New aspects of the diagnosis of Helicobacter pylori infection

Aims: Helicobacter pylori infection, although the prevalence is declining in Western world, is still responsible for several clinically important diseases. None of the diagnostic tests is perfect and in this study, the performance of three stool antigen tests was assessed. In areas of high H. pylori prevalence, the definition of patients with the greatest benefit from eradication therapy may be a problem; the role of duodenal gastric metaplasia in categorizing patients at risk for duodenal ulcer was evaluated in this respect. Whether persistent chronic inflammation and elevated H. pylori antibodies after successful eradication are associated with each other or with atrophic gastritis, a long term sequelae of H. pylori infection, were also studied. Patients and methods: The three stool antigen tests were assessed in pre- and post-eradication settings among 364 subjects in two studies as compared to the rapid urease test (RUT), histology, culture, the 13C-urea breath test (UBT) and enzyme immunoassay (EIA) based H. pylori serology. The association between duodenal gastric metaplasia with duodenal ulcer was evaluated in a retrospective study including 1054 patients gastroscopied due to clinical indications and 154 patients previously operated for duodenal ulcer. The extent of duodenal gastric metaplasia was assessed from histological specimens in different patient groups formed on the basis of gastroscopy findings and H. pylori infection. Chronic gastric inflammation (108 patients) and H. pylori antibodies and serum markers for atrophy (77 patients) were assessed in patients earlier treated for H. pylori. Results: Of the stool antigen tests studied, the monoclonal antibody-based EIA-test showed the highest sensitivity and specificity both in the pre-treatment setting (96.9% and 95.9%) and after therapy (96.9% and 97.8%). The polyclonal stool antigen test and the in-office test had at baseline a sensitivity of 91% and 94%, and a specificity of 96% and 89%, respectively and in a post-treatment setting, a sensitivity of 78% and 91%, and a specificity of 97%, respectively. Duodenal gastric metaplasia was strongly associated with H. pylori positive duodenal ulcer (odds ratio 42). Although common still five years after eradication, persistent chronic gastric inflammation (21%) and elevated H. pylori antibodies (33%) were neither associated with each other nor with atrophic gastritis. Conclusions: Current H. pylori infection can feasibly be diagnosed by a monoclonal antibody-based EIA test with the accuracy comparable to that of reference methods. The performance of the polyclonal test as compared to the monoclonal test was inferior especially in the post-treatment setting. The in-office test had a low specificity for primary diagnosis and hence positive test results should probably be confirmed with another test before eradication therapy is prescribed. The presence of widespread duodenal gastric metaplasia showed promising results in detecting patients who should be treated for H. pylori due to an increased risk of duodenal ulcer. If serology is used later on in patients with earlier successfully treated for H. pylori, it should be taken into account that H. pylori antibodies may persist elevated for years for unknown reason. However, this phenomenon was not found to be associated with persistent chronic inflammation or atrophic changes.

Markers of systemic inflammation in diagnostics and in prediction of outcome of community-acquired infection

Sepsis is associated with a systemic inflammatory response. It is characterised by an early proinflammatory response and followed by a state of immunosuppression. In order to improve the outcome of patients with infection and sepsis, novel therapies that influence the systemic inflammatory response are being developed and utilised. Thus, an accurate and early diagnosis of infection and evaluation of immune state are crucial. In this thesis, various markers of systemic inflammation were studied with respect to enhancing the diagnostics of infection and of predicting outcome in patients with suspected community-acquired infection. A total of 1092 acutely ill patients admitted to a university hospital medical emergency department were evaluated, and 531 patients with a suspicion of community-acquired infection were included for the analysis. Markers of systemic inflammation were determined from a blood sample obtained simultaneously with a blood culture sample on admission to hospital. Levels of phagocyte CD11b/CD18 and CD14 expression were measured by whole blood flow cytometry. Concentrations of soluble CD14, interleukin (IL)-8, and soluble IL-2 receptor α (sIL-2Rα) were determined by ELISA, those of sIL-2R, IL-6, and IL-8 by a chemiluminescent immunoassay, that of procalcitonin by immunoluminometric assay, and that of C-reactive protein by immunoturbidimetric assay. Clinical data were collected retrospectively from the medical records. No marker of systemic inflammation, neither CRP, PCT, IL-6, IL-8, nor sIL-2R predicted bacteraemia better than did the clinical signs of infection, i.e., the presence of infectious focus or fever or both. IL-6 and PCT had the highest positive likelihood ratios to identify patients with hidden community-acquired infection. However, the use of a single marker failed to detect all patients with infection. A combination of markers including a fast-responding reactant (CD11b expression), a later-peaking reactant (CRP), and a reactant originating from inflamed tissues (IL-8) detected all patients with infection. The majority of patients (86.5%) with possible but not verified infection showed levels exceeding at least one cut-off limit of combination, supporting the view that infection was the cause of their acute illness. The 28-day mortality of patients with community-acquired infection was low (3.4%). On admission to hospital, the low expression of cell-associated lipopolysaccharide receptor CD14 (mCD14) was predictive for 28-day mortality. In the patients with severe forms of community-acquired infection, namely pneumonia and sepsis, high levels of soluble CD14 alone did not predict mortality, but a high sCD14 level measured simultaneously with a low mCD14 raised the possibility of poor prognosis. In conclusion, to further enhance the diagnostics of hidden community-acquired infection, a combination of inflammatory markers is useful; 28-day mortality is associated with low levels of mCD14 expression at an early phase of the disease.

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.

The decline of northern malaria and population dynamics of Plamodium vivax

Europe was declared malaria free in 1975. The disappearance of malaria has traditionally been attributed to numerous deliberate actions like vector control, the screening of houses, more efficient medication etc. Malaria, however, disappeared from many countries like Finland before any counter measures had even started. The aim of this thesis is to study the population ecology of P. vivax and its interaction with the human host and the vector. By finding the factors that attributed to the extinction of vivax malaria it might be possible to improve the modern strategy against P. vivax. The parasite was studied with data from Finland, which provides the longest time series (1749-2008) of malaria statistics in the world. The malaria vectors, Anopheles messeae and A. beklemishevi are still common species in the country. The eradication of vivax malaria is difficult because the parasite has a dormant stage that can cause a relapse long after a primary infection. It was now shown that P. vivax is able to detect the presence of a potential vector. A dormant stage is triggered even from a bite of an uninfected Anopheles mosquito. This optimizes the chances for the Plasmodium to reach a mosquito vector for sexual reproduction. The longevity of the dormant stage could be shown to be at least nine years. The parasite spends several years in its human host and the behaviour of the human carrier had a profound impact on the decline of the disease in Finland. Malaria spring epidemics could be explained by a previous warm summer. Neither annual nor summer mean temperature had any impact on the long term malaria trend. Malaria disappeared slowly from Finland without mosquito control. The sociological change from extended families to nuclear families led to decreased household size. The decreased household size correlated strongly with the decline of malaria. That led to an increased isolation of the subpopulations of P. vivax. Their habitat consisted of the bedrooms in which human carriers slept together with the overwintering vectors. The isolation of the parasite ultimately led to the extinction of vivax malaria. Metapopulation models adapted to local conditions should therefore be implemented as a tool for settlement planning and socio-economic development and become an integrated part of the fight against malaria.

Skogsbränslets elementära sammansättning med tanke på förbränningsprocessen och för näringsämnesförluster i ekosystemet

There are several reasons for increasing the usage of forest biomass for energy in Finland. Apart from the fact that forest biomass is a CO2 -neutral energy source, it is also a domestic resource distributed throughout the country. Usage of forest biomass in the form of logging residues decreases Finland’s dependence of energy import and increases both incomes and employment. Wood chips are mainly made from logging residues, which constitute 64 % of the raw material. A large-scale use of forest biomass requires heed also to the potential negative aspects. Forest bioenergy is used extensively, but its impacts on the forests soil nutrition and carbon balance has not been studied much. Nor have there been many studies on the heavy metal or chlorine content of logging residues. The goal of this study was to examine the content of carbon, macronutrients, heavy metals and other for the combustion harmful substances in Scots pine and Norway spruce wood chips, and to estimate the effect of harvesting of logging residues on the forests carbon and nutrient balance. Another goal was to examine the energy content of the clear cut remains. The Wood chips for this study were gathered from pine and spruce dominated clear cut sites in southern Finland, in the costal forests between Hankoo and Siuntio. The number of sample locations were 29, and the average area was 3,15 ha and the average timber volume 212,6 m3 ha -1. The average logged timber volume was for Scots pine timber 70 m3 ha -1 and for Norway spruce timber 124 m3 ha -1 and for deciduous timber (birch and alder) 18,5 m3 ha -1. The proportion of spruce in the logging residues and the stand-volume were relevant for how much nutrients were taken from the forest ecosystem when harvesting logging residues. In this study it was noted that the nutrient content of the logging residues clearly increased when the percentage of spruce in the timber volume increased. The S, K, Na and Cl -contents in the logging residues in this study increased with an increasing percentage of spruce, which is probably due to the fact that the spruce is an effective collector of atmospheric dry-deposition. The amounts of nutrients that were lost when harvesting logging residues were less than those referred to in the literature. Within a circulation period (100 years), the forest soil gets substantially more nutrients from atmospheric deposition, litter fall and weathering than is lost through harvesting of logging residues after a clear cut. Harvesting of the logging residues makes for a relatively modest increase of the quantity of carbon that is removed from the forest compared to traditional forestry. Due to the fact that the clear cut remains in my study showed a high content of chlorine, there is a risk of corrosion in connection to the incineration of the logging residues in power plants especially at coastal areas/forests. The risk of sulphur -related corrosion is probably rather small, because S concentrations are relatively low in woodchips. The clear cut remains showed rather high heavy metal contents. If the heavy metal contents in this study are representative for the clear cut remains in the coastal forests generally, there might be reason to exert some caution when using the ash for forest fertilizing purposes.

Options for selecting dairy cattle for milk coagulation ability

Lypsylehmien maidon juoksettumiskyvyn jalostuskeinot Väitöskirjassa tutkittiin lypsylehmien maidon juustonvalmistuslaadun parantamista jalostusvalinnan avulla. Tutkimusaihe on tärkeä, sillä yhä suurempi osa maidosta käytetään juustonvalmistukseen. Tutkimuksen kohteena oli maidon juoksettumiskyky, sillä se on yksi keskeisistä juustomäärään vaikuttavista tekijöistä. Maidon juoksettumiskyky vaihteli huomattavasti lehmien, sonnien, karjojen, rotujen ja lypsykauden vaiheiden välillä. Vaikka tankkimaidon juoksettumiskyvyssä olikin suuria eroja karjoittain, karja selitti vain pienen osan juoksettumiskyvyn kokonaisvaihtelusta. Todennäköisesti perinnölliset erot lehmien välillä selittävät suurimman osan karjojen tankkimaitojen juoksettumiskyvyssä havaituista eroista. Hyvä hoito ja ruokinta vähensivät kuitenkin jossain määrin huonosti juoksettuvien tankkimaitojen osuutta karjoissa. Holstein-friisiläiset lehmät olivat juoksettumiskyvyltään ayrshire-rotuisia lehmiä parempia. Huono juoksettuminen ja juoksettumattomuus oli vain vähäinen ongelma holstein-friisiläisillä (10 %), kun taas kolmannes ayrshire-lehmistä tuotti huonosti juoksettuvaa tai juoksettumatonta maitoa. Maitoa sanotaan huonosti juoksettuvaksi silloin, kun juustomassa ei ole riittävän kiinteää leikattavaksi puolen tunnin kuluttua juoksetteen lisäyksestä. Juoksettumattomaksi määriteltävä maito ei saostu lainkaan puolen tunnin aikana ja on siksi erittäin huonoa raaka-ainetta juustomeijereille. Noin 40 % lehmien välisistä eroista maidon juoksettumiskyvyssä selittyi perinnöllisillä tekijöillä. Juoksettumiskykyä voikin sanoa hyvin periytyväksi ominaisuudeksi. Kolme mittauskertaa lehmää kohti riittää varsin hyvin lehmän maidon keskimääräisen juoksettumiskyvyn arvioimiseen. Tällä hetkellä juoksettumiskyvyn suoran jalostamisen ongelmana on kuitenkin automatisoidun, laajamittaiseen käyttöön soveltuvan mittalaitteen puute. Tämän takia väitöskirjassa tutkittiin mahdollisuuksia jalostaa maidon juoksettumiskykyä epäsuorasti, jonkin toisen ominaisuuden kautta. Tällaisen ominaisuuden pitää olla kyllin voimakkaasti perinnöllisesti kytkeytynyt juoksettumiskykyyn, jotta jalostus olisi mahdollista sen avulla. Tutkittavat ominaisuudet olivat sonnien kokonaisjalostusarvossa jo mukana olevat maitotuotos ja utareterveyteen liittyvät ominaisuudet sekä kokonaisjalostusarvoon kuulumattomat maidon valkuais- ja kaseiinipitoisuus sekä maidon pH. Väitöskirjassa tutkittiin myös mahdollisuuksia ns. merkkiavusteiseen valintaan tutkimalla maidon juoksettumattomuuden perinnöllisyyttä ja kartoittamalla siihen liittyvät kromosomialueet. Tutkimuksen tulosten perusteella lehmien utareterveyden jalostaminen parantaa jonkin verran myös maidon juoksettumiskykyä sekä vähentää juoksettumattomuutta ayrshire-rotuisilla lehmillä. Lehmien maitotuotos ja maidon juoksettumiskyky sekä juoksettumattomuus ovat sen sijaan perinnöllisesti toisistaan riippumattomia ominaisuuksia. Myöskin maidon valkuais- ja kaseiinipitoisuuden perinnöllinen yhteys juoksettumiskykyyn oli likimain nolla. Maidon pH:n ja juoksettumiskyvyn välillä oli melko voimakas perinnöllinen yhteys, joten maidon pH:n jalostaminen parantaisi myös maidon juoksettumiskykyä. Todennäköisesti sen jalostaminen ei kuitenkaan vähentäisi juoksettumatonta maitoa tuottavien lehmien määrää. Koska maidon juoksettumattomuus on niin yleinen ongelma suomalaisilla ayrshire-lehmillä, väitöksessä selvitettiin tarkemmin ilmiön taustoja. Kaikissa kolmessa tutkimusaineistoissa noin 10 % ayrshire-lehmistä tuotti juoksettumatonta maitoa. Kahden vuoden kuukausittaisen seurannan aikana osa lehmistä tuotti juoksettumatonta maitoa lähes joka mittauskerralla. Maidon juoksettumattomuus oli yhteydessä lypsykauden vaiheeseen, mutta mikään ympäristötekijöistä ei pystynyt täysin selittämään sitä. Sen sijaan viitteet sen periytyvyydestä vahvistuivat tutkimusten edetessä. Lopuksi tutkimusryhmä onnistui kartoittamaan juoksettumattomuutta aiheuttavat kromosomialueet kromosomeihin 2 ja 18, lähelle DNA-merkkejä BMS1126 ja BMS1355. Tulosten perusteella maidon juoksettumattomuus ei ole yhteydessä maidon juoksettumistapahtumassa keskeisiin kaseiinigeeneihin. Sen sijaan on mahdollista, että juoksettumattomuusongelman aiheuttavat kaseiinigeenien syntetisoinnin jälkeisessä muokkauksessa tapahtuvat virheet. Asia vaatii kuitenkin perusteellista tutkimista. Väitöksen tulosten perusteella maidon juoksettumattomuusgeeniä kantavien eläinten karsiminen jalostuseläinten joukosta olisi tehokkain tapa jalostaa maidon juoksettumiskykyä suomalaisessa lypsykarjapopulaatiossa.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Traditionally Protected Forests and Sacred Forests of Zigua and Gweno Ethnic Groups in Tanzania

In Tanzania, indigenous forests can still be found whose existence is based on the management systems of precolonial society. This study covers material from over 900 forests. There are similar types of forests elsewhere in Africa, and similar forests can also be found in indigenous cultures on every continent. In this study they are called traditionally protected forests (TPFs). They have a high level of endemism and a rich biodiversity. The field study was carried out during the years 1997-2003 using participatory methods. An active debate is going on concerning the capacity of local communities to manage their environment. The role of indigenous people and their institutions in the development of the physical environment is a central issue in the debate. This study discusses the opportunities that the local people have had to decide on how to conserve, maintain, utilise, and manage their environment during different political periods. The study explains what kinds of changes have taken place in these forests and institutions in northeastern Tanzania among the matrilinear Zigua and patrilinear Gweno ethnic groups. About 2% of the land area of the communities was still protected by the precolonial structures. The communities have established their protection systems for different reasons, not only because of their beliefs but also because of different secular and clearly environmentally motivated reasons. There are different TPF types. Less than half of them are directly related to spirituality, and more than half are not. In earlier research elsewhere, it has been commonly understood that spiritual reasons played the main role in the protection of these environments. This study is also part of the postcolonial geographical discussion on the precolonial landscape and environmental management which was started by Carl Sauer. In the Zigua case study villages, only two out of five first comer clans have performed rain rituals in the past 30 years. Many of the most respected sacred sites do not have a ritual maker or even a person who knows how to perform rituals any longer. The same is happening with male initiation rites. In all case study villages there have been illegal cuts in the TPFs, but variations can be seen between the communities. The number of those who neither respect indigenous regulations nor accept indigenous penalties is growing. Positive developments have also taken place. Nowadays, the Forest Act of 2002 is in effect, which works as a cornerstone of community-based land ownership and also allows elders to protect TPFs, and by-laws are created with the support of different projects. Moreover, during the field study it was found that many young people are ignorant about their village's TPF sites, but interested in learning about their history and values.

Efficient search for statistically significant dependency rules in binary data

Analyzing statistical dependencies is a fundamental problem in all empirical science. Dependencies help us understand causes and effects, create new scientific theories, and invent cures to problems. Nowadays, large amounts of data is available, but efficient computational tools for analyzing the data are missing. In this research, we develop efficient algorithms for a commonly occurring search problem - searching for the statistically most significant dependency rules in binary data. We consider dependency rules of the form X->A or X->not A, where X is a set of positive-valued attributes and A is a single attribute. Such rules describe which factors either increase or decrease the probability of the consequent A. A classical example are genetic and environmental factors, which can either cause or prevent a disease. The emphasis in this research is that the discovered dependencies should be genuine - i.e. they should also hold in future data. This is an important distinction from the traditional association rules, which - in spite of their name and a similar appearance to dependency rules - do not necessarily represent statistical dependencies at all or represent only spurious connections, which occur by chance. Therefore, the principal objective is to search for the rules with statistical significance measures. Another important objective is to search for only non-redundant rules, which express the real causes of dependence, without any occasional extra factors. The extra factors do not add any new information on the dependence, but can only blur it and make it less accurate in future data. The problem is computationally very demanding, because the number of all possible rules increases exponentially with the number of attributes. In addition, neither the statistical dependency nor the statistical significance are monotonic properties, which means that the traditional pruning techniques do not work. As a solution, we first derive the mathematical basis for pruning the search space with any well-behaving statistical significance measures. The mathematical theory is complemented by a new algorithmic invention, which enables an efficient search without any heuristic restrictions. The resulting algorithm can be used to search for both positive and negative dependencies with any commonly used statistical measures, like Fisher's exact test, the chi-squared measure, mutual information, and z scores. According to our experiments, the algorithm is well-scalable, especially with Fisher's exact test. It can easily handle even the densest data sets with 10000-20000 attributes. Still, the results are globally optimal, which is a remarkable improvement over the existing solutions. In practice, this means that the user does not have to worry whether the dependencies hold in future data or if the data still contains better, but undiscovered dependencies.

Tila tilassa : Liturgian ja tilan dialogi alttarin äärellä

This study examines the organisation and transformation of altar space in the modern Evangelical Lutheran Church of Finland in liturgical and architectural perspective. The research data consists of 65 altar spaces in The Finnish Evangelical Lutheran church buildings. All of these were characterised in Church Government records as churches , built 1962 1999 and had been consecrated. The main data was collected by means of observation, photographing, and drawing sketches of altar spaces. The focus of this study concerns the organisation of modern Finnish Evangelical Lutheran altar spaces and, in particular, their changes also in relation to the liturgical movement. The challenge of this approach was especially in discovering the spatial identity of an altar space in terms of unequivocal boundaries. The analysis was realised in three stages. Interiors, the organisation of altar space, as well as architectonic qualities of altar spaces in terms of floor elevations, shapes of ceilings, lighting, and openings in the altar space were analysed. Moreover, attention was focused on furnishing and fixed versus movable pieces of furniture (such as the altar, altar rail, the pulpit, the baptismal font, and lectern). Finally, the potential qualitative and quantitative changes in altar space were examined. All in all, the majority of churches in the data featured elongated church halls with an altar at the end of the nave. To look at the data in chronological perspective, increasingly wide church halls had been built since the 1980s (yet there was only one central hall in which the altar was placed at the middle point of the church). Every third church altar was movable. As for the focal point of this study and the altar in particular, it was my aim to pay attention to the versus populum altar and its development in relation to the (Lutheran) liturgy. Hence, it was meaningful to determine, in terms of interior design, whether liturgists were able to celebrate facing the people attending the service. In the 1960s and 70s, a versus orientem altar featured in more than half of all new Finnish Lutheran churches, yet in 2000 two out of three churches featured a versus populum altar. For architectural and esthetic reasons (and not primarily due to liturgical ideas), also altars standing freely off the walls had been constructed. In terms of the liturgy, versus populum altars had been realised in expectation of increased communication between liturgist and worshippers. However, the analysis indicated that the altar could also become a divider of space. This aspect is a novel finding in relation to earlier and concurrent discussions concerning the liturgical movement. This study concluded, all in all, that altars had been increasingly constructed closer and closer to the worshiping parish and, accordingly, used increasingly often in the versus populum manner. Lecterns were often movable until the millennium this was the case in most altar spaces. Baptismal fonts did not have a permanent place in this data, and the data even included altar spaces with no baptismal fonts in the choir, nor the church hall. The position and status of fonts was generally weakened even if baptism in the Lutheran Church was regarded as one of the two sacraments together with the eucharist. The study concluded that even if baptism is regarded as a sacrament in the church, the position and status of baptismal fonts had weakened overall in newer church architecture. In other words, the tendency of the liturgical movement to emphasise the service and its celebration had obviously had its effect on the placement of baptismal fonts in the church hall. This research indicated that the pieces of furniture that mostly involved (many kinds of) visual and spatial changes included the altar and the lectern. In certain instances, fixed furnishings had been substituted by movable pieces or, moreover, new pieces of furniture and paraphernalia such as music instruments, pieces of art, tables, chairs and plants were brought in. In the Evangelical Lutheran Church of Finland, liturgical changes were principally inspired by the Catholic Church, in which liturgical changes are essentially based on Canon Law. Unlike Finnish Lutheranism, Catholicism provides detailed rules and principles even regarding the design of an altar space. According to this study, in the Finnish Lutheran Church, the primarily functional nature of given guidelines and instructions characterises several practical solutions in furnishing.

Viimeinen matka : Toimintatutkimus kirkollisen hautauskentän professiostruktuurista

This study is a qualitative examination of the professional structure of the ecclesias-tical funeral field. The research material is based on 13 funeral cases in the archdio-cese. The researcher participated in all the funerals and memorial events, interviewed the closest survivors, the officials of the funeral agency and the ecclesiastical actors. The material was collected by means of observation and recording of the interviews, and was later transcribed and analyzed. The actors in this study are the survivors, the funeral agencies and the church. The survivors act as the buyers and users of the products (funeral services) who require both the funeral agencies and the church to assist them with the problems that the death has caused. The numbers of actions related to the death and to the funerals - the rituals of death - are placed on the action field, which in this study is called the funeral field. In this field, the researchquestion focused space and power, and the actions on the funeral field are highly ritualized. The theoretical model comes from Pierre Bourdieu. The study showed an action structure on the funeral field in which the survivors first contacted a funeral agency, which then contacted the other actors of the field, re-served the date and place for the funeral, and organised the funeral arrangements. The funeral agencies arranged an opportunity for the survivors to have a last look at the deceased when he or she was placed in the coffin, and they held a moment of the prayer (if desired) before removing the deceased from the hospital's chapel. The sur-vivors contacted the pastor of the funeral much later. The pastor also participated in the memorial event. The survivors contacted the church musician through via pastor. In some cases, the survivors had neither met nor even seen the musician prior to the actual funeral service. Still, the music was of great importance to the survivors. In the research interviews, tensions emerged to some extent between the funeral agencies and the ecclesiastical actors; these actors attempted to resolve these tensions through organising negotiations. In the beginning of the 20th century, the family took an active part in the preparations of the deceased and in the arrangements of the funerals, whereas this study showed that these days, survivors often transfer the preparations to the funeral agencies. The professional side of the funeral field has grown. The funeral agencies can be seen as providers of full services that act on the survivors' behalf, aspiring to high individu-ality and aiming to fulfil the survivors' wishes. In practise, the role of the church in carrying out the last journey was reduced in the research cases to the actual funeral. In several cases, the pastor or the cantor of the funeral had never before seen the per-son in the coffin at any stage of life or death. The proportion of cremations in funeral cases has increased rapidly, however, special issues related to these cremations (such as the possibility of holding a funeral service for the already cremated deceased) have seen little consideration in the church. In the church's liturgies on funeral rites, cremation is frequently overlooked. The pastors or the cantors did not participate in either the burial of the funeral urn or in the scattering of the deceased's ashes. The verger took care of it. The parishes had no adopted standard practices for cremations, yet in each case for the survivors that moment was crucial.

Kuka on potilas? : Suomalaisen sikiöseulontakäytännön sosiaalieettistä tarkastelua

Who is the patient? A social-ethical study of the Finnish practice of prenatal screening. The aim of this study is to examine the Finnish practice of prenatal screening from a social-ethical perspective. Analyzing ethical problems in medicine and medical practice only on a general scale may conceal relevant ethical dilemmas. Previous studies have suggested that many pregnant women view the prenatal screening practices customary in the Finnish maternal care system as intimidating and oppressive. This study analyzes the ethical questions of prenatal screening by focusing on the experiences and decision-making of a pregnant woman. Finnish women s experiences of and decision-making on the most common prenatal screening methods are reflected in the basic principles of biomedical ethics described by Tom L. Beauchamp and James F. Childress in Principles of Biomedical Ethics. To concretize women s experiences I refer to studies of Finnish women s experiences of prenatal screenings. This study shows that the principles of autonomy, non-maleficence and beneficence seem to materialize rather poorly in the Finnish practice of prenatal screening. The main ethical problem with prenatal screening is that the likelihood of a foetal cure is very limited and, upon detection of an affected foetus, the choice is usually whether to continue with the pregnancy or to undergo an abortion. Although informed consent should be required, women s participation in prenatal testing is, in many cases at least, not based on their active decision. Many women experience severe anxiety when they receive a positive screening result and must wait for the final results. Medical studies indicate that long- term anxiety may negatively influence the foetus and the mother-child relationship. This study shows that the practice of prenatal screening as such may cause more harm than benefit to many pregnant women and their foetuses. This study examines the decision-making process of a pregnant woman by using the theory of medical casuistry described in Jonsen, Siegler and Winslade s Clinical Ethics. This study focuses on each of the four points of view recommended by the theory. The main problem seems to be the question of whom the patient of prenatal screening is and whom the practice is intended to benefit: the mother, the foetus, the family or society? This study shows that the concepts of health in Finnish maternal care in general, and of the prenatal screening system in particular, differ considerably. It also demonstrates that the purpose and the aims of prenatal screening, aside from the woman s right to choose, has been expressed neither in Finnish public health programmes nor in the public recommendations of prenatal screening. This study suggests that the practice of prenatal screening is a statement, though unexpressed, of public health policy and as such comprises part of the policy of disability. This study further demonstrates that through a single explicit aim (the woman s right to choose) society actually evades its obligation to women by saddling pregnant women with the entire moral responsibility as well as the possible negative consequences of her choice, such as sorrow, regrets and moral balancing. The study reveals several ethical problems in the Finnish practice of prenatal screening. Such problems should be dealt with as the Finnish practice of prenatal screening advances.

Yhteisön ja yhteiskunnan ehdoilla : Seurakuntien ja kuntien yhteistyö vuorovaikutuksen näkökulmasta

In this research, the cooperation between Finnish municipalities and Evangelical Lutheran parishes is studied from the standpoint of institutional interaction. The most essential theoretical background for the study is the differentiation thesis of the secularization theory. Cooperation from the viewpoints of both organizations is examined using the functional approach. Furthermore, the market theory and other theories are applied in order to place the studied phenomenon in the wider context of the theories of the sociology of religion. Sacralization in modern society and its relationship with the differentiation thesis of the secularization theory are in the theoretical foci. In addition, along with a descriptive examination of cooperation, the normative sides of the phenomenon are discussed. The survey was conducted among all municipalities and parishes in continental Finland. The questionnaires were sent to all municipal managers of youth work and afternoon activities and to all managers of child, youth and social work in the parishes. The response rate for the municipalities was 73.9 % and for the parishes 69.5 %. In addition, two qualitative data were utilized. The aim of the study is to scrutinize what kind of limitations of differentiation can be caused by the interaction between the secular and the religious. In order to solve the problem, an empirical study of sacralization in the modern context is required. For this purpose, the survey was carried out to determine the effects of the religious on the secular and the impact of the secular on the religious. In the articles of the study the following relationships are discussed: the positions of municipalities and parishes in relation to the state and civil society; cooperation in relation to differentiation; sacralization in relation to the differentiation thesis and cooperation in relation to pluralism. The results of the study highlighted the significance of the cooperation, which was contrary to the secularization theory connected to religious sacralization. The acceptance of the appearance of religion in cooperation and parishes support for municipal function was high in municipalities. Religious cooperation was more active than secular cooperation within all fields. This was also true between fields: religiously orientated child work was more active than the societally orientated social work of the church. Religious cooperation in modern fields of activity underlined sacralization. However, the acceptance of sacralization was weaker in cities than rural areas. Positive relationships between the welfare function of municipalities and the religious function of parishes emphasized the incompleteness of differentiation and the importance of sacralization. The relationship of the function of municipalities with parishes was neither negative nor neutral. Thus, in the most active fields, that is, child work and the traditional social work of the church, the orientation of parishes in cooperation supported the functions of both organizations. In more passive fields, that is, youth work and the societal social work of the church, parishes were orientated towards supporting the municipal function. The orientation of municipalities to religion underlined the perception that religious function is necessary for cooperation. However, the official character of cooperation supported accommodation to the requirements of societal pluralism. According to the results, sacralization can be effective also at the institutional level. The religious effect of voluntary cooperation means that religious sacralization can also readjust to modern society. At the same time, the results of the study stressed the importance of institutional autonomy. Thus, the public sector has a central role in successful cooperation. The conditions of cooperation are weakened if there is no official support of cooperation or adjustment to the individual rights of modern society. The results called into question the one-directional assumptions in the secularization paradigm and the modernization theory in the background. In these assumptions, religion that represents the traditional is seen to give way to the modern, especially at the institutional level. Lack of an interactional view was identified as a central weakness of the secularization paradigm. In the theoretical approach created in the study, an interactional view between religious and secular institutions was made possible by limiting the core of the differentiation thesis to autonomy. The counter forces of differentiation are despecialization and sacralization. These changes in the secularization theory bring about new interactivity on the institutional level. In addition to the interactional approach, that is, the secularization and sacralization theory created as a synthesis of the study, interaction between the religious and the secular is discussed from the standpoint of multiple modernities. The spiritual welfare role of religion is seen as a potential supporter of secular institutions. Religion is set theoretically amongst other ideologies and agents, which can create communal bonds in modern society. Key words: cooperation, municipalities, parishes, sacralization, secularization, modernization, multiple modernities, differentiation, interaction, democracy, secularism, pluralism, civil society

Ihanteena vapaaehtoisuus : Diakoniatyö Porvoon hiippakunnan seurakunnissa, erityisesti Iitin ja Tampereen rovastikunnissa vuosina 1897-1923

The Ideal of Volunteerism. An institutional approach to social welfare work in the parishes of the Diocese of Porvoo especially in the deaneries of Iitti and Tampere, Finland, in the years 1897-1923 Social welfare work (also known as diakonia) has achieved a high status in the Evangelical Lutheran Church of Finland. Since 1944, provisions of the Finnish Church Act have obliged each parish to employ at least one deacon or deaconess. This study sets out to examine the background and development of social welfare work in the Evangelical Lutheran Church of Finland from the 1890s to the 1920s, by which time social welfare work had become an established practice in the Church. The study investigates the development of social welfare work on the level of parishes. The main source material was collected from sixteen parishes in the Diocese of Porvoo especially in the deaneries of Iitti and Tampere. In the 1890s, two approaches were used in church social work in Finland. The dioceses of Kuopio, Savonlinna and Turku pursued a congregational approach to social work, while the Diocese of Porvoo employed an institutional approach, mainly because of the influence of Bishop Herman Råbergh. This study charts the formation of church social work in Finnish parishes, which took place during a period of tension between the two approaches. The institutional approach to church social work adopted by the Diocese of Porvoo was based on the German system of Asisters= houses@, in which deaconess institutes sent parish sisters to serve congregations. The parish or, in many cases, a separate association dedicated to church social work paid an annual fee to the deaconess institute, which took care of the parish sisters in old age. In the institutional approach, volunteers were recruited to carry out church social work. It was considered as inappropriate to use tax revenue or other public funding for church social work, which was supposed to be based on Christian love for one=s fellow humans and the needy, and for which only voluntary financial contributions were supposed to be used. In the congregational approach, church social work was directly based on the efforts of the parish. The approach relied on the administrative bodies of parishes and the Church, and tax revenue collected by the parishes, as well as other forms of public funding, could be used to carry out the social welfare work. The parishes employed deacons and deaconesses and paid their salaries. The approaches described above were not pursued in their ideal forms; instead, many variations existed. However, in principle, the social welfare work undertaken by the parishes of the Diocese of Porvoo was based on the institutional approach, while the congregational approach was largely employed elsewhere in Finland. Both of the approaches were viable. Parishes began to employ deacons and deaconesses as of the 1890s. The number of parishes which had hired a deacon or deaconess increased particularly in the 1910s, by which time 60% of parishes had employed one. This level was maintained until 1944 when each parish in the Evangelical Lutheran Church of Finland was obliged to employ a deacon or deaconess. Deaconesses usually worked as travelling nurses. The autonomous status of Finland as part of the Russian Empire did not give Finns the right to develop legislation on social affairs and health care. Consequently, the legislation process did not begin until Finland gained its independence in 1917. The social welfare work carried out by parishes and a number of voluntary organisations satisfied the emerging need for medical treatment in Finnish society. Neither the government nor the municipalities had sufficient resources to provide this treatment. Based on the ideal of volunteerism, the institutional social work practiced in the Diocese of Porvoo ran into serious difficulties at the end of the First World War. Because of severe inflation, prices began to rise as of 1915 and tripled in 1917-1918. During the same period, Finnish society went through a deep crisis which escalated into Civil War in spring 1918. This period of economic and social turmoil marked a turning-point which led to a weakening of the status of institutional social work in parishes. Voluntary efforts were no longer sufficient to maintain the practice. In contrast, congregational social work, which was based on public funding, was able to cope with the changes and survived the crisis. The approach to social work adopted by the Diocese of Porvoo turned out to be no more than a brief detour in the history of social work in the Evangelical Lutheran Church of Finland. At the start of the 1920s, the two approaches were integrated into a common vision for establishing church social work as a statutory practice in parishes.

Puukaupan säännöt : Yksityismetsänomistajien ja metsäteollisuuden puukauppa Itä-Suomessa 1919 - 1939

The Finnish forest industry bought more than half of the timber used in factories and sawmills in the 1930s from non-industrial private forests (NIPF). This research investigates the rules conformed to this timber trade. The main research questions are: what were the rules that influenced the timber trade; and by whom they were set up? Attention is also paid to the factors which advanced the forest owners’ negotiation possibilities. A variety of sources were used: legal and company statutes, timber trade contracts, archives of the forest companies and organisations. Moreover, the written reminiscences collected by the Finnish Literature Society in the early 1970s were used to analyse the views of individual sellers and buyers. An institutional economics approach was applied as the theoretical framework of this study. In the timber trade the seller (forest owner) and the buyer (the employee of the forest company) agreed to the rules of the timber trade. They agreed about the amount and the price of the timber on sale, but also rules concerning, e.g., timber marking and harvesting. The forest companies had a strong control over the written contracts. Neither the private forest owners nor the forest organisations had much influence over these contracts. However, they managed to influence the rules which could not be found in the contracts. These written and unwritten rules regulated, for instance, the timber marking and measurement. The forest organisations such as Central Forestry Board Tapio (Keskusmetsäseura Tapio) and associations of forest owners (metsänhoitoyhdistykset) helped private forest owners in gaining more control over the timber marking. In timber marking, the forest owner selected trees to be included in the timber trade and gained more information, which he could use in the negotiations. The other rule, which was changed despite forest companies’ resistance, was the timber measurement. The Central Union of Agricultural Producers (MTK) negotiated with the Central Association of Finnish Woodworking Industries (SPKL) about changing the rules of the measurement practices. Even though SPKL did not support any changes, the new timber measurement law was accepted in the year 1938. The new law also created a supervisory authority to solve possible disagreements. Despite this the forest companies were still in charge of the measurement process in most cases. The private forest owners attained changes in the rules of the timber trade mainly during the 1930s. Earlier the relative weakness of the private forest organisations had diminished their negotiation positions. This changed in the 1930s as the private forest owners and their organisations became more active. At the same time the forest industry experienced a shortage of timber, especially pulp wood, and this provided the private forest owners with more leverage. Full-text (in Finnish) available at http://helda.helsinki.fi/handle/10224/4081