Growth factor induction in intervertebral disc tissue: Observations in basic mechanisms of disc degeneration and rearrangement

The intervertebral disc is composed of concentrically arranged components: annulus fibrosus, the transition zone, and central nucleus pulposus. The major disc cell type differs in various parts of the intervertebral disc. In annulus fibrosus a spindle shaped fibroblast-like cell mainly dominates, whereas in central nucleus pulposus the more rounded chondrocyte-like disc cell is the major cell type. At birth the intervertebral disc is well vascularized, but during childhood and adolescence blood vessels become smaller and less numerous. The adult intervertebral disc is avascular and is nourished via the cartilage endplates. On the other hand, degenerated and prolapsed intervertebral discs are again vascularized, and show many changes compared to normal discs, including: nerve ingrowth, change in collagen turnover, and change in water content. Furthermore, the prolapsed intervertebral disc tissue has a tendency to decrease in size over time. Growth factors are polypeptides which regulate cell growth, extracellular matrix protease activity, and vascularization. Oncoproteins c-Fos and c-Jun heterodimerize, forming the AP-1 transcription factor which is expressed in activated cells. In this thesis the differences of growth factor expression in normal intervertebral disc, the degenerated intervertebral disc and herniated intervertebral disc were analyzed. Growth factors of particular interest were basic fibroblast growth factor (bFGF or FGF-2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta (TGFβ). Cell activation was visualized by the expression of the AP-1 transcription promoters c-Fos and c-Jun. The expression was shown with either mono- or polyclonal antibodies by indirect avidin-biotin-peroxidase immunohistochemical staining method. The normal control material was collected from a tissue bank of five organ donors. The degenerated disc material was from twelve patients operated on for painful degenerative disc disease, and herniated disc tissue material was obtained from 115 patients operated on for sciatica. Normal control discs showed only TGFβ immunopositivity. All other factors studied were immunonegative in the control material. Prolapsed disc material was immunopositive for all factors studied, and this positivity was located either in the disc cells or in blood vessels. Furthermore, neovascularization was noted. Disc cell immunoreaction was shown in chondrocyte-like disc cells or in fibroblast-like disc cells, the former being expressed especially in conglomerates (clusters of disc cells). TGFβ receptor induction was prominent in prolapsed intervertebral disc tissue. In degenerated disc material, the expression of growth factors was analyzed in greater detail in various parts of the disc: nucleus pulposus, anterior annulus fibrosus and posterior annulus fibrosus. PDGF did not show any immunoreactivity, whereas all other studied growth factors were localized either in chondrocyte-like disc cells, often forming clusters, in fibroblast-like disc cells, or in small capillaries. Many of the studied degenerated discs showed tears in the posterior region of annulus fibrosus, but expression of immunopositive growth factors was detected throughout the entire disc. Furthermore, there was a difference in immunopositive cell types for different growth factors. The main conclusion of the thesis, supported by all substudies, is the occurrence of growth factors in disc cells. They may be actively participating in a network regulating disc cell growth, proliferation, extracellular matrix turnover, and neovascularization. Chondrocyte-like disc cells, in particular, expressed growth factors and oncoproteins, highlighting the importance of this cell type in the basic pathophysiologic events involved in disc degeneration and disc rearrangement. The thesis proposes a hypothesis for cellular remodelling in intervertebral disc tissue. In summary, the model presents an activation pattern of different growth factors at different intervertebral disc stages, mechanisms leading to neovascularization of the intervertebral disc in pathological conditions, and alteration of disc cell shape, especially in annulus fibrosus. Chondrocyte-like disc cells become more numerous, and these cells are capable of forming clusters, which appear to be regionally active within the disc. The alteration of the phenotype of disc cells expressing growth factors from fibroblast-like disc cells to chondrocyte-like cells in annulus fibrosus, and the numerous expression of growth factor expressing disc cells in nucleus pulposus, may be a key element both during pathological degeneration of the intervertebral disc, and during the healing process after trauma.

Clinical Phenotype and Genetic Epidemiology of Schizophrenia in a Finnish Isolate

This study is part of the joint project "The Genetic Epidemiology and Molecular Genetics of schizophrenia in Finland" between the Departments of Mental Health and Alcohol Research, and Molecular Medicine at the National Public Health Institute. In the study, we utilized three nationwide health care registers: 1) the Hospital Discharge Register, 2) the Free Medication Register, and 3) the Disability Pension Register, plus the National Population Register, in order to identify all patients with schizophrenia born from 1940 to 1976 (N=33,731) in Finland, and their first degree-relatives. 658 patients with at least one parent born in a homogeneous isolate in northeastern Finland were identified, as well as 4904 familial schizophrenia patients with at least two affected siblings from the whole country. The comparison group was derived from the Health 2000 Study. We collected case records and reassessed the register diagnosis. Were contacted the isolate patients and a random sample of patients from the whole country to make diagnostic clinical interviews and to assess the negative and positive symptoms and signs of schizophrenia. In addition to these patients, we interviewed siblings who were initially healthy according to the Hospital Discharge Register. Of those with a register diagnosis of schizophrenia, schizoaffective or schizophreniform disorder, 69% received a record-based consensus diagnosis and 63% an interview-based diagnosis of schizophrenia. Patients with schizophrenia having first-degree relatives with psychotic disorder had more severe affective flattening and alogia than those who were the only affected individuals in their family. The novel findings were: 1) The prevalence of schizophrenia in the isolate was relatively high based on register (1.5%), case record (0.9-1.3%), and interview (0.7-1.2%) data. 2) Isolate patients, regardless of their familial loading for schizophrenia, had less delusions and hallucinations than the whole country familial patients, which may be related to the genetic homogeneity in the isolate. This phenotype encourages the use of endophenotypes in genetic analyses instead of diagnoses alone. 3) The absence of register diagnosis does not confirm that siblings are healthy, because 7.7% of siblings had psychotic symptoms already before the register diagnoses were identified in 1991. For genetic research, the register diagnosis should therefore be reassessed using either a structured interview or a best- estimate case note consensus diagnosis. Structured clinical interview methods need be considered also in clinical practice.

Yliopisto-opetuksen yhteistoiminnallinen kehittäminen

The main aim of this work is to study the possibility of applying the cooperative learning approach to develop academic learning and teaching culture. In this work cooperative learning refers to a pedagogical approach that applies social psychological knowledge of group dynamics and small group teaching. Furthermore, theories of collaborative learning and organization development have been applied. Based on these theories a model of developing learning and teaching culture was developed. The model was tested in the development project that was carried out in the Faculty of Agriculture and Forestry of Helsinki University. The research questions were: How were the theories of cooperative and collaborative learning and organization development applied in the project? What kind of effects did the development project have on the learning and teaching culture? Through which kind of mechanisms did the project influence this culture? How should the development model be revised after the empirical test? The project lasted five years and the major part of the project consisted of a one-year pedagogical training course. Altogether 145 people (teachers, researchers, library staff, and students) participated in the training, two to three departments at a time. In the pedagogical training cooperative learning methods were widely used. A questionnaire was used to study effects of the development project. The questionnaire was sent to 87 people and 65.5 % answered it. Both the answers to the questionnaire and a sample of learning diaries (n=61) were used to study the mechanism of the project. A sample of the learning diaries consisted of two pedagogical training group members diaries. The frequency distributions were calculated as extrapolations from the answers to the structured questions. Furthermore the answers were classified by the main background variables. The analysis of the open answers to the questionnaire and the learning diaries were data-based. According to the answers to the questionnaire, the effects of the pedagogical training were as follows: The participants consider learning more as an active process of constructing knowledge. Furthermore they considered the individual learning styles and strategies, cooperation and motivation as more important part of the learning process than before the pedagogical training. The role of the teacher was viewed more challenging than before. Additionally the cooperation between teachers, other staff members and students had projected to increase. After the project had ended the teaching methods in the whole faculty were viewed to become varied and the teaching was considered to be more valued than before. According to the answers to the questionnaire, the project influenced through the following ways: the project stimulated the change process, provided new methods for learning and teaching, had an effect on conceptions of learning and teaching and facilitated meaningful communication with others (staff and students). The analysis of the learning diaries supported these findings. In addition, the analysis of the learning diaries deepened the understanding of how the cooperative learning methods supported positive learning atmosphere and reduced the negative effect of the status differences between the members of the group. The critical comments in the learning diaries could be interpreted as collision between cooperative and traditional teaching culture. Cooperative learning gives theory-based methods to develop academic learning and teaching culture. The approach helps the developer to create positive collaborative learning environment and gives ways to support learning in small groups, which can promote cultural change. On the other hand, to understand the whole process of organization development and promote change the theories of organizations and more sosioconstructivist theory of learning are needed. Cooperative learning, collaborative learning, higher education, group dynamics, social constructionism, organisational culture, organisation development

Rot bilong mipela

In my master's thesis I explore the political significance of logging in Papua New Guinea (PNG). In commercial logging the post-colonial state of PNG, its local communities, transnational companies and non-governmental organizations come interestingly together. The central research questions are what forms of political awareness and mobilization does commercial logging bring up in the small scale communities and how – if at all – does logging change the relationship between these communities and the state of PNG. The thesis is based on three months of ethnographic fieldwork conducted in 2007 in a village located in the East New Britain province of PNG. The village, inhabited mainly by the Mengen people, was an interesting case, because logging operations had been conducted in the area with the permission of the people, while on the other hand some villagers had formed a conservation association of their own. Parliamentary elections were also held in PNG during the time of my fieldwork. During my stay in the village I took part in the village life and conducted interviews. In addition to this, much of my material is based on informal discussions with people. On my way to and from the village I also interviewed several Papua New Guinean NGO-workers in the national and provincial capitals. In my thesis I show that environmental conservation in the village is part of a larger attempt to protect local autonomy, culture and the environment, i.e. it is a ”localistic” movement. Locals supporting conservation, as well as those supporting logging, take actively part in national parliamentary as well as local level politics. In my thesis I have attempted to unpack the notion of ”local” by examining internal power relations of the community and describing various lines of thought and opinions that base on local cultural values. Along with this, commercial logging seems also to elicit the role of the state in two-fold way in East New Britain. On the one hand, the government seeks to use logging roads built by logging companies as the basis of its own national infrastructure, even though the company roads are often of manifestably poor quality and short-lived. On the other hand, problems caused by logging, such as land disputes, create a need among local communities for the state and its services. Central themes in my thesis are the local values invested in the environment, as well as the ways in which the locals produce their environment both conceptually as well as physically. As subsistence farmers the locals depend economically on the condition of their environment. However, the value of the environment goes beyond economical questions. For example, the environment holds proof of the history of the community. Conversely, also the state and companies attempt to conceptualize, modify and administer the environment. This is done through processes such as mapping and road building, both crucial political questions in East New Britain. Here the anthropological discussion about space and place, as well as political geography are central. The diverse ways of conceptualizing the environment, as well as logging, cause often disputes about the ownership of land areas. Because of this I discuss local ways of holding the land communally, as well as PNG's land legislation and ways of dispute management. Land tenure and disputes are political questions that the locals have to deal with and in some cases these questions also create a need for the judiciary system of the state. The disputes affect also political activity, which I discuss at some length in my thesis as well. Interestingly, the locals, regardless of their political views and affiliations, establish transnational connections ranging from NGOs to government departments and multinational companies.

Mental Disorders among Burn Patients

ABSTRACT Mental disorders and suicide attempts among acute burn patients were investigated in a collaborative research project between National Institute for Health and Welfare and Departments of Psychiatry and Plastic surgery in University of Helsinki in Finland. This project was realized in two parts. The first cohort of burn patients consisted of all burn patients admitted to the Helsinki Burn Centre during 1989 97. In this retrospective cohort, 5.7% (N=46) of the total of 811 burn patients had attempted suicide. The burn severity of suicide attempters was markedly higher than in the other burn patients. Suicide attempters were more often unemployed or on disability pension and had psychiatric history before the injury. The second sample was a prospective cohort of all acute consecutive burn patients admitted to the Helsinki Burn Centre during 18 months in 2006- 2007. All subjects (N=107) of the cohort were interviewed with the Structured Clinical Interview for DSM-IV for Axis I and II mental disorders (SCID-I and SCID-II) at baseline and then 86 % of all (N=92) with SCID-I at the end of six-month follow-up. Most (61%) patients had at least one lifetime mental disorder before burn; 47 % substance-related, 10% psychotic and 23% personality disorders. The overall prevalence of Axis I mental disorders increased significantly from the month prior to burn to acute care but decreased significantly from acute care to six months. However, more than one half (55%) of the cohort suffered from some mental disorder during follow-up. Less than one half of the burn patients with estimated need for psychiatric care received psychiatric care. Burn severity independently and strongly predicted risk for mental disorders during follow-up and pre-burn psychiatric history, severe burns and estimated need for psychiatric care significantly predicted psychiatric care received. The proportion of patients with self-inflicted burns is not high but mental disorders are common among burn patients. Mental disorders may predispose to burns. After burn injury, more than half of the patients suffer from mental disorders and a strong relationship exists between burn severity and some post-burn mental disorders. A minority of the patients with unequivocal need for psychiatric care actually receive it. Psychiatric consultations and care follow mainly the course of acute burn treatment.

Didactical reconstructions for organizing knowledge in physics teacher education

Physics teachers are in a key position to form the attitudes and conceptions of future generations toward science and technology, as well as to educate future generations of scientists. Therefore, good teacher education is one of the key areas of physics departments education program. This dissertation is a contribution to the research-based development of high quality physics teacher education, designed to meet three central challenges of good teaching. The first challenge relates to the organization of physics content knowledge. The second challenge, connected to the first one, is to understand the role of experiments and models in (re)constructing the content knowledge of physics for purposes of teaching. The third challenge is to provide for pre-service physics teachers opportunities and resources for reflecting on or assessing their knowledge and experience about physics and physics education. This dissertation demonstrates how these challenges can be met when the content knowledge of physics, the relevant epistemological aspects of physics and the pedagogical knowledge of teaching and learning physics are combined. The theoretical part of this dissertation is concerned with designing two didactical reconstructions for purposes of physics teacher education: the didactical reconstruction of processes (DRoP) and the didactical reconstruction of structures (DRoS). This part starts with taking into account the required professional competencies of physics teachers, the pedagogical aspects of teaching and learning, and the benefits of the graphical ways of representing knowledge. Then it continues with the conceptual and philosophical analysis of physics, especially with the analysis of experiments and models role in constructing knowledge. This analysis is condensed in the form of the epistemological reconstruction of knowledge justification. Finally, these two parts are combined in the designing and production of the DRoP and DRoS. The DRoP captures the knowledge formation of physical concepts and laws in concise and simplified form while still retaining authenticity from the processes of how concepts have been formed. The DRoS is used for representing the structural knowledge of physics, the connections between physical concepts, quantities and laws, to varying extents. Both DRoP and DRoS are represented in graphical form by means of flow charts consisting of nodes and directed links connecting the nodes. The empirical part discusses two case studies that show how the three challenges are met through the use of DRoP and DRoS and how the outcomes of teaching solutions based on them are evaluated. The research approach is qualitative; it aims at the in-depth evaluation and understanding about the usefulness of the didactical reconstructions. The data, which were collected from the advanced course for prospective physics teachers during 20012006, consisted of DRoP and DRoS flow charts made by students and student interviews. The first case study discusses how student teachers used DRoP flow charts to understand the process of forming knowledge about the law of electromagnetic induction. The second case study discusses how student teachers learned to understand the development of physical quantities as related to the temperature concept by using DRoS flow charts. In both studies, the attention is focused on the use of DRoP and DRoS to organize knowledge and on the role of experiments and models in this organization process. The results show that students understanding about physics knowledge production improved and their knowledge became more organized and coherent. It is shown that the flow charts and the didactical reconstructions behind them had an important role in gaining these positive learning results. On the basis of the results reported here, the designed learning tools have been adopted as a standard part of the teaching solutions used in the physics teacher education courses in the Department of Physics, University of Helsinki.

The British Intervention in South Russia 1918-1920

Soon after the Bolshevik Revolution of 1917, a three-year civil war broke out in Russia. As in many other civil wars, foreign powers intervened in the conflict. Britain played a leading role in this intervention and had a significant effect on the course of the war. Without this intervention on the White side, the superiority of numbers in manpower and weaponry of the Bolsheviks would have quickly overwhelmed their opponents. The aim of this dissertation is to explain the nature and role of the British intervention on the southern, and most decisive, front of the Civil War. The political decision making in London is studied as a background, but the focus of the dissertation is on the actual implementation of the British policy in Russia. The British military mission arrived in South Russia in late 1918, and started to provide General Denikin s White army with ample supplies. General Denikin would have not been able to build his army of more than 200,000 men or to make his operation against Moscow without the British matériel. The British mission also organized the training and equipping of the Russian troops with British weapons. This made the material aid much more effective. Many of the British instructors took part in fighting the Bolsheviks despite the orders of their government. The study is based on primary sources produced by British departments of state and members of the British mission and military units in South Russia. Primary sources from the Whites, including the personal collections of several key figures of the White movement and official records of the Armed Forces of South Russia are also used to give a balanced picture of the course of events. It is possible to draw some general conclusions from the White movement and reasons for their defeat from the study of the British intervention. In purely material terms the British aid placed Denikin s army in a far more favourable position than the Bolsheviks in 1919, but other military defects in the White army were numerous. The White commanders were unimaginative, their military thinking was obsolete, and they were incapable of organizing the logistics of their army. There were also fundamental defects in the morale of the White troops. In addition to all political mistakes of Denikin s movement and a general inability to adjust to the complex situation in Revolutionary Russia, the Whites suffered a clear military defeat. In South Russia the Whites were defeated not because of the lack of British aid, but rather in spite of it.

Asukkaan Helsinki? : Tapaustutkimus vuorovaikutteisuudesta kaupunkisuunnittelussa

This study examines the interaction between inhabitants and urban planning. In addition to traditional methods of participation there can be seen an increasing need to find new channels and means to influence on one´s environment. Hearing of inhabitants during planning is hoped to decrease the amount of claims and this way to speed up the planning process. Discussion that emphasizes competitiveness and innovativeness in planning has brought out the role of inhabitants as selective consumers and end users. This extension of civil perspective completes the thought of participation in city planning and adds the pressure on developing the interaction and user orientation. The aim of the study is to point out the present situation of inhabitant´s participation and influencing in Helsinki. Helsinki City Planning Department opened a new information and exhibiotion hall called Laituri in 2008. Laituri provides the latest information about planning projects in Helsinki and temporary exhibitions as well as it operates as communication channel and information point for the department. In this study Laituri is examined as a case study of interaction between citizen and planner. The study is divided into two principal themes. The aim is to research action and interactivity at Laituri from the inhabitants´and planners´point of view. The qualitative study has inquiries, interview surveys and observation as research methods. Empiricial data of the study consists of three parts which complement each other: Laituri operational reseach, inquiry directed to the members of Laituri team and interviews of three experts. The aim is to find answers to questions like, does Laituri reach the citizens and will the opportunities to participate improve along Laituri. The study examines also how the local knowledge of inhabitants will come across to planners and further to planning. The study combines discussions of inhabitants´ influencing in Finnish society and science community. Cornerstones of the study are inhabitant participation, interaction and local knowledge in urban planning. The theory behind the study is communicative planning theory. In addition the theory consists of key concepts. The study introduces a concept of Inhabitant´s Helsinki, which reflects the inhabitant as customer-citizen who is an active product developer in participative urban planning. According to the research results the experts of Laituri and majority of inhabitants in Helsinki experience that the inhabitant´s possibilities to participate will improve along Laituri. However half of the citizens in Helsinki believe that local knowledge and ideas will only have minor impact on the final plan. According to city dwellers the present practise used by Helsinki City Planning Department supports only partially adequate interaction. The experts of Laituri experience that the role of Laituri is first of all forum of communication and discussion channel instead of effective local data collector. Based on the results the study introduces a model of inhabitant´s participation field. According to the model Laituri can be seen as phenomenom in Helsinki urban planning which has the elements of network municipality. The planner is more like diplomatic trend-setter and visionary. The inhabitant of Helsinki is an expert in city living and participative producer of local knowledge. Participation methods are increasingly segmented and tailored in every plan and project. The study argues that Inhabitant´s Helsinki is a pluralistic milieu in constant pressure for change. Therefore reaching the everyday life experiencies of inhabintants should be at higher degree in Helsinki City Planning Department´s operations.