Genotype-Phenotype Relationships in Long QT Syndrome: Role of Mental Stress, Adrenergic Activity and a Common KCNH2 Polymorphism

Long QT syndrome is a congenital or acquired arrhythmic disorder which manifests as a prolonged QT-interval on the electrocardiogram and as a tendency to develop ventricular arrhythmias which can lead to sudden death. Arrhythmias often occur during intense exercise and/or emotional stress. The two most common subtypes of LQTS are LQT1, caused by mutations in the KCNQ1 gene and LQT2, caused by mutations in the KCNH2 gene. LQT1 and LQT2 patients exhibit arrhythmias in different types of situations: in LQT1 the trigger is usually vigorous exercise whereas in LQT2 arrhythmia results from the patient being startled from rest. It is not clear why trigger factors and clinical outcome differ from each other in the different LQTS subtypes. It is possible that stress hormones such as catecholamines may show different effects depending on the exact nature of the genetic defect, or sensitivity to catecholamines varies from subject to subject. Furthermore, it is possible that subtle genetic variants of putative modifier genes, including those coding for ion channels and hormone receptors, play a role as determinants of individual sensitivity to life-threatening arrhythmias. The present study was designed to identify some of these risk modifiers. It was found that LQT1 and LQT2 patients show an abnormal QT-adaptation to both mental and physical stress. Furthermore, as studied with epinephrine infusion experiments while the heart was paced and action potentials were measured from the right ventricular septum, LQT1 patients showed repolarization abnormalities which were related to their propensity to develop arrhythmia during intense, prolonged sympathetic tone, such as exercise. In LQT2 patients, this repolarization abnormality was noted already at rest corresponding to their arrhythmic episodes as a result of intense, sudden surges in adrenergic tone, such as fright or rage. A common KCNH2 polymorphism was found to affect KCNH2 channel function as demonstrated by in vitro experiments utilizing mammalian cells transfected with the KCNH2 potassium channel as well as QT-dynamics in vivo. Finally, the present study identified a common β-1-adrenergic receptor genotype that is related a shorter QT-interval in LQT1 patients. Also, it was discovered that compound homozygosity for two common β-adrenergic polymorphisms was related to the occurrence of symptoms in the LQT1 type of long QT syndrome. The studies demonstrate important genotype-phenotype differences between different LQTS subtypes and suggest that common modifier gene polymorphisms may affect cardiac repolarization in LQTS. It will be important in the future to prospectively study whether variant gene polymorphisms will assist in clinical risk profiling of LQTS patients.

Health-Related Quality of Life and Mental Disorders in Finland

Quality of life (QoL) and Health-related quality of life (HRQoL) are becoming one of the key outcomes of health care due to increased respect for the subjective valuations and well-being of patients and an increasing part of the ageing population living with chronic, non-fatal conditions. Preference-based HRQoL measures enable estimation of health utility, which can be useful for rational rationing, evidence-based medicine and health policy. This study aimed to compare the individual severity and public health burden of major chronic conditions in Finland, including and focusing on reliably diagnosed psychiatric conditions. The study is based on the Health 2000 survey, a representative general population survey of 8028 Finns aged 30 and over. Depressive, anxiety and alcohol use disorders were diagnosed with the Composite International Diagnostic Interview (M-CIDI). HRQoL was measured with the 15D and the EQ-5D, with 83% response rate. This study found that people with psychiatric disorders had the lowest 15D HRQoL scores at all ages, in comparison to other main groups of chronic conditions. Considering 29 individual conditions, three of the four most severe (on 15D) were psychiatric disorders; the most severe was Parkinson s disease. Of the psychiatric disorders, chronic conditions that have sometimes been considered relatively mild - dysthymia, agoraphobia, generalized anxiety disorder and social phobia - were found to be the most severe. This was explained both by the severity of the impact of these disorders on mental health domains of HRQoL, and also by the fact that decreases were widespread on most dimensions of HRQoL. Considering the public health burden of conditions, musculoskeletal disorders were associated with the largest burden, followed by psychiatric disorders. Psychiatric disorders were associated with the largest burden at younger ages. Of individual conditions, the largest burden found was for depressive disorders, followed by urinary incontinence and arthrosis of the hip and knee. The public health burden increased greatly with age, so the ageing of the Finnish population will mean that the disease burden caused by chronic conditions will increase by a quarter up to year 2040, if morbidity patterns do not change. Investigating alcohol consumption and HRQoL revealed that although abstainers had poorer HRQoL than moderate drinkers, this was mainly due to many abstainers being former drinkers and having the poorest HRQoL. Moderate drinkers did not have significantly better HRQoL than abstainers who were not former drinkers. Psychiatric disorders are associated with a large part of the non-fatal disease burden in Finland. In particular anxiety disorders appear to be more severe and have a larger public health burden than previously thought.

A Historical Approach to Children s Physics Education : Modelling of DC-circuit Phenomena in a Small Group

This three-phase design research describes the modelling processes for DC-circuit phenomena. The first phase presents an analysis of the development of the DC-circuit historical models in the context of constructing Volta s pile at the turn of the 18th century. The second phase involves the designing of a teaching experiment for comprehensive school third graders. Among other considerations, the design work utilises the results of the first phase and research literature of pupils mental models for DC-circuit phenomena. The third phase of the research was concerned with the realisation of the planned teaching experiment. The aim of this phase was to study the development of the external representations of DC-circuit phenomena in a small group of third graders. The aim of the study has been to search for new ways to guide pupils to learn DC-circuit phenomena while emphasing understanding at the qualitative level. Thus, electricity, which has been perceived as a difficult and abstract subject, could be learnt more comprehensively. Especially, the research of younger pupils learning of electricity concepts has not been of great interest at the international level, although DC-circuit phenomena are also taught in the lower classes of comprehensive schools. The results of this study are important, because there has tended to be more teaching of natural sciences in the lower classes of comprehensive schools, and attempts are being made to develop this trend in Finland. In the theoretical part of the research an Experimental-centred representation approach, which emphasises the role of experimentalism in the development of pupil s representations, is created. According to this approach learning at the qualitative level consists of empirical operations like experimenting, observations, perception, and prequantification of nature phenomena, and modelling operations like explaining and reasoning. Besides planning teaching, the new approach can be used as an analysis tool in describing both historical modelling and the development of pupils representations. In the first phase of the study, the research question was: How did the historical models of DC-circuit phenomena develop in Volta s time? The analysis uncovered three qualitative historical models associated with the historical concept formation process. The models include conceptions of the electric circuit as a scene in the DC-circuit phenomena, the comparative electric-current phenomenon as a cause of different observable effect phenomena, and the strength of the battery as a cause of the electric-current phenomenon. These models describe the concept formation process and its phases in Volta s time. The models are portrayed in the analysis using fragments of the models, where observation-based fragments and theoretical fragements are distinguished from each other. The results emphasise the significance of the qualitative concept formation and the meaning of language in the historical modelling of DC-circuit phenomena. For this reason these viewpoints are stressed in planning the teaching experiment in the second phase of the research. In addition, the design process utilised the experimentation behind the historical models of DC-circuit phenomena In the third phase of the study the research question is as follows: How will the small group s external representations of DC-circuit phenomena develop during the teaching experiment? The main question is divided into the following two sub questions: What kind of talk exists in the small group s learning? What kinds of external representations for DC-circuit phenomena exist in the small group discourse during the teaching experiment? The analysis revealed that the teaching experiment of the small group succeeded in its aim to activate talk in the small group. The designed connection cards proved especially successful in activating talk. The connection cards are cards that represent the components of the electric circuit. In the teaching experiment the pupils constructed different connections with the connection cards and discussed, what kinds of DC-circuit phenomena would take place in the corresponding real connections. The talk of the small group was analysed by comparing two situations, firstly, when the small group discussed using connections made with the connection cards and secondly with the same connections using real components. According to the results the talk of the small group included more higher-order thinking when using the connection cards than with similar real components. In order to answer the second sub question concerning the small group s external representations that appeared in the talk during the teaching experiment; student talk was visualised by the fragment maps which incorporate the electric circuit, the electric current and the source voltage. The fragment maps represent the gradual development of the external representations of DC-circuit phenomena in the small group during the teaching experiment. The results of the study challenge the results of previous research into the abstractness and difficulty of electricity concepts. According to this research, the external representations of DC-circuit phenomena clearly developed in the small group of third graders. Furthermore, the fragment maps uncover that although the theoretical explanations of DC-circuit phenomena, which have been obtained as results of typical mental model studies, remain undeveloped, learning at the qualitative level of understanding does take place.

Immigrant Associations in the Metropolitan Area of Finland : Forms of Mobilisation, Participation and Representation

This study examines the role of immigrant associations in the societal and political integration of immigrants into Finnish society. The societal focus is on the ability of immigrant associations to mobilise their ethnic group members to participate in the socio-economic, cultural and political domains of Finnish society and in certain cases even beyond. The political integrative aims are the opportunities of immigrant associations to participate and represent the interests of their ethnic group in local and national policy making. This study focuses on associations in the Metropolitan Area of Finland, (Espoo, Helsinki and Vantaa).The qualitative research consisted of 71 interviews conducted with members of immigrant associations and civil servants. These interviews were mainly semi-structured, including some additional open-ended questions. Additional data consisted of documents, planning reports and of follow-up enquiries. -- In the analysis of the data I categorised thirty-two immigrant associations according to the activity forms and the description of the goals by the members. The four categories consisted of integrative, societal, ethno-cultural and transnational immigrant associations. Most of the immigrant associations belonged to the integrative category (15 of 32 associations). On the one hand the aims of these associations are to provide access for their ethnic group members into Finnish society, while on the other to strengthen the ethnic identity of their members by organising ethno-cultural activities. The societal associations only focused on activities with the objective of including immigrants into the Finnish labour market and educational system. The goal of ethno-cultural associations was to strengthen the ethnic identity of their ethnic group members. The transnational associations aimed at improving the living conditions of women and children in the members' country of origin. The possibilities for immigrant associations to mobilise their members depends partly on external financing. Subsidies have been allocated for societal activities in particular. There remains a risk of the crowding out of ethno-cultural activities: something which has already taken place in several European countries. Immigrant associations aim to strengthen the identity of immigrants mainly by organising social and ethno-cultural activities. Another important target was to provide peer support and therapy courses. Additionally, immigrant women's associations offer assistance to women who have encountered violence by providing counselling and in some cases access to shelter. The data showed that there is an ever growing need to pay heed to the well-being of women, children and elderly immigrants. The participation of immigrant associations in the municipalities' integrative issues takes place mainly through cooperative projects. Until the end of the 1990s there had not been much cooperation. The problem with the projects was that they had mainly been managed by civil servants, whereas members from immigrant associations had remained in a more passive position. Representation of immigrant associations in councils has been fairly weak. Immigrant associations are included in the multicultural councils of Espoo and Vantaa, but only in the planning stages. The municipality of Helsinki does not include immigrant associations due to the large number of organisations which causes problems in finding fair, democratic representation. At the national level, the ‘Advisory Board for Ethnic Relations’ – ETNO didn’t chose its members based on membership of ethnic associations, but based on belongingness to one of the larger language groups spoken by the foreign population in Finland. Since ETNO’s third period (2005-2007), the representatives of immigrant associations and ethnic minority groups have been chosen from proposed candidates. Key words: immigrant associations, integration, mobilisation, participation, representation, the Metropolitan area of Finland, immigrant (women), civil servants

Mental Disorders among Burn Patients

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

Origins of the sex differences in handedness and mental rotation ability : genetic, environmental and hormonal effects

In humans, well-replicated and robust sex differences in cognitive functions exist for handedness and mental rotation ability. A common characteristic in human cognitive functions is the lateralization of language functions. Handedness is a common measure of laterality and is related to language lateralization. The prevalence of left-handedness is higher in males than in females, the male to female ratio being about 1.2. Among cognitive abilities, the largest sex difference is evident in the Vandenberg and Kuse Mental Rotation Test (MRT), which requires the ability to rotate objects in mental space. On average, males achieve scores one standard deviation higher than females in the MRT. The present thesis investigated the origins of the sex differences in laterality and spatial ability as represented by handedness and mental rotation ability, respectively. Two population-based Finnish twin cohorts were utilized in this study. Handedness was studied in 25 810 twins and 4068 singletons born before 1958 from the Older Finnish Twin Cohort, and in 4736 twins born in 1983-87 from the FinnTwin12. MRT was studied in a sub-sample of 804 young adult participants from the FinnTwin12 sample. The main findings of this study were: 1) the prevalence of left-handedness was higher among males than among females in both singletons and in twins; 2) males had significantly higher scores than females in MRT; 3) about one quarter of the variance in handedness and about half of the variance in MRT was explained by genetic effects, whereas the remainder of the variance in these traits was explained by environmental effects unique to each individual. The magnitude of the genetic effects was similar in both sexes; 4) left-handedness was significantly less common in female co-twins of a male than in female co-twins of a female, and female co-twins of a male scored significantly higher than did female co-twins of a female in the Mental Rotation Test. This dissertation discusses whether these differences between females from opposite- and same-sex twin pairs are due to the prenatal transfer of testosterone from the male fetus in females with male co-twins or whether they arise from postnatal socialization effects.

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.

Representation av kvinnor och män – Hur prioriterar riksdagsledamöter frågor i den finska riksdagen? En kvantitativ studie av motionerna i riksdagen 2007

Pro gradu uppsatsen diskuterar betydelsen av representation för grupper i samhället genom att diskutera kvinnors representation. Kvinnor är en grupp i samhället som länge varit underrepresenterad, men som under de senaste 100 åren fått en betydligt bättre position i den offentliga beslutfattningen. För att ge bakgrund till frågeställningen beskrivs kvinnors deltagande i den finska riksdagen. Begreppen deskriptiv, substantiell och symbolisk representation diskuteras. Undersökningar av kvinnors representation både deskriptivt och substantiellt på parlamentsnivå presenteras. Forskningsfrågan i uppsatsen består av fyra frågeställningar om hur motioner görs i riksdagen och hur kön kan identifieras i motionerna. Frågeställningarna bygger på den teoretiska diskussionen och meningen med frågeställningar är att styra analysen av motionerna. I teoriavsnittet behandlas kvinnors representation och den vetenskapliga diskussionen om sambandet mellan substantiell och deskriptiv representation. Diskussionen utgår från Hanna Pitkins olika kategorier av representation. I den teoretiska diskussionen behandlas även begreppen den kritiska massan, närvarons politik och kritiska aktörer. I stycket diskuteras även vilka frågeställningar, som är relevanta att undersöka när man diskuterar kvinnors representation i samhället. När representationen av kvinnor diskuteras är det viktigt att minnas att kvinnor inte utgör en homogen grupp och att även män kan representera kvinnor innehållsmässigt. Efter den teoretiska diskussionen presenteras metoden för undersökningen. Som metod används kvantitativa statistiska metoder för att kunna undersöka ett större material, som kan ge en bättre helhetsbild av hur kvinnor representeras i motionerna. Materialet för undersökningen är motioner som är gjorda i den finska riksdagen 2007. Resultaten i undersökningen visar att motionerna används av både opposition och regering och att det finns en möjlighet för samarbete över partigränser. Andra faktorer, som påverkade hur aktivt man gjorde motioner var bland annat riksdagsledamöternas ålder och den valregion ledamöterna var från. När man såg speciellt på motionärernas kön framkom det skillnader i kvinnors och mäns motionsbeteende. Överlag gör män mera motioner än kvinnor i den finska riksdagen. Kvinnor har än idag en större tendens att göra motioner om socialpolitik och speciellt familje- och barnpolitik än vad män har. Männen igen väljer att göra motioner, som traditionellt har setts som starkt manliga, så som trafik och allmänna utrymmen. Resultaten visade också att kvinnors intressen inte är vanligt som motivering för motioner. Man fann också att riksdagsledamöters koppling till kvinnoorganisationer hade en betydelse när det gällde sannolikheten att göra motioner som motiverades med kvinnors intressen i samhället. Uppsatsen diskuterar orsaker till resultaten och ser att det finns orsaker att fortsätta diskutera sambandet mellan deskriptiv och substantiell representation.

Quest for authenticity - representation of the Sami image in Christmas tourism

Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.

After interpretation.

Using 58 audio recorded sessions of psychoanalysis (coming from two analysts and three patients) as data and conversation analysis as method, this paper shows how psychoanalysts deal with patients’ responses to interpretations. After the analyst offers an interpretation, the patient responds: at that point (in the “third position”), the analysts recurrently modify the tenor of the description from what it was in the patients’ responses. They intensify the emotional valence of the description, or they reveal layers of the patients’ experience other than those that the patient reported. Both are usually accomplished in an implicit, non-marked way, and they discreetly index possible opportunities for the patients to modify their understandings of the initial interpretation. Although the patients usually do not fully endorse these modifications, the data available suggests that during the sessions that follow, the participants do work with the aspects of patients’ experience that the analyst highlighted. In discussion, it is suggested that actions that the psychoanalysts produce in therapy, such as choices of turn design in third position, may be informed by working understanding of the minds and mental conflicts of individual patients, alongside the more general therapeutic model of mind they hold to.