The Politics and Policies of Reproductive Agency

This study examines the politics and policies of reproductive agency through a redescription of three Finnish policy documents dealing with the declining birth rate: the Government report on the future 'Finland for people of all ages' (2004), Business and Policy Forum EVA report 'Condemned to Diminish?' (Tuomitut vähenemään?) (2003), and the Family Federation's 'Population Policy Program' (2004). The redescription is done with the help of the notion of reproductive agency, which draws on Drucilla Cornell's concepts of the imaginary domain and bodily integrity. The imaginary domain is the moral and psychic space people need in order to form their personality, which is created in constant identificatory processes. The aim of the processes is imaginary coherence. As the personality is embodied, forming one s imaginary coherence always includes attempts for bodily integrity, also entailing attempts to arrive at an understanding of one's procreative capacities. Besides Cornell, I draw on Judith Butler's thinking and comprehend gender performatively as doing, and in relation to that agency as part of the performative process of one's personality. Reproductive agency is understood in this study as the possibilities to live differently the hegemonic forms of procreative life. I deal with three redescriptive themes: the family, economics and gender. The family is a central element in that it is considered the main location of reproduction. With regard to reproductive agency, the documents include problematic conceptions of the family. It is defined as a heterosexual, monogamous, conjugal relationship, which affects reproductive agency in that these notions do not allow for different modes of family life. The second prominent aspect, economics, features on two levels: the macroeconomic level of GDP, employment and competitiveness, and the level of family policies and concern about family finances. Macroeconomic-level argumentation is problematic in the context of reproductive agency because it implies that procreation is a duty of citizens, and thus has effects on values attached to reproductive potential. On the other hand, family policies may advance reproductive agency in supporting families financially. However, such policies also define how the family is understood, thereby affecting reproductive agency. The third theme, gender, intersects with many issues in the policy documents. All three texts consider the roles of men and women differently: women are primarily responsible for the family, and both men's and women's reproductive agency is affected in that the roles in the procreative process are predefined. EVA and the Family Federation see women as the main target of population policies, and consider it legitimate to try to change women s reproductive decisions. Implicit in the notion of reproductive agency is the idea that it should be possible to overcome and live differently the sex difference, but the three documents do not open up opportunities for that. The notion of reproductive agency makes it also possible to question the legitimacy of population policies in general and offers new perspectives on the vocabularies used in the three policy texts, providing insights into the values and logics that support the concepts.

Ancient Philosophers on Mental Illness

This dissertation is about ancient philosophers notions of mental illness, from Plato onwards. Mental illness here means disorders that, in ancient medical thought, were believed to originate in the body but to manifest themselves predominantly through mental symptoms. These illnesses were treated by physical means, which were believed to address the bodily cause of the illness, conceived of as an elemental imbalance or a state of cephalic stricture , for example. Sometimes the mental symptoms were addressed directly by psychotherapeutic means. The first and most important question explored concerns how the ancient philosophers responded to the medical notion of mental illness, and how they explained such illnesses in their theories of physiology and psychology. Although the illnesses are seldom discussed extensively, the philosophers were well aware of their existence and regarded their occurrence an indication of the soul s close dependence on the body. This called for a philosophical account. The second question addressed has to do with the ancient philosophers role as experts in mental problems of a non-medical kind, such as unwanted emotions. These problems were dubbed diseases of the soul , and the philosophers thus claimed to be doctors of the soul. Although the distinction between mental illnesses and diseases of the soul was often presented as rather obvious, there was some vagueness and overlap. There is still a third question that is explored, concerning the status of both mental illnesses and diseases of the soul as unnatural conditions, the role of the human body in the philosophical aetiologies of evil, and the medico-philosophical theories of psycho-physiological temperaments. This work consists of an introduction and five main chapters, focusing on Plato, Aristotle, the Stoics and Galen, and the Sceptics, the Epicureans and later Platonists. The sources drawn on are the original Greek and Latin philosophical and medical texts. It appears that the philosophers accepted the medical notion of mental illness, but interpreted it in various ways. The differences in interpretation were mostly attributable to differences in their theories of the soul. Although the distinction between mental illness and diseases of the soul was important, marking the boundary between the fields of expertise of medicine and philosophy, and of the individual s moral responsibilities, the problematic aspects of establishing it are discussed rather little in ancient philosophy. There may have been various reasons for this. The medical descriptions of mental illness are often extreme, symptoms of the psychotic type excluding the possibility of the condition being of the non-medical kind. In addition, the rigid normativeness of ancient philosophical anthropologies and their rigorous notion of human happiness decreased the need to assess the acceptability of individual variation in their emotional and intellectual lives and external behaviour.

Il mundus muliebris nelle fonti latine e nei contesti Pompeiani

The subject of the study is the classical Latin concept 'mundus muliebris', usually translated simply as women’s toiletry items. The task of the research is, on one hand, to find a more accurate and comprehensive literary definition for the concept as used in the early Imperial period, and on the other, to examine whether it is possible to find corresponding groupings of material objects among the finds from Pompeian houses destroyed by the eruption of Mount Vesuvius in AD 79. The study is based on two different bodies of evidence, literary and material, and consequently uses two independent methods of research. In the philological part of the study, all occurrences of the concept 'mundus muliebris' in classical Latin texts were identified and analysed in their proper literary context, paying special attention to information about the nature of the objects included (name, owner, quantity, value, location in the house). On the basis of this analysis, mirrors were chosen as the key elements of the archaeological research, being ̶ hypothetically ̶ the most probable objects to be found among any extant 'mundus muliebris' contexts in Pompeian houses. In the archaeological part of the study, all mirrors deposited in the Archaeological Storerooms of Pompeii, mostly unpublished, were examined, together with their original find contexts. For more detailed documentation, classification, as well as quantitative and functional analysis, the fifty-nine best preserved household or shop contexts were chosen. Among these contexts, only a few ‘ideal’ groups closely corresponding to the literary definitions were found. However, in most cases a functional artifact pattern of toiletry items could indeed be found grouped together with the mirror. The arrangement of the contexts in the domestic space also revealed a clear pattern. Firstly, the contexts consistently seem to be found in the place of storage, inside locked boxes, not in the place of use. Secondly, they show that for the storage of such objects small closed rooms flanking the main entrance of the house were preferred. Culturally, 'mundus muliebris' can be described as a very complex multi-layered concept intimately interrelated with the female gender, an instrument of its bodily creation and a symbol of its nature. Concretely, it has at its core mirrors and instruments for the care of skin and hair, and includes, in more technical definitions, washing equipment as well. In the Roman domus, lacking specific women’s quarters, this box containing toiletries and other personal objects could be defined as the true, although mobile, private space of the household’s female members.

The Saintly Madman : A Study of the Scholarly Reception History of Buile Shuibhne

This study examines the scholarly reception history of an early Irish text, Buile Shuibhne (The Frenzy of Suibhne), by focusing on the various theoretical and methodological presuppositions which have determined the scholars’ understanding of the text’s religious allegorical significance in the course of the 20th century. The reception-oriented inquiry takes the intersubjective aspect of literary interpretation as the basis for accentuating the importance of communally shared presumptions and reading strategies in the explication of interpretive variety. The materials of the study have been divided into four frameworks of interpretation: historical, pre-Christian, Christian and anthropological. This heuristic division does not denote mutually exclusive paradigms, but rather refers to perceived similarities within each group regarding the questions posed, and the evidence adduced, in textual analysis. The historical framework concentrates on the issues of the origins of the tale and the possible historicity of its main protagonist. The pre-Christian framework covers the theories of the shamanic, Indo-European and Celtic elements in the text, whereas the Christian framework includes readings emphasising the biblical, monastic and ascetic aspects of the tale. The anthropological framework in turn focuses on the parallels drawn between the narrative and the universal structure of the rites of passage. In addition to the examination of these four frameworks, the study also links the question of methodology with wider issues of authorship and textual integrity, and critically reconsiders the manner in which J.G. O'Keeffe's 1913 edition of the text has been reified in previous scholarship as a representation of a 12th century authorial original. The overall objective of the present case-study is to relate theoretical conceptions of literary theory, comparative religion and historiography to the study of early Irish narrative material by considering the communal and institutional dimension of meaning-making, and the implications of comparative methodology for historical research. In this aim, the prevailing methodological presuppositions informing the scholarly discourse on Buile Shuibhne are set against the wider context of Celtic Studies scholarship, in order to draw attention to the need to critically reflect upon the operations of knowledge production in future research.

Turning the Kaleidoscope - (E)FL Educational Experience and Inquiry as Auto/biography

This book is a study on learning, teaching/counselling, and research on the two. My quest has been to find a pedagogically-motivated way of researching learning and teaching interaction, and in particular counselling, in an autonomous language-learning environment. I have tried to develop a method that would make room for lived experience, meaning-making and narrating, because in my view these all characterise learning encounters between language learners and counsellors, and learners and their peers. Lived experience as a source of meaning, telling and co-telling becomes especially significant when we try to listen to the diverse personal and academic voices of the past as expressed in autobiographical narratives. I have aimed at researching various ALMS dialogues (Autonomous Learning Modules, University of Helsinki Language Centre English course and programme), and autobiographical narratives within them, in a way that shows respect for the participants, and that is relevant, reflective and, most importantly, self-reflexive. My interest has been in autobiographical telling in (E)FL [(English as a) foreign language], both in students first-person written texts on their language- learning histories and in the sharing of stories between learners and a counsellor. I have turned to narrative inquiry in my quest and have written the thesis as an experiential narrative. In particular, I have studied learners and counsellors in one and the same story, as characters in one narrative, in an attempt to avoid the impression that I am telling yet another separate, anecdotal story, retrospectively. Through narrative, I have shed light on the subjective dimensions of language learning and experience, and have come closer to understanding the emotional aspects of learning encounters. I have questioned and rejected a distanced and objective approach to describing learning and teaching/counselling. I have argued for a holistic and experiential approach to (E)FL encounters in which there is a need to see emotion and cognition as intertwined, and thus to appreciate learners and counsellors emotionally-charged experiences as integral to their identities. I have also argued for a way of describing such encounters as they are situated in history, time, autobiography, and the learning context. I have turned my gaze on various constellations of lived experience: the data was collected on various occasions and in various settings during one course and consists of videotaped group sessions, individual counselling sessions between students and their group counsellor, biographic narrative interviews with myself, open-ended personally-inspired reflection texts written by the students about their language-learning histories, and student logs and diaries. I do not consider data collection an unproblematic occasion, or innocent practice, and I defend the integrity of the research process. Research writing cannot be separated from narrative field work and analysing and interpreting the data. The foci in my work have turned to be the following: 1) describing ALMS encounters and specifying their narrative aspects; 2) reconceptualising learner and teacher autonomy in ALMS and in (E)FL; 2) developing (E)FL methodologically through a teacher-researcher s identity work; 4) research writing as a dialogical narrative process, and the thesis as an experiential narrative. Identity and writing as inquiry, and the deeply narrative and autobiographical nature of the (E)FL teaching/counselling/researching have come to the fore in this research. Research writing as a relational activity and its implications for situated ways of knowing and knowledge turned out to be important foci. I have also focussed on the context-bound and local teacher knowledge and ways of knowing about being a teacher, and I have argued for personal ways of knowing about, and learning and studying foreign languages. I discuss research as auto/biography: as a practising counsellor I use my own life and (E)FL experience to understand and interpret the stories of the research participants even though I was not involved in their course work. The supposedly static binaries of learner/teacher, and also learner autonomy/teacher autonomy, are thus brought into the discussion. I have highlighted the infinite variability and ever-changing nature of learning and teaching English, but the book is also of relevance to foreign language education in general.

Principles of Pitch Organization in Béla Bartók's 'Duke Bluebeard's Castle'

The topic of my doctoral thesis is to demonstrate the usefulness of incorporating tonal and modal elements into a pitch-web square analysis of Béla Bartók's (1881-1945) opera, 'A kékszakállú herceg vára' ('Duke Bluebeard's Castle'). My specific goal is to demonstrate that different musical materials, which exist as foreground melodies or long-term key progressions, are unified by the unordered pitch set {0,1,4}, which becomes prominent in different sections of Bartók's opera. In Bluebeard's Castle, the set {0,1,4} is also found as a subset of several tetrachords: {0,1,4,7}, {0,1,4,8}, and {0,3,4,7}. My claim is that {0,1,4} serves to link music materials between themes, between sections, and also between scenes. This study develops an analytical method, drawn from various theoretical perspectives, for conceiving superposed diatonic spaces within a hybrid pitch-space comprised of diatonic and chromatic features. The integrity of diatonic melodic lines is retained, which allows for a non-reductive understanding of diatonic superposition, without appealing to pitch centers or specifying complete diatonic collections. Through combining various theoretical insights of the Hungarian scholar Ernő Lendvai, and the American theorists Elliott Antokoletz, Paul Wilson and Allen Forte, as well as the composer himself, this study gives a detailed analysis of the opera's pitch material in a way that combines, complements, and expands upon the studies of those scholars. The analyzed pitch sets are represented on Aarre Joutsenvirta's note-web square, which adds a new aspect to the field of Bartók analysis. Keywords: Bartók, Duke Bluebeard's Castle (Op. 11), Ernő Lendvai, axis system, Elliott Antokoletz, intervallic cycles, intervallic cells, Allen Forte, set theory, interval classes, interval vectors, Aarre Joutsenvirta, pitch-web square, pitch-web analysis.

Incarnate Subjectivity : The Constitutive Significance of Embodiment in Husserlian Phenomenology

This work offers a systematic phenomenological investigation of the constitutive significance of embodiment. It provides detailed analyses of subjectivity in relation to itself, to others, and to objective reality, and it argues that these basic structures cannot be made intelligible unless one takes into account how they are correlated with an embodied subject. The methodological and conceptual starting point of the treatise is the philosophy of Edmund Husserl. The investigation employs the phenomenological method and uses the descriptions and analyses provided by Husserl and his successors. The treatise is motivated and outlined systematically, and textual exegesis serves as a means for the systematic phenomenological investigation. The structure of the work conforms to the basic relations of subjectivity. The first part of the thesis explores the intimate relation between lived-body and selfhood, analyzes the phenomena of localization, and argues that self-awareness is necessarily and fundamentally embodied self-awareness. The second part examines the intersubjective dimensions of embodiment, investigates the corporal foundations of empathy, and unravels the bodily aspects of transcendental intersubjectivity. The third part scrutinizes the role of embodiment in the constitution of the surrounding objective reality: it focuses on the complex relationship between transcendental subjectivity and transcendental intersubjectivity, carefully examines the normative aspects of genetic and generative self-constitution, and argues eventually that what Husserl calls the paradox of subjectivity originates in a tension between primordial and intersubjective normativity. The work thus reinterprets the paradox of subjectivity in terms of a normative tension, and claims that the paradox is ultimately rooted in the structures of embodiment. In this manner, as a whole, the work discloses the constitutive significance of embodiment, and argues that transcendental subjectivity must be fundamentally embodied.

Social perception and cognition : processing of gestures, postures and facial expressions in the human brain

Humans are a social species with the internal capability to process social information from other humans. To understand others behavior and to react accordingly, it is necessary to infer their internal states, emotions and aims, which are conveyed by subtle nonverbal bodily cues such as postures, gestures, and facial expressions. This thesis investigates the brain functions underlying the processing of such social information. Studies I and II of this thesis explore the neural basis of perceiving pain from another person s facial expressions by means of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). In Study I, observing another s facial expression of pain activated the affective pain system (previously associated with self-experienced pain) in accordance with the intensity of the observed expression. The strength of the response in anterior insula was also linked to the observer s empathic abilities. The cortical processing of facial pain expressions advanced from the visual to temporal-lobe areas at similar latencies (around 300 500 ms) to those previously shown for emotional expressions such as fear or disgust. Study III shows that perceiving a yawning face is associated with middle and posterior STS activity, and the contagiousness of a yawn correlates negatively with amygdalar activity. Study IV explored the brain correlates of interpreting social interaction between two members of the same species, in this case human and canine. Observing interaction engaged brain activity in very similar manner for both species. Moreover, the body and object sensitive brain areas of dog experts differentiated interaction from noninteraction in both humans and dogs whereas in the control subjects, similar differentiation occurred only for humans. Finally, Study V shows the engagement of the brain area associated with biological motion when exposed to the sounds produced by a single human being walking. However, more complex pattern of activation, with the walking sounds of several persons, suggests that as the social situation becomes more complex so does the brain response. Taken together, these studies demonstrate the roles of distinct cortical and subcortical brain regions in the perception and sharing of others internal states via facial and bodily gestures, and the connection of brain responses to behavioral attributes.

Luonnoksia käsityön ruumiillisuudesta. : Käsityö Maurice Merleau-Pontyn ruumiinfenomenologian valossa.

Purpose This study focused on craft from a standpoint of phenomenological philosophy and craft was interpreted through Maurice Merleau-Ponty’s phenomenology of the body. The main focus was the physical phase of the craft process, wherein a product is made from material. The aim was to interpret corporality in craft. There is no former research focusing on lived body in craft science. Physical, bodily making is inalienable in craft, but it is not articulated. Recent discussion has focused on craft as ”whole”, which emphasizes designing part in the process, and craft becomes conceptualized with the theories of art and design. The axiomatic yet silenced basis of craft, corporality, deserves to become examined as well. That is why this study answers the questions: how craft manifests in the light of phenomenology of the body and what is corporality in craft? Methods In this study I cultivated a phenomenological attitude and turned my exploring eye on craft ”in itself”. In addition I restrained myself from mere making and placed myself looking at the occurrence of craft to describe it verbally. I read up Maurice Merleau-Ponty’s phenomenology of the body on his principal work (2002) and former interpretations of it. Interpreting and understanding textual data were based on Gadamer’s hermeneutics, and the four-pronged composition of the study followed Koski’s (1995) version of the Gadamerian process of textual interpretation. Conclusions In the construction of bodily phenomenology craft was to be contemplated as a mutual relationship between the maker and the world materializing in bodily making. At the moment of making a human being becomes one with his craft, and the connection between the maker, material and the equipment appears as communication. Operational dimension was distinctive in the intentionality of craft, which operates in many ways, also in craft products. The synesthesia and synergy of craft were emphasized and craft as bodily practice came to life through them. The moment of making appeared as situation generating time and space, where throwing oneself into making may give the maker an experience of upraise beyond the dualism of mind and body. The conception of the implicit nature of craft knowledge was strengthened. In the light of interpretation it was possible to conceptualize craft as a performance and making ”in itself” as a work of art. In that case craft appeared as bodily expression, which as an experience approaches art without being it after all. The concept of aesthetic was settled into making as well. Bodily and phenomenological viewpoint on craft gave material to critically contemplate the concept of “whole craft” (kokonainen käsityö) and provided different kind of understanding of craft as making.

p53 and DNA damage checkpoint responses in the human prostate

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer mortality in men. In 2004, 5237 new cases were diagnosed and altogether 25 664 men suffered from prostate cancer in Finland (Suomen Syöpärekisteri). Although extensively investigated, we still have a very rudimentary understanding of the molecular mechanisms leading to the frequent transformation of the prostate epithelium. Prostate cancer is characterized by several unique features including the multifocal origin of tumors and extreme resistance to chemotherapy, and new treatment options are therefore urgently needed. The integrity of genomic DNA is constantly challenged by genotoxic insults. Cellular responses to DNA damage involve elegant checkpoint cascades enforcing cell cycle arrest, thus facilitating damage repair, apoptosis or cellular senescence. Cellular DNA damage triggers the activation of tumor suppressor protein p53 and Wee1 kinase which act as executors of the cellular checkpoint responses. These are essential for genomic integrity, and are activated in early stages of tumorigenesis in order to function as barriers against tumor formation. Our work establishes that the primary human prostatic epithelial cells and prostatic epithelium have unexpectedly indulgent checkpoint surveillance. This is evidenced by the absence of inhibitory Tyr15 phosphorylation on Cdk2, lack of p53 response, radioresistant DNA synthesis, lack of G1/S and G2/M phase arrest, and presence of persistent gammaH2AX damage foci. We ascribe the absence of inhibitory Tyr15 phosphorylation to low levels of Wee1A, a tyrosine kinase and negative regulator of cell cycle progression. Ectopic Wee1A kinase restored Cdk2-Tyr15 phosphorylation and efficiently rescued the ionizing radiation-induced checkpoints in the human prostatic epithelial cells. As variability in the DNA damage responses has been shown to underlie susceptibility to cancer, our results imply that a suboptimal checkpoint arrest may greatly increase the accumulation of genetic lesions in the prostate epithelia. We also show that small molecules can restore p53 function in prostatic epithelial cells and may serve as a paradigm for the development of future therapeutic agents for the treatment of prostate cancer We hypothesize that the prostate has evolved to activate the damage surveillance pathways and molecules involved in these pathways only to certain stresses in extreme circumstances. In doing so, this organ inadvertently made itself vulnerable to genotoxic stress, which may have implications in malignant transformation. Recognition of the limited activity of p53 and Wee1 in the prostate could drive mechanism-based discovery of preventative and therapeutic agents.

Pain among employees : risk factors and consequences

The overall objective of this study was to gain epidemiological knowledge about pain among employee populations. More specifically, the aims were to assess the prevalence of pain, to identify socio-economic risk groups and work-related psychosocial risk factors, and to assess the consequences in terms of health-related functioning and sickness absence. The study was carried out among the municipal employees of the City of Helsinki. Data comprised questionnaire survey conducted in years 2000-2002 and register data on sickness absence. Altogether 8960 40-60 year old employees participated to the survey (response rate 67%). Pain is common among ageing employees. Approximately 29 per cent of employees reported chronic pain and 15 per cent acute pain, and about seven per cent reported moderately or severely limiting disabling chronic pain. Pain was more common among those with lower level of education or in a low occupational class. -- Psychosocial work environment was associated with pain reports. Job strain, bullying at workplace, and problems in combining work and home duties were associated with pain among women. Among men combining work and home duties was not associated with pain, whereas organizational injustice showed associations. Pain affects functional capacity and predicts sickness absence. Those with pain reported lower level of both mental and physical functioning than those with no pain, physical functioning being more strongly affected than mental. Bodily location of pain or whether pain was acute or chronic had only minor impact on the variation in functioning, whereas the simple count of painful locations was associated with widest variation. Pain accounted for eight per cent of short term (1-3 day) sickness absence spells among men and 13 per cent among women. Of absence spells lasting between four and 14 days pain accounted for 23 per cent among women and 25 per cent among men, corresponding figures for over 14 day absence spells being 37 and 30 per cent. The association between pain and sickness absence was relatively independent of physical and psychosocial work factors, especially among women. The results of this study provide a picture of the epidemiology of pain among employees. Pain is a significant problem that seriously affects work ability. Information on risk groups can be utilized to make prevention measures more effective among those at high risk, and to decrease pain rates and thereby narrow the differences between socio-economic groups. Furthermore, the work-related psychosocial risk factors identified in this study are potentially modifiable, and it should be possible to target interventions on decreasing pain rates among employees.

Terveyteen liittyvä elämänlaatu laitoskuntoutuksen vaikuttavuuden arvioinnissa : RAND-36-mittarin soveltuvuus työikäisten laitoskuntoutuksen ongelmaprofiilin määrittämiseen ja kuntoutuksen vaikutusten arvioimiseen

The aim of the present research was to examine the validity of the RAND-36 measure of health-related quality of life among the working age rehabilitation clients. The research included two cross-sectional studies and one follow-up study. The subjects of the first study (n = 794) participated in the first period of the five following types of rehabilitation: occupationally oriented medical rehabilitation, musculoskeletal rehabilitation, medical rehabilitation for job burnout, rehabilitation for supporting the work ability and capacity of disabled subjects (vocational rehabilitation) and individualized rehabilitation between October 2000 and October 2001. The subjects of the second study (n = 990) participated in the same rehabilitation during their first rehabilitation period between May 2007 and May 2008. The first subjects participated in a follow-up period no later than May 2003 with the exception of the individual rehabilitation clients (n = 588). Based on the ICF classification, the RAND-36 provides a diverse measure of the health-related quality of life and of the capacity for subjective, perceived physical and psycho-social functioning. The construct properties of the RAND-36 measure proved to be very consistent on the basis of both the cluster and confirmatory factor analyses. At the group level, the RAND-36 measure was shown to be illustrative and sensitive in differentiating the clients’ rehabilitation needs. The results of cluster analyses with the two cross-sectional data indicated a consistent five-cluster solution of rehabilitation groups on the basis of the eight subscales of health-related quality of life. Each of these clusters represented a clear difference in their need for rehabilitation. The RAND-36 measure proved to be sensitive to change. The changes observed in the pre- and post-conditions in relation to all the subscales of quality of life were statistically significant. Depending on the rehabilitation type, different changes in the subscales of the measure were observed, and these changes corresponded to the different emphasis and goals of the specific type of rehabilitation intervention. Similarly, changes in the subscales of the measure were observed in relation to the RAND groups formed by cluster analysis, which were logical and corresponded to the problem profiles of these groups. The confirmatory factor analysis indicated a two-factor solution: an index of the capacity for physical functioning (self-rated general health, bodily pain, physical functioning, physical role functioning) and an index of the capacity for psycho-social functioning (psychological well-being, social functioning, psychological role functioning and energy). These two indices describing functional capacity proved also to be sensitive to change. This two-factor solution seems to be usable for group level analyses when assessing the effects of rehabilitation. The moderately strong correlation between the RAND-36 and work ability index suggests that they partly measure the same phenomenon: perceived health-related quality of life, subjective capacity for activity and perceived work ability have strong links. As expected, the capacity for physical functioning had a stronger correlation with work ability index than with the capacity for psycho-social functioning. According to the present research, the RAND-36 measure can be considered as a screening method for rehabilitation orientation in relation to rehabilitation needs and as a follow-up measure for the health-related quality of life among the working age clients. The RAND-36 measure is also shown to be a useful instrument in estimating the benefits of rehabilitation as well as in effectiveness research.

Molecular basis of the kidney filtration barrier : Role of the nephrin protein complex

The kidney filtration barrier consists of fenestrated endothelial cell layer, glomerular basement membrane and slit diaphragm (SD), the specialized junction between glomerular viscelar epithelial cells (podocytes). Podocyte injury is associated with the development of proteinuria, and if not reversed the injury will lead to permanent deterioration of the glomerular filter. The early events are characterized by disruption of the integrity of the SD, but the molecular pathways involved are not fully understood. Congenital nephrotic syndrome of the Finnish type (CNF) is caused by mutations in NPHS1, the gene encoding the SD protein nephrin. Lack of nephrin results in loss of the SD and massive proteinuria beginning before birth. Furthermore, nephrin expression is decreased in acquired human kidney diseases including diabetic nephropathy. This highlights the importance of nephrin and consequently SD in regulating the kidney filtration function. However, the precise molecular mechanism of how nephrin is involved in the formation of the SD is unknown. This thesis work aimed at clarifying the role of nephrin and its interaction partners in the formation of the SD. The purpose was to identify novel proteins that associate with nephrin in order to define the essential molecular complex required for the establishment of the SD. The aim was also to decipher the role of novel nephrin interacting proteins in podocytes. Nephrin binds to nephrin-like proteins Neph1 and Neph2, and to adherens junction protein P-cadherin. These interactions have been suggested to play a role in the formation of the SD. In this thesis work, we identified densin as a novel interaction partner for nephrin. Densin was localized to the SD and it was shown to bind to adherens junction protein beta-catenin. Furthermore, densin was shown to behave in a similar fashion as adherens junction proteins in cell-cell contacts. These results indicate that densin may play a role in cell adhesion and, therefore, may contribute to the formation of the SD together with nephrin and adherens junction proteins. Nephrin was also shown to bind to Neph3, which has been previously localized to the SD. Neph3 and Neph1 were shown to induce cell adhesion alone, whereas nephrin needed to trans-interact with Neph1 or Neph3 from the opposite cell surface in order to make cell-cell contacts. This was associated with the decreased tyrosine phosphorylation of nephrin. These data extend the current knowledge of the molecular composition of the nephrin protein complex at the SD and also provide novel insights of how the SD may be formed. This thesis work also showed that densin was up-regulated in the podocytes of CNF patients. Neph3 was up-regulated in nephrin deficient mouse kidneys, which share similar podocyte alterations and lack of the SD as observed in CNF patients podocytes. These data suggest that densin and Neph3 may have a role in the formation of morphological alterations in podocytes detected in CNF patients. Furthermore, this thesis work showed that deletion of beta-catenin specifically from adult mouse podocytes protected the mice from the development of adriamycin-induced podocyte injury and proteinuria compared to wild-type mice. These results show that beta-catenin play a role in the adriamycin induced podocyte injury. Podocyte injury is a hallmark in many kidney diseases and the changes observed in the podocytes of CNF patient share characteristics with injured podocytes observed in chronic kidney diseases. Therefore, the results obtained in this thesis work suggest that densin, Neph3 and beta-catenin participate in the molecular pathways which result in morphological alterations commonly detected in injured podocytes in kidney diseases.

VEGFR-3 and Tie pathways in vascular network formation

The blood and lymphatic vascular systems are essential for life, but they may become harnessed for sinister purposes in pathological conditions. For example, tumors learn to grow a network of blood vessels (angiogenesis), securing a source of oxygen and nutrients for sustained growth. On the other hand, damage to the lymph nodes and the collecting lymphatic vessels may lead to lymphedema, a debilitating condition characterized by peripheral edema and susceptibility to infections. Promoting the growth of new lymphatic vessels (lymphangiogenesis) is an attractive approach to treat lymphedema patients. Angiopoietin-1 (Ang1), a ligand for the endothelial receptor tyrosine kinases Tie1 and Tie2. The Ang1/Tie2 pathway has previously been implicated in promoting endothelial stability and integrity of EC monolayers. The studies presented here elucidate a novel function for Ang1 as a lymphangiogenic factor. Ang1 is known to decrease the permeability of blood vessels, and could thus act as a more global antagonist of plasma leakage and tissue edema by promoting growth of lymphatic vessels and thereby facilitating removal of excess fluid and other plasma components from the interstitium. These findings reinforce the idea that Ang1 may have therapeutic value in conditions of tissue edema. VEGFR-3 is present on all endothelia during development, but in the adult its expression becomes restricted to the lymphatic endothelium. VEGF-C and VEGF-D are ligands for VEGFR-3, and potently promote lymphangiogenesis in adult tissues, with direct and remarkably specific effects on the lymphatic endothelium in adult tissues. The data presented here show that VEGF-C and VEGF-D therapy can restore collecting lymphatic vessels in a novel orthotopic model of breast cancer-related lymphedema. Furthermore, the study introduces a novel approach to improve VEGF-C/VEGF-D therapy by using engineered heparin-binding forms of VEGF-C, which induced the rapid formation of organized lymphatic vessels. Importantly, VEGF-C therapy also greatly improved the survival and integration of lymph node transplants. The combination of lymph node transplantation and VEGF-C therapy provides a basis for future therapy of lymphedema. In adults, VEGFR-3 expression is restricted to the lymphatic endothelium and the fenestrated endothelia of certain endocrine organs. These results show that VEGFR-3 is induced at the onset of angiogenesis in the tip cells that lead the formation of new vessel sprouts, providing a tumor-specific vascular target. VEGFR-3 acts downstream of VEGF/VEGFR-2 signals, but, once induced, can sustain angiogenesis when VEGFR-2 signaling is inhibited. The data presented here implicate VEGFR-3 as a novel regulator of sprouting angiogenesis along with its role in regulating lymphatic vessel growth. Targeting VEGFR-3 may provide added efficacy to currently available anti-angiogenic therapeutics, which typically target the VEGF/VEGFR-2 pathway.