what is known about Inari Saami culture on the other. This theoretical framework highlights culture as the underlying force behind conceptual metaphors. The recurring metonymies seem to follow a culturally salient indexicality. For example, the Inari Saami conceptual metonymy TIME IS NATURE reflects the seasonal changes in the year s cycle, which was the salient index of time in traditional Inari Saami culture. The recurring metaphors, for their part, follow a culturally salient iconicity. The conceptual metaphor PRIDE IS ANTLERS is based on an iconicity which is experienced and interpreted by the Inari Saami. A proud person is associated with a reindeer who shows off his impressive antlers. The conceptual metaphor/metonymy seems to be a reflection of culture rather than a cognitive means of understanding an abstract domain in terms of a concrete domain, as hypothesized by certain theoreticians. Repeating this study with other languages may lead to the possibility of typologizing the metaphorical systems of the world s languages and understanding the diversity of metaphor systems in the endangered languages of the world.

On Toponymic Constructions as an Alternative to Naming Patterns in Describing Finnish Lake Names

This thesis combines a computational analysis of a comprehensive corpus of Finnish lake names with a theoretical background in cognitive linguistics. The combination results on the one hand in a description of the toponymic system and the processes involved in analogy-based naming and on the other hand some adjustments to Construction Grammar. Finnish lake names are suitable for this kind of study, as they are to a large extent semantically transparent even when relatively old. There is also a large number of them, and they are comprehensively collected in a computer database. The current work starts with an exploratory computational analysis of co-location patterns between different lake names. Such an analysis makes it possible to assess the importance of analogy and patterns in naming. Prior research has suggested that analogy plays an important role, often also in cases where there are other motivations for the name, and the current study confirms this. However, it also appears that naming patterns are very fuzzy and that their nature is somewhat hard to define in an essentially structuralist tradition. In describing toponymic structure and the processes involved in naming, cognitive linguistics presents itself as a promising theoretical basis. The descriptive formalism of Construction Grammar seems especially well suited for the task. However, now productivity becomes a problem: it is not nearly as clear-cut as the latter theory often assumes, and this is even more apparent in names than in more traditional linguistic material. The varying degree of productivity is most naturally described by a prototype-based theory. Such an approach, however, requires some adjustments to onstruction Grammar. Based on all this, the thesis proposes a descriptive model where a new name -- or more generally, a new linguistic expression -- can be formed by conceptual integration from either a single prior example or a construction generalised from a number of different prior ones. The new model accounts nicely for various aspects of naming that are problematic for the traditional description based on analogy and patterns.

Learning challenges of NGOs in development : Co-operation of Finnish NGOs in Morogoro, Tanzania

Non-governmental organisations (NGOs) have gained an important role in development co-operation during the last two decades. The development funding channelled through NGOs has increased and the number of NGOs engaged in development activities, both North and South, has been growing. Supporting NGOs has been seen as one way to strengthen civil society in the South and to provide potential for enhancing more effective development than the state, and to exercise participatory development and partnership in their North-South relationships. This study focuses on learning in the co-operation practices of small Finnish NGOs in Morogoro, Tanzania. Drawing on the cultural-historical activity theory and the theory of expansive learning, in this study I understand learning as a qualitative change in the actual co-operation practices. The qualitative change, for its part, emerges out of attempts to deal with the contradictions in the present activity. I use the concept of developmental contradiction in exploring the co-operation of the small Finnish NGOs with their Tanzanian counterparts. Developmental contradiction connects learning to actual practice and its historical development. By history, in this study I refer to multiple developmental trajectories, such as trajectories of individual participants, organisations, co-operation practices and the institutional system in which the NGO-development co-operation is embedded. In the empirical chapters I explore the co-operation both in the development co-operation projects and in micro-level interaction between partners taking place within the projects. I analyse the perceptions of the Finnish participants about the different developmental trajectories, the tensions, inclusions and exclusions in the evolving object of co-operation in one project, the construction of power relations in project meetings in three projects, and the collision of explicated partnership with the emerging practice of trusteeship in one project. On the basis of the empirical analyses I elaborate four developmental contradictions and learning challenges for the co-operation. The developmental contradictions include: 1) implementing a ready-made Finnish project idea vs. taking the current activities of Tanzanian NGO as a starting point; 2) gaining experiences and cultural interaction vs. access to outside funding; 3) promoting the official tools of development co-operation in training vs. use of tools and procedures taken from the prior activities of both partners in actual practice; and 4) asymmetric relations between the partners vs. rhetoric of equal partnership. Consequently, on the basis of developmental contradictions four learning challenges are suggested: a shift from legitimation of Finnish ideas to negotiation, transcending the separate objects and finding a partly joint object, developing locally shared tools for the co-operation, and identification and reflection of the power relations in the practice of co-operation. Keywords: activity theory; expansive learning; NGO development co-operation; partnership; power

Feature integration in human vision

The earliest stages of human cortical visual processing can be conceived as extraction of local stimulus features. However, more complex visual functions, such as object recognition, require integration of multiple features. Recently, neural processes underlying feature integration in the visual system have been under intensive study. A specialized mid-level stage preceding the object recognition stage has been proposed to account for the processing of contours, surfaces and shapes as well as configuration. This thesis consists of four experimental, psychophysical studies on human visual feature integration. In two studies, classification image a recently developed psychophysical reverse correlation method was used. In this method visual noise is added to near-threshold stimuli. By investigating the relationship between random features in the noise and observer s perceptual decision in each trial, it is possible to estimate what features of the stimuli are critical for the task. The method allows visualizing the critical features that are used in a psychophysical task directly as a spatial correlation map, yielding an effective "behavioral receptive field". Visual context is known to modulate the perception of stimulus features. Some of these interactions are quite complex, and it is not known whether they reflect early or late stages of perceptual processing. The first study investigated the mechanisms of collinear facilitation, where nearby collinear Gabor flankers increase the detectability of a central Gabor. The behavioral receptive field of the mechanism mediating the detection of the central Gabor stimulus was measured by the classification image method. The results show that collinear flankers increase the extent of the behavioral receptive field for the central Gabor, in the direction of the flankers. The increased sensitivity at the ends of the receptive field suggests a low-level explanation for the facilitation. The second study investigated how visual features are integrated into percepts of surface brightness. A novel variant of the classification image method with brightness matching task was used. Many theories assume that perceived brightness is based on the analysis of luminance border features. Here, for the first time this assumption was directly tested. The classification images show that the perceived brightness of both an illusory Craik-O Brien-Cornsweet stimulus and a real uniform step stimulus depends solely on the border. Moreover, the spatial tuning of the features remains almost constant when the stimulus size is changed, suggesting that brightness perception is based on the output of a single spatial frequency channel. The third and fourth studies investigated global form integration in random-dot Glass patterns. In these patterns, a global form can be immediately perceived, if even a small proportion of random dots are paired to dipoles according to a geometrical rule. In the third study the discrimination of orientation structure in highly coherent concentric and Cartesian (straight) Glass patterns was measured. The results showed that the global form was more efficiently discriminated in concentric patterns. The fourth study investigated how form detectability depends on the global regularity of the Glass pattern. The local structure was either Cartesian or curved. It was shown that randomizing the local orientation deteriorated the performance only with the curved pattern. The results give support for the idea that curved and Cartesian patterns are processed in at least partially separate neural systems.

Mediapolulla - Kasvatustieteellistä ja teknisen alan osaamista yhdistämässä : Opiskelijoiden yhteistyö ja oppiminen tieto- ja viestintätekniikkaprojektissa

The study concentrated on interdisciplinary teamwork of students in Helsinki University Department of Education and Helsinki University of Technology. Students worked in small interdisciplinary groups (n 12) to plan and teach in an information- and communication technology (ICT) club in elementary schools. The focus of the study was co-operation in the student groups and students learning experiences. Theoretical background of the study consists of theories of collaboration and socially shared cognition. Study was an qualitative case study and the data was collected with individual focus interviews and learning diaries. The data was categorised and the connections between categories were analysed with a table. Shared cognition appeared as a form of distribution of tasks and in the actual processes of shared expertise. The tasks were shared according to students expertise. Processes of shared expertise were joint knowledge building, integration of interests, awareness and exploitation of others expertise and allowing freedom for others to use their expertise. Additionally expression of ones own views and setting an example to others were one sided sharing of expertise. Students of technology were responsible of technical issues and the responsibility sphere of educational science students was more fragmented. For instance they concentrated in taking children s abilities into consideration. The sphere of shared cognition included also the need for tutoring and learning from others. Usually students did not directly learn from representative of other discipline, instead the learning for instance of social skills happened indirectly. Learning was fostered if learning was set as a goal and prevented if the differences in expertise were too minor. Sharing of cognition was prevented if co-operation was too problematic. Co-operation was usually successful. Good planning, good person chemistry and appreciation of expertise of others promoted success. Problems caused by different backgrounds were usually slight. Successful interaction was complementary and equal. Groups were usually able to circumvent problems in communication and use of justification in discussion promoted co-operation. When comparing the groups in the scope of the study, two were found to be notably opposed and the other groups located between these extreme cases, but the elements of success prevailed. Learning experiences concentrated on social skills, project management, school world and ICT. Essential was achieved field experience and observation of ones own capabilities. In organisation of student interdisciplinary co-operation is important to ensure sufficient differences in expertise and guide students to gain complementary interaction and appropriate setting of goals. Interdisciplinary field project prepared students to face the demands of

"Pintaa syvemmälle" : Eettinen pohdinta opettajan voimavarana luokanopettajan ja erityisopettajan silmin

The purpose of this study is to determine what class teachers and special teachers emphasise in ethical consideration, in which situations they find that ethical difficulties arise and how they would overcome them. In additions, the study aims to describe the effects of ethical con-sideration on the teachers` work. The theoretical backround is based on theories concerning the ethics of the teacher and the literature associated with education and teaching. The empirical study was based on data obtained through questionnaires and interviews. The questionnaires were posted to 470 randomly-selected class teachers and special teachers; 298 of them (63%) completed and returned the questionnaire, and 19 teachers were inter-viewed. The results of the questionnaires and the interviews were examined crosswise with a mixed-methods procedure. The questionnaires were analysed by factor analysis. Those items which rose above the av-erage served as the foundation for the analysis. The questionnaires also included open ques-tions. These questions and the interviews were analysed with a content analysis method. Some principles of this method were combined with the results of the questionnaires to in-crease mutual understanding. In this study, the ethical consideration of the teachers was divided in to four notable parts: 1) moral obligations, 2) respect for the teaching stuff, 3) the demand for responsibility, and 4) dependence on the situation. These items were also notable both in situations that were ethi-cally difficult for teachers and in their solutions to these situations. It became evident that these situations were very common in everyday work and resulted from the character of the teachers´ work. This study showed that the teacher meets the pupils as a group and that the teacher must examine according to the circumstances the truth, individuality, special ar-rangements and co-operation between the school and the parents. The teachers` continuous lack of time limited the ethical consideration. It emerged that the teachers consider their work very multi-faceted and that the sense of obligation, power and responsibility was inevitably received emphasis. The consciousness of authority and the responsibilities associated with it seemed, however, to strengthen this ac-tion. The study showed that the teachers, especially the young female ones, long for more solidarity. Significantly, such experience does not eliminate the importance of ethical consid-eration; on the contrary, it deepens it. According to the results, creating conditions and cir-cumstances for the teachers that open co-operation is inevitable, and easy interaction will in-evitably be possible in the future. There was not observed any differences in ethical consideration between class teachers and special teachers. Therefore, the integration of the pupils to general teaching cannot be consid-ered questionable. Teachers´ answers suggested that ethical consideration improved the tolerance of stress, increased self-confidence and courage as well as belief in the future. The teachers considered ethical consideration important and encouraging for it increased justice and empathy in the teachers´ work.

Epidemiological data of seasonal variation in mood and behaviour

The aim of this study was to measure seasonal variation in mood and behaviour. The dual vulnerability and latitude effect hypothesis, the risk of increased appetite, weight and other seasonal symptoms to develop metabolic syndrome, and perception of low illumination in quality of life and mental well-being were assessed. These variations are prevalent in persons who live in high latitudes and need balancing of metabolic processes to adapt to environmental changes due to seasons. A randomized sample of 8028 adults aged 30 and over (55% women) participated in an epidemiological health examination study, The Health 2000, applying the probability proportional to population size method for a range of socio-demographic characteristics. They were present in a face-to-face interview at home and health status examination. The questionnaires included the modified versions of the Seasonal Pattern Assessment Questionnaire (SPAQ) and Beck Depression Inventory (BDI), the Health Related Quality of Life (HRQoL) instrument 15D, and the General Health Questionnaire (GHQ). The structured and computerized Munich Composite International Diagnostic Interview (M-CIDI) as part of the interview was used to assess diagnoses of mental disorders, and, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria were assessed using all the available information to detect metabolic syndrome. A key finding was that 85% of this nationwide representative sample had seasonal variation in mood and behaviour. Approximately 9% of the study population presented combined seasonal and depressive symptoms with a significant association between their scores, and 2.6% had symptoms that corresponded to Seasonal Affective Disorder (SAD) in severity. Seasonal variations in weight and appetite are two important components that increase the risk of metabolic syndrome. Other factors such as waist circumference and major depressive disorder contributed to the metabolic syndrome as well. Persons reported of having seasonal symptoms were associated with a poorer quality of life and compromised mental well-being, especially if indoors illumination at home and/or at work was experienced as being low. Seasonal and circadian misalignments are suggested to associate with metabolic disorders, and could be remarked if individuals perceive low illumination levels at home and/or at work that affect the health-related quality of life and mental well-being. Keywords: depression, health-related quality of life, illumination, latitude, mental well-being, metabolic syndrome, seasonal variation, winter.

Implications of co-twin dependence for twins' social interactions, mental health and alcohol use : A follow-up study of Finnish twins from adolescence to early adulthood

Objective: The aim of the present study was to examine co-twin dependence and its impact on twins' social contacts, leisure-time activities and psycho-emotional well-being. The role of co-twin dependence was also examined as a moderator of genetic and environmental influences on alcohol use in adolescence and in early adulthood. Methods: The present report is based on the Finnish Twin Cohort Study (FinnTwin16), a population-based study of five consecutive birth cohorts of Finnish twins born in the years 1975-1979. Baseline assessments were collected through mailed questionnaires, within two months of the twins' sixteenth birthday yielding replies from 5563 twin individuals. All respondent twins were sent follow-up questionnaires at ages of 17, 18½, and in early adulthood, when twins were 22-27 years old. Measures: The questionnaires included a survey of health habits and attitudes, a symptom checklist and questions about twins' relationships with parents, peers and co-twin. Measures used were twins' self-reports of their own dependence and their co-twin's dependence at age 16, reports of twins' leisure-time activities and social contacts, alcohol use, psychological distress and somatic symptoms both in adolescence and in early adulthood. Results: In the present study 25.6% of twins reported dependence on their co-twin. There were gender and zygosity differences in dependence, females and MZ twins were more likely to report dependence than males and DZ twins. Co-twin dependence can be viewed on one hand as an individual characteristic, but on the other hand as a pattern of dyadic interaction that is mutually regulated and reciprocal. Most of the twins (80.7%) were either concordantly co-twin dependent or concordantly co-twin independent. The associations of co-twin dependence with twins' social interactions and psycho-emotional characteristics were relatively consistent both in adolescence and in early adulthood. Dependence was related to higher contact frequency and a higher proportion of shared leisure-time activities between twin siblings at the baseline and the follow-up. Additionally co-twin dependence was associated with elevated levels of psycho-emotional distress and somatic complaints, especially in adolescence. In the framework of gene-environment interaction, these results suggest that the genetic contribution to individual differences in drinking patterns is dependent on the nature of the pair-wise relationship of twin siblings. Conclusions: The results of this study indicate that co-twin dependence is a genuine feature of the co-twin relationship and shows the importance of studying the impact of various features of co-twin relationships on individual twins' social and psycho-emotional life and well-being. Our study also offers evidence that differences in inter-personal relationships contribute to the effects of genetic propensities.

The epidemiology of severe Streptococcus pyogenes disease in Europe

Diseases caused by the Lancefield group A streptococcus, Streptococcus pyogenes, are amongst the most challenging to clinicians and public health specialists alike. Although severe infections caused by S. pyogenes are relatively uncommon, affecting around 3 per 100,000 of the population per annum in developed countries, the case fatality is high relative to many other infections. Despite a long scientific tradition of studying their occurrence and characteristics, many aspects of their epidemiology remain poorly understood, and potential control measures undefined. Epidemiological studies can play an important role in identifying host, pathogen and environmental factors associated with risk of disease, manifestation of particular syndromes or poor survival. This can be of value in targeting prevention activities, as well directing further basic research, potentially paving the way for the identification of novel therapeutic targets. The formation of a European network, Strep-EURO, provided an opportunity to explore epidemiological patterns across Europe. Funded by the Fifth Framework Programme of the European Commission s Directorate-General for Research (QLK2.CT.2002.01398), the Strep-EURO network was launched in September 2002. Twelve participants across eleven countries took part, led by the University of Lund in Sweden. Cases were defined as patients with S. pyogenes isolated from a normally sterile site, or non-sterile site in combination with clinical signs of streptococcal toxic shock syndrome (STSS). All participating countries undertook prospective enhanced surveillance between 1st January 2003 and 31st December 2004 to identify cases diagnosed during this period. A standardised surveillance dataset was defined, comprising demographic, clinical and risk factor information collected through a questionnaire. Isolates were collected by the national reference laboratories and characterised according to their M protein using conventional serological and emm gene typing. Descriptive statistics and multivariable analyses were undertaken to compare characteristics of cases between countries and identify factors associated with increased risk of death or development of STSS. Crude and age-adjusted rates of infection were calculated for each country where a catchment population could be defined. The project succeeded in establishing the first European surveillance network for severe S. pyogenes infections, with 5522 cases identified over the two years. Analysis of data gathered in the eleven countries yielded important new information on the epidemiology of severe S. pyogenes infections in Europe during the 2000s. Comprehensive epidemiological data on these infections were obtained for the first time from France, Greece and Romania. Incidence estimates identified a general north-south gradient, from high to low. Remarkably similar age-standardised rates were observed among the three Nordic participants, between 2.2 and 2.3 per 100,000 population. Rates in the UK were higher still, 2.9/100,000, elevated by an upsurge in drug injectors. Rates from these northern countries were reasonably close to those observed in the USA and Australia during this period. In contrast, rates of reports in the more central and southern countries (Czech Republic, Romania, Cyprus and Italy) were substantially lower, 0.3 to 1.5 per 100,000 population, a likely reflection of poorer uptake of microbiological diagnostic methods within these countries. Analysis of project data brought some new insights into risk factors for severe S. pyogenes infection, especially the importance of injecting drug users in the UK, with infections in this group fundamentally reshaping the epidemiology of these infections during this period. Several novel findings arose through this work, including the high degree of congruence in seasonal patterns between countries and the seasonal changes in case fatality rates. Elderly patients, those with compromised immune systems, those who developed STSS and those infected with an emm/M78, emm/M5, emm/M3 or emm/M1 were found to be most likely to die as a result of their infection, whereas those diagnosed with cellulitis, septic arthritis, puerperal sepsis or with non-focal infection were associated with low risk of death, as were infections occurring during October. Analysis of augmented data from the UK found use of NSAIDs to be significantly associated with development of STSS, adding further fuel to the debate surrounding the role of NSAIDs in the development of severe disease. As a largely community-acquired infection, occurring sporadically and diffusely throughout the population, opportunities for control of severe infections caused by S. pyogenes remain limited, primarily involving contact chemoprophylaxis where clusters arise. Analysis of UK Strep-EURO data were used to quantify the risk to household contacts of cases, forming the basis of national guidance on the management of infection. Vaccines currently under development could offer a more effective control programme in future. Surveillance of invasive infections caused by S. pyogenes is of considerable public health importance as a means of identifying long and short-term trends in incidence, allowing the need for, or impact of, public health measures to be evaluated. As a dynamic pathogen co-existing among a dynamic population, new opportunities for exploitation of its human host are likely to arise periodically, and as such continued monitoring remains essential.

Genomic and functional profiling of gastric cancer

Helicobacter pylori infection is a risk factor for gastric cancer, which is a major health issue worldwide. Gastric cancer has a poor prognosis due to the unnoticeable progression of the disease and surgery is the only available treatment in gastric cancer. Therefore, gastric cancer patients would greatly benefit from identifying biomarker genes that would improve diagnostic and prognostic prediction and provide targets for molecular therapies. DNA copy number amplifications are the hallmarks of cancers in various anatomical locations. Mechanisms of amplification predict that DNA double-strand breaks occur at the margins of the amplified region. The first objective of this thesis was to identify the genes that were differentially expressed in H. pylori infection as well as the transcription factors and signal transduction pathways that were associated with the gene expression changes. The second objective was to identify putative biomarker genes in gastric cancer with correlated expression and copy number, and the last objective was to characterize cancers based on DNA copy number amplifications. DNA microarrays, an in vitro model and real-time polymerase chain reaction were used to measure gene expression changes in H. pylori infected AGS cells. In order to identify the transcription factors and signal transduction pathways that were activated after H. pylori infection, gene expression profiling data from the H. pylori experiments and a bioinformatics approach accompanied by experimental validation were used. Genome-wide expression and copy number microarray analysis of clinical gastric cancer samples and immunohistochemistry on tissue microarray were used to identify putative gastric cancer genes. Data mining and machine learning techniques were applied to study amplifications in a cross-section of cancers. FOS and various stress response genes were regulated by H. pylori infection. H. pylori regulated genes were enriched in the chromosomal regions that are frequently changed in gastric cancer, suggesting that molecular pathways of gastric cancer and premalignant H. pylori infection that induces gastritis are interconnected. 16 transcription factors were identified as being associated with H. pylori infection induced changes in gene expression. NF-κB transcription factor and p50 and p65 subunits were verified using elecrophoretic mobility shift assays. ERBB2 and other genes located in 17q12- q21 were found to be up-regulated in association with copy number amplification in gastric cancer. Cancers with similar cell type and origin clustered together based on the genomic localization of the amplifications. Cancer genes and large genes were co-localized with amplified regions and fragile sites, telomeres, centromeres and light chromosome bands were enriched at the amplification boundaries. H. pylori activated transcription factors and signal transduction pathways function in cellular mechanisms that might be capable of promoting carcinogenesis of the stomach. Intestinal and diffuse type gastric cancers showed distinct molecular genetic profiles. Integration of gene expression and copy number microarray data allowed the identification of genes that might be involved in gastric carcinogenesis and have clinical relevance. Gene amplifications were demonstrated to be non-random genomic instabilities. Cell lineage, properties of precursor stem cells, tissue microenvironment and genomic map localization of specific oncogenes define the site specificity of DNA amplifications, whereas labile genomic features define the structures of amplicons. These conclusions suggest that the definition of genomic changes in cancer is based on the interplay between the cancer cell and the tumor microenvironment.