The Role of networks in the internationalization process of Finnish design companies

Finnish design has attracted global attention lately and companies within the industry have potential in international markets. Because networks have been found to be extremely helpful in a firm’s international business operations and usefulness of networks is not fully exploited, their role in Finnish design companies is investigated. Accordingly, this study concentrates on understanding the role of networks in the internationalization process of Finnish design companies. This was investigated through describing the internationalization process of Finnish design companies, analyzing what kind of networks are related to internationalization process of Finnish design companies, and analyzing how networks are utilized in the internationalization process of Finnish design companies. The theoretical framework explores the Finnish design industry, internationalization process and networks. The Finnish design industry is introduced in general and the concept of design is defined to refer to the industries of textiles, furniture, clothing, and lighting equipment in the research. The theories of internationalization process, the Uppsala model and Luostarinen’s operation modes, are explored in detail. The Born Global theory, which is a contrary view to stage models, is also discussed. The concept of network is investigated, networks are classified into business and social networks, and network approach to internationalization is discussed. The research is conducted empirically and the research method is a descriptive case study. In this study, four case companies are investigated: the interior decoration unit of L-Fashion Group, Globe Hope, Klo Design, and Melaja Ltd. Data is collected by semi-structured interviews and the analysis is done in the following way: the case companies are introduced, their internationalization processes and networks are described and, finally, the comparison of the case companies is done in a form of cross-case analysis. This research showed that cooperation with social networks, such as locals or employees who have experience from the target market can be extremely helpful in the beginning of a Finnish design company’s internationalization process. This study also indicated that public organizations do not necessarily enhance the internationalization process in a design company point-of-view. In addition, the research showed that there is cooperation between small Finnish design companies whereas large design companies are not as open to cooperation with competitors.

Virtual Testing of Active Magnetic Bearing Systems based on Design Guidelines given by the Standards

Active Magnetic Bearings offer many advantages that have brought new applications to the industry. However, similarly to all new technology, active magnetic bearings also have downsides and one of those is the low standardization level. This thesis is studying mainly the ISO 14839 standard and more specifically the system verification methods. These verifying methods are conducted using a practical test with an existing active magnetic bearing system. The system is simulated with Matlab using rotor-bearing dynamics toolbox, but this study does not include the exact simulation code or a direct algebra calculation. However, this study provides the proof that standardized simulation methods can be applied in practical problems.

Quality of radiotherapy care by development of e-feedback knowledge

The aim of this three phase study was to develop quality of radiotherapy care by the e-Feedback knowledge of radiotherapy -intervention (e-Re-Know). In Phase I, the purpose was to describe the quality of radiotherapy care and its deficits experienced by cancer patients. Based on the deficits in patient education in Phase II, the purpose was to describe cancer patients’ e-knowledge expectations in radiotherapy. In Phase III, the purpose was to develop and evaluate the outcomes of the e-Re-Know among breast cancer patients. The ultimate aim was to develop radiotherapy care to support patients’ empowerment with patient e-education. In Phase I (2004-2005), the descriptive design was used, and 134 radiotherapy patients evaluated their experiences by Good Nursing Care Scale for Patients (GNCS-P) in the middle of RT period. In Phase II (2006-2008), the descriptive longitudinal design was used and 100 radiotherapy patients’ e-knowledge expectations of RT were evaluated using open-ended questionnaire developed for this study before commencing first RT, in the middle of the treatment, and concluding RT period. In Phase III, firstly (2009-2010), the e-Re-Know intervention, i.e. knowledge test and feedback, was developed in terms of empowering knowledge and implemented with e-feedback approach based on literature and expert reviews. Secondly (2011-2014), the randomized controlled study was used to evaluate the e-Re-Know. Breast cancer patients randomized to either the intervention group (n=65) receiving the e-Re-Know by e-mail before commencing first RT and standard education or the control group (n=63) receiving standard education. The data were collected before commencing first RT, concluding last RT and 3 months after last RT using RT Knowledge Test, Spielberger’s State Trait Inventory (STAI) and Functional Assessment of Cancer Therapy - Breast (FACT-B) –instruments. Data were analyzed using statistical methods and content analysis. The study showed radiotherapy patients experienced quality of care high. However, there were deficits in patient education. Furthermore, radiotherapy patients’ multidimensional e-knowledge expectations through Internet covered mainly bio-physiological and functional knowledge. Thus, the e-Re-Know was developed and evaluated. The study showed when breast cancer patients’ carried out the e-Re-Know their knowledge of side effects self-care was significantly increased and quality of life (QOL) significantly improved in line with decrease in anxiety from time before radiotherapy period to three months after. In addition, the e-Re-Know has potential to have positive effects on anxiety and QOL, regardless of patient characteristics or knowledge level. The results support the theory of empowering patient education suggesting that empowerment can be supported by confirming patients’ understanding of own knowledge level. In summary, the e-Feedback knowledge of radiotherapy (e-Re-Know) intervention can be recommended in development of quality of radiotherapy care experienced by breast cancer patients. Further research is needed to assess and develop patient-centred quality of care by patient education among cancer patients.

Show me your brain! Stories of interdisciplinary knowledge creation in practice. Experiences and observations from Aalto Design Factory, Finland.

This dissertation centres on the themes of knowledge creation, interdisciplinarity and knowledge work. My research approaches interdisciplinary knowledge creation (IKC) as practical situated activity. I argue that by approaching IKC from the practice-based perspective makes it possible to “deconstruct” how knowledge creation actually happens, and demystify its strong intellectual, mentalistic and expertise-based connotations. I have rendered the work of the observed knowledge workers into something ordinary, accessible and routinized. Consequently this has made it possible to grasp the pragmatic challenges as well the concrete drivers of such activity. Thus the effective way of organizing such activities becomes a question of organizing and leading effective everyday practices. To achieve that end, I have conducted ethnographic research of one explicitly interdisciplinary space within higher education, Aalto Design Factory in Helsinki, Finland, where I observed how students from different disciplines collaborated in new product development projects. I argue that IKC is a multi-dimensional construct that intertwines a particular way of doing; a way of experiencing; a way of embodied being; and a way of reflecting on the very doing itself. This places emphasis not only the practices themselves, but also on the way the individual experiences the practices, as this directly affects how the individual practices. My findings suggest that in order to effectively organize and execute knowledge creation activities organizations need to better accept and manage the emergent diversity and complexity inherent in such activities. In order to accomplish this, I highlight the importance of understanding and using a variety of (material) objects, the centrality of mundane everyday practices, the acceptance of contradictions and negotiations well as the role of management that is involved and engaged. To succeed in interdisciplinary knowledge creation is to lead not only by example, but also by being very much present in the very everyday practices that make it happen.

Docosahexaenoic acid ethyl esther (DHAEE) microcapsule production by spray-drying: optimization by experimental design

Docosahexaenoic acid is an essential polyunsaturated fatty acid with important metabolic activities. Its conjugated double bonds make it susceptible to decomposition. Its stability may be improved through fatty acid entrapment with a spray-drying technique; however, the many parameters involved in this technique must be considered to avoid affecting the final product quality. Therefore, this study aimed to evaluate the entrapment conditions and yields of fish oil enriched with docosahexaenoic acid ethyl ester. Microcapsules were obtained from Acacia gum using a spray-drying technique. The experimental samples were analyzed by chromatography and delineated by Statistica software, which found the following optimum entrapment conditions: an inlet temperature of 188 °C; 30% core material; an N2 flow rate of 55 mm; and a pump flow rate of 12.5 mL/minute. These conditions provided a 66% yield of docosahexaenoic acid ethyl ester in the oil, corresponding to 19.8% of entrapped docosahexaenoic acid ethyl ester (w/w). This result was considered significant since 30% corresponded to wall material.

The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps-Brazil): Design, data and methodology

Introduction: The chronic kidney disease outcomes and practice patterns study (CKDopps) is an international observational, prospective, cohort study involving patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment period, each one of the 22 selected clinics will enroll up to 60 advanced CKD patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). Exclusion criteria: age < 18 years old, patients on chronic dialysis or prior kidney transplant. The study timeline include up to one year for enrollment of patients at each clinic starting in the end of 2013, followed by up to 2-3 years of patient follow-up with collection of detailed longitudinal patient-level data, annual clinic practice-level surveys, and patient surveys. Analyses will apply regression models to evaluate the contribution of patient-level and clinic practice-level factors to study outcomes, and utilize instrumental variable-type techniques when appropriate. Conclusion: Launching in 2013, CKDopps Brazil will study advanced CKD care in a random selection of nephrology clinics across Brazil to gain understanding of variation in care across the country, and as part of a multinational study to identify optimal treatment practices to slow kidney disease progression and improve outcomes during the transition period to end-stage kidney disease.

Organisational purchasing of service design – Agency and client perspectives

There has been an increase in the interest in service design, as companies have become more customer-centric and their focus has shifted to customer experiences. The actual organisational purchasing of service design has been given little attention, until recent years. The purpose of this study is to explore the purchasing of service design from the perspectives of sellers (service design agencies) and buying clients (business organisations). In order to understand the phenomenon, also agencies and clients’ approaches to service design discipline, purchasing processes, challenges related to purchasing and ways of facilitating the purchasing are explored. The research follows qualitative research method and utilises abductive reasoning. A proposition framework was formed by combining services marketing, design and organisational buying behaviour literatures, and was tested against real-life business cases. Empirical data was gathered by interviewing eight service design agency representatives and five client representatives in Finland. The results of semi-structural interviews were analysed by finding repetitive themes. The proposition framework was updated according to interview findings. There were both similarities and differences in service design agencies and clients’ approaches to service design. Service design represents a strategic activity to both parties, and it helps in clients’ business development and in discovering opportunities. It is an ideology; a way of thinking and working. The driving force for purchasing service design seemed to be something else than service design itself. Projects have been bought for 1) change and innovation related development, 2) channel related development or for 3) customer experience related development. Seven purchasing challenge themes were recognised: 1) poor or differing service design understanding, 2) selling of service design, 3) varying expectations, 4) difficulty of pre-evaluation, 5) buyers and buying companies, 6) project process and nature and 7) unclear project results. These all can be considered to cause challenges in organisational service design purchasing. Challenges can be caused by either participant, the agency or the client, and take place at any point of the purchasing process. Some of the challenges could be considered as barriers to purchasing or they play a role in an unsuccessful service project – and therefore, result in an unsuccessful organisational purchase. Purchasing could be facilitated in various ways by either participant; some ways are more attitude based, others actionable improvements. Thesis’s theoretical and managerial findings can be utilised to both improve the selling and purchasing of service design services.

In search of good relationships to music : understanding aspiration and challenge in developing music school teacher practices

This study focuses on teacher practices in publicly funded music schools in Finland. As views on the aims of music education change and broaden, music schools across Europe share the challenge of developing their activities in response. In public and scholarly debate, there have been calls for increased diversity of contents and concepts of teaching. In Finland, the official national curriculum for state-funded music schools builds on the ideal that teaching and learning should create conditions which promote ‘a good relationship to music’. The meaning of this concept has been deliberately left open in order to leave room for dialogue, flexibility, and teacher autonomy. Since what is meant by ‘good’ is not defined in advance, the notion of ‘improving’ practices is also open to discussion. The purpose of the study is to examine these issues from teachers’ point of view by asking what music school teachers aim to accomplish as they develop their practices. Methodologically, the study introduces a suggestion for building empirical research on Alperson’s ‘robust’ praxial approach to music education, a philosophical theory which is strongly committed to practitioner perspectives and musical diversity. A systematic method for analysing music education practices, interpretive practice analysis, is elaborated with support from interpretive research methods originally used in policy analysis. In addition, the research design shows how reflecting conversations (a collaborative approach well-known in Nordic social work) can be fruitfully applied in interpretive research and combined with teacher inquiry. Data have been generated in a collaborative project involving five experienced music school teachers and the researcher. The empirical material includes transcripts from group conversations, data from teacher inquiry conducted within the project, and transcripts from follow-up interviews. The teachers’ aspirations can be understood as strivings to reinforce the connection between musical practices and various forms of human flourishing such that music and flourishing can sustain each other. Examples from their practices show how the word ‘good’ receives its meaning in context. Central among the teachers’ concerns is their hope that students develop a free and sustainable interest in music, often described as inspiration. I propose that ‘good relationships to music’ and ‘inspiration’ can be understood as philosophical mediators which support the transition from an indeterminate ‘interest in music’ towards specific ways in which music can become a (co-)constitutive part of living well in each person’s particular circumstances. Different musical practices emphasise different aspects of what is considered important in music and in human life. Music school teachers consciously balance between a variety of such values. They also make efforts to resist pressure which might threaten the goods they think are most important. Such goods include joy, participation, perseverance, solid musical skills related to specific practices, and a strong sense of vitality. The insights from this study suggest that when teachers are able to create inspiration, they seem to do so by performing complex work which combines musical and educational aims and makes general positive contributions to their students’ lives. Ensuring that teaching and learning in music schools remain as constructive and meaningful as possible for both students and teachers is a demanding task. The study indicates that collaborative, reflective and interdisciplinary work may be helpful as support for development processes on both individual and collective levels of music school teacher practices.

Examining human-centered design practice in the mobile apps era

Human-Centered Design (HCD) is a well-recognized approach to the design of interactive computing systems that supports everyday and professional lives of people. To that end, the HCD approach put central emphasis on the explicit understanding of users and context of use by involving users throughout the entire design and development process. With mobile computing, the diversity of users as well as the variety in the spatial, temporal, and social settings of the context of use has notably expanded, which affect the effort of interaction designers to understand users and context of use. The emergence of the mobile apps era in 2008 as a result of structural changes in the mobile industry and the profound enhanced capabilities of mobile devices, further intensify the embeddedness of technology in the daily life of people and the challenges that interaction designers face to cost-efficiently understand users and context of use. Supporting interaction designers in this challenge requires understanding of their existing practice, rationality, and work environment. The main objective of this dissertation is to contribute to interaction design theories by generating understanding on the HCD practice of mobile systems in the mobile apps era, as well as to explain the rationality of interaction designers in attending to users and context of use. To achieve that, a literature study is carried out, followed by a mixed-methods research that combines multiple qualitative interview studies and a quantitative questionnaire study. The dissertation contributes new insights regarding the evolving HCD practice at an important time of transition from stationary computing to mobile computing. Firstly, a gap is identified between interaction design as practiced in research and in the industry regarding the involvement of users in context; whereas the utilization of field evaluations, i.e. in real-life environments, has become more common in academic projects, interaction designers in the industry still rely, by large, on lab evaluations. Secondly, the findings indicate on new aspects that can explain this gap and the rationality of interaction designers in the industry in attending to users and context; essentially, the professional-client relationship was found to inhibit the involvement of users, while the mental distance between practitioners and users as well as the perceived innovativeness of the designed system are suggested in explaining the inclination to study users in situ. Thirdly, the research contributes the first explanatory model on the relation between the organizational context and HCD; essentially, innovation-focused organizational strategies greatly affect the cost-effective usage of data on users and context of use. Last, the findings suggest a change in the nature of HCD in the mobile apps era, at least with universal consumer systems; evidently, the central attention on the explicit understanding of users and context of use shifts from an early requirements phase and continual activities during design and development to follow-up activities. That is, the main effort to understand users is by collecting data on their actual usage of the system, either before or after the system is deployed. The findings inform both researchers and practitioners in interaction design. In particular, the dissertation suggest on action research as a useful approach to support interaction designers and further inform theories on interaction design. With regard to the interaction design practice, the dissertation highlights strategies that encourage a more cost-effective user- and context-informed interaction design process. With the continual embeddedness of computing into people’s life, e.g. with wearable devices and connected car systems, the dissertation provides a timely and valuable view on the evolving humancentered design.

Ontario high school sport : an investigation of organizational design and its context

In 2002, The Ontario Federation of School Athletic Associations (OFSAA) identified that in providing extracurricular sport programs schools are faced with the 'new realities' of the education system. Although research has been conducted exploring the pressures impacting the provision of extracurricular school sport (Donnelly, Mcloy, Petherick, & Safai, 2000), few studies within the field have focused on understanding extracurricular school sport from an organizational level. The focus of this study was to examine the organizational design (structure, systems, and values) of the extracurricular sport department within three Ontario high schools, as well as to understand the context within which the departments exist. A qualitative multiple case study design was adopted and three public high schools were selected from one district school board in Ontario to represent the cases under investigation. Interviews, observations and documents were used to analyze the extracurricular sport department design of each case and to better understand the context within which the departments exist. As the result of the analysis of the structure, systems and values of each case, two designs emerged- Design KT1 and Design KT2. Differences in the characteristics of design archetype KT1 and KT2 centered on the design dimension of values, and therefore this study identified that contrasting organizational values reflect differences in design types. The characteristics of the Kitchen Table archetype were found to be transferable to the sub-sector of extracurricular school sport, and therefore this research provides a springboard for further research in organizational design within the education sector of extracurricular high school sport. Interconnections were found between the data associated with the external and internal contexts within which the extracurricular sport departments exist. The analysis of the internal context indicated the important role played by organizational members in shaping the context within which the departments exist. The analysis of the external context highlighted the institutional pressures that were present within the education environment. Both political and cultural expectations related to the role of extracurricular sport within schools were visible and were subsequently used by the high schools to create legitimacy and prestige, and to access resources.

Understanding value congruence : a sport organization case study

With the recent growth in cultural complexity, many organizations are faced with increasingly diverse employee pools. Gaining a greater understanding of the values that employees possess is the first step in effectively satisfying their needs and achieving a more productive workforce (lung & Avolio, 2000). Values playa significant role in influencing individual behaviours. It is therefore necessary to assess the qualities of employee value systems and directly link them to the values of the organization. The importance of values and value congruence has been emphasized by many organizational behaviour researchers (cf. Adkins & Caldwell, 2004; Erdogan, Kraimer, & Liden, 2004; Jung & Avolio, 2000; Rokeach, 1973); however the emphasis on value studies remains fairly stagnant within the sport industry (Amis, Slack, & Hinings, 2002). In order to examine the realities that were constructed by the participants in this study a holistic view of the impact of values within a specific sport organization were provided. The purpose of this case study was to examine organizational and employee values to understand the effects of values and value congruence on employee behaviours within the context of a large Canadian sport organization. A mUltiple methods case study approach was adopted in order to fully serve the purpose and provide a comprehensive view of the organization being examined. Document analysis, observations, surveys, as well as semi-structured interviews were conducted. The process allowed for triangulation and confirmability of the findings. Each method functioned to create an overarching understanding of the values and value congruence within this organization. The analysis of the findings was divided into qualitative and quantitative sections. The qualitative documents were analyzed twice, once manually by the researcher and once via AtIas.ti Version 4 (1998). The a priori and emergent coding that took place was based on triangulating the findings and uncovering common themes throughout the data. The Rokeach Value Survey (1973) that was incorporated into the survey design of the study was analyzed using descriptive statistics, as well as Mann-Whitney U, and Kruskal Wallis formulas. These were deemed appropriate for analysis given the non-parametric nature of the survey instrument (Kinnear & Gray, 2004). The quantitative survey served to help define the values and value congruence that was then holistically examined through the qualitative interviews, document analyses, and observations. The results of the study indicated incongruent value levels between employees and those stated or perceived as the organization's values. Each finding demonstrated that varying levels of congruence may have diverse affects on individual behaviours. These behaviours range from production levels to interactions with fellow employees to turnover. In addition to the findings pertaining to the research questions, a number of other key issues were uncovered regarding departmentalization, communication, and board relations. Each has contributed to a greater understanding of the organization and has created direction for further research within this area of study.

Understanding the Origin of Selectivity in the Asymmetric Lithiation Reaction of N-Heterocycles: A Theoretical Study

The natural abundance of the N-heterocycle containing compounds has pushed the synthetic community toward the invention of new synthetic methods that result in the structural diversity of N-heterocycles. Among this, is the efficient and highly selective diamine mediated asymmetric lithiation process. Amongst the diamine chiral ligands, (-)-sparterine, which is a naturally occurring alkaloid proved to be an efficient one. Many successful, good yielding and highly selective lithiation reactions have been accomplished with the mediation by this chiral diamine base. Although, there are some examples of experimental and theoretical mechanistic studies in the literature, there is a lack of detailed understanding as to how it exactly induces the chirality. In this thesis is described a systematic investigation of how (-)-sparteine influences the stereoselectivity in the course of asymmetric lithiation reaction. This led us to the establishment of the function of A-ring’s β-CH2 effect and D-ring effect. Consequently, the importance of the A-ring and D-ring portions of (-)-sparteine in the stereoselectivity is unraveled. Another part of this thesis deals with the asymmetric lithiation of BF3-activated N,N- dimethylaminoferrocene in the presence of (1R, 2R)-N1,N2-bis(3,3-dimethylbutyl)-N1,N2-dimethylcyclohexane-1,2-diamine ( a (R,R)-TMCDA surrogate) with i-PrLi. Computational findings were in full accord with the experimental observations. Subsequently, the theoretically provided insights into the mechanism of the reaction were exploited in computational design of a new ligand. Unfortunately, the outcome of this design was not experimentally robust and an updated approach towards a successful design was explained.

Directed evolution of human dihydrofolate reductase: towards a better understanding of binding at the active site

La dihydrofolate réductase humaine (DHFRh) est une enzyme essentielle à la prolifération cellulaire, ce qui en fait une cible de choix pour le traitement de différents cancers. À cet effet, plusieurs inhibiteurs spécifiques de la DHFRh, les antifolates, ont été mis au point : le méthotrexate (MTX) et le pemetrexed (PMTX) en sont de bons exemples. Malgré l’efficacité clinique certaine de ces antifolates, le développement de nouveaux traitements s’avère nécessaire afin de réduire les effets secondaires liés à leur utilisation. Enfin, dans l’optique d’orienter la synthèse de nouveaux composés inhibiteurs des DHFRh, une meilleure connaissance des interactions entre les antifolates et leur enzyme cible est primordiale. À l’aide de l’évolution dirigée, il a été possible d’identifier des mutants de la DHFRh pour lesquels l’affinité envers des antifolates cliniquement actifs se voyait modifiée. La mutagenèse dite ¬¬de saturation a été utilisée afin de générer des banques de mutants présentant une diversité génétique au niveau des résidus du site actif de l’enzyme d’intérêt. De plus, une nouvelle méthode de criblage a été mise au point, laquelle s’est avérée efficace pour départager les mutations ayant entrainé une résistance aux antifolates et/ou un maintient de l’activité enzymatique envers son substrat natif, soient les phénotypes d’activité. La méthode de criblage consiste dans un premier temps en une sélection bactérienne à haut débit, puis dans un second temps en un criblage sur plaques permettant d’identifier les meilleurs candidats. Plusieurs mutants actifs de la DHFRh, résistants aux antifolates, ont ainsi pu être identifiés et caractérisés lors d’études de cinétique enzymatique (kcat et IC50). Sur la base de ces résultats cinétiques, de la modélisation moléculaire et des données structurales de la littérature, une étude structure-activité a été effectuée. En regardant quelles mutations ont les effets les plus significatif sur la liaison, nous avons commencé à construire un carte moléculaire des contacts impliqués dans la liaison des ligands. Enfin, des connaissances supplémentaires sur les propriétés spécifiques de liaison ont put être acquises en variant l’inhibiteur testé, permettant ainsi une meilleure compréhension du phénomène de discrimination du ligand.

Studies on the exaggerated inflammatory response caused by streptococcus suis at systemic and central nervous system levels

Streptococcus suis de type 2 est un microorganisme pathogène d’importance chez le porc. Il est la cause de différentes pathologies ayant comme caractéristique commune la méningite. C’est également un agent émergeant de zoonose : des cas cliniques humains ont récemment été rapportés en Asie. Cependant, la pathogénèse de S. suis n’est pas encore complètement élucidée. Jusqu’à présent, la réponse pro-inflammatoire initiée par S. suis n’a été étudiée qu’in vitro. L’étude du choc septique et de la méningite requiert toujours des modèles expérimentaux appropriés. Au cours de cette étude, nous avons développé un modèle in vivo d’infection chez la souris qui utilise la voie d’inoculation intra-péritonéale. Ce modèle a servi à l’étude de la réponse pro-inflammatoire associée à ce pathogène, tant au niveau systémique qu’au niveau du système nerveux central (SNC). Il nous a également permis de déterminer si la sensibilité aux infections à S. suis pouvait être influencée par des prédispositions génétiques de l’hôte. Le modèle d’infection par S. suis a été mis au point sur des souris de lignée CD1. Les résultats ont démontré une bactériémie élevée pendant les trois jours suivant l’infection. Celle-ci était accompagnée d’une libération rapide et importante de différentes cytokines pro-inflammatoires (TNF-α, IL-6, IL-12p40/p70, IFN-ɣ) et de chémokines (KC, MCP-1 and RANTES), qui ont entraîné un choc septique et la mort de 20 % des animaux. Ensuite, pour confirmer le rôle de l’inflammation sur la mortalité et pour déterminer si les caractéristiques génétiques de l’hôte pouvaient influencer la réponse inflammatoire et l’issue de la maladie, le modèle d’infection a été étendu à deux lignées murines consanguines différentes considérées comme résistante : la lignée C57BL/6 (B6), et sensible : la lignée A/J. Les résultats ont démontré une importante différence de sensibilité entre les souris A/J et les souris B6, avec un taux de mortalité atteignant 100 % à 20 h post-infection (p.i.) pour la première lignée et de seulement 16 % à 36 h p.i. pour la seconde. La quantité de bactéries dans le sang et dans les organes internes était similaire pour les deux lignées. Donc, tout comme dans la lignée CD1, la bactériémie ne semblait pas être liée à la mort des souris. La différence entre les taux de mortalité a été attribuée à un choc septique non contrôlé chez les souris A/J infectées par S. suis. Les souris A/J présentaient des taux exceptionnellement élevés de TNF-α, IL-12p40/p70, IL-1β and IFN- γ, significativement supérieurs à ceux retrouvés dans la lignée B6. Par contre, les niveaux de chémokines étaient similaires entre les lignées, ce qui suggère que leur influence est limitée dans le développement du choc septique dû à S. suis. Les souris B6 avaient une production plus élevée d’IL-10, une cytokine anti-inflammatoire, ce qui suppose que la cascade cytokinaire pro-inflammatoire était mieux contrôlée, entraînant un meilleur taux de survie. Le rôle bénéfique potentiel de l’IL-10 chez les souris infectées par S. suis a été confirmé par deux approches : d’une part en bloquant chez les souris B6 le récepteur cellulaire à l’IL-10 (IL-10R) par un anticorps monoclonal anti-IL-10R de souris et d’autre part en complémentant les souris A/J avec de l’IL-10 de souris recombinante. Les souris B6 ayant reçu le anticorps monoclonal anti-IL-10R avant d’être infectées par S. suis ont développé des signes cliniques aigus similaires à ceux observés chez les souris A/J, avec une mortalité rapide et élevée et des taux de TNF-α plus élevés que les souris infectées non traitées. Chez les souris A/J infectées par S. suis, le traitement avec l’IL-10 de souris recombinante a significativement retardé l’apparition du choc septique. Ces résultats montrent que la survie au choc septique dû à S. suis implique un contrôle très précis des mécanismes pro- et anti-inflammatoires et que la réponse anti-inflammatoire doit être activée simultanément ou très rapidement après le début de la réponse pro-inflammatoire. Grâce à ces expériences, nous avons donc fait un premier pas dans l’identification de gènes associés à la résistance envers S. suis chez l’hôte. Une des réussites les plus importantes du modèle d’infection de la souris décrit dans ce projet est le fait que les souris CD1 ayant survécu à la septicémie présentaient dès 4 jours p.i. des signes cliniques neurologiques clairs et un syndrome vestibulaire relativement similaires à ceux observés lors de méningite à S. suis chez le porc et chez l’homme. L’analyse par hybridation in situ combinée à de l’immunohistochimie des cerveaux des souris CD1 infectées a montré que la réponse inflammatoire du SNC débutait avec une augmentation significative de la transcription du Toll-like receptor (TLR)2 et du CD14 dans les microvaisseaux cérébraux et dans les plexus choroïdes, ce qui suggère que S. suis pourrait se servir de ces structures comme portes d’entrée vers le cerveau. Aussi, le NF-κB (suivi par le système rapporteur de l’activation transcriptionnelle de IκBα), le TNF-α, l’IL-1β et le MCP-1 ont été activés, principalement dans des cellules identifiées comme de la microglie et dans une moindre mesure comme des astrocytes. Cette activation a également été observée dans différentes structures du cerveau, principalement le cortex cérébral, le corps calleux, l’hippocampe, les plexus choroïdes, le thalamus, l’hypothalamus et les méninges. Partout, cette réaction pro-inflammatoire était accompagnée de zones extensives d’inflammation et de nécrose, de démyélinisation sévère et de la présence d’antigènes de S. suis dans la microglie. Nous avons mené ensuite des études in vitro pour mieux comprendre l’interaction entre S. suis et la microglie. Pour cela, nous avons infecté des cellules microgliales de souris avec la souche sauvage virulente (WT) de S. suis, ainsi qu’avec deux mutants isogéniques, un pour la capsule (CPS) et un autre pour la production d’hémolysine (suilysine). Nos résultats ont montré que la capsule était un important mécanisme de résistance à la phagocytose pour S. suis et qu’elle modulait la réponse inflammatoire, en dissimulant les composants pro-inflammatoires de la paroi bactérienne. Par contre, l’absence d’hémolysine, qui est un facteur cytotoxique potentiel, n’a pas eu d’impact majeur sur l’interaction de S. suis avec la microglie. Ces études sur les cellules microgliales ont permis de confirmer les résultats obtenus précédemment in vivo. La souche WT a induit une régulation à la hausse du TLR2 ainsi que la production de plusieurs médiateurs pro-inflammatoires, dont le TNF-α et le MCP-1. S. suis a induit la translocation du NF-kB. Cet effet était plus rapide dans les cellules stimulées par le mutant déficient en CPS, ce qui suggère que les composants de la paroi cellulaire représentent de puissants inducteurs du NF-kB. De plus, la souche S. suis WT a stimulé l’expression de la phosphotyrosine, de la PKC et de différentes cascades liées à l’enzyme mitogen-activated protein kinase (MAPK). Cependant, les cellules microgliales infectées par le mutant déficient en CPS ont montré des profils de phosphorylation plus forts et plus soutenus que celles infectées par le WT. Finalement, la capsule a aussi modulé l’expression de l’oxyde nitrique synthétase inductible (iNOS) induite par S. suis et par la production subséquente d’oxyde nitrique par la microglie. Ceci pourrait être lié in vivo à la neurotoxicité et à la vasodilatation. Nous pensons que ces résultats contribueront à une meilleure compréhension des mécanismes sous-tendant l’induction de l’inflammation par S. suis, ce qui devrait permettre, d’établir éventuellement des stratégies plus efficaces de lutte contre la septicémie et la méningite. Enfin, nous pensons que ce modèle expérimental d’infection chez la souris pourra être utilisé dans l’étude de la pathogénèse d’autres bactéries ayant le SNC pour cible.

S’exercer à l’empathie : une expérience pédagogique en design d’intérieur

Les professionnels ont par définition un public bénéficiaire de leurs services : le patient pour le médecin, le psychologue ou l’infirmière ; le client pour l’avocat ; le consommateur pour le gestionnaire d’une entreprise commerciale ; etc. L’usager ou l’habitant du cadre bâti constitue un des destinataires des services professionnels du designer d’intérieur. De quelle manière peut-on apprendre aux étudiants/futurs professionnels du design d’intérieur à se mettre à la place de l’usager/habitant des espaces qu’ils conçoivent ? Le concept de l’empathie, communément décrit comme la capacité de se mettre à la place de l’autre, de le comprendre et de ressentir ses sentiments et ses émotions, est bien adapté pour explorer cette attitude. Cet article est composé de deux parties. La première présente une expérience pédagogique en design d’intérieur où des étudiants apprennent à se représenter les usagers de leur projet d’aménagement en utilisant un outil méthodologique appelé « boussole éthique ». Cette boussole est constituée essentiellement de trois pôles qui renvoient aux trois rapports fondamentaux de l’être humain tels qu’étudiés dans la tradition stoïcienne : rapport à soi-même, à autrui et à la nature. Dans la seconde partie, l’article met en relief plusieurs éléments théoriques qui permettent de comprendre, de consolider et, éventuellement, de faire évoluer les bases conceptuelles qui sous-tendent cette démarche. Il s’agira notamment des théories éthiques et de certaines approches spécifiques au concept de l’empathie.