Ultrasound-assisted surface engineering of pharmaceutical powders

Effective processing of powdered particles can facilitate powder handling and result in better drug product performance, which is of great importance in the pharmaceutical industry where the majority of active pharmaceutical ingredients (APIs) are delivered as solid dosage forms. The purpose of this work was to develop a new ultrasound-assisted method for particle surface modification and thin-coating of pharmaceutical powders. The ultrasound was used to produce an aqueous mist with or without a coating agent. By using the proposed technique, it was possible to decrease the interparticular interactions and improve rheological properties of poorly-flowing water-soluble powders by aqueous smoothing of the rough surfaces of irregular particles. In turn, hydrophilic polymer thin-coating of a hydrophobic substance diminished the triboelectrostatic charge transfer and improved the flowability of highly cohesive powder. To determine the coating efficiency of the technique, the bioactive molecule β-galactosidase was layered onto the surface of powdered lactose particles. Enzyme-treated materials were analysed by assaying the quantity of the reaction product generated during enzymatic cleavage of the milk sugar. A near-linear increase in the thickness of the drug layer was obtained during progressive treatment. Using the enzyme coating procedure, it was confirmed that the ultrasound-assisted technique is suitable for processing labile protein materials. In addition, this pre-treatment of milk sugar could be used to improve utilization of lactose-containing formulations for populations suffering from severe lactose intolerance. Furthermore, the applicability of the thin-coating technique for improving homogeneity of low-dose solid dosage forms was shown. The carrier particles coated with API gave rise to uniform distribution of the drug within the powder. The mixture remained homogeneous during further tabletting, whereas the reference physical powder mixture was subject to segregation. In conclusion, ultrasound-assisted surface engineering of pharmaceutical powders can be effective technology for improving formulation and performance of solid dosage forms such as dry powder inhalers (DPI) and direct compression products.

Ruumiillinen esine, materiaalinen suku : Tutkimus Pyhä Anna itse kolmantena -aiheisista keskiajan puuveistoksista Suomessa

Embobied Object, Material Family. Late-Medieval Wood Sculptures Depicting Saint Anne with the Virgin and Child in Finland Saint Anne, the mother of the Virgin Mary, was one of the most popular saints in Western Europe in the late Middle Ages. She was often depicted with two other figures, the Virgin and the Christ Child (Anna Selbdritt). The dissertation examines the polychrome wood sculptures showing this motif, with a special focus on those remaining in Finland. It investigates the meanings these sculptures had to their observers in the fifteenth-century Finland. The study sheds light to important material heritage which is little known and offers new insights into the cult and imagery of the holy grandmother. Methodologically the study is based on iconology and post-formalist art history, and it appropriates concepts such as spatiality, sanctity, corporeality, and gender. Taking a comparative approach it knits together larger tendencies and local people and incidents. By conflating methodological domains it renews the ways how fragmentary wood sculptures, lacking documentary written sources, can be contextually interpreted and comprehended. The sculptures are analyzed from three angles. Firstly, the study explores the sculptures by focusing on their materiality and facture, which is to consider them as records of their own making. The analysis provides new information concerning the quantity, location, and current condition of the sculptures and it also elucidates problems regarding attribution, dating, display, and craftsmanship. The book presents the results of the empirical study of 45 Saint Anne groups; these works are individually described in the large Appendix. Secondly, the works are contextualized to the specific historical conditions in which they were observed. The study discusses closely the circumstances in the Turku Cathedral around the shrine of Saint Anne, the popular belief, and the piety of individual persons. The sculptures, deemed as the embodiments of the holy characters, interacted with the devotees. Thirdly, the works are examined within the wider theological and ideological currents of the era centered on the body and Incarnation. Saint Anne with the Virgin and Child motif demonstrated the Carnal Trinity, the motherly side of the Holy Trinity. The dissertation argues that Saint Anne was interpreted as the female counterpart or, in a mythical sense, wife of God. Furthermore, the Child s implicit, simultaneous presence as a suffering or dead man imbues the sculptures with a sense of the Passion, thus associating them with the pietà and the Mater dolorosa motifs. The naked Christ Child underlines him as the offering and, eventually, the Eucharistic wafer. The study suggests that the sculptures mediate continuity and the bloodline between the generations by the intertwined and repeated gestures, clothing and positions of the portrayed figures. Regardless of the ostensible homeliness of the sculptures, so readily reiterated by earlier scholars, these sculptures represented creation and birth through the carnal yet holy mothers.

Jacopo Bassano freskomaalarina : Cartiglianon ja Enegon kirkkojen freskot: konteksti, rekonstruktio ja tulkinta

The object of this study is Jacopo Bassano (c. 1510 1592) as a fresco painter and the significance of frescoes in his late production. The research focuses on the only surviving cycle of frescoes of his later years in the Cartigliano parish church, bearing the date 1575. The other cycle studied here was painted for the 16th century parish church of Enego. It contained one of the most extensive fresco decorations executed by Jacopo Bassano together with his eldest son Francesco. However, nothing has survived of the fresco cycle and the ceiling paintings of the church, nor is any visual documentation of them left. Only the small altarpiece attributed to Jacopo Bassano and depicting Saints Justine, Sebastian, Anthony Abbott, and Roch (dated to c. 1555/1560) has been preserved. I have suggested that the frescoes of the Cartigliano parish church should be examined in the interpretational context of the spirituality of the post-Tridentine period. This period frames the historical context for the frescoes and functions as a basis for the iconographical interpretation that I have proposed. I have shown that the iconographic programme of the frescoes in the choir of the Cartigliano parish church has obvious points of contact with the Catholic doctrines reconfirmed by the Council of Trent (1545 1563). I also argue that the fresco cycle and the ceiling paintings of the Enego church should be placed in the same interpretational context as the frescoes of Cartigliano. I present a reconstruction of the frescoes in the choir attributed to Jacopo Bassano and of those on the walls of the nave attributed to his son Francesco Bassano. According to my reconstruction, the frescoes in the choir and nave walls formed a coherent cycle with a unitary iconographic programme which included the 28 paintings with Old Testament subjects in the nave ceiling. The reconstruction includes the dating and the iconography of the fresco programme and its interpretative basis. The reconstruction is based on visitation records and inventories from the 16th and 17th centuries as well as on the oldest relevant literature, namely the descriptions offered by Carlo Ridolfi (1648) and G. B. Verci (1775). I also consider the relationship of the large compositional sketches attributed to Jacopo Bassano and depicting Christological subjects to the lost frescoes in Enego. These studies have been executed with coloured chalks, and many of them are also dated 1568 or 1569 by the painter. I suggest in this study that these large studies in coloured chalks were preparatory drawings for the fresco cycle in Enego, depicting scenes from the life and suffering of Christ. All the subjects of the aforesaid drawings were included in the Enego cycle.

Fictionalising Trauma : The Aesthetics of Marguerite Duras's India Cycle

Marguerite Duras (1914−1996) was one of the most original French writers and film directors, whose cycles are renowned for a transgeneric repetition variation of human suffering in the modern condition. Her fictionalisation of Asian colonialism, the India Cycle (1964−1976), consists of three novels, Le ravissement de Lol V. Stein (1964), Le Vice-consul (1966) and L'amour (1971), a theatre play, India Song (1973), and three films, La Femme du Gange (1973), India Song (1974) and Son nom de Venise dans Calcutta desért (1976). Duras’s cultural position as a colon in inter-war ‘Indochina’ was the backdrop for this “théâtre-text-film”, while its creation was provoked by the atrocities of World War II and post-war decolonisation. Fictionalising Trauma analyses the aesthetics of the India Cycle as Duras’s critical working-through of historical trauma. From an emotion-focused cognitive viewpoint, the study sheds light on trauma’s narrativisation using the renewed concept of traumatic memory developed by current social neuroscience. Duras is shown to integrate embodied memory and narrative memory into an emotionally progressing fiction. Thus the rhetoric of the India Cycle epitomises a creative symbolisation of the unsayable, which revises the concept of trauma from a semiotic failure into an imaginative metaphorical process. The India Cycle portrays the stagnated situation of a white society in Europe and British India during the thirties. The narratives of three European protagonists and one fictional Cambodian mendicant are organised as analogues mirroring the effects of rejection and loss on both sides of the colonial system. Using trauma as a conceptual prism, the study rearticulates this composition as three roles: those of witnessing writers, rejected survivors and colonial perpetrators. Three problems are analysed in turn by reading the non-verbal markers of the text: the white man as a witness, the subversive trope of the madwoman and the deadlock of the colonists’ destructive passion. The study reveals emotion and fantasy to be crucial elements in critical trauma fiction. Two devices intertwine throughout the cycle: affective images of trauma expressing the horror of life and death, and self-reflexive metafiction distancing the face-value of the melodramatic stories. This strategy dismantles racist and sexist discourses underpinning European life, thus demanding a renewal of cultural memory by an empathic listening to the ‘other’. And as solipsism and madness lead the lives of the white protagonists to tragic ends, the ‘real’ beggar in Calcutta lives in ecological harmony with Nature. This emphasises the failure of colonialism, as the Durasian phantasm ambiguously strives for a deconstruction of the exotic mythical fiction of French ‘Indochina’.

Passion vallassa : Hermostunut aika Minna Canthin teoksissa

Under the power of passion. The age of nervousness in Minna Canth s works This research contemplates the psychology of Minna Canth s characters through the historical image of man in late 19th century Europe. The central operative term of the study is passion , understood as a twofold philosophical concept that includes both desire and suffering. The method of this study is historical and contextual. The study interprets the passions and the psychology of Canth s characters as they were understood in their own time. The indicator of the relevant contexts is the realist and naturalist genre of Canth s works. New research on the genre of the time is also the basis of a new kind of psychological approach to Canth s works. The most important context of passion in Canth s works is the positivistic and pathological image of man at the end of the 19th century. Then, passion was widely discussed, and was perceived as a physiological phenomenon that influenced humans neurologically and caused different kinds of physiological symptoms and nervous disorders. But at the same time, passion was understood as a manifestation of human instincts and drives. The naturalistic literature of the day aimed at creating deterministic studies of human morality and psychology following Émile Zola s application of experimental science methods in his writing. The pathological image of man is most explicitly manifested in Canth s formerly unknown short story Lääkäri (Doctor, 1891), in which a doctor who is interested in psychology visits a jail to meet a peculiar criminal, a girl who feels no remorse for her multiple crimes. In other works of Canth the medically motivated viewpoint is more hidden in the deterministic narrative and depiction of the characters. The present study approaches the passion in Minna Canth s works through five thematic chapters, in witch characters are interpreted suffering from blind love, ennui, crippling romantic idealism, melancholy, guilt and nostalgia, and their stories can be prescribed as medical histories which depict the born of the passion and its development towards ruin. All protagonists are also manifestations of their own time. Canth criticises the modern life and its demands as well as social defects through the tragic stories of individuals. The study demonstrates that Canth did not, like previous research has suggested, wait until the 1890s before writing works of a psychological nature but had already written according to the psychological paradigm of her time in Työmiehen vaimo (1885). The social and psychological interests intertwine in Canth s works and are not exclusionary as has formerly been interpreted. Canth is also critical of the medical power implicit in the naturalist experimental method and this shows itself especially in her depiction of working class women.

Kodin ja työn rajavyöhykkeellä - yhteensovittamisen jännitteitä ja ratkaisuja arjessa

The aim of this research is to study the boundary zone of home and work and the tensions people experience while reconciling home and work? How are the requirements of the family, the home and the work taken care of in everyday life? What kind of difficulties does the individual experience when reconciling home activities and job requirements together? What kind of activity policies have families created to ease the everyday life? What kind of goals and requirements do families feel behind the difficulties in adjusting home and work? What kind of changes would make the adjusting of home and work easier? The changing family life, everyday home activities and the changing Finnish working life are studied to describe the adjusting of home and work. In addition the boundary zone of home and work and its tensions are studied. 337 research persons who find reconciling home and work challenging were elected from different sectors of the working life. Research persons were gathered from the public, private and third sectors. The research material was gathered with a semi-structured qualitative questionnaire published in internet. Contents analysis was the analysis method of the research material. The tensions of adjusting home and work are various. Several activity systems meet on the boundary zone of home and work causing boundary zones to expand and tensions to increase and expand like a network. In the everyday life of an individual the boundary zone fades out and home and work overlap. Tensions can be examined as internal conflicts of the individual through the activity system of everyday life. Individuals balance between individualism and familism, feeling bad, suffering from lack of time and struggling with childcare organizing problems and inflexible employers. The solutions to reconciling home and work difficulties are situational. Often is the help of family and friends required without any solid solutions. The conflict of the goals, requirements and the reality is behind the problems as well as the tightening terms of the working life and its growing expectations. Change requests are proposed on the levels of individual, home, work and the society. Reconciling home and work is not only a challenge between the employee and the employer. It s a problem that needs multilateral solutions and changes on the levels of individual, home, work and society. The challenge remaining is to find out if it would be successful to take the everyday life as starting point to negotiate the reconciling of home and work and how the possible family, social and work political solutions appear in everyday life.

The scientific basis and development of a matrix metalloproteinase (MMP) -8 specific chair-side test for monitoring of periodontal health and disease from gingival crevicular fluid

Matrix metalloproteinase (MMP) -8, collagenase-2, is a key mediator of irreversible tissue destruction in chronic periodontitis and detectable in gingival crevicular fluid (GCF). MMP-8 mostly originates from neutrophil leukocytes, the first line of defence cells which exist abundantly in GCF, especially in inflammation. MMP-8 is capable of degrading almost all extra-cellular matrix and basement membrane components and is especially efficient against type I collagen. Thus the expression of MMP-8 in GCF could be valuable in monitoring the activity of periodontitis and possibly offers a diagnostic means to predict progression of periodontitis. In this study the value of MMP-8 detection from GCF in monitoring of periodontal health and disease was evaluated with special reference to its ability to differentiate periodontal health and different disease states of the periodontium and to recognise the progression of periodontitis, i.e. active sites. For chair-side detection of MMP-8 from the GCF or peri-implant sulcus fluid (PISF) samples, a dip-stick test based on immunochromatography involving two monoclonal antibodies was developed. The immunoassay for the detection of MMP-8 from GCF was found to be more suitable for monitoring of periodontitis than detection of GCF elastase concentration or activity. Periodontally healthy subjects and individuals suffering of gingivitis or of periodontitis could be differentiated by means of GCF MMP-8 levels and dipstick testing when the positive threshold value of the MMP-8 chair-side test was set at 1000 µg/l. MMP-8 dipstick test results from periodontally healthy and from subjects with gingivitis were mainly negative while periodontitis patients sites with deep pockets ( 5 mm) and which were bleeding on probing were most often test positive. Periodontitis patients GCF MMP-8 levels decreased with hygiene phase periodontal treatment (scaling and root planing, SRP) and even reduced during the three month maintenance phase. A decrease in GCF MMP-8 levels could be monitored with the MMP-8 test. Agreement between the test stick and the quantitative assay was very good (κ = 0.81) and the test provided a baseline sensitivity of 0.83 and specificity of 0.96. During the 12-month longitudinal maintenance phase, periodontitis patients progressing sites (sites with an increase in attachment loss ≥ 2 mm during the maintenance phase) had elevated GCF MMP-8 levels compared with stable sites. General mean MMP-8 concentrations in smokers (S) sites were lower than in non-smokers (NS) sites but in progressing S and NS sites concentrations were at an equal level. Sites with exceptionally and repeatedly elevated MMP-8 concentrations during the maintenance phase were clustered in smoking patients with poor response to SRP (refractory patients). These sites especially were identified by the MMP-8 test. Subgingival plaque samples from periodontitis patients deep periodontal pockets were examined by polymerase chain reaction (PCR) to find out if periodontal lesions may serve as a niche for Chlamydia pneumoniae. Findings were compared with the clinical periodontal parameters and GCF MMP-8 levels to determine the correlation with periodontal status. Traces of C. pneumoniae were identified from one periodontitis patient s pooled subgingival plaque sample by means of PCR. After periodontal treatment (SRP) the sample was negative for C. pneumoniae. Clinical parameters or biomarkers (MMP-8) of the patient with the positive C. pneumoniae finding did not differ from other study patients. In this study it was concluded that MMP-8 concentrations in GCF of sites from periodontally healthy individuals, subjects with gingivitis or with periodontitis are at different levels. The cut-off value of the developed MMP-8 test is at an optimal level to differentiate between these conditions and can possibly be utilised in identification of individuals at the risk of the transition of gingivitis to periodontitis. In periodontitis patients, repeatedly elevated GCF MMP-8 concentrations may indicate sites at risk of progression of periodontitis as well as patients with poor response to conventional periodontal treatment (SRP). This can be monitored by MMP-8 testing. Despite the lower mean GCF MMP-8 concentrations in smokers, a fraction of smokers sites expressed very high MMP-8 concentrations together with enhanced periodontal activity and could be identified with MMP-8 specific chair-side test. Deep periodontal lesions may be niches for non-periodontopathogenic micro-organisms with systemic effects like C. pneumoniae and possibly play a role in the transmission from one subject to another.

Fumarate Hydratase and Succinate Dehydrogenase in Neoplasia

Germline mutations in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell cancer (HLRCC). FH is a nuclear encoded enzyme which functions in the Krebs tricarboxylic acid cycle, and homozygous mutation in FH lead to severe developmental defects. Both uterine and cutaneous leiomyomas are components of the HLRCC phenotype. Most of these tumours show loss of the wild-type allele and, also, the mutations reduce FH enzyme activity, which indicate that FH is a tumour suppressor gene. The renal cell cancers associated with HLRCC are of rare papillary type 2 histology. Other genes involved in the Krebs cycle, which are also implicated in neoplasia are 3 of the 4 subunits encoding succinate dehydrogenase (SDH); mutations in SHDB, SDHC, and SDHD predispose to paraganglioma and phaeochromocytoma. Although uterine leiomyomas (or fibroids) are very common, the estimations of affected women ranging from 25% to 77%, not much is known about their genetic background. Cytogenetic studies have revealed that rearrangements involving chromosomes 6, 7, 12 and 14 are most commonly seen in fibroids. Deletions on the long arm of chromosome 7 have been reported to be involved in about 17 to 34 % of leiomyomas and the small commonly deleted region on 7q22 suggests that there might be an underlying tumour suppressor gene in that region. The purpose of this study was to investigate the genetic mechanisms behind the development of tumours associated with HLRCC, both renal cell cancer and uterine fibroids. Firstly, a database search at the Finnish cancer registry was conducted in order to identify new families with early-onset RCC and to test if the family history was compatible with HLRCC. Secondly, sporadic uterine fibroids were tested for deletions on 7q in order to define the minimal deleted 7q-region, followed by mutation analysis of the candidate genes. Thirdly, oligonucleotide chips were utilised to study the global gene expression profiles of uterine fibroids in order to test whether 7q-deletions and FH mutations significantly affected fibroid biology. In the screen for early-onset RCC, 214 families were identified. Subsequently, the pedigrees were constructed and clinical data obtained. One of the index cases (RCC at the age of 28) had a mother who had been diagnosed with a heart tumour, which in further investigation turned out to be a paraganglioma. This lead to an alternative hypothesis that SDH, instead of FH, could be involved. SDHA, SDHB, SDHC and SDHD were sequenced from these individuals; a germline SDHB R27X mutation was detected with loss of the wild-type allele in both tumours. These results suggest that germline mutations in the SDHB gene predispose to early-onset RCC establishing a novel form of hereditary RCC. This has immediate clinical implications in the surveillance of patients suffering from early-onset RCC and phaeochromocytoma/paraganglioma. For the studies on sporadic uterine fibroids, a set of 166 fibroids from 51 individuals were collected. The 7q LOH mapping defined a commonly deleted region of about 3.2 mega bases in 11 of the 166 tumours. The deletion was consistent with previously reported allelotyping studies of leiomyomas and it therefore suggested the presence of a tumour suppressor gene in the deleted region. Furthermore, the high-resolution aCGH-chip analysis refined the deleted region to only 2.79Mb. When combined with previous data, the commonly deleted region was only 2.3Mb. The mutation screening of the known genes within the commonly deleted region did not reveal pathogenic mutations, however. The expression microarray analysis revealed that FH-deficient fibroids, both sporadic and familial, had their distinct gene expression profile as they formed their own group in the unsupervised clustering. On the other hand, the presence or absence of 7q-deletions did not significantly alter the global gene expression pattern of fibroids, suggesting that these two groups do not have different biological backgrounds. Multiple differentially expressed genes were identified between FH wild-type and FH-mutant fibroids, and the most significant increase was seen in the expression of carbohydrate metabolism-related and hypoxia inducible factor (HIF) target genes.

Spatial variation of climate and the impact of disturbances on local climate and forest recovery in northern Finland

The structure and function of northern ecosystems are strongly influenced by climate change and variability and by human-induced disturbances. The projected global change is likely to have a pronounced effect on the distribution and productivity of different species, generating large changes in the equilibrium at the tree-line. In turn, movement of the tree-line and the redistribution of species produce feedback to both the local and the regional climate. This research was initiated with the objective of examining the influence of natural conditions on the small-scale spatial variation of climate in Finnish Lapland, and to study the interaction and feedback mechanisms in the climate-disturbances-vegetation system near the climatological border of boreal forest. The high (1 km) resolution spatial variation of climate parameters over northern Finland was determined by applying the Kriging interpolation method that takes into account the effect of external forcing variables, i.e., geographical coordinates, elevation, sea and lake coverage. Of all the natural factors shaping the climate, the geographical position, local topography and altitude proved to be the determining ones. Spatial analyses of temperature- and precipitation-derived parameters based on a 30-year dataset (1971-2000) provide a detailed description of the local climate. Maps of the mean, maximum and minimum temperatures, the frost-free period and the growing season indicate that the most favourable thermal conditions exist in the south-western part of Lapland, around large water bodies and in the Kemijoki basin, while the coldest regions are in highland and fell Lapland. The distribution of precipitation is predominantly longitudinally dependent but with the definite influence of local features. The impact of human-induced disturbances, i.e., forest fires, on local climate and its implication for forest recovery near the northern timberline was evaluated in the Tuntsa area of eastern Lapland, damaged by a widespread forest fire in 1960 and suffering repeatedly-failed vegetation recovery since that. Direct measurements of the local climate and simulated heat and water fluxes indicated the development of a more severe climate and physical conditions on the fire-disturbed site. Removal of the original, predominantly Norway spruce and downy birch vegetation and its substitution by tundra vegetation has generated increased wind velocity and reduced snow accumulation, associated with a large variation in soil temperature and moisture and deep soil frost. The changed structural parameters of the canopy have determined changes in energy fluxes by reducing the latter over the tundra vegetation. The altered surface and soil conditions, as well as the evolved severe local climate, have negatively affected seedling growth and survival, leading to more unfavourable conditions for the reproduction of boreal vegetation and thereby causing deviations in the regional position of the timberline. However it should be noted that other factors, such as an inadequate seed source or seedbed, the poor quality of the soil and the intensive logging of damaged trees could also exacerbate the poor tree regeneration. In spite of the failed forest recovery at Tunsta, the position and composition of the timberline and tree-line in Finnish Lapland may also benefit from present and future changes in climate. The already-observed and the projected increase in temperature, the prolonged growing season, as well as changes in the precipitation regime foster tree growth and new regeneration, resulting in an advance of the timberline and tree-line northward and upward. This shift in the distribution of vegetation might be decelerated or even halted by local topoclimatic conditions and by the expected increase in the frequency of disturbances.

Lake sediment research as a part of lake management - case studies and implications from southern Finland

In Finland one of the most important current issues in the environmental management is the quality of surface waters. The increasing social importance of lakes and water systems has generated wide-ranging interest in lake restoration and management, concerning especially lakes suffering from eutrophication, but also from other environmental impacts. Most of the factors deteriorating the water quality in Finnish lakes are connected to human activities. Especially since the 1940's, the intensified farming practices and conduction of sewage waters from scattered settlements, cottages and industry have affected the lakes, which simultaneously have developed in to recreational areas for a growing number of people. Therefore, this study was focused on small lakes, which are human impacted, located close to settlement areas and have a significant value for local population. The aim of this thesis was to obtain information from lake sediment records for on-going lake restoration activities and to prove that a well planned, properly focused lake sediment study is an essential part of the work related to evaluation, target consideration and restoration of Finnish lakes. Altogether 11 lakes were studied. The study of Lake Kaljasjärvi was related to the gradual eutrophication of the lake. In lakes Ormajärvi, Suolijärvi, Lehee, Pyhäjärvi and Iso-Roine the main focus was on sediment mapping, as well as on the long term changes of the sedimentation, which were compared to Lake Pääjärvi. In Lake Hormajärvi the role of different kind of sedimentation environments in the eutrophication development of the lake's two basins were compared. Lake Orijärvi has not been eutrophied, but the ore exploitation and related acid main drainage from the catchment area have influenced the lake drastically and the changes caused by metal load were investigated. The twin lakes Etujärvi and Takajärvi are slightly eutrophied, but also suffer problems associated with the erosion of the substantial peat accumulations covering the fringe areas of the lakes. These peat accumulations are related to Holocene water level changes, which were investigated. The methods used were chosen case-specifically for each lake. In general, acoustic soundings of the lakes, detailed description of the nature of the sediment and determinations of the physical properties of the sediment, such as water content, loss on ignition and magnetic susceptibility were used, as was grain size analysis. A wide set of chemical analyses was also used. Diatom and chrysophycean cyst analyses were applied, and the diatom inferred total phosphorus content was reconstructed. The results of these studies prove, that the ideal lake sediment study, as a part of a lake management project, should be two-phased. In the first phase, thoroughgoing mapping of sedimentation patterns should be carried out by soundings and adequate corings. The actual sampling, based on the preliminary results, must include at least one long core from the main sedimentation basin for the determining the natural background state of the lake. The recent, artificially impacted development of the lake can then be determined by short-core and surface sediment studies. The sampling must be focused on the basis of the sediment mapping again, and it should represent all different sedimentation environments and bottom dynamic zones, considering the inlets and outlets, as well as the effects of possible point loaders of the lake. In practice, the budget of the lake management projects of is usually limited and only the most essential work and analyses can be carried out. The set of chemical and biological analyses and dating methods must therefore been thoroughly considered and adapted to the specific management problem. The results show also, that information obtained from a properly performed sediment study enhances the planning of the restoration, makes possible to define the target of the remediation activities and improves the cost-efficiency of the project.

The church must become the people of Soweto : Manas Buthelezi’s existential-Christocentric understanding of the church

The aim of this study has been to discern what Manas Buthelezi (1935-), a black South African Lutheran theologian and later also a bishop, regards as the requirements a church has to fulfill in order to be credible in the apartheid society. Buthelezi’s dissertation and several articles written between the years 1968 and 1993 are the sources of this study. Also the lectures held in Heidelberg in 1972 are referred to. Systematic analysis is the method used. The question of the credibility of the church is studied through three concepts that play an important role in Buthelezi’s ecclesiological thought, namely the wholeness of life, incarnation and liberation. The notion of the wholeness of life stems from the African tradition. Buthelezi takes the concept into the Christian church: the church should realize that God is the Creator of all life and Christ the lord of every aspect of human existence. Life is one entity coram Deo. However, the church is not to become the world; solidarity between the two must remain critical as the church is also called to play a prophetic role in the society. The church is in an open relationship with the world. It has a unique message of forgiveness and reconciliation. Nevertheless, the message is not a possession of the church but it is addressed to the whole world. The meaning of incarnation comes close to that of the wholeness of life. Following the example of Christ’s incarnation, the church must become human in the reality of the people. The church in Soweto is to become the people of Soweto, that is, the church must become as vulnerable as the people are. An incarnate church cannot be immune to the oppression that people experience, because the people are the church. The church is therefore bound to suffer. Buthelezi’s theology of the cross is pragmatic: the suffering of the church aims at the liberation of the oppressed. At times the physical presence of the church by the side of the suffering people is the only way to preach the incarnate gospel. In the South Africa of the late 1960s onwards the liberation of the oppressed black people was high on the agenda of Black Theology. As a leader of the early South African Black Theology, Buthelezi is concerned about the racial injustice in his country. He urges the churches to join the struggle against it as one people of God. The notions of liberation and the wholeness of life emerge in Buthelezi’s holistic understanding of liberation that involves the inner liberation of the black spirit and the liberation of the economic, social and political aspects of life. Interpreting Tillich’s correlation method in the South African situation, and also paralleling other liberation theologians, Buthelezi takes the existential situation of the people as the starting point for liberation. The gospel has to respond to the existential questions of people. The church is called to work for the liberation of society but it must also be liberated itself. Buthelezi initiated the LWF statement on the status confessionis in South Africa (1977). In line with the statement, he calls for church unity on the human level. For the unity to be true, it has to be experienced on the grassroots’ level. All the three concepts covered urge the church to come down from any ivory tower and out of any spiritual haven it might hide in. A lot of the credibility of the church derives from the behavior of the people. Buthelezi’s concentration on how the people who constitute the church should live their faith leaves less attention to how God constitutes the church. I have labeled Buthelezi’s understanding of the church existential-Christocentric due to the emphasis he lays on the need of the church to take the existential situation of the people seriously and on the other hand, on Christ as the exemplar for the church.

Kristallivalheita : Itsepetos filosofisen tulkinnan lähtökohtana eräissä draaman klassikoissa

The philosophical problem of self-deception focuses the relation between desire, advantage, evidence and harm. A self-deceptive person is irrational because he or she belives or wants to belive contrary to the available evidence. The study focuses on different forms of self-deception that come out in certain classical Western dramas. The first self-deception forms are: "S knows that ~p but still belives that p because he wants that ~p", "S wants that p and therefore belives that p.", "S belives that p against evidence t because he wants to belive that p.", "S belives that p if t but S would belive that p even if ~t because S wants to belive that p.", "S belives that p (even if there is t that ~p) because S is ignorant of it." and "S belives that p (even if there is t that ~p) because of ignorant of t due to an internal deception." The main sources on self-deception are the views of contemporary researchers of the subject, such as Robert Audi, Marcia Baron, Bas C. van Fraassen, Mark Johnston, Mike W. Martin, Brian MaLaughlin, Alfred Mele, Amélie Oksenberg Rorty, William Ruddick and Stephen L. White. In this study it is claimed that Shakespeare´s Othello presents self-deception as a tragic phenomenom from witch it follows deceptions and murders. Moliére´s Tartuffe deals with a phony hypocrite´s attempts at cheating. Ibsen´s Wild Duck defends the necessity of vital lies. Beckett´s Waiting for Godot deals with the self-deception witch is related to the waiting of the supernatural rescuer. Miller´s The Death of a Salesman tells about a man who, while pursuing the American myth of success, winds both himself and his family into the skeins of self-deception. They are studied with a Barthesian method that emphasizes the autonomy of literary work and its interpretation independently of the author´s personal history and social conditions. Self-deception has been regarded as an immoral way of thinking or way of action. However, vital lies show the necessity or necessity of the self-deception when it brings joy and optimism to the human being and supports his or her self-esteem and does not cause a suffering or damage, either to self or others. In the study, the processual character of self-deception is brought out.

Venous thromboembolism during pregnancy and the impact of thrombophilia in pregnancy complications

Venous thromboembolism (VTE) is the greatest single cause of maternal mortality in pregnant women in developed countries. Pregnancy is a hypercoagulable state and brings about an enhanced risk of deep venous thrombosis (DVT) in otherwise healthy women. Traditionally, unfractionated heparin (UFH) has been used for treatment of DVT during pregnancy. We showed in our observational study that low molecular weight heparin (LMWH) is as effective and safe as UFH in the treatment of DVT during pregnancy. Although DVT during pregnancy is often massive, increasing the risk of developing long-term consequences, namely post-thrombotic syndrome (PTS), only 11% of all patients had confirmed PTS 3 4 years after DVT. In our studies the prevalence of PTS was not dependent on treatment (UFH vs LMWH). Low molecular weight heparin is more easily administered, few laboratory controls are required and the hospital stay is shorter, factors that lower the costs of treatment. Cervical insufficiency is defined as repeated very preterm delivery during the second or early third trimester. Infection is a well-known risk factor of preterm delivery. We found overpresentation of thrombophilic mutations (FV Leiden, prothrombin G20210A)among 42 patients with cervical insufficiency compared with controls (OR 6.7, CI 2.7 18.4). Thus, thrombophilia might be a risk factor of cervical insufficiency possibly explained by interaction of coagulation and inflammation processes. The presence of antiphospholipid (aPL) antibodies increases the risk for recurrent miscarriage (RM). Annexins are proteins which all bind to anionic phospholipids (PLs) preventing clotting on vascular phospholipid surfaces. Plasma concentrations of circulating annexin IV and V were investigated in 77 pregnancies at the beginning of pregnancy among women with a history of RM, and in connection to their aPL antibody status. Control group consisted unselected pregnant patients (n=25) without history of adverse pregnancy outcome. Plasma levels of annexin V were significantly higher at the beginning (≤5th week) of pregnancy in women with aPL antibodies compared with those without aPL antibodies (P=0.03). Levels of circulating annexin V were also higher at the 6th (P= 0.01) and 8th week of pregnancy in subjects with aPL antibodies (P=0.01). Results support the hypothesis that aPL could displace annexin from anionic phospholipid surfaces of syncytiotrophoblasts (STBs) and may exert procoagulant activities on the surfaces of STBs Recurrent miscarriage (RM) has been suggested to be caused by mutations in genes coding for various coagulation factors resulting in thrombophilia. In the last study of my thesis were investigated the prevalence of thrombomodulin (TM) and endothelial protein C receptor polymorphism EPCR among 40 couples and six women suffering RM. This study showed that mutations in the TM or EPCR genes are not a major cause of RM in Finnish patients.

Essential Thrombocythaemia : Diagnosis, Prognostic Aspects, and the Outcome of Finnish patients

Essential thrombocythaemia (ET) is a myeloproliferative disease (MPD) characterized by thrombocytosis, i.e. a constant elevation of platelet count. Thrombocytosis may appear in MPDs (ET, polycythaemia vera, chronic myeloid leukaemia, myelofibrosis) and as a reactive phenomenon. The differential diagnosis of thrombocytosis is important, because the clinical course, need of therapy, and prognosis are different in patients with MPDs and in those with reactive thrombocytosis. ET patients may remain asymptomatic for years, but serious thrombohaemorrhagic and pregnancy-related complications may occur. The complications are difficult to predict. The aims of the present study were to evaluate the diagnostic findings, clinical course, and prognostic factors of ET. The present retrospective study consists of 170 ET patients. Two thirds had a platelet count < 1000 x 109/l. The diagnosis was supported by an increased number of megakaryocytes with an abnormal morphology in a bone marrow aspirate, aggregation defects in platelet function studies, and the presence of spontaneous erythroid and/or megakaryocytic colony formation in in vitro cultures of haematopoietic progenitors. About 70 % of the patients had spontaneous colony formation, while about 30 % had a normal growth pattern. Only a fifth of the patients remained asymptomatic. Half had a major thrombohaemorrhagic complication. The proportion of the patients suffering from thrombosis was as high as 45 %. About a fifth had major bleedings. Half of the patients had microvascular symptoms. Age over 60 years increased the risk of major bleedings, but the occurrence of thrombotic complications was similar in all age groups. Male gender, smoking in female patients, the presence of any spontaneous colony formation, and the presence of spontaneous megakaryocytic colony formation in younger patients were identified as risk factors for thrombosis. Pregnant ET patients had an increased risk of complications. Forty-five per cent of the pregnancies were complicated and 38 % of them ended in stillbirth. Treatment with acetylsalicylic acid alone or in combination with platelet lowering drugs improved the outcome of the pregnancy. The present findings about risk factors in ET as well as treatment outcome in the pregnancies of ET patients should be taken into account when planning treatment strategies for Finnish patients.

Gastrointestinal complications after kidney transplantation

The aim of the study was to evaluate gastrointestinal (GI) complications after kidney transplantation in the Finnish population. The adult patients included underwent kidney transplantation at Helsinki University Central Hospital in 1990-2000. Data on GI complications were collected from the Finnish Kidney Transplantation Registry, patient records and from questionnaires sent to patients. Helicobacter pylori IgG and IgA antibodies were measured from 500 patients before kidney transplantation and after a median 6.8-year follow up. Oesophagogastroduodenoscopy with biopsies was performed on 46 kidney transplantation patients suffering from gastroduodenal symptoms and 43 dyspeptic controls for studies of gastroduodenal cytomegalovirus (CMV) infection. Gallbladder ultrasound was performed on 304 patients after a median of 7.4 years post transplantation. Data from these 304 patients were also collected on serum lipids, body mass index and the use of statin medication. Severe GI complications occurred in 147 (10%) of 1515 kidney transplantations, 6% of them fatal after a median of 0.93 years. 51% of the complications occurred during the first post transplantation year, with highest incidence in gastroduodenal ulcers and complications of the colon. Patients with GI complications were older and had more delayed graft function and patients with polycystic kidney disease had more GI complications than the other patients. H.pylori seropositivity rate was 31% and this had no influence on graft or patient survival. 29% of the H.pylori seropositive patients seroreverted without eradication therapy. 74% of kidney transplantation patients had CMV specific matrix protein pp65 or delayed early protein p52 positive findings in the gastroduodenal mucosa, and 53% of the pp65 or p52 positive patients had gastroduodenal erosions without H.pylori findings. After the transplantation 165 (11%) patients developed gallstones. A biliary complication including 1 fatal cholecystitis developed in 15% of the patients with gallstones. 13 (0.9%) patients had pancreatitis. Colon perforations, 31% of them fatal, occurred in 16 (1%) patients. 13 (0.9%) developed a GI malignancy during the follow up. 2 H.pylori seropositive patients developed gastroduodenal malignancies during the follow up. In conclusion, severe GI complications usually occur early after kidney transplantation. Colon perforations are especially serious in kidney transplantation patients and colon diverticulosis and gallstones should be screened and treated before transplantation. When found, H.pylori infection should also be treated in these patients.