Lukemisen vaikeuden kuntoutus ensiluokkalaisilla : Kolme pedagogista interventiota

Remediation of Reading Difficulties in Grade 1. Three Pedagogical Interventions Keywords: initial teaching, learning to read, reading difficulties, intervention, dyslexia, remediation of dyslexia, home reading, computerized training In this study three different reading interventions were tested for first-graders at risk of reading difficulties at school commencement. The intervention groups were compared together and with a control group receiving special education provided by the school. First intervention was a new approach called syllable rhythmics in which syllabic rhythm, phonological knowledge and letter-phoneme correspondence are emphasized. Syllable rhythmics is based on multi-sensory training elements aimed at finding the most functional modality for every child. The second intervention was computerized training of letter-sound correspondence with the Ekapeli learning game. The third intervention was home-based shared book reading, where every family was given a story book, and dialogic reading style reading and writing exercises were prepared for each chapter of the book. The participants were 80 first-graders in 19 classes in nine schools. The children were matched in four groups according to pre-test results: three intervention and one control. The interventions took ten weeks starting from September in grade 1. The first post-test including several measures of reading abilities was administered in December. The first delayed post-test was administered in March, the second in September in grade 2, and the third, “ALLU” test (reading test for primary school) was administered in March in grade 2. The intervention and control groups differed only slightly from each other in grade 1. However, girls progressed significantly more than boys in both word reading and reading comprehension in December and this difference remained in March. The children who had been cited as inattentive by their teachers also lagged behind the others in the post-tests in December and March. When participants were divided into two groups according to their initial letter knowledge at school entry, the weaker group (maximum 17 correctly named letters in pre-test) progressed more slowly in both word reading and reading comprehension in grade 1. Intervention group and gender had no interaction effect in grade 1. Instead, intervention group and attentiveness had an interaction effect on most test measures the inattentive students in the syllable rhythmic group doing worst and attentive students in the control group doing best in grade 1. The smallest difference between results of attentive and inattentive students was in the Ekapeli group. In grade 2 still only minor differences were found between the intervention groups and control group. The only significant difference was in non-word reading, with the syllable rhythmics group outperforming the other groups in the fall. The difference between girls’ and boys’ performances in both technical reading and text comprehension disappeared in grade 2. The difference between the inattentive and attentive students cold no longer be found in technical reading, and the difference became smaller in text comprehension as well. The difference between two groups divided according to their initial letter knowledge disappeared in technical reading but remained significant in text comprehension measures in the ALLU test in the spring of grade 2. In all, the children in the study did better in the ALLU test than expected according to ALLU test norms. Being the weakest readers in their classes in the pre-test, 52.3 % reached the normal reading ability level. In the norm group 72.3 % of all students attained normal reading ability. The results of this study indicate that different types of remediation programs can be effective, and that special education has been apparently useful. The results suggest careful consideration of first-graders’ initial reading abilities (especially letter knowledge) and possible failure of attention; remediation should be individually targeted while flexibly using different methods.

Kouluruokailuhenkilöstö matkalla kasvattajaksi

The National Board of Education in Finland has defined school catering as a part of education in comprehensive schools. School catering is defined in Finnish law and is financed by the municipalities. The emphasis on supplementary education in the school curriculum obliges the whole staff to learn new professional roles and to co-operate in the school com-munity. An in-service training programme, Smart Catering Staff (SCS) was designed and put into practice among school catering staff. The aim of the one-year SCS programme was to add to and encourage the development of the know-how of catering personnel regarding new challenges in the school community as well as to enhance and empower their educator’s role in the school. The content of the programme consisted of four two-day intensive teaching sessions as well as assignments which were carried out between theese sessions. The main contents of the SCS programme were personal and organizational learning, school curriculum concerning school catering, school culture and co-operation, customer service, and the role of catering staff as educators. The data in this action research was gathered from 2000 to 2008. The results show that the SCS programme can change the work community culture in that the catering staff is more encouraged to participate in the development projects of the school, and can see themselves more as educators alongside the teaching staff. It is concluded that in school communities all adults can be educators, but to achieve this aim empowering in-service training is needed. The school catering staff’s commitment to participation in the education align with the educational goals of the school unite children’s and teens safety nets. This can affect for example the growth of communal responsibility and prevention of alienation. Key words: School Catering, Smart School Catering Staff, Expanded Education, School Community, Action Research

Gone with the Wind? : Immigrant Women and Transnational Everyday Life in Finland

Increased mass migration, as a result of economic hardship, natural disasters and wars, forces many people to arrive on the shores of cultures very different from those they left. How do they manage the legacy of the past and the challenges of their new everyday life? This is a study of immigrant women living in transnational families that act and communicate across national borders on a near-daily basis. The research was carried out amongst immigrant women who were currently living in Finland. The research asks how transnational everyday life is constructed. As everyday life, due to its mundane nature, is difficult to operationalise for research purposes, mixed data collection methods were needed to capture the passing moments that easily become invisible. Thus, the data were obtained from photographic diaries (459 photographs) taken by the research participants themselves. Additionally, stimulated recall discussions, structured questionnaires and participant observation notes were used to complement the photographic data. A tool for analysing the activities devealed in the data was created on the assumption that a family is an active unit that accommodates the current situation in which it is embedded. Everyday life activities were analysed emphasizing social, modal and spatial dimensions. Important daily moments were placed on a continuum: for me , for immediate others and with immediate others . They portrayed everyday routines and exceptions to it. The data matrix was developed as part of this study. The spatial dimensions formed seven units of activity settings: space for friendship, food, resting, childhood, caring, space to learn and an orderly space. Attention was also paid to the accommodative nature of activities; how women maintain traditions and adapt to Finnish life or re-create new activity patterns. Women s narrations revealed the importance of everyday life. The transnational chain of women across generations and countries, comprised of the daughters, mothers and grandmothers was important. The women showed the need for information technology in their transnational lives. They had an active relationship to religion; the denial or importance of it was obvious. Also arranging one s life in Finnish society was central to their narrations. The analysis exposed everyday activities, showed the importance of social networks and the uniqueness of each woman and family. It revealed everyday life in a structured way. The method of analysis that evolved in this study together with the research findings are of potential use to professionals, allowing the targeting of interventions to improve the everyday lives of immigrants.

Kumppanuus on tiiviimpää kuin yhteistyö : Maahanmuuttajataustaisten vanhempien näkemyksiä kasvatuskumppanuudesta

The main idea of this study was to find out how immigrants understand and define successful co-operation and professional partnership in early childhood education. Another target of this research was to think over how the parents see professional partnership from their viewpoint, and how willing / ready the they are in engaging in the professional partnership with the day care personnel. The theoretical part of this research is based on theories of immigration and theories of it s different forms, theories of cultural varieties and theory of modernizing co-operation through using professional partnership. Also guidelines and policies for day care and early childhood education play a part in the theory section. Theory part is written to support research problems. The research method used in this study is peer interview. The interviewed are both immigrants and customers of day care services. The data collected is comprised of materials from peer interviews and personal background information. The interviewed were of Somalia and Russian ethnic groups. Interview were carried out in each group in the participants own mother tongue. These peer interviews showed that parents were interested and willing to discuss professional partnership. From this research one can conclude that the term professional partnership is seen as a complex term, and as a term difficult to understand. From the results it is seen that quite often the principles of professional partnership are not carried out in practise. According to the material gathered, the parents feel that lack of common language and prejudice against immigrants effectively prevents the professional partnership from being formed. The cultural differences can become challenging in a professional partnership. Based on this research, one can conclude that when different cultures meet, there has to be mutual will to understand and to be understood in order to make sure that the children s development, both educational and physical, is supported in a best possible way.

"Sitte se menee koulus" : Eri kieli- ja kulttuuritaustaisen lapsen suomen kielen taito esiopetuksen päättövaiheessa

A child learns new things, creates social relationships and participates in play with the help of language. How can a child overcome these challenges if the surrounding language is not his mother tongue? The objective of learning a new language in the Pre-school education is an active bilingualism in all fields of the language. Theoretical context of the research rises from bilingualism, learning a language, language skills and evaluating them. Object of the research was to understand language skills of a child from a different linguistic and cultural background in the final stage of Pre-school education and to clarify how learning Finnish was supported during the Pre-school year. Answers to the research issues will be searched with the following questions: 1) What kind of language skills does a child from a different linguistic and cultural backgrounds have at the final stage of Pre-school education?, 1.1) What kind of listening comprehension skills?, 1.2) What kind of speech and vocabulary skills?, 1.3) What kind of structural skills?, 2) What kind of individual differences are there in language skills of children from different linguistic and cultural backgrounds?, and 3) How has a child from a different linguistic and cultural background been supported in learning Finnish during the Pre-school education? The view of language skills in this research is holistic even though it will be analysed in separate fields. The aim of this research is to form an overall impression of Finnish skills of the children participating in the research. Eight Pre-school-aged children with different linguistic and cultural backgrounds and their kindergarten teachers participated in this research. The children had taken part in Finnish activities for about three years. The research material consists of the test series (KITA), which evaluate children’s language skills – and of the questionnaire to the kindergarten teachers. The purpose of the questionnaire was to provide additional information on children’s language skills in Pre-school teaching situations and on supporting Finnish in Pre-school education. This research is qualitative and processing of the material is based on content analysis. According to the kindergarten teachers, the children’s social language skills were sufficient to cope in everyday life but children needed assistance with longer instructions. The same phenomenon could also be seen with the KITA tests – in which long and abstract instructions turned out to be difficult. Individual differences of the children were perceived in productivity skills, which were realised in fluent or influent speech. The children were supported in learning Finnish individually, in small-groups and in the activities of a whole group. ‘Finnish as the second language’ small-groups were the most common form of support in learning the language. The support at understanding activities was emphasized in whole group situations as well as in individual situations while assisting the child’s language skills. Generally, the children’s language skills were in the same level with developing basic language skills. The data of this research help to understand children’s language skills after three years of adopting Finnish. The results can be utilised in planning and evaluation of teaching another language.

Demokratiaa luokkahuoneessa : Toimintatutkimus kolmasluokkalaisten osallistamisesta päätöksentekoon

The crucial questions that define democracy relate to its depth and width: who can participate in decision making and what kind of things can be commonly decided? Theories deeper than representative democracy emphasize discussion, in which by evaluating justifications it is possible to achieve consensus in ideal situation. The aim of my research is to develop tools for promoting the participation of third graders in decision making in the classroom. In addition I study the development of depth and width of democracy in the classroom, the development of skills and competencies in the decision making and the challenges of the project. My research method is participative action research. I collected my data between October 2007 and March 2008. I used videos and observation diaries as my primary data. Additional data consisted of the interviews of the students, the conversations between the adults and the material produced by the teacher. Since we discussed the matters students had highlighted in specific lessons, my analysis proceeds according to these lessons constructing a general view of the process. The width and depth of classroom democracy are difficult to define. Though the system we had created enabled third graders to discuss matters they found important the participation was unequal: some of the students couldn’t among other things give justifications for their opinions. This poses challenges for models that emphasize deliberation since these theories presuppose that everyone has concordant competencies. But then again only critical citizens who are able to make justifications and to evaluate them are able to oppose indoctrination. This makes teaching these competencies justified. Different decision making procedures define the classroom democracy. Deliberation doesn’t necessarily provide deeper information about the preferences of the participants than mere voting. But then again voting doesn’t express the reasons which support one’s preferences. Structured conversation can equalize the time used for every participant’s opinions, but doesn’t solve the challenge of unequal competencies. Children’s suggestion box diversified the possibilities to participate, and also the silent ones used it during the research. The asymmetry in deliberation might also be caused by the social structure of the students. Teacher’s directing and participation encouraging role in deliberation was significant. Diversifying the participation by different roles could equalize the asymmetry in participation.

Developmental, functional brain imaging and electrophysiological evidence of visual and auditory working memory

Intact function of working memory (WM) is essential for children and adults to cope with every day life. Children with deficits in WM mechanisms have learning difficulties that are often accompanied by behavioral problems. The neural processes subserving WM, and brain structures underlying this system, continue to develop during childhood till adolescence and young adulthood. With functional magnetic resonance imaging (fMRI) it is possible to investigate the organization and development of WM. The present thesis aimed to investigate, using behavioral and neuroimaging methods, whether mnemonic processing of spatial and nonspatial visual information is segregated in the developing and mature human brain. A further aim in this research was to investigate the organization and development of audiospatial and visuospatial information processing in WM. The behavioral results showed that spatial and nonspatial visual WM processing is segregated in the adult brain. The fMRI result in children suggested that memory load related processing of spatial and nonspatial visual information engages common cortical networks, whereas selective attention to either type of stimuli recruits partially segregated areas in the frontal, parietal and occipital cortices. Deactivation mechanisms that are important in the performance of WM tasks in adults are already operational in healthy school-aged children. Electrophysiological evidence suggested segregated mnemonic processing of visual and auditory location information. The results of the development of audiospatial and visuospatial WM demonstrate that WM performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The development of the performance of spatial WM tasks follows a different time course in boys and girls indicating a larger degree of immaturity in the male than female WM systems. Furthermore, the differences in mastering auditory and visual WM tasks may indicate that visual WM reaches functional maturity earlier than the corresponding auditory system. Spatial WM deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. Alternatively, anxiety or depressive symptoms may affect WM function and the ability to concentrate, being thus the primary cause of poor academic achievement in children.

Oral Health among Iranian Preadolescents : A School-Based Health Education Intervention

The present study assessed oral health and its determinants among Iranian preadolescents, and evaluated a school-based health education programme aimed to promote their oral health. The target population of this study comprised a random sample of the third-grade school children (n = 459) of all public primary schools in 19 areas of Tehran city. The data came from a clinical examination of the children and two self-administered questionnaires: one for children, and one for mothers. The clinical dental examination was performed for recording children's oral health. The mothers' questionnaires covered background factors, oral self-care (OSC) behaviours and oral health-related knowledge and attitude statements. After baseline data collection, a community trial was designed as a 3-month school-based intervention study. For the intervention trial, the third-grade classes as the clusters were randomly assigned to the intervention and control groups. Three kinds of intervention were implemented, one in class, one via the parents, and one as a combination of these. One group served as controls with no intervention. The outcome measures of the study were changes in plaque and bleeding scores recorded. The results showed that mean dmft was 3.75 (SD = 2.8) for the primary teeth and mean DMFT was 0.4 (SD = 0.9) for the permanent teeth. All children had plaque on at least one index tooth and bleeding on probing in at least one index tooth occurred in 81%. About one-third (34%) of the children reported favourable OSC and less than half (46%) of the children reported brushing their teeth at least twice daily. Girls reported favourable OSC (OR = 2.0), had decay-free teeth (OR = 1.8) and treated permanent teeth (OR = 3.3) more than did boys. Mother's oral health-related aspects, i.e., mother's favourable OSC, high knowledge levels of and positive attitudes towards oral health, and active supervision of the child's tooth brushing had a positive effect on all aspects of children's oral health status and behaviours (ORs from 1.3 to 1.9). After the intervention, the results showed a strong intervention effect on healthy gingiva in both groups where parents were involved: the parental-aid group (OR = 7.7, 95% CI 2.2-27.7) and combined group (OR = 6.6, 95% CI 2.0-22.1). To improve children's oral health, community school-based oral health educational programmes should be established to include all primary schools. These programmes should benefit from the common risk factor approach and a multi-sectored approach to employ for communication between the community, the school, and the family. Oral health interventions should empower the parents' ability to improve their own oral health behaviour and then to transfer that healthy behaviour to their children.

Cervical headgear in Class II division 1 correction in children : Academic Dissertation

Class II division 1 malocclusion occurs in 3.5 to 13 percent of 7 12 year-old children. It is the most common reason for orthodontic treatment in Finland. Correction is most commonly performed using headgear treatment. The aim of this study was to investigate the effects of cervical headgear treatment on dentition, facial skeletal and soft tissue growth, and upper airway structure, in children. 65 schoolchildren, 36 boys and 29 girls were studied. At the onset of treatment a mean age was 9.3 (range 6.6 12.4) years. All the children were consequently referred to an orthodontist because of Class II division 1 malocclusion. The included children had protrusive maxilla and an overjet of more than 2mm (3 to 11 mm). The children were treated with a Kloehn-type cervical headgear as the only appliance until Class I first molar relationships were achieved. The essential features of the headgear were cervical strong pulling forces, a long upward bent outer bow, and an expanded inner bow. Dental casts and lateral and posteroanterior cephalograms were taken before and after the treatment. The results were compared to a historical, cross-sectional Finnish cohort or to historical, age- and sex-matched normal Class I controls. The Class I first molar relationships were achieved in all the treated children. The mean treatment time was 1.7 (range 0.3-3.1) years. Phase 2 treatments were needed in 52% of the children, most often because of excess overjet or overbite. The treatment decreased maxillary protrusion by inhibiting alveolar forward growth, while the rest of the maxilla and mandible followed normal growth. The palate rotated anteriorly downward. The expansion of the inner bow of the headgear induced widening of the maxilla, nasal cavity, and the upper and lower dental arches. Class II malocclusion was associated with narrower oro- and hypopharyngeal space than in the Class I normal controls. The treatment increased the retropalatal airway space, while the rest of the airway remained unaffected. The facial profile improved esthetically, while the facial convexity decreased. Facial soft tissues masked the facial skeletal convexity, and the soft tissue changes were smaller than skeletal changes. In conclusion, the headgear treatment with the expanded inner bow may be used as an easy and simple method for Class II correction in growing children.

Evidence-based perspective on CP rehabilitation : Reviews on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices

This thesis utilises an evidence-based approach to critically evaluate and summarize effectiveness research on physiotherapy, physiotherapy-related motor-based interventions and orthotic devices in children and adolescents with cerebral palsy (CP). It aims to assess the methodological challenges of the systematic reviews and trials, to evaluate the effectiveness of interventions in current use, and to make suggestions for future trials Methods: Systematic reviews were searched from computerized bibliographic databases up to August 2007 for physiotherapy and physiotherapy-related interventions, and up to May 2003 for orthotic devices. Two reviewers independently identified, selected, and assessed the quality of the reviews using the Overview Quality Assessment Questionnaire complemented with decision rules. From a sample of 14 randomized controlled trials (RCT) published between January 1990 and June 2003 we analysed the methods of sampling, recruitment, and comparability of groups; defined the components of a complex intervention; identified outcome measures based on the International Classification of Functioning, Disability and Health (ICF); analysed the clinical interpretation of score changes; and analysed trial reporting using a modified 33-item CONSORT (Consolidated Standards of Reporting Trials) checklist. The effectiveness of physiotherapy and physiotherapy-related interventions in children with diagnosed CP was evaluated in a systematic review of randomised controlled trials that were searched from computerized databases from January 1990 up to February 2007. Two reviewers independently assessed the methodological quality, extracted the data, classified the outcomes using the ICF, and considered the level of evidence according to van Tulder et al. (2003). Results: We identified 21 reviews on physiotherapy and physiotherapy-related interventions and five on orthotic devices. These reviews summarized 23 or 5 randomised controlled trials and 104 or 27 observational studies, respectively. Only six reviews were of high quality. These found some evidence supporting strength training, constraint-induced movement therapy or hippotherapy, and insufficient evidence on comprehensive interventions. Based on the original studies included in the reviews on orthotic devices we found some short-term effects of lower limb casting on passive range of movement, and of ankle-foot orthoses on equinus walk. Long term effects of lower limb orthoses have not been studied. Evidence of upper limb casting or orthoses is conflicting. In the sample of 14 RCTs, most trials used simple randomisation, complemented with matching or stratification, but only three specified the concealed allocation. Numerous studies provided sufficient details on the components of a complex intervention, but the overlap of outcome measures across studies was poor and the clinical interpretation of observed score changes was mostly missing. Almost half (48%) of the applicable CONSORT-based items (range 28 32) were reported adequately. Most reporting inadequacies were in outcome measures, sample size determination, details of the sequence generation, allocation concealment and implementation of the randomization, success of assessor blinding, recruitment and follow-up dates, intention-to-treat analysis, precision of the effect size, co-interventions, and adverse events. The systematic review identified 22 trials on eight intervention categories. Four trials were of high quality. Moderate evidence of effectiveness was established for upper extremity treatments on attained goals, active supination and developmental status, and of constraint-induced therapy on the amount and quality of hand use and new emerging behaviours. Moderate evidence of ineffectiveness was found for strength training's effect on walking speed and stride length. Conflicting evidence was found for strength training's effect on gross motor function. For the other intervention categories the evidence was limited due to the low methodological quality and the statistically insignificant results of the studies. Conclusions: The high-quality reviews provide both supportive and insufficient evidence on some physiotherapy interventions. The poor quality of most reviews calls for caution, although most reviews drew no conclusions on effectiveness due to the poor quality of the primary studies. A considerable number of RCTs of good to fair methodological and reporting quality indicate that informative and well-reported RCTs on complex interventions in children and adolescents with CP are feasible. Nevertheless, methodological improvement is needed in certain areas of the trial design and performance, and the trial authors are encouraged to follow the CONSORT criteria. Based on RCTs we established moderate evidence for some effectiveness of upper extremity training. Due to limitations in methodological quality and variations in population, interventions and outcomes, mostly limited evidence on the effectiveness of most physiotherapy interventions is available to guide clinical practice. Well-designed trials are needed, especially for focused physiotherapy interventions.

Living arrangements and health

In line with major demographic changes in other Northern European and North American countries and Australia, being nonmarried is becoming increasingly common in Finland, and the proportion of cohabiters and of persons living alone has grown in recent decades. Official marital status no longer reflects an individual s living arrangement, as single, divorced and widowed persons may live alone, with a partner, with children, with parents, with siblings, or with unrelated persons. Thus, more than official marital status, living arrangements may be a stronger discriminator of one s social bonds and health. The general purpose of this study was to deepen our current understanding of the magnitude, trends, and determinants of ill health by living arrangements in the Finnish working-age population. Distinct measures of different dimensions of poor health, as well as an array of associated factors, provided a comprehensive picture of health differences by living arrangements and helped to assess the role of other factors in the interpretation of these differences . Mortality analyses were based on Finnish census records at the end of 1995 linked with cause-of-death registers for 1996 2000. The data included all persons aged 30 and over. Morbidity analyses were based on two comparable cross-sectional studies conducted twenty years apart (the Mini-Finland Survey in 1978 80 and the Health 2000 Survey in 2000 01). Both surveys were based on nationally representative samples of Finns aged 30 and over, and benefited from high participation rates. With the exception of mortality analyses, this study focused on health differences among the working-age population (mortality in age groups 30-64 and 65 and over, self-rated health and mental health in the age group 30-64, and unhealthy alcohol use in the age group 30-54). Compared with all nonmarried groups, married men and women exhibited the best health in terms of mortality, self-rated health, mental health and unhealthy alcohol use. Cohabiters did not differ from married persons in terms of self-rated health or mental health, but did exhibit excess unhealthy alcohol use and high mortality, particularly from alcohol-related causes. Compared with the married, persons living alone or with someone other than a partner exhibited elevated mortality as well as excess poor mental health and unhealthy alcohol use. By all measures of health, men and women living alone tended to be in the worst position. Over the past twenty years, SRH had improved least among single men and women and widowed women, and most among cohabiting women. The association between living arrangements and health has many possible explanations. The health-related selection theory suggests that healthy people are more likely to enter and maintain a marriage or a consensual union than those who are unhealthy (direct selection) or that a variety of health-damaging behavioural and social factors increase the likelihood of ill health and the probability of remaining without a partner or becoming separated from one s partner (indirect selection). According to the social causation theory, marriage or cohabitation has a health-promoting effect, whereas living alone or with others than a partner has a detrimental effect on health. In this study, the role of other factors that are mainly assumed to reflect selection, appeared to be rather modest. Social support, which reflects social causation, contributed only modestly to differences in unhealthy alcohol use by living arrangements, but had a larger effect on differences in poor mental health. Socioeconomic factors and health-related behaviour, which reflect both selection and causation, appeared to play a more important role in the excess poor health of cohabiters and of persons living alone or with someone other than a partner, than of married persons. Living arrangements were strongly connected to various dimensions of ill health. In particular, alcohol consumption appeared to be of great importance in the association between living arrangements and health. To the extent that the proportion of nonmarried persons continues to grow and their health does not improve at the same rate as that of married persons, the challenges that currently nonmarried persons pose to public health will likely increase.

Familial aggregation of type 1 diabetes and diabetic nephropathy in Finland

Type 1 diabetes (T1D) is a common, multifactorial disease with strong familial clustering. In Finland, the incidence of T1D among children aged 14 years or under is the highest in the world. The increase in incidence has been approximately 2.4% per year. Although most new T1D cases are sporadic the first-degree relatives are at an increased risk of developing the same disease. This study was designed to examine the familial aggregation of T1D and one of its serious complications, diabetic nephropathy (DN). More specifically the study aimed (1) to determine the concordance rates of T1D in monozygotic (MZ) and dizygotic (DZ) twins and to estimate the relative contributions of genetic and environmental factors to the variability in liability to T1D as well as to study the age at onset of diabetes in twins; (2) to obtain long-term empirical estimates of the risk of T1D among siblings of T1D patients and the factors related to this risk, especially the effect of age at onset of diabetes in the proband and the birth cohort effect; (3) to establish if DN is aggregating in a Finnish population-based cohort of families with multiple cases of T1D, and to assess its magnitude and particularly to find out whether the risk of DN in siblings is varying according to the severity of DN in the proband and/or the age at onset of T1D: (4) to assess the recurrence risk of T1D in the offspring of a Finnish population-based cohort of patients with childhood onset T1D, and to investigate potential sex-related effects in the transmission of T1D from the diabetic parents to their offspring as well as to study whether there is a temporal trend in the incidence. The study population comprised of the Finnish Young Twin Cohort (22,650 twin pairs), a population-based cohort of patients with T1D diagnosed at the age of 17 years or earlier between 1965 and 1979 (n=5,144) and all their siblings (n=10,168) and offspring (n=5,291). A polygenic, multifactorial liability model was fitted to the twin data. Kaplan-Meier analyses were used to provide the cumulative incidence for the development of T1D and DN. Cox s proportional hazards models were fitted to the data. Poisson regression analysis was used to evaluate temporal trends in incidence. Standardized incidence ratios (SIRs) between the first-degree relatives of T1D patients and background population were determined. The twin study showed that the vast majority of affected MZ twin pairs remained discordant. Pairwise concordance for T1D was 27.3% in MZ and 3.8% in DZ twins. The probandwise concordance estimates were 42.9% and 7.4%, respectively. The model with additive genetic and individual environmental effects was the best-fitting liability model to T1D, with 88% of the phenotypic variance due to genetic factors. The second paper showed that the 50-year cumulative incidence of T1D in the siblings of diabetic probands was 6.9%. A young age at diagnosis in the probands considerably increased the risk. If the proband was diagnosed at the age of 0-4, 5-9, 10-14, 15 or more, the corresponding 40-year cumulative risks were 13.2%, 7.8%, 4.7% and 3.4%. The cumulative incidence increased with increasing birth year. However, SIR among children aged 14 years or under was approximately 12 throughout the follow-up. The third paper showed that diabetic siblings of the probands with nephropathy had a 2.3 times higher risk of DN compared with siblings of probands free of nephropathy. The presence of end stage renal disease (ESRD) in the proband increases the risk three-fold for diabetic siblings. Being diagnosed with diabetes during puberty (10-14) or a few years before (5-9) increased the susceptibility for DN in the siblings. The fourth paper revealed that of the offspring of male probands, 7.8% were affected by the age of 20 compared with 5.3% of the offspring of female probands. Offspring of fathers with T1D have 1.7 times greater risk to be affected with T1D than the offspring of mothers with T1D. The excess risk in the offspring of male fathers manifested itself through the higher risk the younger the father was when diagnosed with T1D. Young age at onset of diabetes in fathers increased the risk of T1D greatly in the offspring, but no such pattern was seen in the offspring of diabetic mothers. The SIR among offspring aged 14 years or under remained fairly constant throughout the follow-up, approximately 10. The present study has provided new knowledge on T1D recurrence risk in the first-degree relatives and the risk factors modifying the risk. Twin data demonstrated high genetic liability for T1D and increased heritability. The vast majority of affected MZ twin pairs, however, remain discordant for T1D. This study confirmed the drastic impact of the young age at onset of diabetes in the probands on the increased risk of T1D in the first-degree relatives. The only exception was the absence of this pattern in the offspring of T1D mothers. Both the sibling and the offspring recurrence risk studies revealed dynamic changes in the cumulative incidence of T1D in the first-degree relatives. SIRs among the first-degree relatives of T1D patients seems to remain fairly constant. The study demonstrates that the penetrance of the susceptibility genes for T1D may be low, although strongly influenced by the environmental factors. Presence of familial aggregation of DN was confirmed for the first time in a population-based study. Although the majority of the sibling pairs with T1D were discordant for DN, its presence in one sibling doubles and presence of ESRD triples the risk of DN in the other diabetic sibling. An encouraging observation was that although the proportion of children to be diagnosed with T1D at the age of 4 or under is increasing, they seem to have a decreased risk of DN or at least delayed onset.

Animal model and molecular interactions of Cln5

Neuronal ceroid lipofuscinoses (NCLs) are a family of inherited pediatric neurodegenerative disorders, leading to retinal degeneration, death of selective neuronal populations and accumulation of autofluorscent ceroid-lipopigments. The clinical manifestations are generally similar in all forms. The Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCLFin) is a form of NCL, especially enriched in the Finnish population. The aim of this thesis was to analyse the brain pathology of vLINCLFin utilising the novel Cln5-/- mouse model. Gene expression profiling of the brains of already symptomatic Cln5-/- mice revealed that inflammation, neurodegeneration and defects in myelinization are the major characteristics of the later stages of the disease. Histological characterization of the brain pathology confirmed that the thalamocortical system is affected in Cln5-/- mice, similarly to the other NCL mouse models. However, whereas the brain pathology in all other analyzed NCL mice initiate in the thalamus and spread only months later to the cortex, we observed that the sequence of events is uniquely reversed in Cln5-/- mice; beginning in the cortex and spreading to the thalamus only months later. We could also show that even though neurodegeneration is inititated in the cortex, reactive gliosis and loss of myelin are evident in specific nuclei of the thalamus already in the 1 month old brain. To obtain a deeper insight into the disturbed metabolic pathways, we performed gene expression profiling of presymptomatic mouse brains. We validated these findings with immunohistological analyses, and could show that cytoskeleton and myelin were affected in Cln5-/- mice. Comparison of gene expression profiling results of Cln5-/- and Cln1-/- mice, further highlighted that these two NCL models share a common defective pathway, leading to disturbances in the neuronal growth cone and cytoskeleton. Encouraged by the evidence of this defected pathway, we analyzed the molecular interactions of NCL-proteins and observed that Cln5 and Cln1/Ppt1 proteins interact with each other. Furthermore, we demonstrated that Cln5 and Cln1/Ppt1 share an interaction partner, the F1-ATP synthase, potentially linking both vLINCLFIN and INCL diseases to disturbed lipid metabolism. In addition, Cln5 was shown to interact with other NCL proteins; Cln2, Cln3, Cln6 and Cln8, implicating a central role for Cln5 in the NCL pathophysiology. This study is the first to describe the brain pathology and gene expression changes in the Cln5-/- mouse. Together the findings presented in this thesis represent novel information of the disease processes and the molecular mechanisms behind vLINCLFin and have highlighted that vLINCLFin forms a very important model to analyze the pathophysiology of NCL diseases.

Microarrays in Molecular Profiling of Ewing Sarcoma Family of Tumors and CDKN2A Aberrations

Background: The Ewing sarcoma family of tumors (ESFT) are rare but highly malignant neoplasms that occur mainly in bone or but also in soft tissue. ESFT affects patients typically in their second decade of life, whereby children and adolescents bear the heaviest incidence burden. Despite recent advances in the clinical management of ESFT patients, their prognosis and survival are still disappointingly poor, especially in cases with metastasis. No targeted therapy for ESFT patients is currently available. Moreover, based merely on current clinical and biological characteristics, accurate classification of ESFT patients often fails at the time of diagnosis. Therefore, there is a constant need for novel molecular biomarkers to be applied in tandem with conventional parameters to further intensify ESFT risk-stratification and treatment selection, and ultimately to develop novel targeted therapies. In this context, a greater understanding of the genetics and immune characteristics of ESFT is needed. Aims: This study sought to open novel insights into gene copy number changes and gene expression in ESFT and, further, to enlighten the role of inflammation in ESFT. For this purpose, microarrays were used to provide gene-level information on a genomewide scale. In addition, this study focused on screening of 9p21.3 deletion sizes and frequencies in ESFT and, in another pediatric cancer, acute lymphocytic leukemia (ALL), in order to define more exact criteria for highrisk patient selection and to provide data for developing a more reliable diagnostic method to detect CDKN2A deletions. Results: In study I, 20 novel ESFT-associated suppressor genes and oncogenes were pinpointed using combined array CGH and expression analysis. In addition, interesting chromosomal rearrangements were identified: (1) Duplication of derivative chromosome der(22)(11;22) was detected in three ESFT patients. This duplication included the EWSR1-FLI1 fusion gene leading to increase in its copy number; (2) Cryptic amplifications on chromosomes 20 and 22 were detected, suggesting a novel translocation between chromosomes 20 and 22, which most probably produces a fusion between EWSR1 and NFATC2. In study II, bioinformatic analysis of ESFT expression profiles showed that inflammatory gene activation is detectable in ESFT patient samples and that the activation is characterized by macrophage gene expression. Most interestingly, ESFT patient samples were shown to express certain inflammatory genes that were prognostically significant. High local expression of C5 and JAK1 at the tumor site was shown to associate with favorable clinical outcome, whereas high local expression of IL8 was shown to be detrimental. Studies III and IV showed that the smallest overlapping region of deletion in 9p21.3 includes CDKN2A in all cases and that the length of this region is 12.2 kb in both Ewing sarcoma and ALL. Furthermore, our results showed that the most widely used commercial CDKN2A FISH probe creates false negative results in the narrowest microdeletion cases (<190 kb). Therefore, more accurate methods should be developed for the detection of deletions in the CDKN2A locus. Conclusions: This study provides novel insights into the genetic changes involved in the biology of ESFT, in the interaction between ESFT cells and immune system, and in the inactivation of CDKN2A. Novel ESFT biomarker genes identified in this study serve as a useful resource for future studies and in developing novel therapeutic strategies to improve the survival of patients with ESFT.

Diet and the development of atherosclerosis: a whole-diet approach from childhood to adulthood

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world. Studies of the impact of single nutrients on the risk for CVD have often provided inconclusive results, and recent research in nutritional epidemiology with a more holistic whole-diet approach has proven fruitful. Moreover, dietary habits in childhood and adolescence may play a role in later health and disease, either independently or by tracking into adulthood. The main aims of this study were to find childhood and adulthood determinants of adulthood diet, to identify dietary patterns present among the study population and to study the associations between long-term food choices and cardiovascular health in young Finnish adults. The study is a part of the multidisciplinary Cardiovascular Risk in Young Finns study, which is an ongoing, prospective cohort study with a 21-year follow-up. At baseline in 1980, the subjects were children and adolescents aged 3 to 18 years (n included in this study = 1768), and young adults aged 24 to 39 years at the latest follow-up study in 2001 (n = 1037). Food consumption and nutrient intakes were assessed with repeated 48-hour dietary recalls. Other determinations have included comprehensive risk factor assessments using blood tests, physical measurements and questionnaires. In the latest follow-up, ultrasound examinations were performed to study early atherosclerotic vascular changes. The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, whereas the consumption of fruits and vegetables had increased. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of adult diet. Additionally, a principal component analysis was conducted to identify major dietary patterns at each study point. A similar set of two major patterns was recognised throughout the study. The traditional dietary pattern positively correlated with the consumption of traditional Finnish foods, such as rye, potatoes, milk, butter, sausages and coffee, and negatively correlated with fruit, berries and dairy products other than milk. This type of diet was independently associated with several risk factors of CVD, such as total and low-density lipoprotein cholesterol, apolipoprotein B and C-reactive protein concentrations among both genders, as well as with systolic blood pressure and insulin levels among women. The traditional pattern was also independently associated with intima media thickness (IMT), a subclinical predictor of CVD, in men but not in women. The health-conscious pattern, predominant among female subjects, non-smokers and urbanites, was characterised by more health-conscious food choices such as vegetables, legumes and nuts, tea, rye, fish, cheese and other dairy products, as well as by the consumption of alcoholic beverages. This pattern was inversely, but less strongly, associated with cardiovascular risk factors. Tracking of the dietary pattern scores was observed, particularly among subjects who were adolescents at baseline. Moreover, a long-term high intake of protein concurrent with a low intake of fat was positively associated with IMT. These findings suggest that food behaviour and food choices are to some extent established as early as in childhood or adolescence and may significantly track into adulthood. Long-term adherence to traditional food choices seems to increase the risk for developing CVD, especially among men. Those with intentional or unintentional low fat diets, but with high intake of protein may also be at increased risk for CVD. The findings offer practical, food-based information on the relationship between diet and CVD and encourage further use of the whole-diet approach in epidemiological research. The results support earlier findings that long-term food choices play a role in the development of CVD. The apparent influence of childhood habits is important to bear in mind when planning educational strategies for the primary prevention of CVD. Further studies on food choices over the entire lifespan are needed.