Kampen om Eros : Om kön och kärlek i Pahlensviten

The Struggle for Eros: On Love and Gender in the Pahlen Series The present dissertation examines how gender, sexuality and motherhood are constructed in the novel series Fröknarna von Pahlen (The Misses von Pahlen, I VII, 1930 1935) by the Swedish author Agnes von Krusenstjerna. The aim of the study is to analyze how the Pahlen series relates to the discourses on gender and sexuality circulating in the 1930s, and how the series opens a dialogue with the feminist thinking of the time especially with the book Lifslinjer I (Love and Marriage, 1903) by the Swedish author Ellen Key. Fröknarna von Pahlen holds a central position in the research on Agnes von Krusenstjerna partly due to the literary debate that the novel series triggered. The debate was connected to the development taking place in the Swedish society in the beginning of the 1930s, in the so-called second phase of the Modern Breakthrough. Sweden was at that time characterized by struggle over the definitions of gender, sexuality and parenthood, and this struggle is also visible in the Pahlen series. The literary debate took place in 1934 1935 and it began after an article by the modernist writer Karin Boye was published in Social-Demokraten on 28 January 1934. In her polemic article, Boye saw the Pahlen series as a sign that the family institution is on the verge of a breakdown and with it the whole moral system that has come to existence through it . Boye went on to state that Krusenstjerna only sees and describes and that she explores neither new literary forms nor new values. Boye wrote the article before the last two parts of the novel series were published, so obviously she could not discuss the utopian vision characterizing those parts. This study, however, strives to demonstrate that Krusenstjerna not only sees and describes, but that she like many of her contemporary female colleagues appears to take the request of Friedrich Nietzsche to revaluate all values seriously. Like the works of her contemporaries, Krusenstjerna s Pahlen series is marked by a double vision on the one hand a critique of the prevailing social order, and on the other hand a dream of a new world and a new human being. In this research the vision of the Pahlen series is characterized as queer in order to emphasize that the series not only criticizes the prevailing gender order and its morals, but is also open for new ways of doing gender, parenthood, and family.

Det pedagogiska självet : en narrativ studie av direktvalda svensklärarstudenters berättelser

The Pedagogical Self: a narrative study of stories by prospective subject teachers of Swedish The aim of this study is to examine how prospective subject teachers of Swedish experience themselves, their lives and their studies in university context. By answering this question I try to shed light on the pedagogical self of the students, i.e. to reach a deeper understanding of the narrative construction of their teacher identity. My material consists of stories written by one group of students and of transcribed interviews with another group of students at Nordica. All these students have entered both the teacher education programme and studies in their major subject simultaneously, through the so called direct admission. My study focuses on the students first year at the university. I define teacher identity, the pedagogical self, as the part of an individual s self-concept where he/she makes an assessment of himself/herself as a teacher(-to-be). The frame of reference of this interdisciplinary narrative study is founded on phenomenology, hermeneutics, social constructionism and dialogism. The main analysis of the stories is thematic, with the addition of linguistic and metaphorical analysis. With reference to the theories of Paul Ricoeur and Katharine Young, I regard the textual world of the stories as a world of its own. This implies that the researcher can feel free to concentrate on the texts, thus being able to leave the mental processes of the writers disregarded. The theoretician that has influenced my research the most is Max van Manen. He combines a pedagogical attitude with a phenomenological-hermeneutic philosophy. My research results imply that most of these students are drawn to studying Swedish by the clear professional orientation of the studies; their identity as teachers seems to be stronger than their identity as language teachers. The image of a teacher is relatively traditional: a teacher is seen as a self-evident authority, but at the same time as a fostering educator. The students see their studies in a larger perspective: studies as well as the future profession are only one part of life, albeit an important one. Keywords: narrativity, teacher identity

J. L. Runebergs samlade skrifter i textkritisk belysning

The Collected Works of J. L. Runeberg from the Viewpoint of Textual Scholarship The theoretical framework of this dissertation builds on textual scholarship. The dissertation explores the history of Runeberg’s publications and his relations with his publishers, from his debut and the first editions, through the editions of collected works published during the course of his life, to the later commercial editions, including the critical edition, published in 1933–2005 by the Svenska Vitterhetssamfundet (The Swedish Society for Belles Lettres) and The Svenska litteratursällskapet i Finland (The Society of Swedish Literature in Finland). The various editions of Runeberg’s collected works are situated in their respective critical traditions, from the 19th century German Ausgabe letzter Hand, to the influence of Anglo-American bibliography on Swedish textual criticism in the late 20th century. By making use of primary material previously not used for research purposes, the author is able to present a new view on Runebergian publishing history, including Runeberg’s fees and his relations with the censor authorities. There are indications that his Finnish publishers could not bear the cost of his sizable fees, that were in proportion neither with the book market in Finland nor with the numbers of copies sold. Apart from a certain body of editions the primary material is comprised of correspondences, publishing contracts, printing house invoices, as well as censor authority records. One of the conclusions drawn is that the early and detailed biography, Biografiska anteckningar om Johan Ludvig Runeberg (Biographical Notes on …) by J. E. Strömborg is not reliable in matters concerning publishing history, and that this work has been used far too uncritically. The history of the critical edition gets a chapter of its own, based on primary material in Swedish and Finnish archives. Finally, the author analyses the critical choices, made primarily in the critical edition, and uses examples from the commercial editions to study the editors’ interventions over time, from the 1850s to the 1920s. The changes to the text are usually small and subtle, but cumulative – and in some cases, crucial for the interpretation of the work. One objective of textual scholarship should be to examine the publishing history of a single work or of an author’s œuvre, and another to pay attention both to changes in a work as such and to the shifts of meaning they might entail.

My Fair Lady på skandinaviska : En studie i funktionell sångöversättning

The dissertation presents a functional model for analysis of song translation. The model is developed on the basis of an examination of theatrical songs and a comparison of three translations: the songs of the Broadway musical My Fair Lady (Lerner and Loewe, 1956), made for the premiere productions (1959–1960) in Swedish, Danish, and Norwegian. The analysis explores the three challenges of a song translator: the fitting of a text to existing music, the consideration of a prospective sung performance, and the verbal approximation of the content of the source lyric. The theoretical foundation is based on a functional approach to translation studies (Christiane Nord) and a structuralist/semiotic analysis of a theatrical message (Ivo Osolsobě, building on Roman Jakobson). Thus, three functional levels in the fitting of a text to music are explored: first, a prosodic/phonetic format; secondly, a poetic/rhetoric format; and thirdly, semantic/reflexive values (verbalizing musical expression). Similarly, three functional levels in the textual connections to a prospective performance are explored: first, a presentational goal; secondly, the theatrical potential; and thirdly, dramaturgic values (for example dramatic information and linguistic register). The functionality of Broadway musical theatre songs is analyzed, and the song score of My Fair Lady, source and target lyrics, is studied, with an in-depth analysis of seven of the songs. The three translations were all considered very well-made and are used in productions of the musical to this day. The study finds that the song translators appear to have worked from an understanding of the presentational goal, designed their target texts on the prosodic and poetic shape of the music, and pursued the theatrical functionality of the song, not by copying, but by recreating connections to relevant contexts, partly independently of the source lyrics, using the resources of the target languages. Besides metaphrases (closest possible transfer), paraphrases and additions seem normally to be expected in song translation, but song translators may also follow highly individual strategies – for example, the Norwegian translator is consistently more verbally faithful than the Danish and Swedish translators. As a conclusion, it is suggested that although linguistic and cultural difference play a significant role, a translator’s solution must nevertheless be arrived at, and assessed, in relation to the song as a multimedial piece of material. As far as a song can be considered a theatrical message – singers representing the voice, person, and situation of the song – the descriptive model presented in the study is also applicable to the translation of other types of song.

Genus i östra Nyland : från dialektutjämning till dialektmarkör

Gender in eastern Nyland – from dialect levelling to identity marking The study of dialect leveling in eastern Nyland focuses on variation and change in the Swedish dialects of Nyland (Fi. Uusimaa) on the south coast of Finland. During the last century the grammatical gender system of the dialects in the area has been reduced from a three-gender system to a two-gender system (cf. Corbett 1991). The present study is based on five linguistic variables in the gender system: the anaphoric pronouns (han, hon, den) when used for inanimates; the neuter pronouns he(t) and de(t) – when used anaphorically or as expletives; and three different types of morphological postposed definite articles. For all these variables, both dialect variants and standard variants are used in the dialects. Within the study of processes of variation and change, the work focuses on the mechanisms of leveling, simplification and reallocation; cf. Trudgill (1986) and Hinskens, Auer Kerswill (2005). With regard to the reductions of the gender system, the possibility that some of these variables might have turned into becoming dialect markers (Labov 1972) in the modern varieties of eastern Nyland is given special attention. The primary data consist of tape recordings with 25 informants done in the 1960s and 1970s. The informants were born in 1881–1913. In addition, recent changes were investigated in detail in tape recordings from 2005–2008 with 15 informants, who were born in the period 1927–1947 or 1976–1988. The study combines quantitative and qualitative methods in the systematic analysis of the data. Theoretically and methodologically the study relies on methods and results from variation studies and socio-dialectology, as well as on methods and results from traditional dialectology; cf. Ahlbäck (1946) and the dictionary of Swedish dialects, Ordbok över Finlands svenska folkmål, (1976–). The results show that there are different strategies among the informants in their use of the features studied. In the modern varieties of the dialects, most of the informants use only two genders, uter and neuter. Of the variables, the masculine pronoun for inanimates, the traditional neuter pronoun he(t) and some variants of the traditional definite articles have received a new function as dialect markers in my data. These changes first affect the gender distinctions, and the function of marking gender is lost; gradually the features then get new functions as dialect markers through processes of dialect leveling and reallocation. These processes are connected to changes taking place in the communities in eastern Nyland because of urbanization. When the dialect speakers experience that the traditional values of both the dialects and the culture are threatened, they begin to mark their dialectal identity by using dialect markers in their speech.

I konstens namn - scenen som arbetsmiljö : Arbetsplatsmobbning ur skådespelarperspektiv

Workplace bullying is a topic of current interest in Finland. Workplace bullying is found in all professions, including the artistic ones. This thesis aims to explore workplace bullying from the view of the Finland-Swedish actors as a phenomenon that within dramatic art is difficult to define due to the fact that the body and emotions of an actor constitute his or her working tools. The research aims to deepen the understanding of the actors’ working situation, and particularly of the difficulties and problems actors face when exercising their job. The research problems are: What forms of bullying are the actors exposed to? Who is bullying? How is the bullying received by the actors, and what are the possible consequences? The theoretical orientation of this thesis is based upon dialogical philosophy where phenomenology, hermeneutics and dialog meet in an orientation where the unseen is emphasized and made visible. Artistic leadership should be based upon a pedagogic understanding that by an open and equal dialog with the Other recognizes human diversity. The narrative research was undertaken by using an interview guide for the interviews with eleven actors, six women and five men with the voice of a sixth man represented by an article. The interviews, each on average 118 minutes, were recorded and transcribed. The method of discursive analysis was initiated by numerous reflective readings based on analytic induction. The inductive part of the analysis consisted of mapping out the individual experiences of bullying where after the process of finding connecting common features in the extensive material took place. The coded data was then deductively grouped together according to the research problems, and subgroups were formed for deeper description. The research findings show that workplace bullying is an everyday occurrence within the field of dramatic art. Actors are bullied by theatre managers and directors as well as by colleagues and other personnel. The main areas of bullying is depreciation of one’s professional skills, the existing jargon, sexual harassment, collective bullying and bullying because of personal qualities. A significant finding concerning this problem was the existing culture of silence. Even if actually seeing and hearing a colleague being bullied, few stood up to defend the person being bullied because of fear of retaliation. Even the person actually being the object for bullying found it difficult to take any actions.

Kouluromaanien opettajakuva 1930-luvulta 1990-luvulle : ihanteellisia, kapinallisia ja oman tien kulkijoita

The aim of this research is to define what kind of characters and images of teachers appear in Finnish school novels describing social changes and educational political reform from the 1930s to the 1990s written by teachers, particularly grammar school teachers. As comparison material, I use school novels written by Swedish school teachers, in which the changes in Swedish society and educational system and their expressions in the characters of teachers of the school novels are studied. The main focus of my study is centred particularly on school novels in which the images of grammar school teachers are described during times of school reform. From these starting points, the main objectives of the study are novels written by Finnish school teachers Anneli Toijala and Sampo Haahtela and Swedish school teacher Hugo Swensson, who was inspired by Haahtela. The research is qualitative multidisciplinary case analysis. The research method is content analysis, and the approach is hermeneutic. The research is divided into eight main chapters. After the introduction I introduce the essential concepts of my research. In the third main chapter I define the research function. In that context, besides the research objectives, I introduce former research on character description in literature, I define the methodological solutions with grounds and present the research material. Both literary research methods and sociological terminology are applied in the research alongside with pedagogical research. The research results show that images of teachers are diverse. At one end of the spectrum these represent immature pictures of teachers withdrawn into the routines of everyday life; at the other, they advance and reflect the reformist teacher. This becomes clearly evident when comparing the teacher "monsters" of the classic authors to the educational optimists at the end of the 20th century. The results show that the images of teachers in school novels are almost without exception coherent, psychologically credible and consistent, and hardly any different from the images of teachers in the Swedish school novels used as comparison material. On the contrary, plenty of similarities are found. The comprehensive school reform, educational political discourse and teachers' feelings are realistically clarified in the school novels that describe the period. Keywords: literature image, school reform, school novel, teacher image, reflection, internal co-operation in school

"Mut ei tää oo hei midsommarista!" - ruotsin kielen viestinnällinen suullinen harjoittelu yhteistoiminnallisten skeema- ja elaborointitehtävien avulla

Communicative oral practice in Swedish through collaborative schema-based and elaboration tasks The general aim of this study was to learn how to better understand foreign language communicative oral practice and to develop it as part of communicative language teaching. The language-specific aim was to study how Swedish was being practised communicatively and orally in a classroom context as part of the didactic teaching-studying-learning process, and how the students' communicative oral practice in Swedish was carried out through collaborative schema-based and elaboration tasks. The scientific problem of this study focused on the essence of foreign language communicative oral proficiency. The research questions were concerned with 1) the students' involvement in carrying out the given oral tasks; 2) the features of communication and interaction strategies; 3) thematic vocabulary, and 4) the students' experiences and conceptions of the communicative oral tasks used. The study consisted of two groups of students from a Helsinki-area school (a group of upper secondary school students, Swedish Level A, Courses 2 and 3, n=9; and a group of basic education students, Swedish Level B, Course 2, n=13). The study was carried out as a pedagogically oriented case study which included certain features of ethnographic research and where the students' teacher acted as a researcher of her own work. The communicative oral practice contained five different tasks. The research data were gathered through systematic observation, audio recordings and by a questionnaire. The data were analysed through ethnographic content analysis methods. The main research finding was that a good deal of social interaction, collaboration and communication took place between the students when involved in communicative oral practice in Swedish. The students took almost optimal advantage of the allocated training time. They mostly used Swedish when participating in interactional communication. Finnish was mostly used by the students when they were deciding how to carry out a given task, aiming at intersubjectivity or negotiating meaning. The students were relaxed when practising Swedish. They also asked for and gave linguistic help in the spirit of collaborative learning principles. This resulted in interaction between students that highlighted certain features of negotiation of meaning, scaffolding and collaborative dialogue. Asking for and giving help in language issues concentrated mainly on vocabulary, and only in a few cases on grammar or pronunciation. The students also needed the teacher as a mentor. As well, the students had an enjoyable time when practising, which was most often related to carrying out the oral tasks. The thematic vocabulary used by the students corresponded well to the thematic lexis that served as a basis for the practice. At its most efficient, this lexis was most evident when the basic education students were carrying out schema-based tasks. The students' questionnaire answers agreed with the research findings gained through systematic observation and the analysis of audio recordings. The communicative tasks planned by the teacher and implemented by the students were very much in line. The language-didactic theory as presented in this study and the research findings can be widely utilised in pre-service and in-service teacher education, as well as, more generally, when developing communicative language teaching. Key words: communicative oral practice; the Swedish language; foreign language; didactic teaching-studying-learning process; communicative language teaching; collaborative task; schema-based task; elaboration task.

Kivaa ja hyödyllistä, mutta jo se riittää : Yläasteen kielikylpyoppilaiden käsityksiä ruotsinkielisestä kielikylpyopetuksesta Helsingissä

The aim of this study was to find out how immersion students experience immersion education, how they feel about the implementation of immersion education methods and what role immersion plays in immersion students’ lives outside the school context. In addition, the influence of sex, grade level, school and type of immersion education on students’ perceptions was studied. The population included all students at the lower secondary level in Helsinki who participated in Swedish immersion education during 2002–2003. The sample consisted of 128 students who represented two different forms of immersion: 47% of the students had previously participated in early total immersion while 53 % of the students had taken part in early partial immersion. The data were gathered through a questionnaire and interviews. All 128 students answered the questionnaire, and 10 students were chosen to focus interviews through purposive sampling. In addition, students’ parents were invited to fill in a questionnaire where students’ background information was requested. The data were collected during the spring of 2003. Principal Component Analysis and one-way variance analysis were used as statistical analysis methods. Also frequencies, average, correlations and cross tabs were studied. In the PCA a right-angled varimax-rotation was performed separately to every thematic entity that arose from the theoretical background. Sum variables were formed from the Principal Components by summing up all the items that received over .400 charges for the specific Principal Component. Significance testing of the mean was performed with F and t-tests. Results indicate that immersion students in lower secondary school experience immersion quite diversely as a whole. Students are satisfied with the fact that they are in the immersion class but not with the amount of teaching in Swedish. Students feel it is very important and useful to learn Swedish bearing in mind their future studies and working life. The students estimate their language skills to be very high. Yet they prefer using Finnish during classes. The fact that teachers use Swedish does not considerably affect how well the students learn the factual content in various subjects, especially if the student knows Swedish well. Theoretical subjects seemed to cause most problems. Swedish played only a very small part in students’ lives outside the school context and it was used merely when travelling abroad and in different kinds of guiding situations. Unless the students were talked to in Swedish, they kept on speaking Finnish. When asked about students’ experiences no statistically significant differences between sexes were found in this study. On the contrary, in some cases their grade level but especially their school and form of immersion had clear statistically significant differences on students’ perceptions.

Quantitative and molecular genetics of juvenile wood traits in radiata and slash/Caribbean pines.

The Juvenile Wood Initiative (JWI) project has been running successfully since July 2003 under a Research Agreement with FWPA and Letters of Association with the consortium partners STBA (Southern Tree Breeding Association), ArborGen and FPQ (Forestry Plantations Queensland). Over the last five and half years, JWI scientists in CSIRO, FPQ, and STBA have completed all 12 major milestones and 28 component milestones according to the project schedule. We have made benchmark progress in understanding the genetic control of wood formation and interrelationships among wood traits. The project has made 15 primary scientific findings and several results have been adopted by industry as summarized below. This progress was detailed in 10 technical reports to funding organizations and industry clients. Team scientists produced 16 scientific manuscripts (8 published, 1 in press, 2 submitted, and several others in the process of submission) and 15 conference papers or presentations. Primary Scientific Findings. The 15 major scientific findings related to wood science, inheritance and the genetic basis of juvenile wood traits are: 1. An optimal method to predict stiffness of standing trees in slash/Caribbean pine is to combine gravimetric basic density from 12 mm increment cores with a standing tree prediction of MoE using a time of flight acoustic tool. This was the most accurate and cheapest way to rank trees for breeding selection for slash/Caribbean hybrid pine. This method was also recommended for radiata pine. 2. Wood density breeding values were predicted for the first time in the STBA breeding population using a large sample of 7,078 trees (increment cores) and it was estimated that selection of the best 250 trees for deployment will produce wood density gains of 12.4%. 3. Large genetic variation for a suite of wood quality traits including density, MFA, spiral grain, shrinkage, acoustic and non-acoustic stiffness (MoE) for clear wood and standing trees were observed. Genetic gains of between 8 and 49% were predicted for these wood quality traits with selection intensity between 1 to 10% for radiata pine. 4. Site had a major effect on juvenile-mature wood transition age and the effect of selective breeding for a shorter juvenile wood formation phase was only moderate (about 10% genetic gain with 10% selection intensity, equivalent to about 2 years reduction of juvenile wood). 5. The study found no usable site by genotype interactions for the wood quality traits of density, MFA and MoE for both radiata and slash/Caribbean pines, suggesting that assessment of wood properties on one or two sites will provide reliable estimates of the genetic worth of individuals for use in future breeding. 6. There were significant and sizable genotype by environment interactions between the mainland and Tasmanian regions and within Tasmania for DBH and branch size. 7. Strong genetic correlations between rings for density, MFA and MoE for both radiata and slash/Caribbean pines were observed. This suggests that selection for improved wood properties in the innermost rings would also result in improvement of wood properties in the subsequent rings, as well as improved average performance of the entire core. 8. Strong genetic correlations between pure species and hybrid performance for each of the wood quality traits were observed in the hybrid pines. Parental performance can be used to identify the hybrid families which are most likely to have superior juvenile wood properties of the slash/Caribbean F1 hybrid in southeast Queensland. 9. Large unfavourable genetic correlations between growth and wood quality traits were a prominent feature in radiata pine, indicating that overcoming this unfavourable genetic correlation will be a major technical issue in progressing radiata pine breeding. 10. The project created the first radiata pine 18 k cDNA microarray and generated 5,952 radiata pine xylogenesis expressed sequence tags (ESTs) which assembled into 3,304 unigenes. 11. A total of 348 genes were identified as preferentially expressed genes in earlywood or latewood while a total of 168 genes were identified as preferentially expressed genes in either juvenile or mature wood. 12. Juvenile earlywood has a distinct transcriptome relative to other stages of wood development. 13. Discovered rapid decay of linkage disequilibrium (LD) in radiata pine with LD decaying to approximately 50% within 1,700 base pairs (within a typical gene). A total of 913 SNPS from sequencing 177,380 base pairs were identified for association genetic studies. 14. 149 SNPs from 44 genes and 255 SNPs from a further 51 genes (total 95 genes) were selected for association analysis with 62 wood traits, and 30 SNPs were shortlisted for their significant association with variation of wood quality traits (density, MFA and MoE) with individual significant SNPs accounting for between 1.9 and 9.7% of the total genetic variation in traits. 15. Index selection using breeding objectives was the most profitable selection method for radiata pine, but in the long term it may not be the most effective in dealing with negative genetic correlations between wood volume and quality traits. A combination of economic and biological approaches may be needed to deal with the strong adverse correlation.

Candidate gene studies on cardiovascular traits

Cardiovascular diseases (CVD) are a major cause of death and disability in Western countries and a growing health problem in the developing world. The genetic component of both coronary heart disease (CHD) and ischemic stroke events has been established in twin studies, and the traits predisposing to CVD, such as hypertension, dyslipidemias, obesity, diabetes, and smoking behavior, are all partly hereditary. Better understanding of the pathophysiology of CVD-related traits could help to target disease prevention and clinical treatment to individuals at an especially high disease risk and provide novel pharmaceutical interventions. This thesis aimed to clarify the genetic background of CVD at a population level using large Nordic population cohorts and a candidate gene approach. The first study concentrated on the allelic diversity of the thrombomodulin (THBD) gene in two Finnish cohorts, FINRISK-92 and FINRISK-97. The results from this study implied that THBD variants do not substantially contribute to CVD risk. In the second study, three other candidate genes were added to the analyses. The study investigated the epistatic effects of coagulation factor V (F5), intercellular adhesion molecule -1 (ICAM1), protein C (PROC), and THBD in the same FINRISK cohorts. The results were encouraging; we were able to identify several single SNPs and SNP combinations associating with CVD and mortality. Interestingly, THBD variants appeared in the associating SNP combinations despite the negative results from Study I, suggesting that THBD contributes to CVD through gene-gene interactions. In the third study, upstream transcription factor -1 (USF1) was analyzed in a cohort of Swedish men. USF1 was associated with metabolic syndrome, characterized by accumulation of different CVD risk factors. A putative protective and a putative risk variant were identified. A direct association with CVD was not observed. The longitudinal nature of the study also clarified the effect of USF1 variants on CVD risk factors followed in four examinations throughout adulthood. The three studies provided valuable information on the study of complex traits, highlighting the use of large study samples, the importance of replication, and the full coverage of the major allelic variants of the target genes to assure reliable findings. Although the genetic basis of coronary heart disease and ischemic stroke remains unknown, single genetic findings may facilitate the recognition of high-risk subgroups.

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.

Portrait of Arthur Segal Portraits Men

LBI

Molecular Genetics of Lactase Deficiencies

Congenital lactase deficiency (CLD) (MIM 223000) is a rare autosomal recessive gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. The CLD locus was previously assigned by linkage and linkage disequilibrium analyses on 2q21 in 19 Finnish families. In this study, the molecular background of this disorder is reported. The CLD locus was refined in 32 CLD patients in 24 families by using microsatellite and single nucleotide polymorphism (SNP) haplotypes. Mutation analyses were performed by direct sequencing. We identified 5 distinct mutations in the lactase (LCT) gene, encoding the enzyme that hydrolyzes lactose in the intestinal lumen. These findings facilitate genetic testing of CLD in clinical practice and enable genetic counseling. The present data also provide the basis for detailed characterization of the molecular pathogenesis of this disorder. Adult-type hypolactasia (MIM 223100) (lactase non-persistence, lactose intolerance) is an autosomal recessive gastrointestinal condition that is a result of a decline in the activity of lactase in the intestinal lumen after weaning. Adult-type hypolactasia is considered to be a normal phenomenon among mammals and symptoms are remarkably milder than experienced in CLD. Recently, a variant C/T-13910 was shown to associate with the adult-type hypolactasia trait, locating 13.9 kb upstream of the LCT gene. In this study, the functional significance of the C/T-13910 variant was determined by studying the LCT mRNA levels in intestinal biopsy samples in children and adults with different genotypes. RT-PCR followed by solid-phase minisequencing was applied to determine the relative expression levels of the LCT alleles using an informative SNP located in exon 1. In children, the C-13910 allele was observed to be downregulated after five years of age in parallel with lactase enzyme activity. The expression of the LCT mRNA in the intestinal mucosa in individuals with the T-13910 A-22018 alleles was 11.5 times higher than that found in individuals with the C-13910, G-22018 alleles. These findings suggest that the C/T-13910 associated with adult-type hypolactasia is associated with the transcriptional regulation of the LCT gene. The presence of the T-13910 A-22018 allele also showed significant elevation lactase activity. Galactose, the hydrolysing product of the milk sugar lactose, has been hypothesized to be poisonous to ovarian epithelial cells. Hence, consumption of dairy products and lactase persistence has been proposed to be a risk factor for ovarian carcinoma. To investigate whether lactase persistence is related to the risk of ovarian carcinoma the C/T-13910 genotype was determined in a cohort of 782 women with ovarian carcinoma 1331 individuals serving as controls. Lactase persistence did not associate significantly with the risk for ovarian carcinoma in the Finnish, in the Polish or in the Swedish populations. The findings do not support the hypothesis that lactase persistence increases the risk for ovarian carcinoma.

Molecular Genetic Background of Tumours in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a hereditary tumour predisposition syndrome. Its phenotype includes benign cutaneous and uterine leiomyomas (CLM, ULM) with high penetrance and rarer renal cell cancer (RCC), most commonly of papillary type 2 subtype. Over 130 HLRCC families have been identified world-wide but the RCC phenotype seems to concentrate in families from Finland and North America for unknown reasons. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. FH encodes the enzyme fumarase from mitochondrial citric acid cycle. Fumarase enzyme activity or type or site of the FH mutation are unassociated with disease phenotype. The strongest evidence for tumourigenesis mechanism in HLRCC supports a hypoxia inducible factor driven process called pseudohypoxia resulting from accumulation of the fumarase substrate fumarate. In this study, to assess the importance of gene- or exon-level deletions or amplifications of FH in patients with HLRCC-associated phenotypes, multiplex ligation-dependent probe amplification (MLPA) method was used. One novel FH mutation, deletion of exon 1, was found in a Swedish male patient with an evident HLRCC phenotype with CLM, RCC, and a family history of ULM and RCC. Six other patients with CLM and 12 patients with only RCC or uterine leiomyosarcoma (ULMS) remained FH mutation-negative. These results suggest that copy number aberrations of FH or its exons are an infrequent cause of HLRCC and that only co-occurrence of benign tumour types justifies FH-mutation screening in RCC or ULMS patients. Determination of the genomic profile of 11 HLRCC-associated RCCs from Finnish patients was performed by array comparative genomic hybridization. The most common copy number aberrations were gains of 2, 7, and 17 and losses of 13q12.3-q21.1, 14, 18, and X. When compared to aberrations of sporadic papillary RCCs, HLRCC-associated RCCs harboured a distinct DNA copy number profile and lacked many of the changes characterizing the sporadic RCCs. The findings suggest a divergent molecular pathway for tumourigenesis of papillary RCCs in HLRCC. In order to find a genetic modifier of RCC risk in HLRCC, genome-wide linkage and identical by descent (IBD) analysis studies were performed in Finnish HLRCC families with microsatellite marker mapping and SNP-array platforms. The linkage analysis identified only one locus of interest, the FH gene locus in 1q43, but no mutations were found in the genes of the region. IBD analysis yielded no convincing haplotypes shared by RCC patients. Although these results do not exclude the existence of a genetic modifier for RCC risk in HLRCC, they emphasize the role of FH mutations in the malignant tumourigenesis of HLRCC. To study the benign tumours in HLRCC, genome-wide DNA copy number and gene expression profiles of sporadic and HLRCC ULMs were defined with modern SNP- and gene-expression array platforms. The gene expression array suggests novel genes involved in FH-deficient ULM tumourigenesis and novel genes with putative roles in propagation of sporadic ULM. Both the gene expression and copy number profiles of HLRCC ULMs differed from those of sporadic ULMs indicating distinct molecular basis of the FH-deficient HLRCC tumours.