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.

Hospital-related fears and coping strategies in 4-6-year-old children

There is only little information available on the 4-6-year-old child s hospital-related fears, and on the coping with such fears, as expressed by the children themselves. However, previous data collected from parents and hospital personnel indicate that hospitalization is an anxiety-producing experience for young children. The purpose of this study was to describe the experience of hospital-related fears and the experience of coping with hospital-related fears of 4-6-year-old children. The aim of this study was to form a descriptive model of the subjective experience of hospital-related fears and coping strategies of 4-6-year old children. The data were collected by interviewing 4-6-year-old children from a hospital and kindergarten settings in Finland from 2004 to 2006. Ninety children were interviewed in order to describe the hospital-related fear and the experience of fear, and 89 to describe their coping with the fear and the experience of coping. The children were chosen through purposive sampling. The data were gathered by semi-structured interview, supported by pictures. The data about hospital-related fears and on strategies for coping with hospital-related fears were reviewed by qualitative and quantitative methods. The experience of hospital-related fears and coping with these fears were analyzed using Colaizzi s Method of Phenomenological Analysis. The results revealed that more than 90 % of the children said they were afraid of at least one thing in hospital. Most of the fears could be categorized as nursing interventions, fears of being a patient, and fears caused by the developmental stage of the child. Children interviewed in the hospital expressed substantially more fears than children interviewed in kindergarten. Children s meanings of hospital-related fears were placed into four main clusters: 1) insecurity, 2) injury, 3) helplessness, 4) and rejection. The results also showed that children have plenty of coping strategies, to deal with their fears, especially such strategies in which the children themselves play an active role. Most often mentioned coping strategies were 1) the presence of parents and other family members, 2) the help of the personnel, 3) positive images and humour, 4) play, and 5) the child s own safety toy. The children interviewed in the hospital mentioned statistically significantly more often play, positive imagination and humour as their coping strategy than children interviewed in kindergarten. The meaning of coping with hospital fears consisted of six clusters: pleasure, security, care, understanding the meaning of the situation participating, and protecting oneself. Being admitted to a hospital is an event which may increase the fears of a 4-6-year-old child. Children who have personal experience of being admitted to a hospital describe more fears than healthy children in kindergarten. For young children, hospital-related fear can be such a distressing experience that it reflects on their feelings of security and their behaviour. Children can sometimes find it difficult to admit their fear. Children need the help of adults to express their hospital-related fears, the objects of the fears, and to cope with the fears. Personnel should be aware of children s fears and support them in the use of coping strategies. In addition to the experiences of security and care, pre-school-aged children need active coping strategies that they can use themselves, regardless of the presence of the parents or nurses. Most of all, children need the possibility to play and experience pleasure. Children can also be taught coping strategies which give them an active, positive role.

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.

Biovalta, toiseus ja naisten toimijuus hedelmöityshoidoissa

Biopower, Otherness and Women's Agency in Assisted Reproduction. This sociological study analyses how, why and with what kind of consequences assisted reproductive technologies (ART) have become the primary technology for governing infertility in Finland both on the level of individuals and society. The phenomenon is construed as one the strategies of the Focaultian biopower since ART are political techniques of the beginning of life par excellence, as they are used to prepare the bodies of certain types of women to create certain kind of life, i.e. certain kind of children. Moreover, ART are interpreted to be gendered control techniques with which the pure, and at the same time prevailing, social order symbolised by a female body is maintained by naming and excluding otherness, unsuitable mother candidates and children. Finally, it is considered how the agency, subjectivity, of women experiencing infertility and seeking treatment appears in the prevailing context of ART. The introduction of IVF-based reproductive technologies to Finland and the treatment practices of the early 1990s have been studied on the basis of a clinic questionnaire, medical doctor interviews and articles of the Medical Journal Duodecim from 1969 to 2000. Opinions on the method of the treatment providers were studied by conducting a theme interview with fertilisation doctors in 1993. Experiences of women who have received treatment or experienced infertility were studied by means of a survey in 1994 and by analysing the content of messages in an online discussion forum in 2000. On the basis of the medical doctor interviews, significant criterion for choosing mother candidates turned out to be her vitality and her mental and physical health, which are considered prerequisites for a vitality of the child to be born. The hierarchies concerning children became evident. While people normally make their children on their own, this is what people experiencing infertility are trying to do as well. In the era of ART, the primary child is genetically the parents' own child, a secondary option for Finnish parents is a genetically Finnish child conceived by donated Finnish gametes or embryos and the last option is an adopted child of foreign origin. Women's agency mainly appears in their way of using ART as a technology of the self for self-control on one's own nature, which helps them to prepare their bodies in order to become pregnant in co-operation with a fertilisation doctor. Women's creative free agency exceeding governance appeared as a distinctive use of language with which they created shared meaning for their infertility experience, their own individual and group identity and distinctive reality. ART are very political techniques as they have a possibility to change the methods of having children and to shape life. Therefore, further sociological research on them is important and needed. Key words: practises of assisted reproduction, women's agency, biopower, vital politics of the beginning of life, otherness

Cultural Trauma and Life Stories

The purpose of this work is to use the concepts of human time and cultural trauma in a biographical study of the turning points in the recent history of Estonia. This research is primarily based on 148 in-depth biographical interviews conducted in Estonia and Sweden in 1995-2005, supplemented by excerpts from 5 collections and 10 individually published autobiographies. The main body of the thesis consists of six published and of two forthcoming separate refereed articles, summarised in the theoretical introduction, and Appendix of the full texts of three particular life stories. The topic of the first article is the generational composition and the collective action frames of anti-Soviet social mobilisation in Estonia in 1940-1990. The second article details the differentiation of the rites of passage and the calendar traditions as a strategy to adapt to the rapidly changed political realities, comparatively in Soviet Estonia and among the boat-refugees in Sweden. The third article investigates the life stories of the double-minded strategic generation of the Estonian-inclined Communists, who attempted to work within the Soviet system while professing to uphold the ideals of pre-war Estonia. The fourth article is concentrated on the problems of double mental standards as a coping strategy in a contradictory social reality. The fifth article implements the theory of cultural trauma for the social practice of singing nationalism in Estonia. The sixth article bridges the ideas of Russian theoreticians concerning cultural dialogue and the Western paradigm of cultural trauma, with examples from Estonian Russian life stories. The seventh article takes a biographical look at the logic of the unraveling of cultural trauma through four Soviet decades. The eighth article explores the re-shaping of citizen activities as a strategy of coping with the loss of the independent nation state, comparatively in Soviet Estonia and among Swedish Estonians. Cultural trauma is interpreted as the re-ordering of the society s value-normative constellation due to sharp, violent, usually political events. The first one under consideration was caused by the occupations of the Republic of Estonia by the Soviet army in 1940-45. After half a century of suppression the memories of these events resurfaced as different stories describing the long-term, often inter-generational strategies of coping with the value collapse. The second cultural trauma is revealed together with the collapse of the Soviet power and ideology in Estonia in 1991. According to empirical data, the following three trauma discourses have been reconstructed: - the forced adaptation to Soviet order of the homeland Estonians; - the difficulty of preserving Estonian identity in exile (Sweden); - the identity crisis of the Russian population of Estonia. Comparative analyses of these discourses have shown that opposing experiences and worldviews cause conflicting interpretations of the past. Different social and ethnic groups consider coping with cultural trauma as a matter of self-defence and create appropriate usable pasts to identify with. Keywords: human time, cultural trauma, frame analysis, discourse, life stories

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.

Global processes, local strategies : migration of educated Dominicans.

The aim of this thesis is to examine migration of educated Dominicans in light of global processes. Current global developments have resulted in increasingly global movements of people, yet people tend to come from certain places in large numbers rather than others. At the same time, international migration is increasingly selective, which shows in the disproportional number of educated migrants. This study discovers individual and societal motivations that explain why young educated Dominicans decide to migrate and return. The theoretical framework of this thesis underlines that migration is a dynamic process rooted in other global developments. Migratory movements should be seen as a result of interacting macro- and microstructures, which are linked by a number of intermediate mechanisms, meso-structures. The way individuals perceive opportunity structures concretises the way global developments mediate to the micro-level. The case of the Dominican Republic shows that there is a diversity of local responses to the world system, as Dominicans have produced their own unique historical responses to global changes. The thesis explains that Dominican migration is importantly conditioned by socioeconomic and educational background. Migration is more accessible for the educated middle class, because of the availability of better resources. Educated migrants also seem less likely to rely on networks to organize their migrations. The role of networks in migration differs by socioeconomic background on the one hand, and by the specific connections each individual has to current and previous migrants on the other hand. The personal and cultural values of the migrant are also pivotal. The central argument of this thesis is that a veritable culture of migration has evolved in the Dominican Republic. The actual economic, political and social circumstances have led many Dominicans to believe that there are better opportunities elsewhere. The globalisation of certain expectations on the one hand, and the development of the specifically Dominican feeling of ‘externalism’ on the other, have for their part given rise to the Dominican culture of migration. The study also suggests that the current Dominican development model encourages migration. Besides global structures, local structures are found to ve pivotal in determining how global processes are materialised in a specific place. The research for this thesis was conducted by using qualitative methodology. The focus of this thesis was on thematic interviews that reveal the subject’s point of view and give a fuller understanding of migration and mobility of the educated. The data was mainly collected during a field research phase in Santo Domingo, the Dominican Republic in December 2009 and January 2010. The principal material consists of ten thematic interviews held with educated Dominican current or former migrants. Four expert interviews, relevant empirical data, theoretical literature and newspaper articles were also comprehensively used.

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.

A DISCURSIVE PERSPECTIVE ON LEGITIMATION STRATEGIES IN MULTINATIONAL CORPORATIONS

Few studies have examined legitimation in multinational corporations from a discursive perspective. To complement the existing institutional literature, we adopt a critical discourse analysis perspective that allows us to examine the microlevel processes of discursive legitimation. We provide an example of a media text— dealing with a production unit shutdown—to demonstrate how this perspective elucidates the various textual strategies used to legitimate multinational corporations’ actions and their controversial consequences.

Strategies as Discursive Constructions: The Case of Airline Alliances

In this paper, we argue that by examining the discursive elements in strategy talk we can contribute to our understanding of the myriad of microprocesses and practices that make up strategies. We focus on airline alliances as a particularly illustrative case. Based on a critical discourse analysis of an extensive material of strategy talk on airline alliances, we point to five types of discursive practices that characterize strategizing in this context in 1995–2000: (1) problematization of traditional strategies; (2) rationalization, objectification and factualization of alliance benefits; (3) fixation of ambiguous independence concerns; (4) reframing of cooperation problems as ‘implementation’ issues; and (5) naturalization of alliance strategies. While we want to emphasize the context-specificity of these practices, we claim that similar types of discursive practices are also likely to be an inherent part of strategizing in other settings.

Struggles over legitimacy in global organizational restructuring: A rhetorical perspective on legitimation strategies and dynamics in a shutdown case

Critical organization scholars have focused increasing attention on industrial and organizational restructurings such as shutdown decisions. However, we know little about the rhetorical strategies used to legitimate or resist plant closures in organizational negotiations. In this paper, we draw from New Rhetoric to analyze rhetorical struggles, strategies and dynamics in unfolding organizational negotiations. We focus on the shutdown of the bus body unit of the Swedish company Volvo in Finland. We distinguish five types of rhetorical legitimation strategies and dynamics. These include the three classical dynamics of logos (rational arguments), pathos (emotional moral arguments), and ethos (authority-based arguments), but also autopoiesis (autopoietic narratives), and cosmos (cosmological constructions). Our analysis adds to the previous studies explaining how organizational restructuring as a phenomenon is legitimated, how this legitimation has changed over time, and how contemporary industrial closures are legitimated in the media. This study also increases our theoretical understanding of the role of rhetoric in legitimation more generally.

Prevalence and Forms of Bullying among Business Professionals: A Comparison of Two Different Strategies for Measuring Bullying

The aim of this study was to analyse the prevalence and forms of workplace bullying among business professionals holding predominantly managerial or expert positions. A cross-sectional survey study was conducted among Finnish professionals with a university degree in business studies. In the study two different strategies for measuring bullying were used and compared. When provided a definition of bullying, 8.8% of the respondents reported that they had at least occasionally been bullied during the past 12 months. However, when using a slightly modified version of the Negative Acts Questionnaire (Einarsen & Hoel 2001), containing a list of 32 predefined negative and potentially harassing acts, as many as 24.1% of the respondents reported that they had been subjected to at least one of the negative acts on a weekly basis. The respondents had experienced predominantly work-related negative acts, e.g. that their opinions and views were ignored, that they were given unreasonable deadlines or that information was withheld. Although the prevalence rates reported with the two strategies varied considerably, there was still consistency between the two strategies in the sense that those who had classified themselves as bullied also reported higher exposure rates to almost all of the negative acts included.