Conducting Gestures : Institutional and Educational Construction of Conductorship in Finland, 1973-1993

Anu Konttinen: Conducting Gestures Institutional and Educational Construction of Conductorship in Finland, 1973-1993. This doctoral thesis concentrates on those Finnish conductors who have participated in Professor Jorma Panula s conducting class at the Sibelius Academy during the years 1973 1993. The starting point was conducting as a myth, and the goal has been to find its practical opposite the practical core of the profession. What has been studied is whether one can theorise and analyse this core, and how. The theoretical goal has been to find out what kind of social construction conductorship is as a historical, sociological and practical phenomenon. In practical terms, this means taking the historical and social concept of a great conductor apart to look for the practical core gestural communication. The most important theoretical tool is the concept of gesture. The idea has been to sketch a theoretical model based on gestural communication between a conductor and an orchestra, and to give one example of the many possible ways of studying the gestures of a conductor.

Suomen Taideyhdistyksestä Ateneumiin : Fredrik Cygnaeus, Carl Gustaf Estlander ja taidekokoelman roolit

From the Finnish Art Society to the Ateneum: Fredrik Cygnaeus, Carl Gustaf Estlander and the Roles of the Art Collection My dissertation deals with the Finnish Art Society and the development of its collection in the evolving field of the visual arts from the foundation of the society in 1846 to its exhibition in the Ateneum, a palace of art that was opened to the public in Helsinki in 1888. The main questions that it addresses are why and how the collection came into being, what its purpose was and what kind of future prospects were projected for it in the rapidly evolving field of the visual arts. I have examined the subject of my study from the perspectives of institutional history, the organisation of the field of art and the history of art collections. The prisms through which I have viewed the subject are the history of museums in Europe, the written history of art, the art association movement and the organisation of art education in relation to an ideology of enlightenment. Thus the activities of the Finnish Art Society are here mirrored for the first time in a wider context and the history of its collection located on the map of European collections. My research shows that the history of the collection of the Finnish Art Society initially depended on certain players in the visual arts and their particular leanings. The most important of these custodians were two long-serving chairmen of the society, Fredrik Cygnaeus (1807 1881) and Carl Gustaf Estlander (1834 1910). When the foundations for art activities had been laid through the establishment of the society, Cygnaeus and Estlander began to plan how the field of art might be moulded so as to improve the level of training for artists and to improve the quality of the collections and the opportunities for their display. Cygnaeus campaigned for the establishment of the Finnish Fine Arts Academy, while Estlander saw opportunities to combine the visual and applied arts. The findings of my research bring new information about the history of the collection of the Finnish Art Society, its profile, the professional abilities of those who were mainly responsible for developing it and the relationship between it and plans for reforming art education. The major findings are connected with the position of the collection in the field of art at different stages of its development. Despite the central monopoly of the Finnish Art Society in the field of art, the position of the collection was closely bound up with leading players in the field of art and their personal interests. This subservience also created an impediment to its full-blown enhancement and purposeful profiling, and it remained evident for a long time when the collection was seeking its own place in the Finnish art world.

"En plan för jämställdhet borde kanske utarbetas, men förekommer det ett behov?" : En kartläggning av 26 svenskspråkiga kommuners främjande av jämställdhet

Jämställdhetslagen från 1995 kräver att både myndigheter och arbetsgivare med aktiva och målinriktade åtgärder främjar jämställdheten, och denna pro gradu-avhandling undersöker närmare hur denna lag implementerats i de finlandssvenska kommunerna (kommuner med majoritetsspråk svenska) under en 10årsperiod. I kommunerna jobbar 80% kvinnor, och 38% av alla kvinnliga arbetstagare hittas i arbeten inom den offentliga sektorn. Kommunens skyldighet att trygga dessa kvinnors lika villkor inom kommunorganisationen ingår både som en del i arbetsgivaransvaret, men även som del i statens demokratiska utövande genom myndighetsansvaret. De tre planer som ingår i mitt material innehåller en kartläggning av jämställdhetsområdet i olika omfattning, definierade mål och åtgärder och ingen av planerna har följts upp efter att de godkänts. Planerna varierar både i utformning och omfattning men också i ansvarsspecificering och åtgärdernas konkretisering, vilken ger en varierande kvalitet och därmed även varierande förutsättning att genomdrivas och därmed uppfylla lagens ålägganden. Två av kommunerna har eller har haft en jämställdhetskommitté. I de 26 inkomna svarsformulär görs en närläsning av hur begreppet jämställdhet används och hur jämställdhetslagen tolkas och orsakerna till frånvaron av jämställdhetsåtgärder. På frågan om varför jämställdhetsarbetet inte genomförts helt eller delvis utkristalliserade sig sex olika argumentationsteman: 1. Myten om den jämställda kommunen, innebär en hänvisning till att det inte förekommit några problem med jämställdheten. 2. Den naturligt integrerade jämställdheten, är kommunens policy och sker utan planer, men en liten kritik av problematiken med frånvaron av planer framförs av några kommuner. 3. Könens komplettering, utgår jämställdhetsbegreppet ifrån i några kommuner. 4. Den matematiska jämställdheten, är argument där man genom hänvisningar till kvinnor på olika högre positioner visar på att jämställdheten är uppnådd. 5.En fråga om resurser, används som ett argument till jämställdhetsarbetets frånvaro i kommunen. 6. Avsaknad av intresse, hos personalen och allmänheten är ett annat argument för ogenomförda jämställdhetsåtgärder. Det framkommer tydligt i materialet att kommunerna anser sig följa jämställdhetslagen, samtidigt som det blir tydligt att det råder en oklarhet om vad jämställdhetslagen från 1995 egentligen innehåller. En tydlig sammanblandning mellan den lagstadgade kvoteringen och skyldigheten att aktivt främja jämställdhet träder fram i materialet. Det ofullständiga jämställdhetsarbetet strandar på olika punkter, men en avgörande anser punkt är oförståelsen inför begreppet jämställdhet och därmed också lagens syfte och innehåll. Avhandlingens slutsats är att frånvaron av en könsmaktanalys försvårar förståelsen av ojämställdhetens komplexhet, dvs. dess orsaker, mångskiftande funktion och olika uttryck i organisationens strukturer och i de handlande aktörerna.

Vuorovaikutus ääniterapiassa : Keskustelunanalyyttinen tutkimus harjoittelun rakenteesta, terapeutin antamasta palautteesta ja oppimisesta

This conversation analytical study analyses the interactional practices adopted by speech therapists and their clients during their training in voice therapy. This study also describes how learning takes place during the therapy process. In contrast to traditional voice therapy studies, change is examined here by using qualitative research methodology, namely conversation analysis. This study describes the structures of interaction in voice therapy, shows how the shortcomings in the client s performance are evaluated and corrected and finally, how the voice training sequence and the participation changes during therapy. The database consists of 51 videotaped voice therapy sessions from six clients with voice disorders. The analytic focus is on the practices in one voice training exercise of the trilled /r/. All the sequences of this exercise (in total 36) and all adjacency pairs within (N = 627) were transcribed and analysed in detail. This study shows that voice training consists of successive model imitation adjacency pairs. This adjacency pair works as a resource in voice training. Furthermore, the use of this particular adjacency pair is an institutional practice in all therapies in this study. The structure of interaction in voice training sequences resembles the practices found in aphasia therapy and in speech therapy of children, as well as the practices of educational and counselling interaction and physiotherapy. More than half of the adjacency pairs were expanded to three (or more) part structures as client s responses were typically followed by therapist s feedback. With their feedback turns, therapists: 1) maintain training practice, 2) evaluate the problem of client s performance, 3) deliver information, 4) activate the client to observe the performance and 5) assist her in correcting the performance. This study describes the four different ways that therapists help their clients to improve the performance after encountering a problem. The longitudinal data shows that learning in therapy is manifested in the changing participation. As clients learn to identify their voice features, they can participate in evaluating or correcting their performances by themselves. This study describes the recurrent professional practices of voice therapists and shows how the institutional commitments of voice therapy are managed in and through talk and interaction. The study also provides detailed description of the management of help in voice training. By describing the interaction in training sequences, this study expands the conception of voice rehabilitation and how it can be researched. The results demonstrate that the learning process and therapy outcomes can be assessed by analysing interaction in therapy. Moreover, this analysis lays the foundation for a novel understanding of the practices in speech therapy and for the development of speech therapy theory. By revealing the activities of interaction, it also makes it possible to discuss them explicitly with speech therapy students. Key words: voice therapy, conversation analysis, institutional interaction, learning, change in participation, feedback, evaluation, error correction, self-repair

Collaborative Design in a Virtual Learning Environment : Three Design Experiments in Textile Teacher Education

The aim of the study was to analyze and facilitate collaborative design in a virtual learning environment (VLE). Discussions of virtual design in design education have typically focused on technological or communication issues, not on pedagogical issues. Yet in order to facilitate collaborative design, it is also necessary to address the pedagogical issues related to the virtual design process. In this study, the progressive inquiry model of collaborative designing was used to give a structural level of facilitation to students working in the VLE. According to this model, all aspects of inquiry, such as creating the design context, constructing a design idea, evaluating the idea, and searching for new information, can be shared in a design community. The study consists of three design projects: 1) designing clothes for premature babies, 2) designing conference bags for an international conference, and 3) designing tactile books for visually impaired children. These design projects constituted a continuum of design experiments, each of which highlighted certain perspectives on collaborative designing. The design experiments were organized so that the participants worked in design teams, both face-to-face and virtually. The first design experiment focused on peer collaboration among textile teacher students in the VLE. The second design experiment took into consideration end-users needs by using a participatory design approach. The third design experiment intensified computer-supported collaboration between students and domain experts. The virtual learning environments, in these design experiments, were designed to support knowledge-building pedagogy and progressive inquiry learning. These environments enabled a detailed recording of all computer-mediated interactions and data related to virtual designing. The data analysis was based on qualitative content analysis of design statements in the VLE. This study indicated four crucial issues concerning collaborative design in the VLE in craft and design education. Firstly, using the collaborative design process in craft and design education gives rise to special challenges of building learning communities, creating appropriate design tasks for them, and providing tools for collaborative activities. Secondly, the progressive inquiry model of collaborative designing can be used as a scaffold support for design thinking and for reflection on the design process. Thirdly, participation and distributed expertise can be facilitated by considering the key stakeholders who are related to the design task or design context, and getting them to participate in virtual designing. Fourthly, in the collaborative design process, it is important that team members create and improve visual and technical ideas together, not just agree or disagree about proposed ideas. Therefore, viewing the VLE as a medium for collaborative construction of the design objects appears crucial in order to understand and facilitate the complex processes in collaborative designing.

Mitä autismin kirjon opiskelijat oppivat valmentavassa koulutuksessa

The purpose of this research was to evaluate the special vocational training programme, which aimed at enhancing the pupils with autism spectrum to prepare themselves for work and independent life. The vocational training programme is based on TEACCH (Treatment and Education of Autistic and Related Communication handicapped CHildren), which takes into account the autism spectrum disorders and autistic behaviour. TEACCH is based on the principles of structured teaching, functional teaching and preparation training for work and independent life. The TEACCH has been adapted to Finnish society and the educational system. Treatment programmes were individually designed for each student´s educational needs. There is also an important role for the AAPEP rating scale (Adolescent and Adult Psychoeducational Profile). The AAPEP has been the major tool for planning and following the courses. The AAPEP is an assessment instrument designed by the TEACCH programme, and it is used to provide an evaluation of current and potential skills. The AAPEP contains three scales: a direct observation scale, a home scale and a school / work scale. The AAPEP includes six test variables: vocational skills, independent functions, functional communication, interpersonal behaviour, vocational behaviour and leisure skills; these are evaluated at three levels: pass, emerge and fail. The subjects were 49 students (65% male and 35 % female) with autism spectrum, who have been followed and tested several times, also one year after the vocational training. The design is therefore a longitudinal one. The research data were collected 1997-2004 using the AAPEP rating scales. The teachers have used the AAPEP scales and the codings have been checked by the researcher. The results of the principal component analysis (PCA) suggested that the structure of AAPEP rating scales works quite well as a hypothesis. The factor structure of the scales of the AAPEP was almost the same in these data as in the original publications. The learning-and-changes results showed that learning is a slow process, but that there were also intended changes in several AAPEP areas. The Cohen´s kappa was used as an effect-size measure and the most important result of this research showed that the student´s skills were developing on a school / work scale; vocational skills variable (0,34), vocational behaviour variable (0,28), leisure skills variable (0,26) and on a direct observation scale; interpersonal behaviour variable (0,21). On a home scale skills of some students were developing negatively and also that effect-size was small. The results showed that the students´ vocational skills and vocational behaviour will continue to develop after school in many areas. There were differences between scales. The result of this research shows that the student´s skills were developing significantly in 3 of 48 variables on a direct observation scale and also on a home scale. On a school / work scale student´s skills were developing significantly in 17 of 48 variables. This result implies that students can do the work without extra assistance if there exist continuing supports for the skills after the vocational training. The fully independent life of students will be difficult, because their independent functions, functional communications and leisure skills regressed after the schooling. This seems to indicate that they will not manage their daily life without support. The students and their parents said that the treatment programmes were individually designed for each student s educational needs, and that they were satisfied with the programmes and services. Generally, it can be concluded that vocational special education can be developed for pupils with autistic syndrome and the detailed teaching can be done using TEACCH principles and applying the tool of AAPEP.

Uskonnonopetuksen tunnustuksellisuus koulun kiistakysymyksenä : Evankelinen herätysliike oppivelvollisuuskoulun kristillisyyden asialla 1912-1926

In the early years of independence the Finnish school system went through a major change. Both the Compulsory school attendance act (1921) and the Religious freedom act (1923) were legislated almost simultaneously. Although the legislators were deciding on the whole content of the citizenship education given in the compulsory school, their attention was mainly concentrated on the issue of the religious education. The former study concerning the subject shows that this issue was strongly influenced by the political power struggle between the conservative and the socialist parties. One of the underlying factors was also the Church s decreased authority concerning the elementary school. The aim of this research was to study the Finnish evangelical movement s attitude and opinions on the issue of religious education and on its status and nature. Their opinions on the issue were especially investigated from the point of view of their own evangelical lower elementary school teachers seminar, which was deeply connected with the matter of confessionalism. The source material of this research of educational history consist of documents of the school administration and the Lutheran Evangelical Association as well as of vast collection of educational, Church s and evangelical movement s journals. According to the results of this study, the evangelical movement plead very strongly for denominational religious education. However, the confessionalism they were pursuing differed from the common understanding of the concept at that time. This became evident both because of their demands for increased education on the Christian doctrine and because of their sharp criticism against loosely confessional, generally Christian religious education. The evangelical movement s strict opinion was combined with their effort to emphasize the Lutherian doctrine in the Evangelical Lutheran Church in Finland. The founding of the Evangelical seminar for lower elementary school teachers in Karkku was a significant indication of the evangelical movement s dedication to strive towards school s Christianity. The objective of the evangelical seminar was to change the school by means of training evangelical minded teachers. The seminar was only a part of much larger plans of evangelical education and home missionary work. However, maintaining the seminar proved to be impossible, especially as the National Board of Education was absolutely against it, claiming that it would endanger the unity of the compulsory school. The National Board of Education indicated that the objectivity of citizenship education would be forfeit, if every marginal ideological movement could educate their own teachers.

Biophysical Characterization of Oxidized Phospholipids : Implications for Altered Membrane Structure and Function

The present study aims to elucidate the modifications in the structure and functionality of the phospholipid matrix of biological membranes brought about by free radical-mediated oxidative damage of its molecular constituents. To this end, the surface properties of two oxidatively modified phospholipids bearing an aldehyde or carboxyl function at the end of truncated sn-2 acyl chain were studied using a Langmuir balance. The results obtained reveal both oxidized species to have a significant impact on the structural dynamics of phospholipid monolayers, as illustrated by the progressive changes in force-area isotherms with increasing mole fraction of the oxidized lipid component. Moreover, surface potential measurements revealed considerable modifications in the electric properties of oxidized phospholipid containing monolayers during film compression, suggesting a packing state-controlled reorientation of the intramolecular electric dipoles of the lipid headgroups and acyl chains. Based on the above findings, a model describing the conformational state of oxidized phospholipid molecules in biological membranes is proposed, involving the protrusion of the acyl chains bearing the polar functional groups out from the hydrocarbon phase to the surrounding aqueous medium. Oxidative modifications alter profoundly the physicochemical properties of unsaturated phospholipids and are therefore readily anticipated to have important implications for their interactions with membrane-associating molecules. Along these lines, the carboxyl group bearing lipid was observed to bind avidly the peripheral membrane protein cytochrome c. The binding was reversed following increase in ionic strength or addition of polyanionic ATP, thus suggesting it to be driven by electrostatic interactions between cationic residues of the protein and the deprotonated lipid carboxyl exposed to the aqueous phase. The presence of aldehyde function bearing oxidized phospholipid was observed to enhance the intercalation of four antimicrobial peptides into phospholipid monolayers and liposomal bilayers. Partitioning of the peptides to monolayers was markedly attenuated by the aldehyde scavenger methoxyamine, revealing it to be mediated by the carbonyl moiety possibly through efficient hydrogen bonding or, alternatively, formation of covalent adduct in form of a Schiff base between the lipid aldehydes and primary amine groups of the peptide molecules. Lastly, both oxidized phospholipid species were observed to bind with high affinity three small membrane-partitioning therapeutic agents, viz. chlorpromazine, haloperidol, and doxorubicin. In conclusion, the results of studies conducted using biomimetic model systems support the notion that oxidative damage influences the molecular architecture as well as the bulk physicochemical properties of phospholipid membranes. Further, common polar functional groups carried by phospholipids subjected to oxidation were observed to act as molecular binding sites at the lipid-water interface. It is thus plausible that oxidized phospholipid species may elicit cellular level effects by modulating integration of various membrane-embedded and surface-associated proteins and peptides, whose conformational state, oligomerization, and functionality is known to be controlled by highly specific lipid-protein interactions and proper physical state of the membrane environment.

Stem Cell Markers in Cancer: Do They Have Clinical Significance?

In cancer, a subpopulation of malignant cells expresses markers of normal stem cells. These cells have the potential of initiating tumor growth and therefore also tumor recurrence. Thus, these cells are called cancer stem cells. A myriad of markers have been applied to identify these cells, but no single marker can be found exclusively in cancer stem cells. In many types of cancer, clinical recurrence and tumor progression are the main causes of mortality, despite intense oncological treatment. It has been proposed that the presence of cancer stem cells causes this resistance to therapy. The scope of this thesis is to investigate the role of stem cell markers and genes in the clinical setting. Especially, the aim was to elucidate the clinical significance of stem cell markers as novel prognostic and diagnostic tools in cancer. Tumor biopsy material from central nervous system tumors (oligodendroglioma, astrocytoma and glioblatoma), neural crest derived tumors (pheochromocytomas) and oral carcinoma was screened for stem cell markers. Initially, 15 stem cell markers were screened in a test series of gliomas. The markers applied for expanded tumor analyses (in 305 cases of glioma, 42 cases of pheochromocytoma, and 73 cases of oral carcinoma) were BMI-1, Snail, p16, mdm2, and c-Myc. Data on marker expression was compared with clinical and pathological parameters. In gliomas, BMI-1 expression was found in nearly all tumors analyzed, but the frequency of BMI-1 expressing cells was highly variable, ranging from 1 to 100%. In oligodendroglioma, BMI-1 expression was identified as a prognostic marker independent of tumor grade and clinical parameters. In pheochromocytoma, Snail expression was shown to distinguish between the metastatic and non-metastatic forms of the tumor. Snail expression was seen only in metastatic tumors, whereas non-metastatic tumors did not commonly express Snail. Finally, in oral carcinoma, BMI-1 expression was seen in roughly 80% of tumors, and Snail expression was high or very high in all cases. The lack of BMI-1 expression was associated with early relapse in oral carcinoma.

Studies on Matrix Metalloproteinase (MMP-2, -9 and -14) and β2 Integrin Targeting as Potential Anticancer Therapeutics

Proteolytic enzymes, such as matrix metalloproteinases (MMP), are associated to the progression of several cancers. They degrade extracellular components, which helps tumors to expand and cancer cells to escape from the primary site. Of all MMPs, gelatinases (MMP-2 and -9) and membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14), in particular, are often associated to more aggressive types of head and neck carcinomas as well as to a poorer outcome in patient survival. Although therapies during the last decades have advanced, the mortality of the disease is still rather high and adjuvant therapies are searched for continuously. MMP-9 and MT1-MMP are also involved in neo-angiogenesis, which is necessary for tumor expansion. For this reason, we have identified synthetic peptides-targeting gelatinases and MT1-MMP, and have also evaluated their anticancer effects in vitro and in vivo. Antigelatinolytic peptides effectively inhibited tongue-carcinoma cell invasion and reduced the growth of xenografted tumors. In tumor samples of mice that were treated with antigelatinolytic peptides, the micro-vessel density was significantly reduced. We also identified a novel MT1-MMP targeting peptide and demonstrated that it exerted anticancer effects against several malignant cell lines in vitro. The effects of MT1-MMP inhibition on tongue-squamous cell carcinomas were evaluated by using xenograft tumors, which it effectively inhibited. Tranexamic acid was also demonstrated to inhibit tongue-squamous cell carcinoma invasion, most probably due to its ability to prevent the plasmin-mediated activation of proMMP-9. Leukocyte β2 integrins are another interesting option when evaluating targets for the therapeutic intervention of inflammatory conditions or malignancies of hematopoietic origin, since β2 integrins are expressed mainly by leukocytes. We identified a novel technique for screening small-molecule libraries against β2 integrins, and by using this technique we identified a novel αMβ2 integrin-binding chemical (IMB-10). IMB-10 significantly enhances leukocyte adhesion and inhibits their motility. We also demonstrated that IMB-10 can be used to inhibit inflammation and lymphoma growth in vivo. Interestingly, IMB-10 also reduced leukocyte tumor infiltration and inhibited tumor invasion.

Early Childhood Caries and a Community Trial of its Prevention in Tehran, Iran

Varhaislapsuuden karies ja sen ehkäisy kehittyvän terveydenhuollon maassa Varhaislapsuuden karies on merkittävä kansanterveysongelma varsinkin lapsirikkaissa maissa ja väestöissä. Karieksen hoitaminen vie paljon voimavaroja ja aiheuttaa mittavia taloudellisia seuraamuksia. Karies voi ilmaantua lapselle jo vauvaikäisenä, pian ensimmäisten maitohampaiden puhjettua suuhun. Alle 3-vuotiaiden karieksesta on kuitenkin niukasti tilastotietoja. Maailman terveysjärjestökin suosittaa tietojen keräämistä vasta 3-vuotiaiden ikäryhmästä. Heistä kariesta sairastaa Suomessa 16 %, Yhdysvalloissa 25 %, Englannissa 30 %, Iranissa 46 % ja Saudi-Arabiassa 61 %. Tämä väitöstutkimus selvitti karieksen esiintymistä ja sen vaaratekijöitä 1─3-vuotiailla Teheranissa. Lisäksi tutkimus arvioi perusterveydenhuoltoon sisällytetyn karieksen ehkäisyn tuloksellisuutta. Tutkimuskohteiksi arvottiin Teheranista 18 neuvolaa. Jokaisessa oltiin 4 päivää, jolloin kaikkia rokotuksiin tulleita 1─3-vuotiaita äiteineen pyydettiin osallistumaan tutkimukseen. Kahta lukuun ottamatta kaikki äidit suostuivat, ja aineistoon tuli kaikkiaan 504 lasta äiteineen. Kaikki 1-vuotiaat, 242 lasta äiteineen, valittiin karieksen ehkäisykokeiluun. Sitä varten neuvolat jaettiin kolmeen ryhmään, joista kaksi (A ja B) oli koeryhmiä ja yksi (C) oli vertailuryhmä. Tutkimus alkoi äidin haastattelulla. Siinä selvitettiin perheen koulutus- ja tulotaso sekä lapsen ruokinnasta imetyksen kesto, yösyötöt ja päiväaikaan nautitut makeat. Vielä kysyttiin lapsen ja äidin suuhygieniatavoista ja äidin kokemuksista lapsen suun puhdistamisessa. Sitten hammaslääkäri tutki lapsen suun ja kirjasi karieksen ja hammasplakin esiintymät. Suun tutkimuksen jälkeen äiti ja lapsi siirtyivät rokotushuoneeseen. Koeryhmissä (A ja B) äidit saivat terveydenhoitajalta suunterveyttä koskevan esitteen ja kehotuksen lukea se huolellisesti. Lisäksi ryhmässä A terveydenhoitaja kertoi suun ja hampaiden terveydenhoidosta saman esitteen avulla, ja neuvolan henkilökunta muistutti suunhoidon tärkeydestä puhelimitse kahdesti seuraavan puolen vuoden kuluessa. Vertailuryhmässä äideille ei annettu suunhoidon ohjeita. Kaikissa ryhmissä äitejä muistutettiin seuraavan rokotuskerran ajankohdasta, muttei mainittu tulevaa toista hammastarkastusta. Varhaislapsuuden kariesta sairasti ikäryhmästä riippuen 3─26 % tutkituista 1─3-vuotiaista, ja 65─76 %:lla oli hammasplakkia. Äideistä 68 % harjasi hampaansa päivittäin ja 39 % puhdisti lapsensa suun päivittäin. Mitä useammin äiti harjasi omat hampaansa, sitä paremmin hän huolehti lapsen suun puhtaudesta. Rintaruokinta oli yleistä eikä lisännyt kariesvaaraa. Yöllä pullomaitoa saavilla karies oli 5 kertaa yleisempää kuin muilla. Neuvolassa saatu ohjeistus ehkäisi selvästi karieksen syntyä puolen vuoden kokeessa.

Perspectives on prescribing in nursing homes in Helsinki

Prescribing for older patients is challenging. The prevalence of diseases increases with advancing age and causes extensive drug use. Impairments in cognitive, sensory, social and physical functioning, multimorbidity and comorbidities, as well as age-related changes in pharmacokinetics and pharmacodynamics all add to the complexity of prescribing. This study is a cross-sectional assessment of all long-term residents aged ≥ 65 years in all nursing homes in Helsinki, Finland. The residents’ health status was assessed and data on their demographic factors, health and medications were collected from their medical records in February 2003. This study assesses some essential issues in prescribing for older people: psychotropic drugs (Paper I), laxatives (Paper II), vitamin D and calcium supplements (Paper III), potentially inappropriate drugs for older adults (PIDs) and drug-drug interactions (DDIs)(Paper IV), as well as prescribing in public and private nursing homes. A resident was classified as a medication user if his or her medication record indicated a regular sequence for its dosage. Others were classified as non-users. Mini Nutritional Assessment (MNA) was used to assess residents’ nutritional status, Beers 2003 criteria to assess the use of PIDs, and the Swedish, Finnish, INteraction X-referencing database (SFINX) to evaluate their exposure to DDIs. Of all nursing home residents in Helsinki, 82% (n=1987) participated in studies I, II, and IV and 87% (n=2114) participated in the study III. The residents’ mean age was 84 years, 81% were female, and 70% were diagnosed with dementia. The mean number of drugs was 7.9 per resident; 40% of the residents used ≥ 9 drugs per day, and were thus exposed to polypharmacy. Eighty percent of the residents received psychotropics; 43% received antipsychotics, and 45% used antidepressants. Anxiolytics were prescribed to 26%, and hypnotics to 28% of the residents. Of those residents diagnosed with dementia, 11% received antidementia drugs. Fifty five percent of the residents used laxatives regularly. In multivariate analysis, those factors associated with regular laxative use were advanced age, immobility, poor nutritional status, chewing problems, Parkinson’s disease, and a high number of drugs. Eating snacks between meals was associated with lower risk for laxative use. Of all participants, 33% received vitamin D supplementation, 28% received calcium supplementation, and 20% received both vitamin D and calcium. The dosage of vitamin D was rather low: 21% received vitamin D 400 IU (10 µg) or more, and only 4% received 800 IU (20 µg) or more. In multivariate analysis, residents who received vitamin D supplementation enjoyed better nutritional status, ate snacks between meals, suffered no constipation, and received regular weight monitoring. Those residents receiving PIDs (34% of all residents) more often used psychotropic medication and were more often exposed to polypharmacy than residents receiving no PIDs. Residents receiving PIDs were less often diagnosed with dementia than were residents receiving no PIDs. The three most prevalent PIDs were short-acting benzodiazepine in greater dosages than recommended, hydroxyzine, and nitrofurantoin. These three drugs accounted for nearly 77% of all PID use. Of all residents, less than 5% were susceptible to a clinically significant DDI. The most common DDIs were related to the use of potassium-sparing diuretics, carbamazepine, and codeine. Residents exposed to potential DDIs were younger, had more often suffered a previous stroke, more often used psychotropics, and were more often exposed to PIDs and polypharmacy than were residents not exposed to DDIs. Residents in private nursing homes were less often exposed to polypharmacy than were residents in public nursing homes. Long-term residents in nursing homes in Helsinki use, on average, nearly eight drugs daily. The use of psychotropic drugs in our study was notably more common than in international studies. The prevalence of laxatives equaled other prior international studies. Regardless of the known benefit and recommendation of vitamin D supplementation for elderly residing mostly indoors, the proportion of nursing home residents receiving vitamin D and calcium was surprisingly low. The use of PIDs was common among nursing home residents. PIDs increased the likelihood of DDIs. However, DDIs did not seem a major concern among the nursing home population. Monitoring PIDs and potential drug interactions could improve the quality of prescribing.

The social patterning of health, smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004

The Baltic countries share public health problems typical of most Eastern European transition economies: morbidity and mortality from non-communicable diseases is higher than in Western European countries. This situation has many similarities compared to a neighbouring country, Finland during the late 1960s. There are reasons to expect that health disadvantage may be increasing among the less advantaged population groups in the Baltic countries. The evidence on social differences in health in the Baltic countries is, however, scattered to studies using different methodologies making comparisons difficult. This study aims to bridge the evidence gap by providing comparable standardized cross-sectional and time trend analyses to the social patterning of variation in health and two key health behaviours i.e. smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004 representing Eastern European transition countries and a stable Western European country. The data consisted of similar cross-sectional postal surveys conducted in 1994, 1996, 1998, 2000, 2002 and 2004 on adult populations (aged 20 64 years) in Estonia (n=9049), Latvia (n=7685), Lithuania (n=11634) and Finland (n=18821) in connection with the Finbalt Health Monitor project. The main statistical method was logistic regression analysis. Perceived health was found to be worse among both men and women in the Baltic countries than in Finland. Poor health was associated with older age and lower education in all countries studied. Urbanization and marital status were not consistently related to health. The existing educational inequalities in health remained generally stable over time from 1994 to 2004. In the Baltic countries, however, improvement in perceived health was mainly found among the better educated men and women. Daily smoking was associated with young age, lower education and psychological distress in all countries. Among women smoking was also associated with urbanisation in all countries except Estonia. Among Lithuanian women, the educational gradient in smoking was weakest, and the overall prevalence of smoking increased over time. Drinking was generally associated with young age among men and women, and with education among women. Better educated women were more often frequent drinkers and less educated binge drinkers. The exception was that in Latvian men and women both frequent drinking and binge drinking were associated with low education. In conclusion, the Baltic countries are likely to resemble Western European countries rather than other transition societies. While health inequalities did not markedly change, substantial inequalities do remain, and there were indications of favourable developments mainly among the better educated. Pressures towards increasing health inequalities may therefore be visible in the future, which would be in accordance with the results on smoking and drinking in this study.

Defects in tricarboxylic acid cycle enzymes Fumarate hydratase and Succinate dehydrogenase in cancer

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a recently characterized cancer syndrome which predisposes to cutaneous and uterine leiomyomas as well as renal cell carcinoma (RCC). Uterine leiomyosarcoma (ULMS) has also been observed in certain Finnish HLRCC families. The predisposing gene for this syndrome, fumarate hydratase (FH), was identified in 2002. The well-known function of FH is in the tricarboxylic acid cycle (TCAC) in the energy metabolism of cells. As FH is a novel cancer gene, the role of FH mutations in tumours is in general unknown. Similarly, the mechanisms through which defective FH is associated with tumourigenesis are unclear. The loss of a wild type allele has been observed in virtually all HLRCC patients tumours and the FH enzyme activities are either totally lost or remarkably reduced in the tissues of mutation carrier patients. Therefore, FH is assumed to function as a tumour suppressor. Mutations in genes encoding subunits of other TCAC enzyme SDH have also been reported recently in tumours: mutations in SDHB, SDHC, and SDHD genes predispose to paraganglioma and pheochromocytoma. In the present study, mutations in the SDHB gene were observed to predispose to RCC. This was the first time that mutations in SDHB have been detected in extra-paraganglial tumours. Two different SDHB mutations were observed in two unrelated families. In the first family, the index patient was diagnosed with RCC at the age of 24 years. Additionally, his mother with a paraganglioma (PGL) of the heart and his maternal uncle with lung cancer were both carriers of the mutation. The RCC of the index patient and the PGL of his mother showed LOH. In the other family, an SDHB mutation was detected in two siblings who were both diagnosed with RCC at the ages of 24 and 26 years. Both of the siblings also suffered PGL. All these tumours showed LOH. Therefore, we concluded that mutations in SDHB predispose also for RCC in certain families. Several tumour types were analysed for FH mutations to define the role of FH mutations in these tumour types. In addition, patients with a putative cancer phenotype were analysed to identify new HLRCC families. Three FH variants were detected, of which two were novel. One of the variants was observed in a patient diagnosed with ULMS at the age of 41 years. However, LOH was not detected in the tumour tissue. The FH enzyme activity of the mutated protein was clearly reduced, being 43% of the activity of the normal protein. Together with the results from an earlier study we calculated that the prevalence of FH mutations in Finnish non-syndromic ULMS is around 2.4%. Therefore, FH mutations seem to have a minor role in the pathogenesis on non-syndromic ULMS. Two other germline variants were detected in a novel tumour type, ovarian mucinous cystadenoma. However, tumour tissues of the patients were not available for LOH studies and therefore LOH status remained unclear. Therefore, it is possible that FH mutations predispose also for ovarian tumours but further studies are needed to verify this result. A novel variant form of the FH gene (FHv) was identified and characterized in more detail. FHv contains an alternative first exon (1b), which appeared to function as 5 UTR sequence. The translation of FHv is initiated in vitro from exons two and three. The localization of FHv is both cytosolic and nuclear, in contrast to the localization of FH in mitochondria. FHv is expressed at low levels in all human tissues. Interestingly, the expression was induced after heat shock treatment and in chronic hypoxia. Therefore, FHv might have a role e.g. in the adaptation to unfavourable growth conditions. However, this remains to be elucidated.

Novel Multiple Sclerosis Predisposing Genetic Variants Outside the HLA Region

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Both environmental factors and several predisposing genes are required to generate MS. Despite intensive research these risk factors are still largely unknown, the pathogenesis of MS demyelination is poorly understood, and no curative treatment exists. Both prevalence and familial occurrence of MS are exceptionally high in a Finnish population subisolate, Southern Ostrobothnia, presumably due to enrichment of predisposing genetic variants within this region. Previous linkage scan on MS pedigrees from Southern Ostrobothnia detected three main MS loci on chromosomes 5p, 6p (HLA) and 17q. Linkage studies in other populations have also provided independent evidence for the location of MS susceptibility genes in these regions. Further, these loci are syntenic to the experimental autoimmune encephalomyelitis (EAE) susceptibility loci of rodents. In this thesis work an effort was made to localize MS predisposing alleles of the linked loci outside the HLA region by studying familial MS cases from the Southern Ostrobothnia isolate. Analysis of the 5p locus revealed one region, flanking the complement component 7 (C7) gene. The identified relatively rare haplotype seems to have a fairly large effect on genetic susceptibility of MS (frequency MS 12%, controls 4%; p=0.000003, OR=2.73). Evidence for association with alleles of the region and MS was seen also in more heterogeneous populations. Convincingly, plasma C7 protein levels and complement activity correlated with the risk haplotype identified. The finding stimulated us to study other complement cascade genes in MS. No evidence for association could be observed with the complement component coding genes outside 5p. A scan of the 17q locus provided evidence for association with variants of the protein kinase C alpha (PRKCA) gene (p=0.0001). Modest evidence for association with PRKCA was observed also in Canadian MS families. Finally we used a candidate gene based approach to identify potential MS loci. Mutations of DAP12 and TREM2 cause a recessively inherited CNS white matter disease PLOSL. Interestingly, DAP12 and TREM2 are located in MS regions on 6p and 19q, and we tested them as potential candidate genes in the Finnish MS sample. No evidence for association with MS was observed. This thesis provides an example of how extended families from special populations can be utilized in fine-mapping of the linked loci. A first relatively rare MS variant was identified utilizing the strength of a Finnish population subisolate. This variant seems to have an effect on activity of the complement system, which has previously been suggested to have an important role in the pathogenesis of MS.