Studies of the genetic epidemiology of cardiovascular disease: focus on inflammatory candidate genes

Cardiovascular disease (CVD) is a complex disease with multifactorial aetiology. Both genetic and environmental factors contribute to the disease risk. The lifetime risk for CVD differs markedly between men and women, men being at increased risk. Inflammatory reaction contributes to the development of the disease by promoting atherosclerosis in artery walls. In the first part of this thesis, we identified several inflammatory related CVD risk factors associating with the amount of DNA from whole blood samples, indicating a potential source of bias if a genetic study selects the participants based on the available amount of DNA. In the following studies, this observation was taken into account by applying whole genome amplification to samples otherwise subjected to exclusion due to very low DNA yield. We continued by investigating the contribution of inflammatory genes to the risk for CVD separately in men and women, and looked for sex-genotype interaction. In the second part, we explored a new candidate gene and its role in the risk for CVD. Selenoprotein S (SEPS1) is a membrane protein residing in the endoplasmic reticulum where it participates in retro-translocation of unfolded proteins to cytosolic protein degradation. Previous studies have indicated that SEPS1 protects cells from oxidative stress and that variations in the gene are associated with circulating levels of inflammatory cytokines. In our study, we identified two variants in the SEPS1 gene, which associated with coronary heart disease and ischemic stroke in women. This is, to our knowledge, the first study suggesting a role of SEPS1 in the risk for CVD after extensively examining the variation within the gene region. In the third part of this thesis, we focused on a set of seven genes (angiotensin converting enzyme, angiotensin II receptor type I, C-reactive protein (CRP), and fibrinogen alpha-, beta-, and gamma-chains (FGA, FGB, FGG)) related to inflammatory cytokine interleukin 6 (IL6) and their association with the risk for CVD. We identified one variant in the IL6 gene conferring risk for CVD in men and a variant pair from IL6 and FGA genes associated with decreased risk. Moreover, we identified and confirmed an association between a rare variant in the CRP gene and lower CRP levels, and found two variants in the FGA and FGG genes associating with fibrinogen. The results from this third study suggest a role for the interleukin 6 pathway genes in the pathogenesis of CVD and warrant further studies in other populations. In addition to the IL6 -related genes, we describe in this thesis several sex-specific associations in other genes included in this study. The majority of the findings were evident only in women encouraging other studies of cardiovascular disease to include and analyse women separately from men.

Novel prognostic factors in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a malignant clonal blood disease that originates from a pluripotent hematopoietic stem cell. The cytogenetic hallmark of CML, the Philadelphia chromosome (Ph), is formed as a result of reciprocal translocation between chromosomes 9 and 22, which leads to a formation of a chimeric BCR-ABL fusion gene. The BCR-ABL protein is a constitutively active tyrosine kinase that changes the adhesion properties of cells, constitutively activates mitogenic signaling, enhances cell proliferation and reduces apoptosis. This results in leukemic growth and the clinical disease, CML. With the advent of targeted therapies against the BCR-ABL fusion protein, the treatment of CML has changed considerably during the recent decade. In this thesis, the clinical significance of different diagnostic methods and new prognostic factors in CML have been assessed. First, the association between two different methods for measuring CML disease burden (the RQ-PCR and the high mitotic index metaphase FISH) was assessed in bone marrow and peripheral blood samples. The correlation between positive RQ-PCR and metaphase FISH samples was high. However, RQ-PCR was more sensitive and yielded measurable transcripts in 40% of the samples that were negative by metaphase FISH. The study established a laboratory-specific conversion factor for setting up the International Scale when standardizing RQ-PCR measurements. Secondly, the amount of minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) was determined. For this, metaphase FISH was done for the bone marrow samples of 102 CML patients. Most (68%), had no residual cells during the entire follow-up time. Some (12 %) patients had minor (<1%) MRD which decreased even further with time, whereas 19% had a progressive rise in MRD that exceeded 1% or had more than 1% residual cells when first detected. Residual cells did not become eradicated spontaneously if the frequency of Ph+ cells exceeded 1% during follow-up. Next, the impact of deletions in the derivative chromosome 9, was examined. Deletions were observed in 15% of the CML patients who later received alloHSCT. After alloHSCT, there was no difference in the total relapse rate in patients with or without deletions. Nor did the estimates of overall survival, transplant-related mortality, leukemia-free survival and relapse-free time show any difference between these groups. When conventional treatment regimens are used, the der(9) status could be an important criterion, in conjunction with other prognostic factors, when allogeneic transplantation is considered. The significance of der(9) deletions for patients treated with tyrosine kinase inhibitors is not clear and requires further investigation. In addition to the der(9) status of the patient, the significance of bone marrow lymphocytosis as a prognostic factor in CML was assessed. Bone marrow lymphocytosis during imatinib therapy was a positive predictive factor and heralded optimal response. When combined with major cytogenetic response at three months of treatment, bone marrow lymphocytosis predicted a prognostically important major molecular response at 18 months of imatinib treatment. Although the validation of these findings is warranted, the determination of the bone marrow lymphocyte count could be included in the evaluation of early response to imatinib treatment already now. Finally, BCR-ABL kinase domain mutations were studied in CML patients resistant against imatinib treatment. Point mutations detected in the kinase domain were the same as previously reported, but other sequence variants, e.g. deletions or exon splicing, were also found. The clinical significance of the other variations remains to be determined.

Estimation of local forest attributes, utilizing two-phase sampling and auxiliary data

This thesis examines the feasibility of a forest inventory method based on two-phase sampling in estimating forest attributes at the stand or substand levels for forest management purposes. The method is based on multi-source forest inventory combining auxiliary data consisting of remote sensing imagery or other geographic information and field measurements. Auxiliary data are utilized as first-phase data for covering all inventory units. Various methods were examined for improving the accuracy of the forest estimates. Pre-processing of auxiliary data in the form of correcting the spectral properties of aerial imagery was examined (I), as was the selection of aerial image features for estimating forest attributes (II). Various spatial units were compared for extracting image features in a remote sensing aided forest inventory utilizing very high resolution imagery (III). A number of data sources were combined and different weighting procedures were tested in estimating forest attributes (IV, V). Correction of the spectral properties of aerial images proved to be a straightforward and advantageous method for improving the correlation between the image features and the measured forest attributes. Testing different image features that can be extracted from aerial photographs (and other very high resolution images) showed that the images contain a wealth of relevant information that can be extracted only by utilizing the spatial organization of the image pixel values. Furthermore, careful selection of image features for the inventory task generally gives better results than inputting all extractable features to the estimation procedure. When the spatial units for extracting very high resolution image features were examined, an approach based on image segmentation generally showed advantages compared with a traditional sample plot-based approach. Combining several data sources resulted in more accurate estimates than any of the individual data sources alone. The best combined estimate can be derived by weighting the estimates produced by the individual data sources by the inverse values of their mean square errors. Despite the fact that the plot-level estimation accuracy in two-phase sampling inventory can be improved in many ways, the accuracy of forest estimates based mainly on single-view satellite and aerial imagery is a relatively poor basis for making stand-level management decisions.

Genetic Diversity and Adaptation of Date Palm (Phoenix dactylifera L.)

Acquiring sufficient information on the genetic variation, genetic differentiation, and the ecological and genetic relationships among individuals and populations are essential for establishing guidelines on conservation and utilization of the genetic resources of a species, and more particularly when biotic and abiotic stresses are considered. The aim of this study was to assess the extent and pattern of genetic variation in date palm (Phoenix dacttylifera L) cultivars; the genetic diversity and structure in its populations occurring over geographical ranges; the variation in economically and botanically important traits of it and the variation in its drought adaptive traits, in conservation and utilization context. In this study, the genetic diversity and relationships among selected cultivars from Sudan and Morocco were assessed using microsatellite markers. Microsatellite markers were also used to investigate the genetic diversity within and among populations collected from different geographic locations in Sudan. In a separate investigation, fruits of cultivars selected from Sudan, involved morphological and chemical characterization, and morphological and DNA polymorphism of the mother trees were also investigated. Morphological and photosynthetic adjustments to water stress were studied in the five most important date palm cultivars in Sudan, namely, Gondaila, Barakawi, Bitamoda, Khateeb and Laggai; and the mechanism enhancing photosynthetic gas exchange in date palm under water stress was also investigated. Results showed a significant (p < 0.001, t-test) differentiation between Sudan and Morocco groups of cultivars. However, the major feature of all tested cultivars was the complete lack of clustering and the absence of cultivars representing specific clones. The results indicated high genetic as well as compositional and morphological diversity among cultivars; while, compositional and morphological traits were found to be characteristic features that strongly differentiate cultivars as well as phenotypes. High genetic diversity was observed also in different populations. Slight but significant (p < 0.01, AMOVA) divergence was observed for soft and dry types; however, the genetic divergence among populations was relatively weak. The results showed a complex genetic relationships between some of the tested populations especially when isolation by distance was considered. The results of the study also revealed that date palm cultivars and phenotypes possess specific direct or interaction effects due to water availability on a range of morphological and physiological traits. Soft and dry phenotypes responded differently to different levels of water stress, while the dry phenotype was more sensitive and conservative. The results indicated that date palm has high fixation capacity to photosynthetic CO2 supply with interaction effect to water availability, which can be considered as advantageous when coping with stresses that may arise with climate change. In conclusion, although a large amount of diversity exists among date palm germplasm, the findings in this study show that the role of biological nature of the tree, isolation by distance and environmental effects on structuring date palm genome was highly influenced by human impacts. Identity of date palm cultivars as developed and manipulated by date palm growers, in the absence of scientific breeding programmes, may continue to mainly depend on tree morphology and fruit characters. The pattern of genetic differentiation may cover specific morphological and physiological traits that contribute to adaptive mechanisms in each phenotype. These traits can be considered for further studies related to drought adaptation in date palm.

Undersowing in a northern climate: effects on spring cereal yield and risk of nitrate leaching

Disadvantages of invariable cereal cropping, concern of nutrient leaching and prices of nitrogen (N) fertilizer have all increased during last decades. An undersown crop, which grows together with a main crop and after harvest, could mitigate all those questions. The aim of this study was to develop undersowing in Finnish conditions, so that it suits for spring cereal farming as well as possible and enhances taking care of soil and environment, especially when control of N is concerned. In total, 17 plant species were undersown in spring cereals during the field experiments between 1991-1999 at four sites in South and Central Finland, but after selection, eight of them were studied more thoroughly. Two legumes, one grass species and one mixture of them were included in long-term trials in order to study annually repeated undersowing. Further, simultaneous broadcasting of seeds instead of separate undersowing was studied. Grain yield response and the capacity of the undersown crop to absorb soil N or fix N from atmosphere, and the release of N were of greatest interest. Seeding rates of undersown crops and N fertilization rates during annually repeated undersowing were also studied. Italian ryegrass (Lolium multiflorum Lam., IR) absorbed soil nitrate N (NO3-N) most efficiently in autumn and timothy (Phleum pratense L.) in spring. The capacity of other grass species to absorb N was low, or it was insufficient considering the negative effect on grain yield. Red clover (Trifolium pratense L.) and white clover (Trifolium repens L.) suited well in annually repeated undersowing, supplying fixed N for cereals without markedly increased risk of N leaching. Autumn oriented growth rhythm of the studied legumes was optimal for undersowing, whereas the growth rhythm of grasses was less suited but varied between species. A model of adaptive undersowing system was outlined in order to emphasize allocation of measures according needs. After defining the goal of undersowing, many decisions are to be done. When diminishing N leaching is primarily sought, a mixture of IR and timothy is advantageous. Clovers suit for replacing N fertilization, as the positive residual effect is greater than the negative effect caused by competition. A mixture of legume and non legume is a good choice when increased diversity is the main target. Seeding rate is an efficient means for adjusting competition and N effects. Broadcasting with soil covering equipment can be used to establish an undersown crop. In addition, timing and method of cover crop termination have an important role in the outcome. Continuous observing of the system is needed as for instance conditions significantly affect growth of undersown crop and on the other hand N release from crop residues may increase in long run.

Quantitative trait loci detection and benefits from marker-assisted selection in dairy cattle

Knowing the chromosomal areas or actual genes affecting the traits under selection would add more information to be used in the selection decisions which would potentially lead to higher genetic response. The first objective of this study was to map quantitative trait loci (QTL) affecting economically important traits in the Finnish Ayrshire population. The second objective was to investigate the effects of using QTL information in marker-assisted selection (MAS) on the genetic response and the linkage disequilibrium between the different parts of the genome. Whole genome scans were carried out on a grand-daughter design with 12 half-sib families and a total of 493 sons. Twelve different traits were studied: milk yield, protein yield, protein content, fat yield, fat content, somatic cell score (SCS), mastitis treatments, other veterinary treatments, days open, fertility treatments, non-return rate, and calf mortality. The average spacing of the typed markers was 20 cM with 2 to 14 markers per chromosome. Associations between markers and traits were analyzed with multiple marker regression. Significance was determined by permutation and genome-wise P-values obtained by Bonferroni correction. The benefits from MAS were investigated by simulation: a conventional progeny testing scheme was compared to a scheme where QTL information was used within families to select among full-sibs in the male path. Two QTL on different chromosomes were modelled. The effects of different starting frequencies of the favourable alleles and different size of the QTL effects were evaluated. A large number of QTL, 48 in total, were detected at 5% or higher chromosome-wise significance. QTL for milk production were found on 8 chromosomes, for SCS on 6, for mastitis treatments on 1, for other veterinary treatments on 5, for days open on 7, for fertility treatments on 7, for calf mortality on 6, and for non-return rate on 2 chromosomes. In the simulation study the total genetic response was faster with MAS than with conventional selection and the advantage of MAS persisted over the studied generations. The rate of response and the difference between the selection schemes reflected clearly the changes in allele frequencies of the favourable QTL. The disequilibrium between the polygenes and QTL was always negative and it was larger with larger QTL size. The disequilibrium between the two QTL was larger with QTL of large effect and it was somewhat larger with MAS for scenarios with starting frequencies below 0.5 for QTL of moderate size and below 0.3 for large QTL. In conclusion, several QTL affecting economically important traits of dairy cattle were detected. Further studies are needed to verify these QTL, check their presence in the present breeding population, look for pleiotropy and fine map the most interesting QTL regions. The results of the simulation studies show that using MAS together with embryo transfer to pre-select young bulls within families is a useful approach to increase the genetic merit of the AI-bulls compared to conventional selection.

F-18 Labelling Synthesis, Radioanalysis and Evaluation of A Dopamine Transporter and A Hypoxia Tracer

Positron emission tomography (PET) is an imaging technique in which radioactive positron-emitting tracers are used to study biochemical and physiological functions in humans and in animal experiments. The use of PET imaging has increased rapidly in recent years, as have special requirements in the fields of neurology and oncology for the development of syntheses for new, more specific and selective radiotracers. Synthesis development and automation are necessary when high amounts of radioactivity are needed for multiple PET studies. In addition, preclinical studies using experimental animal models are necessary for evaluating the suitability of new PET tracers for humans. For purification and analysing the labelled end-product, an effective radioanalytical method combined with an optimal radioactivity detection technique is of great importance. In this study, a fluorine-18 labelling synthesis method for two tracers was developed and optimized, and the usefulness of these tracers for possible prospective human studies was evaluated. N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP) is a candidate PET tracer for the dopamine transporter (DAT), and 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([18F]FMISO) is a well-known hypoxia marker for hypoxic but viable cells in tumours. The methodological aim of this thesis was to evaluate the status of thin-layer chromatography (TLC) combined with proper radioactivity detection measurement systems as a radioanalytical method. Three different detection methods of radioactivity were compared: radioactivity scanning, film autoradiography, and digital photostimulated luminescence (PSL) autoradiography. The fluorine-18 labelling synthesis for [18F]β-CFT-FP was developed and carbon-11 labelled [11C]β-CFT-FP was used to study the specificity of β-CFT-FP for the DAT sites in human post-mortem brain slices. These in vitro studies showed that β-CFT-FP binds to the caudate-putamen, an area rich of DAT. The synthesis of fluorine-18 labelled [18F]FMISO was optimized, and the tracer was prepared using an automated system with good and reproducible yields. In preclinical studies, the action of the radiation sensitizer estramustine phosphate on the radiation treatment and uptake of [18F]FMISO was evaluated, with results of great importance for later human studies. The methodological part of this thesis showed that radioTLC is the method of choice when combined with an appropriate radioactivity detection technique. Digital PSL autoradiography proved to be the most appropriate when compared to the radioactivity scanning and film autoradiography methods. The very high sensitivity, good resolution, and wide dynamic range of digital PSL autoradiography are its advantages in detection of β-emitting radiolabelled substances.

Host Rock Classification (HRC) system for nuclear waste disposal in crystalline bedrock

A new rock mass classification scheme, the Host Rock Classification system (HRC-system) has been developed for evaluating the suitability of volumes of rock mass for the disposal of high-level nuclear waste in Precambrian crystalline bedrock. To support the development of the system, the requirements of host rock to be used for disposal have been studied in detail and the significance of the various rock mass properties have been examined. The HRC-system considers both the long-term safety of the repository and the constructability in the rock mass. The system is specific to the KBS-3V disposal concept and can be used only at sites that have been evaluated to be suitable at the site scale. By using the HRC-system, it is possible to identify potentially suitable volumes within the site at several different scales (repository, tunnel and canister scales). The selection of the classification parameters to be included in the HRC-system is based on an extensive study on the rock mass properties and their various influences on the long-term safety, the constructability and the layout and location of the repository. The parameters proposed for the classification at the repository scale include fracture zones, strength/stress ratio, hydraulic conductivity and the Groundwater Chemistry Index. The parameters proposed for the classification at the tunnel scale include hydraulic conductivity, Q´ and fracture zones and the parameters proposed for the classification at the canister scale include hydraulic conductivity, Q´, fracture zones, fracture width (aperture + filling) and fracture trace length. The parameter values will be used to determine the suitability classes for the volumes of rock to be classified. The HRC-system includes four suitability classes at the repository and tunnel scales and three suitability classes at the canister scale and the classification process is linked to several important decisions regarding the location and acceptability of many components of the repository at all three scales. The HRC-system is, thereby, one possible design tool that aids in locating the different repository components into volumes of host rock that are more suitable than others and that are considered to fulfil the fundamental requirements set for the repository host rock. The generic HRC-system, which is the main result of this work, is also adjusted to the site-specific properties of the Olkiluoto site in Finland and the classification procedure is demonstrated by a test classification using data from Olkiluoto. Keywords: host rock, classification, HRC-system, nuclear waste disposal, long-term safety, constructability, KBS-3V, crystalline bedrock, Olkiluoto

Teot ja pelastus varhaisessa juutalaisuudessa

Työn tarkoituksena on selvittää, miten varhaisessa juutalaisuudessa on ymmärretty tekojen ja pelastuksen välinen yhteys, ja osana sitä, mikä on ei-juutalaisten rooli pelastuksen kannalta. Pelastus määritellään Jumalan aikaansaamaksi myönteiseksi muutokseksi, joka tapahtuu jostakin huonommasta johonkin parempaan, ja voi liittyä sekä tämän- että tuonpuoleiseen elämään. Aineistona käytetään seuraavia tekstejä: Tobitin kirja, 1.-4. makkabilaiskirjat, Henokin kirja, Kahdentoista patriarkan testamentit, Abrahamin testamentti, Sibyllan oraakkelit, Salomon psalmit, Toinen Barukin kirja ja Qumranin Yhdyskuntasääntö (1QS). Tarkasteltavana on juutalainen ajattelu ajanjaksolla n. 300 eKr. - 70 jKr. Aineiston valinta perustellaan, ja siinä käytetään kirjallisuuden lisäksi apuna pelastussanojen esiintymisfrekvenssejä. Työn pääosa muodostuu siten, että kustakin kirjasta etsitään ja järjestetään pelastusta koskevat kohdat. Tätä tarkastelua täydennetään kirjallisuuden tiedoilla siten, että kustakin tekstistä on yksi luku, jossa kirjan pelastusta koskevat ajatukset käydään läpi. Lisäksi tarkastellaan myös kirjoitusten taustalla vaikuttaneita ryhmittymiä, apokalyptiikkaa ja messiashahmoa. Löydetty materiaali järjestetään edelleen johtopäätöksiksi. Työ sisältää joitakin suomeksi julkaisemattomien kirjoitusten kohtia, jotka tekijä on kääntänyt alkukielestä. Teoista ja pelastuksesta nousevat esille seuraavat asiat. Tooran noudattaminen on keskeisellä sijalla varhaisessa juutalaisuudessa, mutta ei vastaa tyhjentävästi tekojen vaatimukseen. Pelastus voi seurata lain määräysten noudattamisesta, mutta asiasta on erilaisia painotuksia ja tulkintoja. Lakia voidaan ymmärtää eri tavoin, eikä kaikkia määräyksiä pidetä välttämättä sitovina. Elinympäristökin sanelee lain noudattamiselle omat reunaehtonsa. Varhaisen juutalaisuuden keskuspaikkana on Jerusalemin temppeli, jossa harjoitettuun temppelikulttiin osallistuminen tekee osalliseksi myös pelastuksesta. Temppelikultti saattaa kuitenkin olla mahdotonta harjoittaa, tai jotkut ryhmät katsovat sen saastuneen. Tällöin tilalle nousee muita tekoja, joilla on pelastava vaikutus. Teot, jotka ovat jo aiemmin kuuluneet hurskauselämään, saavat nyt paljon suuremman painoarvon. Almujen antaminen pelastaa ja varjelee, samoin paasto ja nöyrtyminen. Juhlien ja sapatin vietto korvaa temppelin puuttumista, mutta sapattimääräysten sitovuus sota-aikana joudutaan arvioimaan. Keskeisiä säädöksiä pelastuksen kannalta ovat myös ruokamääräykset, siveys ja avioliitto omaan kansaan tai sukuun kuuluvan kanssa. Oikean asian puolesta sodittaessa Jumala voi pelastaa viholliselta ja antaa voittoja omissa sotatoimissa, mutta tappioiden jälkeen pelastusajatukset suuntautuvat täydeltä tuholta välttymiseen tai eskatologiseen pelastukseen. Kärsimys tuottaa sovinnon Jumalan kanssa. Joissakin teksteissä marttyyrien veri tuottaa sovituksen koko kansalle, ja vastarintaan kehotetaankin nousemaan empimättä. Myös ennenaikaisen kuoleman katsotaan pelastavan niin, ettei kuolemanjälkeistä rangaistusta enää tule. Rukous on monissa kohdissa keskeinen teko, joka vaikuttaa pelastumiseen sekä maanpäällisessä että kuolemanjälkeisessä elämässä, ja sekä toisten että rukoilijan omalta osalta. Tuonpuoleiseen kohtaloon vaikuttavat teot punnitaan kuoleman jälkeen. Myös itse kuolintapahtuman lempeys tai julmuus riippuu maanpäällisistä teoista. Pelastusodotukset kohdistuvat joissakin teksteissä Messiaaseen, joka kuvataan osittain eri tavoin ja eri henkilöinäkin. Yleinen käsitys on daavidilainen sotaisa hahmo. Joissakin kirjoituksissa kuvataan universaali henkimaailma, joka vaikuttaa niin juutalaisten kuin muihinkin kansoihin kuuluvien ihmisten tekojen taustalla. Ohjeita annetaan siitä, mikä tekee oikeat teot ylipäätään mahdollisiksi tehdä. Paitsi että järki on avuksi, niin hyvän tekeminen ja sydämen täyttyminen rakkaudella pelastavat vihasta ja saavat toimimaan oikein. Ei-juutalaiset voidaan nähdä pahoina valloittajina, mutta syynä heidän raakuuksilleen ovat sittenkin oman kansan synnit. Juutalaisten kohtalo toimii muille kansoille varoituksena ja esimerkkinä. Joissakin teksteissä uskalletaan rinnastaa juutalaisten ja ei-juutalaisten pelastus melko pitkällekin, joissakin taas on jyrkempi rajanveto. Sibyllan oraakkeleissa on suoranaisia määräyksiä muille kansoille. Ajattelutavassa on eroja eri juutalaisten ryhmien välillä. Jotkut käsitykset pelastuksesta ovat yhdistettävissä sadokilaiseen temppelipapistoon, makkabilaisiin, essealaisiin, Qumranin yhteisöön, fariseuksiin tai vähemmän tunnettuihin ryhmiin, sen mukaan kuin tekstejä voidaan yhdistää näihin.

Ennaltamäärätty kääntymys: Predestinaatio ja vapaan tahdon ongelma Jonathan Edwardsin teologiassa

Tämän tutkielman tehtävänä on ollut selvittää onko ihmisellä vapaata tahtoa Jonathan Edwardsin mukaan. Lähteenäni minulla on ollut Edwardsin Freedom of the Will -teos sekä Miscellaneous- sarjasta Concerning the Divine Degrees -kirjoitus. Metodina minulla on ollut systemaattinen analyysi. Edwardsin taustana oli puritanismi. Esimerkiksi sakramenteilla ei ollut puritanismin piirissä samaa ratkaisevaa merkitystä uskon synnyttäjänä ja ylläpitäjänä kuin perinteisissä kristillisissä kirkoissa oli ollut. Puritanistien keskeinen armonväline oli saarna. Saarnalla pyrittiin vaikuttamaan ihmisen tahtoon antamalla rationaalisia perusteita Raamatun pelastustapahtumasta. Tämä on nähtävissä myös Jonathan Edwardsin teologiassa. Deismi ja valistus vaikuttivat myös Edwardsin aikaiseen ajatteluun voimakkaasti. Edwardsin Berkeleytä muistuttava idealismi kuitenkin takasi sen, että Jumala ei irronnut maailmasta vaan oli kaikessa koko ajan läsnä. Erityisesti Locke Newtonin luonnontieteiden filosofina vaikutti Edwardsin filosofiseen ajatteluun tahdon vapaus -kysymyksen osalta. Edwards pyrki Locken ja Newtonin avulla puolustamaan perinteistä kalvinistista kristillisyyttä. Tämän kilpailijaksi puritanismin piirissä oli tullut ajan henkeen sopiva järkiperäinen arminiolaisuus, joka edusti myös anti-revivalismia. Tähän arminiolaisuuteen liittyi perinteisistä kristillisistä opeista luopuminen. Tämä arminiolaisuus oli kehittynyt antropologisempaan suuntaan Remonstranssin ajoista korostaen ihmisen vapaita tahdon akteja. Näin ihminen pystyi päättämään uskoiko hän vai ei. Edwardsille usko ja pelastuminen perustuivat Jumalan valintaan, jossa kolmiyhteinen Jumala otti ihmisen yhteyteensä. Tämä kääntymys ilmeni kommuuniona ja uniona Kristuksen kanssa. Edwardsin ajattelua tahdon vapauden osalta avaa kompatibilismi. Kompatibilismin mukaan ennaltamäärääminen ei ole ristiriidassa vapaan tahdon kanssa, vaan päinvastoin sen lähtökohta ja perusta. Kääntymissä olemme eri näkökulmista täysin passivisia ja täysin aktiivisia. Kompatibilismin myötä Edwardsin kirjoitusten pohjalta pystytään johtamaan ennalta määrätty uskonratkaisu. Myöhemmin Edwardsin seuraajat New Lights harppasivat ironisesti arminiolaiseen suuntaan korostaen juuri uskonratkaisua. Vaikka Jumalalla on sanan varsinaisessa merkityksessä vapaa tahto, niin silti Hän toimii välttämättä pyhästi. Samoin Jeesus Kristus on linkkinä ihmisten välttämättömälle, mutta vastuulliselle toiminnalle. Jeesuksen valinta on kaikkien pyhien valinnan perusta. Ne, jotka Jumala hylkää helvettiin saavat oikeudenmukaisen rangaistuksen, koska Jumala rankaisee heissä itsessään olevaa pahaa. Se, miksi Jumala valitsee toiset ja hylkää toiset, kuuluu Jumalan salattuun tahtoon. Jumalan ilmoitetun tahdon mukaan Hän tahtoo kaikkien pelastuvan. Arminiolaiset hylkäävät ennaltamääräämisen, mutta hyväksyvät ennalta tietämisen. Edwardsille nämä ovat sama asia. Edwardsin mukaan välttämättömyys ei ole ristiriidassa vapauden kanssa. Luonnollisella ja moraalisella välttämättömyydellä on yhteys. Arkikielessä moraalista välttämättömyyttä ei oleteta. Koko tahdon vapaus -kysymys on pitkälti kielellinen. Arkikielessä ja filosofisessa kielessä on ero. Tahto ei ole agentti, joka voi valita itsenäisesti. Vapaus on ihmisen, ei tahdon ominaisuus. Siksi kysymys tahdon vapaudesta tulisi esittää onko ihminen vapaa. Edwards ja arminiolaiset ymmärtävät vapauden eri tavoin. Edwardsin mukaan tahdolla on oltava alku, eikä tahto voi koskaan arminiolaisten tavoin neutraali. Arminiolaiset hylkäävät perisyntiopin klassisessa merkityksessä, mistä seuraa erilainen lähtökohta. Sellaisena kuin arminiolaiset esittävät vapaan tahdon, meillä ei sitä Edwardsin mukaan ole. Vaikka kaikki tapahtuu Edwardsin mukaan välttämättä, niin silti olemme vastuullisia moraalisia agentteja.

Humanitaarinen interventio ja Suomen sotilaallinen kriisinhallinta

Tämän tutkielman tarkoitus on selvittää, voidaanko humanitaarisen intervention käsitteellä kuvata Suomen sotilaallista kriisinhallintaa. Lähtökohta on, että kriisinhallintatehtävien vaarallisuus ja tavoite auttaa kriisien uhreja edellyttävät tämän suhteen avaamista. Tutkimusmetodi on systemaattinen analyysi, jonka lähdekirjallisuutta ovat etiikan, kansainvälisen politiikan ja sotataidon teokset, lainsäädäntö, hallinnolliset asiakirjat sekä mielipidetutkimukset. Kansainvälisesti humanitaarista interventiota on tutkittu paljon; sen luonnetta Suomen sotilaallisessa kriisinhallinnassa vähän. Tutkimuskysymys ratkaistaan välitavoittein: 1) Mikä on humanitaarisen intervention merkitys kriisinhallinnan käsitteistössä?, 2) miten se on oikeutettavissa ja mikä on sen oikeutettu määritelmä?, 3) onko humanitaarisen intervention käsitteellä vastaavuus Suomen sotilaallisessa kriisinhallinnassa ja 4) ovatko kansallinen etu ja kansainvälinen vastuu ristiriidassa päätettäessä sotilaallisesta kriisinhallinnasta? Neljä välitavoitetta vastaa tämän tutkielman neljää päälukua. Ensimmäiseksi osoitetaan, että humanitaarinen interventio on sotilaallisen kriisinhallinnan laji, jolla sotataidon menetelmin voidaan vaikuttaa tehokkaasti vakavaan valtionsisäiseen kriisin. Kansainvälisesti se on yleistynyt perinteisen rauhanturvaamisen vähetessä. Asevoiman käyttö voi olla passiivista tai aktiivista ja siihen pätee samat vaaran ja virheen lainalaisuudet kuin sodankäyntiin yleensä. Toiseksi tarkastellaan 1) kansainvälisoikeudellista, 2) oikeutetun sodan koulukunnan, 3) uusliberalistista, 4) kansalaisjärjestöjen näkökulmaan pohjautuvaa sekä 5) synteettistä oikeuttamismallia. Parhaiten ilmiötä kuvaa synteettinen toiminnallinen oikeuttamismalli, joka perustuu sekä etiikan teoriaan että sotataidon empiriaan. Oikeuttamistarkastelusta johdetaan tämän tutkielman määritelmä: ”Humanitaarinen interventio on valtion tai siihen verrattavan ryhmittymän pakottaminen sotilaallisella voimankäytöllä lopettamaan alueellaan tapahtuvat vakavat ja välittömät ihmisoikeusloukkaukset. Humanitaarisella interventiolla tulee olla kansainvälisen yhteisön enemmistön tuki. Humanitaarisen intervention operaatiotyypit ovat: 1) avun perillemenon varmistaminen, 2) avustusoperaatioiden suojaaminen, 3) uhrien pelastaminen ja 4) pahantekijäin lyöminen.” Kolmanneksi verrataan määritelmän vastaavuutta Suomen sotilaallisen kriisinhallinnan teoriaan ja käytäntöön. Ilmenee, että lainsäädännössä ja hallintokielessä korrektit ilmaisut kuten ´erittäin vaativat kriisinhallintatehtävät´ perinteisen rauhanturvaamisen vastakohtana peittävät yhden tarkoitteistaan, joka sotataidon kielessä on humanitaarinen interventio. Luokitellaan myös puolustusvoimien verkkosivuillaan ilmoittamat kriisinhallintaoperaatiot suhteessa humanitaarisen intervention neljään tyyppiin. Ilmenee, että valtaosa henkilöstöresursseista sitoutuu humanitaarisiin interventioihin tai intervention tyyppejä sisältäviin sekoittuneisiin operaatioihin. Esimerkkinä sekoittuneesta operaatiotilanteesta käsitellään Afganistania. Vähemmistö henkilöstöstä on puhtaissa perinteisen rauhanturvaa-misen tai puhtaissa humanitaarisen intervention operaatioissa kuten EU:n Tshadin operaatiossa. Neljänneksi tutkitaan kansallista etua kriisinhallinnassa hyötyinä yksilölle ja valtiolle. Analysoidaan kansallisen edun ja kansainvälisen vastuun suhdetta, jossa valinnan ääripäät painottavat pelkkää valtion etua tai vain globaalia vastuuta. Ääripäiden keskiväli on eettisen politiikan valinta. Todetaan, että sotilaallisen kriisinhallinnan tulos on mitattava kriisin uhrien näkökulmasta. Tulee ilmi sotataidon perimmäinen kysymys ihmishengen samanaikaisesta itseis- ja välinearvosta, mikä on eettisen harkinnan perusta lähetettäessä kansalaisia kuolemanvaaraan. Globaalia vastuuta ja kansallista etua ei voida ristiriidattomasti sovittaa yhteen päätettäessä sotilaallisesta kriisinhallinnasta. Tämän tutkielman johtopäätös on, että näin määritellyllä humanitaarisen intervention käsitteellä voidaan kuvata Suomen sotilaallisen kriisinhallinnan vaativia tehtäviä perinteisen rauhanturvaamisen vastakohtana. Ilmiön monimuotoisuus edellyttää teoreettista ja empiiristä jatkotutkimusta, jonka tavoite on myös kriisinhallinnan tavoite, – hyveen ja hyvän elämän edistäminen.

Concordia-lehti Lutherin ja luterilaisen ortodoksian teologian tulkitsijana 1994-2003

Concordia-lehti alkaessaan ilmestyä 1994 herätti ristiriitaisia reaktioita esimerkiksi SLEY:n henkilöstön keskuudessa. Alusta alkaen avainhenkilöitä ovat olleet Hannu Lehtonen, Hannu Halonen, Simo Kiviranta ja Sakari Korpinen. Ekumeniaan Concordia on suhtautunut kriittisesti arvioidessaan Porvoon sopimusta ja Yhteistä julistusta vanhurskauttamisesta. Keskeisiä teemoja tässä lehdessä ovat olleet tutkittavana aikana yleinen ja uskon kautta tapahtuva vanhurskauttaminen, Raamatun arvovallan korostaminen, sakramenttien merkityksen esillä pitäminen ja tietyt moraaliset ja eettiset periaatteet ja näkökulmat. Concordiassa on esiintynyt runsaasti sitaatteja Martti Lutherin teoksista, melko paljon myös luterilaisen ortodoksian edustajilta, kuten Martin Chemnitziltä ja Johann Gerhardilta. Ylivoimaisesti eniten artikkeleja kymmenen vuoden aikana on tehnyt päätoimittaja, pastori Hannu Lehtonen. Kirjoittajien joukossa maallikkojen osuus on ollut huomattava. Karismaattisia ilmiöitä arvioitaessa nähtiin osan armolahjoista kuuluneen ennen kaikkea alkukirkon aikaan, vaikka samalla todettiin ihmeitä voivan tapahtua nykyaikanakin. Concordian kirjoittajat eivät hyväksyneet läheskään kaikkia Suomen evankelis-luterilaisessa kirkossa tapahtuneita päätöksiä, asioita ja ilmiöitä. Voimakkaasti todettiin, että kirkossa ei tulisi samanaikaisesti sallia sekä totuutta että erilaisia harhaoppeja. Myös evankelisen liikkeen tai muiden herätysliikkeiden toimintaa ei aina pidetty tarpeeksi rohkeana, vaan katsottiin niiden mukautuneen liikaa yhteiskuntaan ja yleiseen ja valtaa pitävään kirkollisuuteen. Esimerkiksi Helsingin yliopistossa käytettyä historiallis-kriittistä metodia parempana metodina pidettiin historiallis-dogmaattista. Opetusta maailman syntymisestä pitkän evoluutio-prosessin seurauksena ei Concordiassa hyväksytty, vaan opetettiin Jumalan luoneen maailman kuudessa päivässä. Concordiassa kirjoittajina on esiintynyt myös useita tunnustuksellisen luterilaisuuden edustajia lähinnä Yhdysvalloista ja Pohjoismaista. Tutkitun lehden merkitys kirkollisessa kentässä ei ole tilaajamäärän pienuuden vuoksi kovin merkittävä, mutta eräänlaisena taustalla vaikuttajana ja keskustelun herättäjänä vaikutus on ollut suurempi. Concordian näkemyksen mukaan suuri enemmistö ei läheskään aina ole ollut oikeassa hengellisissä kysymyksissä. Evankeliseen liikkeeseen Concordian kirjoittajilla on ollut tietynlainen viha-rakkaussuhde, vaikka se on ollut monen kirjoittajan hengellinen koti. Lehdessä esiintynyttä pietismin arviointia tutkimus ei ole kovin paljon käsitellyt, koska se ei olisi kovin hyvin sopinut eri lukujen otsi- koiden alle. Helluntailaisuuden eri opinkäsityksiä Concordia on myös pyrkinyt kumoamaan. Lehti on halunnut koko ajan perustella opetuksensa selkeillä raamatunkohdilla ja edistää näin luterilaisen uskon ja opin tuntemusta. Tässä tutkimuksessa on ollut tietoinen valinta käyttää samoja raamatunkohtia lähteenä, joita Concordian kirjoittajat ovat itse käyttäneet. Kirkkohistoriaan kuuluvassa opinnäytteessä ei ole yleensä tyypillistä käyttää näin paljon viittauksia Raamattuun, mutta tällainen dogmatiikan mukaan ottaminen on perusteltua, koska se on niin olennainen osa Concordia-lehden teologiaa ja tapaa tuoda esille asioita. Tiivistetysti todeten ihmisten ainoa vapahtaja ja pelastaja on ollut tutkitun lehden mukaan ja on edelleen Jeesus Kristus.

Conservation of Atlantic salmon by supplementary stocking of juvenile fish

Wild salmon stocks in the northern Baltic rivers became endangered in the second half of the 20th century, mainly due to recruitment overfishing. As a result, supplementary stocking was widely practised, and supplementation of the Tornionjoki salmon stock took place over a 25 year period until 2002. The stock has been closely monitored by electrofishing, smolt trapping, mark-recapture studies, catch samples and catch surveys. Background information on hatchery-reared stocked juveniles was also collected for this study. Bayesian statistics was applied to the data as this method offers the possibility of bringing prior information into the analysis and an advanced ability for incorporating uncertainty, and also provides probabilities for a multitude of hypotheses. Substantial divergences between reared and wild Tornionjoki salmon were identified in both demographic and phenological characteristics. The divergences tended to be larger the longer the duration spent in hatchery and the more favourable the hatchery conditions were for fast growth. Differences in environment likely induced most of the divergences, but selection of brood fish might have resulted in genotypic divergence in maturation age of reared salmon. Survival of stocked 1-year old juveniles to smolt varied from about 10% to about 25%. Stocking on the lower reach of the river seemed to decrease survival, and the negative effect of stocking volume on survival raises the concern of possible similar effects on the extant wild population. Post-smolt survival of wild Tornionjoki smolts was on average two times higher than that of smolts stocked as parr and 2.5 times higher than that of stocked smolts. Smolts of different groups showed synchronous variation and similar long-term survival trends. Both groups of reared salmon were more vulnerable to offshore driftnet and coastal trapnet fishing than wild salmon. Average survival from smolt to spawners of wild salmon was 2.8 times higher than that of salmon stocked as parr and 3.3 times higher than that of salmon stocked as smolts. Wild salmon and salmon stocked as parr were found to have similar lifetime survival rates, while stocked smolts have a lifetime survival rate over 4 times higher than the two other groups. If eggs are collected from the wild brood fish, stocking parr would therefore not be a sensible option. Stocking smolts instead would create a net benefit in terms of the number of spawners, but this strategy has serious drawbacks and risks associated with the larger phenotypic and demographic divergences from wild salmon. Supplementation was shown not to be the key factor behind the recovery of the Tornionjoki and other northern Baltic salmon stocks. Instead, a combination of restrictions in the sea fishery and simultaneous occurrence of favourable natural conditions for survival were the main reasons for the revival in the 1990 s. This study questions the effectiveness of supplementation as a conservation management tool. The benefits of supplementation seem at best limited. Relatively high occurrences of reared fish in catches may generate false optimism concerning the effects of supplementation. Supplementation may lead to genetic risks due to problems in brood fish collection and artificial rearing with relaxed natural selection and domestication. Appropriate management of fisheries is the main alternative to supplementation, without which all other efforts for long-term maintenance of a healthy fish resource fail.

Phylogeography and Adaptive Divergence of Three-spined Stickleback Populations

Genetic studies on phylogeography and adaptive divergence in Northern Hemisphere fish species such as three-spined stickleback (Gasterosteus aculeatus) provide an excellent opportunity to investigate genetic mechanisms underlying population differentiation. According to the theory, the process of population differentiation results from a complex interplay between random and deterministic processes as well historical factors. The main scope in this thesis was to study how historical factors like the Pleistocene ice ages have shaped the patterns molecular diversity in three-spined stickleback populations in Europe and how this information could be utilized in the conservation genetic context. Furthermore, identifying footprints of natural selection at the DNA level might be used in identifying genes involved in evolutionary change. Overall, the results from phylogeographic studies indicate that the three-spined stickleback has colonized the Atlantic basin relatively recently but constitutes three major evolutionary lineages in Europe. In addition, the colonization of freshwater appears to result from multiple and independent invasions by the marine conspecifics. Molecular data together with morphology suggest that the most divergent freshwater populations are located in the Balkan Peninsula and these populations deserve a special conservation genetic status without warranting further taxonomical classification. In order to investigate the adaptive divergence in Fennoscandian three-spined stickleback populations several approaches were used. First, sequence variability in the Eda-gene, coding for the number of lateral plates, was concordant with the previously observed global pattern. Full plated allele is in high frequencies among marine populations whereas low plated allele dominates in the freshwater populations. Second, a microsatellite based genome scan identified both indications of balancing and directional selection in the three-spined stickleback genome, i.e. loci with unusually similar or unusually different allele frequencies over populations. The directionally selected loci were mainly associated with the adaptation to freshwater. A follow up study conducting a more detailed analysis in a chromosome region containing a putatively selected gene locus identified a fairly large genomic region affected by natural selection. However, this region contained several gene predictions, all of which might be the actual target of natural selection. All in all, the phylogeographic and adaptive divergence studies indicate that most of the genetic divergence has occurred in the freshwater populations whereas the marine populations have remained relatively uniform.

Sinusta kiinni : Tutkimus puolisohoivan arjen toimijuuksista

Depending on you – A study of spousal care, everyday life and agency The present aim of the aging policy is to promote old peoples´ possibilities to live at their own home. It is also many elderly couples´ own wish. At home a persons spouse is the most natural care giver, if she or he is able to give care. Spousal care means living together, giving and receiving care and interdependency between the spouses. The aim of the policy is to support spousal care by paying financial support to a carer and arrang-ing formal home care services. The purpose of this research is to study the agency of care giving and receiving spouses as care givers and receivers and also as home care service users. The data of the study consist of the interviews of 21 elderly couples. Both spouses were interviewed seper-ately, with the exception of five couples who were interviewed together. In these inter-views a care receiver had difficulties in communicating by speaking and a spouse was her or his interpreter. The study is based on a social constructionistic and a discourse analytical view of con-struction of meanings in human communication. Talking is a social action: people achieve identities, realities, social order and social relationship through talking. In inter-pretating the spouses agency I have used of Harvey Sack´s method of Membership Categorization Device (MCD). The spouses construct social categories which made the meaning of their agency visible. Care changes the routines and actions of everyday life. The couples have to negotiate their duties and rights between each other. Care giving and receiving are both physical and emotional actions. In the end it becomes a part of the couples´ normal life. The pur-pose of couples´ action is to live together as long as possible. They want to strengthen both their own agency and their spouses´ agency. The living together depends on both of them. The spouses decided together what home care services they would like to use and on which conditions they have to use services. Spouses have different kind of agencies as service users which describe their relationship and confidency on formal home care support and services. Services must support the elderly couples´ shared life at home. They cannot be against the conditions on the spousal care. When you want to arrange services to elderly care giving and receiving couples, you have to consider their own wishes and the meanings of their own relationship and shared life.