On the Importance of Mutual Fund Families in Emerging Markets

This study contributes to the mutual fund literature by looking at performance persistence on a fund family level, allowing for individual equity, bond and balanced funds to be included under single family umbrellas. The study is conducted on the emerging Finnish mutual fund market, an environment in which the importance of superior fund family teams is likely to be accentuated. Using both non–parametric and parametric tests we find robust evidence of performance persistence for the fund families. Persistence is particularly strong in the first half of the investigation period, which highlights the importance of fund families at early stages of market development.

Murtuva säätyvalta, kestävä eliitti : Senaattori Lennart Gripenbergin sukupiiri ja sääty-yhteiskunnan muodonmuutos

This study examines the transformation of the society of estates in the Finnish Grand Duchy through the case study of Senator Lennart Gripenberg and his family circle. While national borders and state structures changed, the connections between old ruling elite families remained intact as invisible family networks, ownership relations, economic collaboration and power of military families. These were the cornerstones of trust, which helped to strengthen positions gained in society. Also, these connections often had a central if unperceivable impact on social development and modernization. Broadly speaking, the intergenerational social reproduction made it possible for this network of connections to remain in power and, as an imperceptible factor, also influenced short-term developments in the long run. Decisions which in the short term appeared unproductive, would in the long run produce cumulative immaterial and material capital across generations as long-term investments. Social mobility, then, is a process which clearly takes several generations to become manifest. The study explores long-term strategies of reproducing and transferring the capital accumulated in multinational elite networks. Also, what was the relationship of these strategies to social change? For the representatives of the military estate the nobility and for those men of the highest estates who had benefited from military training, this very education of a technical-military nature was the key to steering, controlling and dealing with the challenges following the industrial breakthrough. The disintegration of the society of estates and the rising educational standards also increased the influence of those professionals previously excluded, which served to intensify competition for positions of power. The family connections highlighted in this study overlapped in many ways, working side by side and in tandem to manage the economic and political life in Finland, Russia and Sweden. The analysis of these ties has opened up a new angle to economic co-operation, for example, as seen in the position of such family networks not only in Finnish, but also Swedish and Russian corporations and in the long historical background of the collaboration. This also highlights in a new way the role of women in transferring the cumulative social capital and as silent business partners. The marriage strategies evident in business life clearly had an impact on the economic life. The collaborative networks which transcended generations, national boundaries and structures also uncover, as far as the elites are concerned, serious problems in comparative studies conducted from purely national premises. As the same influential families and persons in effect held several leading positions in society, the line would blur between public and invisible uses of power. The power networks thus aimed to build monopolies to secure their key positions at the helm. This study therefore examines the roles of Lennart Gripenberg senator, business executive, superintendent of the Department of Industry, factory inspector, and founding member of industrial interest groups as part of the reproduction strategies of the elite. The family and other networks of the powerful leaders of society, distinguished by social, economic and cultural capital, provided a solid backdrop for the so-called old elites in their quest for strategies to reproducing power in a changing world. Crucially, it was easier for the elites to gain expertise to steer the modernization process and thereby secure for the next generation a leading position in society, something that they traditionally, too, had had the greatest interest in.

Molecular Genetics of Schizophrenia and Related Intermediate Phenotypes in a Founder Population

Schizophrenia, affecting about 1% of population worldwide, is a severe mental disorder characterized by positive and negative symptoms, such as psychosis and anhedonia, as well as cognitive deficits. At present, schizophrenia is considered a complex disorder of neurodevelopmental origin with both genetic and environmental factors contributing to its onset. Although a number of candidate genes for schizophrenia have been highlighted, only very few schizophrenia patients are likely to share identical genetic liability. This study is based on the nation-wide schizophrenia family sample of the National Institute for Health and Welfare, and represents one of the largest and most well-characterized familial series in the world. In the first part of this study, we investigated the roles of the DTNBP1, NRG1, and AKT1 genes in the background of schizophrenia in Finland. Although these genes are associated with schizophrenia liability in several populations, any significant association with clinical diagnostic information of schizophrenia remained absent in our sample of 441 schizophrenia families. In the second part of this study, we first replicated schizophrenia linkage on the long arm of chromosome 7 in 352 schizophrenia families. In the following association analysis, we utilized additional clinical disorder features and intermediate phenotypes – endophenotypes - in addition to diagnostic information from altogether 290 neuropsychologically assessed schizophrenia families. An intragenic short tandem repeat allele of the regional RELN gene, supposed to play a role in the background of several neurodevelopmental disorders, showed significant association with poorer cognitive functioning and more severe schizophrenia symptoms. Additionally, this risk allele was significantly more prevalent among the individuals affected with schizophrenia spectrum disorders. We have previously identified linkage of schizophrenia and its cognitive endophenotypes on the long arms of chromosomes 2, 4, and 5. In the last part of this study, we selected altogether 104 functionally relevant candidate genes from the linked regions. We detected several promising associations, of which especially interesting are the ERBB4 gene, showing association with the severity of schizophrenia symptoms and impairments in traits related to verbal abilities, and the GRIA1 gene, showing association with the severity of schizophrenia symptoms. Our results extend the previous evidence that the genetic risk for schizophrenia is at least partially mediated via the effects of the candidate genes and their combinations on relevant brain systems, resulting in alterations in different disorder domains, such as the cognitive deficits.

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

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

Lignin biosynthesis in Norway spruce: from a model system to the tree

Lignin is a hydrophobic polymer that is synthesised in the secondary cell walls of all vascular plants. It enables water conduction through the stem, supports the upright growth habit and protects against invading pathogens. In addition, lignin hinders the utilisation of the cellulosic cell walls of plants in pulp and paper industry and as forage. Lignin precursors are synthesised in the cytoplasm through the phenylpropanoid pathway, transported into the cell wall and oxidised by peroxidases or laccases to phenoxy radicals that couple to form the lignin polymer. This study was conducted to characterise the lignin biosynthetic pathway in Norway spruce (Picea abies (L.) Karst.). We focused on the less well-known polymerisation stage, to identify the enzymes and the regulatory mechanisms that are involved. Available data for lignin biosynthesis in gymnosperms is scarce and, for example, the latest improvements in precursor biosynthesis have only been verified in herbaceous plants. Therefore, we also wanted to study in detail the roles of individual gene family members during developmental and stress-induced lignification, using EST sequencing and real-time RT-PCR. We used, as a model, a Norway spruce tissue culture line that produces extracellular lignin into the culture medium, and showed that lignin polymerisation in the tissue culture depends on peroxidase activity. We identified in the culture medium a significant NADH oxidase activity that could generate H2O2 for peroxidases. Two basic culture medium peroxidases were shown to have high affinity to coniferyl alcohol. Conservation of the putative substrate-binding amino acids was observed when the spruce peroxidase sequences were compared with other peroxidases with high affinity to coniferyl alcohol. We also used different peroxidase fractions to produce synthetic in vitro lignins from coniferyl alcohol; however, the linkage pattern of the suspension culture lignin could not be reproduced in vitro with the purified peroxidases, nor with the full complement of culture medium proteins. This emphasised the importance of the precursor radical concentration in the reaction zone, which is controlled by the cells through the secretion of both the lignin precursors and the oxidative enzymes to the apoplast. In addition, we identified basic peroxidases that were reversibly bound to the lignin precipitate. They could be involved, for example, in the oxidation of polymeric lignin, which is required for polymer growth. The dibenzodioxocin substructure was used as a marker for polymer oxidation in the in vitro polymerisation studies, as it is a typical substructure in wood lignin and in the suspension culture lignin. Using immunolocalisation, we found the structure mainly in the S2+S3 layers of the secondary cell walls of Norway spruce tracheids. The structure was primarily formed during the late phases of lignification. Contrary to the earlier assumptions, it appears to be a terminal structure in the lignin macromolecule. Most lignin biosynthetic enzymes are encoded for by several genes, all of which may not participate in lignin biosynthesis. In order to identify the gene family members that are responsible for developmental lignification, ESTs were sequenced from the lignin-forming tissue culture and developing xylem of spruce. Expression of the identified lignin biosynthetic genes was studied using real-time RT-PCR. Candidate genes for developmental lignification were identified by a coordinated, high expression of certain genes within the gene families in all lignin-forming tissues. However, such coordinated expression was not found for peroxidase genes. We also studied stress-induced lignification either during compression wood formation by bending the stems or after Heterobasidion annosum infection. Based on gene expression profiles, stress-induced monolignol biosynthesis appeared similar to the developmental process, and only single PAL and C3H genes were specifically up-regulated by stress. On the contrary, the up-regulated peroxidase genes differed between developmental and stress-induced lignification, indicating specific responses.

Women and Marital Breakdown in South India : Reconstructing Homes, Bonds and Persons

Women and Marital Breakdown in South India: Reconstructing Homes, Bonds and Persons is an ethnographic analysis of the situation of divorced and separated women and their families in the South Indian city of Bangalore. The study is based on 16 months of anthropological fieldwork, i.e., participant observation and life history interviews among 50 divorced and separated women from different socio-religious backgrounds in their homes, in the women s organisations and in the Family Court. The study follows the divorced and separated women from their natal homes to their affinal homes through homelessness and legal battles to their reconstructed natal, affinal or single homes in order to find out what it means to be a person within hierarchical gender and kinship relations in South India. Marital breakdown impacts on kin relations and discloses the existing gender relations and power structure through its consequences. It makes the transformability of relational personhood as well as the transformability of relational society and culture visible. Although the study reveals the painful history of women s ill-treatment in marriage, family and kinship systems, it also demonstrates the women s rejection of the domination; and shows their ability to re-negotiate and promote changes not only to their own positions but to the whole hierarchical system as well. The study explores the divorced and separated women s manifold dilemmas, complicated legal battles, and endless arrangements when they have to struggle with the very practical problems of supporting themselves financially, finding and making a new home for themselves, and re-arranging relationships with their kin and friends. As marital breakdown fundamentally transforms the women s relational field, it forces them to recreate substitutive relations in a flexible way and, simultaneously, to re-construct themselves and their lives without a ready or positive cultural or behavioural template. This process reveals the agency of the divorced and separated women as well as shedding light on issues of gender and the cultural construction of the person in South India. This topical study explores the previously neglected subject of marital breakdown in India and shows the new meaning of kinship in South India.

ICT and the Shaping of Society: Exploring Human -ICT Relationships in Everyday Life (summary section only)

This thesis explores the relationship between humans and ICTs (information and communication technologies). As ICTs are increasingly penetrating all spheres of social life, their role as mediators – between people, between people and information, and even between people and the natural world – is expanding, and they are increasingly shaping social life. Yet, we still know little of how our life is affected by their growing role. Our understanding of the actors and forces driving the accelerating adoption of new ICTs in all areas of life is also fairly limited. This thesis addresses these problems by interpretively exploring the link between ICTs and the shaping of society at home, in the office, and in the community. The thesis builds on empirical material gathered in three research projects, presented in four separate essays. The first project explores computerized office work through a case study. The second is a regional development project aiming at increasing ICT knowledge and use in 50 small-town families. In the third, the second project is compared to three other longitudinal development projects funded by the European Union. Using theories that consider the human-ICT relationship as intertwined, the thesis provides a multifaceted description of life with ICTs in contemporary information society. By oscillating between empirical and theoretical investigations and balancing between determinist and constructivist conceptualisations of the human-ICT relationship, I construct a dialectical theoretical framework that can be used for studying socio-technical contexts in society. This framework helps us see how societal change stems from the complex social processes that surround routine everyday actions. For example, interacting with and through ICTs may change individuals’ perceptions of time and space, social roles, and the proper ways to communicate – changes which at some point in time result in societal change in terms of, for example, new ways of acting and knowing things.

The British Intervention in South Russia 1918-1920

Soon after the Bolshevik Revolution of 1917, a three-year civil war broke out in Russia. As in many other civil wars, foreign powers intervened in the conflict. Britain played a leading role in this intervention and had a significant effect on the course of the war. Without this intervention on the White side, the superiority of numbers in manpower and weaponry of the Bolsheviks would have quickly overwhelmed their opponents. The aim of this dissertation is to explain the nature and role of the British intervention on the southern, and most decisive, front of the Civil War. The political decision making in London is studied as a background, but the focus of the dissertation is on the actual implementation of the British policy in Russia. The British military mission arrived in South Russia in late 1918, and started to provide General Denikin s White army with ample supplies. General Denikin would have not been able to build his army of more than 200,000 men or to make his operation against Moscow without the British matériel. The British mission also organized the training and equipping of the Russian troops with British weapons. This made the material aid much more effective. Many of the British instructors took part in fighting the Bolsheviks despite the orders of their government. The study is based on primary sources produced by British departments of state and members of the British mission and military units in South Russia. Primary sources from the Whites, including the personal collections of several key figures of the White movement and official records of the Armed Forces of South Russia are also used to give a balanced picture of the course of events. It is possible to draw some general conclusions from the White movement and reasons for their defeat from the study of the British intervention. In purely material terms the British aid placed Denikin s army in a far more favourable position than the Bolsheviks in 1919, but other military defects in the White army were numerous. The White commanders were unimaginative, their military thinking was obsolete, and they were incapable of organizing the logistics of their army. There were also fundamental defects in the morale of the White troops. In addition to all political mistakes of Denikin s movement and a general inability to adjust to the complex situation in Revolutionary Russia, the Whites suffered a clear military defeat. In South Russia the Whites were defeated not because of the lack of British aid, but rather in spite of it.

An Axiom of Military Law : Applicability of National Criminal Law to Military Personnel and Associated Civilians Abroad

States regularly deploy elements of their armed forces abroad. When that happens, the military personnel concerned largely remain governed by the penal law of the State that they serve. This extraterritorial extension of national criminal law, which has been treated as axiomatic in domestic law and ignored by international law scholarship, is the subject of this dissertation. The first part of the study considers the ambit of national criminal law without any special regard to the armed forces. It explores the historical development of the currently prevailing system of territorial law and looks at the ambit that national legal systems claim today. Turning then to international law, the study debunks the oddly persistent belief that States enjoy a freedom to extend their laws to extraterritorial conduct as they please, and that they are in this respect constrained only by some specific prohibitions in international law. Six arguments historical, empirical, ideological, functional, doctrinal and systemic are advanced to support a contrary view: that States are prohibited from extending the reach of their legal systems abroad, unless they can rely on a permissive principle of international law for doing so. The second part of the study deals specifically with State jurisdiction in a military context, that is to say, as applied to military personnel in the strict sense (service members) and various civilians serving with or accompanying the forces (associated civilians). While the status of armed forces on foreign soil has transformed from one encapsulated in the customary concept of extraterritoriality to a modern regulation of immunities granted by treaties, elements of armed forces located abroad usually do enjoy some degree of insulation from the legal system of the host State. As a corollary, they should generally remain covered by the law of their own State. The extent of this extraterritorial extension of national law is revealed in a comparative review of national legislation, paying particular attention to recent legal reforms in the United States and the United Kingdom two states that have sought to extend the scope of their national law to cover the conduct of military contractor personnel. The principal argument of the dissertation is that applying national criminal law to service members and associated civilians abroad is distinct from other extraterritorial claims of jurisdiction (in particular, the nationality principle or the protective principle of jurisdiction). The service jurisdiction over the armed forces has a distinct aim: ensuring the coherence and indivisibility of the forces and maintaining discipline. Furthermore, the exercise of service jurisdiction seeks to reduce the chances of the State itself becoming internationally liable for the conduct of its service members and associated civilians. Critically, the legal system of the troop-deploying State, by extending its reach abroad, seeks to avoid accountability gaps that might result from immunities from host State law.

Bysanttilaisten ja Akhaian ruhtinaskunnan väliset sotatoimet vuosina 1259-83 : Tapaustutkimus myöhäis-bysanttilaisesta sodankäynnistä

In my master thesis I analyse Byzantine warfare in the late period of the empire. I use military operations between Byzantines and crusader Principality of Achaia (1259–83) as a case study. Byzantine strategy was based (in “oriental manner”) on using ambushes, diplomacy, surprise attacks, deception etc. Open field battles that were risky in comparison with their benefits were usually avoided, but the Byzantines were sometimes forced to seek open encounter because their limited ability to keep strong armies in field for long periods of time. Foreign mercenaries had important place in Byzantine armies and they could simply change sides if their paymasters ran out of resources. The use of mercenaries with short contracts made it possible that the composition of an army was flexible but on the other hand heterogeneous – in result Byzantine armies were sometimes ineffective and prone to confusion. In open field battles Byzantines used formation that was made out from several lines placed one after another. This formation was especially suitable for cavalry battles. Byzantines might have also used other kinds of formations. The Byzantines were not considered equal to Latins in close combat. West-Europeans saw mainly horse archers and Latin mercenaries on Byzantine service as threats to themselves in battle. The legitimacy of rulers surrounding the Aegean sea was weak and in many cases political intrigues and personal relationships can have resolved the battles. Especially in sieges the loyalty of population was decisive. In sieges the Byzantines used plenty of siege machines and archers. This made fast conquests possible, but it was expensive. The Byzantines protected their frontiers by building castles. Military operations against the Principality of Achaia were mostly small scale raids following an intensive beginning. Byzantine raids were mostly made by privateers and mountaineers. This does not fit to the traditional picture that warfare belonged to the imperial professional army. It’s unlikely that military operations in war against the Principality of Achaia caused great demographic or economic catastrophe and some regions in the warzone might even have flourished. On the other hand people started to concentrate into villages which (with growing risks for trade) probably caused disturbance in economic development and in result birth rates might have decreased. Both sides of war sought to exchange their prisoners of war. These were treated according to conventional manners that were accepted by both sides. It was possible to sell prisoners, especially women and children, to slavery, but the scale of this trade does not seem to be great in military operations treated in this theses.

Vammaisen lapsen äidin vanhemmuuden kokemus sekä lähiympäristön ja kasvatuskumppanuuden merkitys

The parenthood experience of a mother with a disabled child and the meaning of the social environment and parent-professional partnerships The importance of parental guidance when a family has a child with a disability or autism has been pointed out by several studies. The present research was based on the premise that by supporting the mother we can help the whole family to cope better and the professionals in day care or at school are able to support parents. The starting point was the subjective experience, which is also the central focus of the phenomenological method. The purpose of this study was firstly to describe the experience of the mother and the dialogue between mother and educational professionals. Secondly it was the task of this research to discover what kind of support and information the mother obtains from her social environment. At the background of this study there was the ecological theory of Bronfenbrenner, the ecocultural approach by Gallimore and the interactive examination of family that take into consideration the whole environment and personal situation. The research data was collected by interviewing the mothers, the day care personnel and the teachers at school. In this research there were a total of 32 interviews and 24 informants: 10 mothers who have a child with a disability and/or autism, 8 professionals in day care and 6 teachers at school. This study was longitudinal because the same mothers were interviewed twice, first in 1998 and then after five years in 2003. It was thus possible to get information on whether their life situation had changed and the nature of those changes. The data of this study was analysed by the method of phenomenological psychology that was applied for this study. The findings indicated that all mothers had experienced many complicated emotional feelings such as: anger, mourning, fear and sadness as well as love and bonding. It can be said that several human feelings existed at the same time. Mothers experienced that the support of the social environment, for example, relatives, families in the same situation and persons taking care of the child had significant meaning for their coping. However the life situation among the mothers varied. Mostly mothers received valuable support for their parenthood and they have adopted a strong emotion for manage ring. Mothers with an autistic child were more stressed than mothers with a mentally retarded child. A few mothers had numerous problems with taking care of their child and they did not get enough help. Same mothers were very exhausted too and the situation was quite the same after five years, when their child was teenager. All mothers said that after starting school the support for the family had significally diminished. Mothers said that dialogue with teacher got on without problems, but there were meetings seldom, so it wasn´t possible to get enough support for their parenthood. Keywords: parenthood, motherhood, disability, early special education, family-centred.

Lapsi, lapsuus ja perhe varhaiskasvatusasiakirjoissa 1967-1999

The aim of this study is to describe and interpret discourses in Finnish national early childhood education and care (ECEC) documents concerning the child, childhood and family, including preschool education of six-year-old children. The study begins with preparation phase of the Act on Children s Day Care (1967) and concludes with the definition of ECEC policy (1999). The research data consists of committee memoranda and national ECEC curriculum guidelines. The total number of documents studied was 20, comprising some 1700 pages. The research data was examined with qualitative text analysis and employed a discursive approach. A semiotic square (Greimas rectangle) served as a tool for clarifying the discourses and constructions reflected in the research data. The theoretical framework of the study consists of the theories of childhood and family studies. The main concepts from childhood studies used in this study were childhood as a cultural construct and child-centred pedagogy in ECEC. The theoretical approaches from family studies used were the formation of modern and late-modern parenthood and family, as well as the concept of familism. Two main discursive lines were constructed from the ECEC documents. The notion of universalistic childhood suggests that early education and care aim to create the same good childhood for all children, regardless of their family background or living area. The second discursive line followed in the documents is the familistic discourse. This discourse contains emphasis on the priority of parental care. The construct of the competent child was found in the research data as early as in the mid-1970s. On the other hand, the construct of the weak family is distinguishable throughout almost the entire research period. This raises the question of whether Finnish ECEC system has been developed for the competent and self-sufficient child of a weak family which needs constant support and guidance of welfare experts. According to the study, it appears that within the Finnish ECEC system the relatively heavy emphasis on social work rather than on early education has been legitimised by the construct of the weak family. This study also shows that a more thorough analysis should be given to what we mean when we say that the main task of ECEC system is to support families in the upbringing of their children. The study was completed during the period when historical decisions concerning the administration in Finland were in the making (i.e. the potential transfer of ECEC services from the Ministry of Social Affairs and Health to the Ministry of Education). Also, over the past decade, a major reformation of the Act on Children s Daycare has been on the agenda, but no concrete measures have been implemented. Based on the findings of this study, we can ask for what kind of child and family we are preparing the ECEc reforms of the new millennium. Key words: ECEC policy Finland, childhood, family, familism, discourse analysis, semiotic square

Molecular Genetics of Lactase Deficiencies

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

Mutation analysis of TGF-β signaling pathway genes among Finnish patients with primary pulmonary hypertension and hereditary hemorrhagic telangiectasia

Primary pulmonary hypertension (PPH), or according to the recent classification idiopathic pulmonary hypertension (IPAH), is a rare, progressive disease of pulmonary vasculature leading to pulmonary hypertension and right heart failure. Most of the patients are sporadic but in about 6% of cases the disease is familial (FPPH). In 2000 two different groups identified the gene predisposing to PPH. This gene, Bone morphogenetic protein receptor type 2 (BMPR2), encodes a subunit of transforming growth factor β (TGF-β) receptor complex. There is a genetic connection between PPH and hereditary hemorrhagic telangiectasia (HHT), a bleeding disorder characterized by local telangiectasias and sometimes with pulmonary hypertension. In HHT, mutations in ALK1 (activin like kinase type 1) and Endoglin, another members of the TGF-β signaling pathway are found. In this study we identified all of the Finnish PPH patients for the years 1986-1999 using the hospital discharge registries of Finnish university hospitals. During this period we found a total of 59 confirmed PPH patients: 55 sporadic and 4 familial representing 3 different families. In 1999 the prevalence of PPH was 5.8 per million and the annual incidence varied between 0.2-1.3 per million. Among 28 PPH patients studied, heterozygous BMPR2 mutations were found in 12% (3/26) of sporadic patients and in 33% of the PPH families (1/3). All the mutations found were different. Large deletions of BMPR2 were excluded by single-stranded chain polymomorphism analysis. As a candidate gene approach we also studied ALK1, Endoglin, Bone Morphogenetic Receptor Type IA (BMPR1A or ALK3), Mothers Against Decapentaplegic Homolog 4 (SMAD4) and Serotonine Transporter Gene (SLC6A4) using single-strand conformational polymorphism (SSCP) analysis and direct sequencing. Among patients and family members studied, we found two mutations in ALK1 in two unrelated samples. We also identified all the HHT patients treated at the Department of Otorhinolaryngology at Helsinki University Central Hospital between the years of 1990-2005 and 8 of the patients were studied for Endoglin and ALK1 mutations using direct sequencing. A total of seven mutations were found and all the mutations were different. The absence of a founder mutation in the Finnish population in both PPH and HHT was somewhat surprising. This suggests that the mutations of BMPR2, ALK1 and Endoglin are quite young and the older mutations have been lost due to repetitive genetic bottlenecks and/or negative selection. Also, other genes than BMPR2 may be involved in the pathogenesis of PPH. No founder mutations were found in PPH or HHT and thus no simple genetic test is available for diagnostics.