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

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

Representing the epistemic nature of teachers’ practical knowledge : The case of class teachers’ general pedagogy

The present study addressed the epistemology of teachers’ practical knowledge. Drawing from the literature, teachers’ practical knowledge is defined as all teachers’ cognitions (e.g., beliefs, values, motives, procedural knowing, and declarative knowledge) that guide their practice of teaching. The teachers’ reasoning that lies behind their practical knowledge is addressed to gain insight into its epistemic nature. I studied six class teachers’ practical knowledge; they teach in the metropolitan region of Helsinki. Relying on the assumptions of the phenomenographic inquiry, I collected and analyzed the data. I analyzed the data in two stages where the first stage involved an abductive procedure, and the second stage an inductive procedure for interpretation, and thus developed the system of categories. In the end, a quantitative analysis nested into the qualitative findings to study the patterns of the teachers’’ reasoning. The results indicated that teachers justified their practical knowledge based on morality and efficiency of action; efficiency of action was found to be presented in two different ways: authentic efficiency and naïve efficiency. The epistemic weight of morality was embedded in what I call “moral care”. The core intention of teachers in the moral care was the commitment that they felt about the “whole character” of students. From this perspective the “dignity” and the moral character of the students should not replaced for any other “instrumental price”. “Caring pedagogy” was the epistemic value of teachers’ reasoning in the authentic efficiency. The central idea in the caring pedagogy was teachers’ intentions to improve the “intellectual properties” of “all or most” of the students using “flexible” and “diverse” pedagogies. However, “regulating pedagogy” was the epistemic condition of practice in the cases corresponding to naïve efficiency. Teachers argued that an effective practical knowledge should regulate and manage the classroom activities, but the targets of the practical knowledge were mainly other “issues “or a certain percentage of the students. In these cases, the teachers’ arguments were mainly based on the notion of “what worked” regardless of reflecting on “what did not work”. Drawing from the theoretical background and the data, teachers’ practical knowledge calls for “praxial knowledge” when they used the epistemic conditions of “caring pedagogy” and “moral care”. It however calls for “practicable” epistemic status when teachers use the epistemic condition of regulating pedagogy. As such, praxial knowledge with the dimensions of caring pedagogy and moral care represents the “normative” perspective on teachers’ practical knowledge, and thus reflects a higher epistemic status in comparison to “practicable” knowledge, which represents a “descriptive” perception toward teachers’ practical knowledge and teaching.

Automatic Lameness Detection in a Milking Robot : Instrumentation, measurement software, algorithms for data analysis and a neural network model

The aim of this thesis is to develop a fully automatic lameness detection system that operates in a milking robot. The instrumentation, measurement software, algorithms for data analysis and a neural network model for lameness detection were developed. Automatic milking has become a common practice in dairy husbandry, and in the year 2006 about 4000 farms worldwide used over 6000 milking robots. There is a worldwide movement with the objective of fully automating every process from feeding to milking. Increase in automation is a consequence of increasing farm sizes, the demand for more efficient production and the growth of labour costs. As the level of automation increases, the time that the cattle keeper uses for monitoring animals often decreases. This has created a need for systems for automatically monitoring the health of farm animals. The popularity of milking robots also offers a new and unique possibility to monitor animals in a single confined space up to four times daily. Lameness is a crucial welfare issue in the modern dairy industry. Limb disorders cause serious welfare, health and economic problems especially in loose housing of cattle. Lameness causes losses in milk production and leads to early culling of animals. These costs could be reduced with early identification and treatment. At present, only a few methods for automatically detecting lameness have been developed, and the most common methods used for lameness detection and assessment are various visual locomotion scoring systems. The problem with locomotion scoring is that it needs experience to be conducted properly, it is labour intensive as an on-farm method and the results are subjective. A four balance system for measuring the leg load distribution of dairy cows during milking in order to detect lameness was developed and set up in the University of Helsinki Research farm Suitia. The leg weights of 73 cows were successfully recorded during almost 10,000 robotic milkings over a period of 5 months. The cows were locomotion scored weekly, and the lame cows were inspected clinically for hoof lesions. Unsuccessful measurements, caused by cows standing outside the balances, were removed from the data with a special algorithm, and the mean leg loads and the number of kicks during milking was calculated. In order to develop an expert system to automatically detect lameness cases, a model was needed. A probabilistic neural network (PNN) classifier model was chosen for the task. The data was divided in two parts and 5,074 measurements from 37 cows were used to train the model. The operation of the model was evaluated for its ability to detect lameness in the validating dataset, which had 4,868 measurements from 36 cows. The model was able to classify 96% of the measurements correctly as sound or lame cows, and 100% of the lameness cases in the validation data were identified. The number of measurements causing false alarms was 1.1%. The developed model has the potential to be used for on-farm decision support and can be used in a real-time lameness monitoring system.

On probability-based inference under data missing by design

Whether a statistician wants to complement a probability model for observed data with a prior distribution and carry out fully probabilistic inference, or base the inference only on the likelihood function, may be a fundamental question in theory, but in practice it may well be of less importance if the likelihood contains much more information than the prior. Maximum likelihood inference can be justified as a Gaussian approximation at the posterior mode, using flat priors. However, in situations where parametric assumptions in standard statistical models would be too rigid, more flexible model formulation, combined with fully probabilistic inference, can be achieved using hierarchical Bayesian parametrization. This work includes five articles, all of which apply probability modeling under various problems involving incomplete observation. Three of the papers apply maximum likelihood estimation and two of them hierarchical Bayesian modeling. Because maximum likelihood may be presented as a special case of Bayesian inference, but not the other way round, in the introductory part of this work we present a framework for probability-based inference using only Bayesian concepts. We also re-derive some results presented in the original articles using the toolbox equipped herein, to show that they are also justifiable under this more general framework. Here the assumption of exchangeability and de Finetti's representation theorem are applied repeatedly for justifying the use of standard parametric probability models with conditionally independent likelihood contributions. It is argued that this same reasoning can be applied also under sampling from a finite population. The main emphasis here is in probability-based inference under incomplete observation due to study design. This is illustrated using a generic two-phase cohort sampling design as an example. The alternative approaches presented for analysis of such a design are full likelihood, which utilizes all observed information, and conditional likelihood, which is restricted to a completely observed set, conditioning on the rule that generated that set. Conditional likelihood inference is also applied for a joint analysis of prevalence and incidence data, a situation subject to both left censoring and left truncation. Other topics covered are model uncertainty and causal inference using posterior predictive distributions. We formulate a non-parametric monotonic regression model for one or more covariates and a Bayesian estimation procedure, and apply the model in the context of optimal sequential treatment regimes, demonstrating that inference based on posterior predictive distributions is feasible also in this case.

Bayesian fisheries stock assessment: integrating and updating knowledge

In this thesis the use of the Bayesian approach to statistical inference in fisheries stock assessment is studied. The work was conducted in collaboration of the Finnish Game and Fisheries Research Institute by using the problem of monitoring and prediction of the juvenile salmon population in the River Tornionjoki as an example application. The River Tornionjoki is the largest salmon river flowing into the Baltic Sea. This thesis tackles the issues of model formulation and model checking as well as computational problems related to Bayesian modelling in the context of fisheries stock assessment. Each article of the thesis provides a novel method either for extracting information from data obtained via a particular type of sampling system or for integrating the information about the fish stock from multiple sources in terms of a population dynamics model. Mark-recapture and removal sampling schemes and a random catch sampling method are covered for the estimation of the population size. In addition, a method for estimating the stock composition of a salmon catch based on DNA samples is also presented. For most of the articles, Markov chain Monte Carlo (MCMC) simulation has been used as a tool to approximate the posterior distribution. Problems arising from the sampling method are also briefly discussed and potential solutions for these problems are proposed. Special emphasis in the discussion is given to the philosophical foundation of the Bayesian approach in the context of fisheries stock assessment. It is argued that the role of subjective prior knowledge needed in practically all parts of a Bayesian model should be recognized and consequently fully utilised in the process of model formulation.

Statistical and Information-Theoretic Methods for Data-Analysis

In this Thesis, we develop theory and methods for computational data analysis. The problems in data analysis are approached from three perspectives: statistical learning theory, the Bayesian framework, and the information-theoretic minimum description length (MDL) principle. Contributions in statistical learning theory address the possibility of generalization to unseen cases, and regression analysis with partially observed data with an application to mobile device positioning. In the second part of the Thesis, we discuss so called Bayesian network classifiers, and show that they are closely related to logistic regression models. In the final part, we apply the MDL principle to tracing the history of old manuscripts, and to noise reduction in digital signals.

Computing the Stochastic Complexity of Simple Probabilistic Graphical Models

Minimum Description Length (MDL) is an information-theoretic principle that can be used for model selection and other statistical inference tasks. There are various ways to use the principle in practice. One theoretically valid way is to use the normalized maximum likelihood (NML) criterion. Due to computational difficulties, this approach has not been used very often. This thesis presents efficient floating-point algorithms that make it possible to compute the NML for multinomial, Naive Bayes and Bayesian forest models. None of the presented algorithms rely on asymptotic analysis and with the first two model classes we also discuss how to compute exact rational number solutions.

Modeling Efficient Classification as a Process of Confidence Assessment and Delegation

In visual object detection and recognition, classifiers have two interesting characteristics: accuracy and speed. Accuracy depends on the complexity of the image features and classifier decision surfaces. Speed depends on the hardware and the computational effort required to use the features and decision surfaces. When attempts to increase accuracy lead to increases in complexity and effort, it is necessary to ask how much are we willing to pay for increased accuracy. For example, if increased computational effort implies quickly diminishing returns in accuracy, then those designing inexpensive surveillance applications cannot aim for maximum accuracy at any cost. It becomes necessary to find trade-offs between accuracy and effort. We study efficient classification of images depicting real-world objects and scenes. Classification is efficient when a classifier can be controlled so that the desired trade-off between accuracy and effort (speed) is achieved and unnecessary computations are avoided on a per input basis. A framework is proposed for understanding and modeling efficient classification of images. Classification is modeled as a tree-like process. In designing the framework, it is important to recognize what is essential and to avoid structures that are narrow in applicability. Earlier frameworks are lacking in this regard. The overall contribution is two-fold. First, the framework is presented, subjected to experiments, and shown to be satisfactory. Second, certain unconventional approaches are experimented with. This allows the separation of the essential from the conventional. To determine if the framework is satisfactory, three categories of questions are identified: trade-off optimization, classifier tree organization, and rules for delegation and confidence modeling. Questions and problems related to each category are addressed and empirical results are presented. For example, related to trade-off optimization, we address the problem of computational bottlenecks that limit the range of trade-offs. We also ask if accuracy versus effort trade-offs can be controlled after training. For another example, regarding classifier tree organization, we first consider the task of organizing a tree in a problem-specific manner. We then ask if problem-specific organization is necessary.

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.

The Catholic Internet discussion on cloning : A study in cognitive rhetoric

This work combines the cognitive theory of folk-theoretical thought with the classical Aristotelian theory of artistic proof in rhetoric. The first half of the work discusses the common ground shared by the elements of artistic proof (logos, pathos, ethos) and the elements of folk-theoretical thought (naïve physics, folk biology, folk psychology, naïve sociology). Combining rhetoric with the cognitive theory of folk-theoretical thought creates a new point of view for argumentation analysis. The logos of an argument can be understood as the inferential relations established between the different parts of an argument. Consequently, within this study the analysis of logos is to be viewed as the analysis of the inferential folk-theoretical elements that make the suggested factual states-of-things appear plausible within given argumentative structures. The pathos of an argumentative structure can be understood as determining the quality of the argumentation in question in the sense that emotive elements play a great part in what can be called a distinction between good and deceptive rhetoric. In the context of this study the analysis of pathos is to be viewed as the analysis of the emotive content of argumentative structures and of whether they aim at facilitating surface- or deep cognitive elaboration of the suggested matters. The ethos of an argumentative structure means both the speaker-presentation and audience-construct that can be discerned within a body of argumentation. In the context of this study, the analysis of ethos is to be understood as the analysis of mutually manifest cognitive environments in the context of argumentation. The theory is used to analyse Catholic Internet discussion concerning cloning. The discussion is divided into six themes: Human Dignity, Sacred Family, Exploitation / Dehumanisation, Playing God, Monsters and Horror Scenarios and Ensoulment. Each theme is analysed for both the rhetorical and the cognitive elements that can be seen creating persuasive force within the argumentative structures presented. It is apparent that the Catholic voices on the Internet extensively oppose cloning. The voices utilise rhetoric that is aggressive and pejorative more often than not. Furthermore, deceptive rhetoric (in the sense presented above) plays a great part in argumentative structures of the Catholic voices. The theory of folk-theoretical thought can be seen as a useful tool for analysing the possible reasons why the Catholic speakers think about cloning and choose to present cloning in their argumentation as they do. The logos utilized in the argumentative structures presented can usually be viewed as based on folk-theoretical inference concerning biology and psychology. The structures of pathos utilized generally appear to aim at generating fear appeal in the assumed audiences, often incorporating counter-intuitive elements. The ethos utilised in the arguments generally revolves around Christian mythology and issues of social responsibility. These structures can also be viewed from the point of view of folk psychology and naïve sociological assumptions.

Helluntailiikkeen spiritualiteetti : Tilastollinen tutkimus Helsingin Saalem-seurakunnan tilaisuuksiin osallistuvien spiritualiteetista

Yleisellä tasolla tutkimuksen kohteena oli Suomen helluntailiikkeen spiritualiteetti. Tutkimuksen kehysperusjoukkona oli Helsingin Saalem-seurakunnan tilaisuuksiin osallistuvat ihmiset. Aineisto kerättiin kyselylomakkeilla syksyllä 2004 Saalem-seurakunnan tilaisuuksissa. Täytettyjä lomakkeita kertyi 230. Vastaajien ikä vaihteli 13-87 vuoteen ja heistä 36% olimiehiä. 70% kuului Saalem-seurakuntaan ja 17% johonkin toiseen helluntaiseurakuntaan. Ei-helluntailaisia oli 13% vastaajista. Rajoittuneelta osin käytössä oli myös 500 vastaajan vertailuaineisto Kallion kaupunginosan alueelta. Tämän niinsanotun Case Kallio -aineiston vastaajat olivat pääsääntöisesti heikosti sitoutuneita kristinuskon oppeihin sekä hartaudenharjoittamiseen. Vastaajista 50% oli miehiä. Ikä vaihteli 18-39-uoden välillä. Teoreettisena lähtökohtana tutkimukselle toimi yhdysvaltalaisen Daniel Albrechtin empiirinen tutkimus helluntailais-karismaattisesta spiritualiteetista. Hän määrittelee helluntailais-karismaattisen spiritualiteetin muodostuvan kolmesta tekijästä: uskomuksista, käytännöistä sekä niin sanotuista sensibiliteeteistä. Sensibiliteeteillä tarkoitettaan asennoitumista toimintaa kohti. Albrechtin luomien kategorioiden pohjalta laadittiin kyselylomakkeeseen kaksi mittaria. Toinen mittasi koko helluntailaisen spiritualiteetin kenttää kuvaavia perustekijöitä, joihin sisältyivät uskomukset, käytännöt sekä sensibiliteetit. Toinen mittari keskittyi mittaamaan vain yhtä spiritualiteettimääritelmän osaa, sensibiliteettejä. Helluntailaisuuteen painottuvan näkökulman lisäksi tutkimuksessa käytettiin hyväksi David Hayn spiritualiteettinäkemystä. Hän määrittelee spiritualiteetin arkitodellisuuden ylittäväksi tietoisuudeksi. Hayn laatimien kategorioiden avulla kartoitettiin yleisinhimillistä spiritualiteettia. Tutkimuksen tarkoituksena oli selvittää Saalem-seurakunnan spiritualiteetin ilmenemismuotoja ja eroavaisuuksia suhteessa taustoihin. Lisäksi verrattiin Saalemista kerättyä aineistoa vertailuaineistoon (Case Kallio) sekä selvitettiin kahden erilaisesta lähtökohdasta nousevan spiritualitteettinäkemyksen yhteyttä toisiinsa. Tutkimus oli luonteeltaan kvantitatiivinen. Tutkimusmenetelminä käytettiin tilastollisia testejä sekä faktorianalyysiä. Faktorianalyysin rinnalla käytettiin niin kutsutta Bayes-mallinnusta, jolla ei ole parametrisille menetelmille asetettuja tiukkoja käyttöehtoja. Saalem-seurakunnasta tutkimustulokseksi saatiin 11 eritasoista spiritualiteettiulottuvuutta. Albrechtin esittämät seitsemän sensibiliteettikategoriaa löytyivät lähes sellaisenaan aineistosta, kun taas helluntailaisen spiritualiteetin perustekijöiden sekä yleisinhimillisen spiritualiteetin kohdalla käytössä olleet mittarit eivät toimineet täysin odotetulla tavalla. Kahta erilaista aineistoa voitiin vertailla yleisinhimillisen spiritualiteetin osalta. Yleisinhimillinen spiritualiteetti ei ollut vieras ilmiö kristillisestä opista ja hartaudenharjoittamisesta vieraantuneille vastaajille. Kuitenkin se sai korkeampia vastauspistemääriä helluntailaisten parissa. Kyseistä spiritualiteettia eriytyi kuvaamaan kaksi ulottuvuutta: yhteisöllinen altruismi sekä arjen kauneus. Pelkästään Saalem-seurakunnasta kerätystä aineistosta eriytyi lisäksi kolme helluntailaisen spiritualiteetin perustekijää: sana ja missio, johtajakeskeisyys sekä ylistys -ulottuvuudet. Samasta aineistosta nousi kuusi sensibiliteettiulottuvuutta: ylistys,yleinen puhdistuminen, seremoniallisuus, armolahjat, tavoitteellisuus sekä hengellinen puhdistuminen ja muutos. Toinen ylistysulottuvuus kuvasi ylistyksen merkitystä, toinen ylistystapaa. Saalem-seurakunnasta kerätyn aineiston keskiöön asettui sanaa ja missiota kuvaava ulottuvuus. Korkeimman vastauskeskiarvon sai tavoitteellisuusulottuvuus, samoin kuin molemmat yleisinhimillistä spiritualiteettia kuvastaneet ulottuvuudet saivat korkeita vastauskeskiarvoja. Helluntailaisen spiritualiteetin ulottuvuudet korreloivat positiivisesti yleisinhimillisen spiritualiteetin ulottuvuuksien kanssa. Tulokset voitiin yleistää koskemaan Helsingin Saalem-seurakunnan jäsenistöä sekä pääkaupunkiseudun helluntailaisuutta. Koko Suomen helluntailiikkeen kohdalla tuloksia voitiin pitää suuntaa-antavina. Avainsanat: helluntailiike, spiritualiteetti, Saalem, kvantitatiivinen tutkimus, monimuuttujamenetelmät, Bayes-mallinnus, Daniel Albrecht, David Hay

Essays on Misplanning Wealth and Health: A Behavioural Approach

The dissertation consists of three essays on misplanning wealth and health accumulation. The conventional economics assumes that individual's intertemporal preferences are exponential (exponential preferences, EP). Recent findings in behavioural economics have shown that, actually, people do discount near future relatively heavier than distant future. This implies hyperbolic intertemporal preferences (HP). Essays I and II concentrate especially on the effects of a delayed completion of tasks, a feature of behaviour that HP enables. Essay III uses current Finnish data to analyse the evolvement of the quality adjusted life years (QALYs) and inconsistencies in measuring that. Essay I studies the existence effects of a lucrative retirement savings program (SP) on the retirement savings of different individual types having HP. If the individual does not know that he will have HP also in the future, i.e. he is the naïve, for certain conditions, he delays the enrolment on SP until he abandons it. Very interesting finding is that the naïve retires then poorer in the presence than in the absence of SP. For the same conditions, the individual who knows that he will have HP also in the future, i.e. he is the sophisticated, gains from the existence of SP, and retires with greater retirement savings in the presence than in the absence of SP. Finally, capabilities to learn from past behaviour and about intertemporal preferences improve possibilities to gain from the existence but an adequate time to learn must be then guaranteed. Essay II studies delayed doctor's visits, theirs effects on the costs of a public health care system and government's attempts to control patient behaviour and fund the system. The controlling devices are a consultation fee and a deductible for that. The deductible is effective only for a patient whose diagnosis reveals a disease that would not get cured without the doctor's visit. The naives delay their visits the longest while EP-patients are the quickest visitors. To control the naives, the government should implement a low fee and a high deductible, while for the sophisticates the opposite is true. Finally, if all the types exist in an economy then using an incorrect conventional assumption that all individuals have EP leads to worse situation and requires higher tax rates than assuming incorrectly but unconventionally that only the naives exists. Essay III studies the development of QALYs in Finland 1995/96-2004. The essay concentrates on developing a consistent measure, i.e. independent of discounting, for measuring the age and gender specific QALY-changes and their incidences. For the given time interval, use of a relative change out of an attainable change seems to be almost intact to discounting and reveals that the greatest gains are for older age groups.

Genetics of T cell co-stimulatory receptors -CD28, CTLA4, ICOS and PDCD1 in immunity and transplantation

Co-stimulatory signals are essential for the activation of naïve T cells and productive immune response. Naïve T cells receive first, antigen-specific signal through T cell receptor. Co-stimulatory receptors provide the second signal which can be either activating or inhibitory. The balance between signals determines the outcome of an immune response. CD28 is crucial for T cell activation; whereas cytotoxic T lymphocyte associated antigen 4 (CTLA4) mediates critical inhibitory signal. Inducible co-stimulator (ICOS) augments cytokine expression and plays role in immunoglobulin class switching. Programmed cell death 1 (PDCD1) acts as negative regulator of T cell proliferation and cytokine responses. The co-stimulatory receptor pathways are potentially involved in self-tolerance and thus, they provide a promising therapeutic strategy for autoimmune diseases and transplantation. The genes encoding CD28, CTLA4 and ICOS are located adjacently in the chromosome region 2q33. The PDCD1 gene maps further, to the region 2q37. CTLA4 and PDCD1 are associated with the risk of a few autoimmune diseases. There is strong linkage disequilibrium (LD) on the 2q33 region; the whole gene of CD28 exists in its own LD block but CTLA4 and the 5' part of ICOS are within a same LD block. The 3' part of ICOS and PDCD1 are in their own separate LD blocks. Extended haplotypes covering the 2q33 region can be identified. This study focuses on immune related conditions like coeliac disease (CD) which is a chronic inflammatory disease with autoimmune features. Immunoglobulin A deficiency (IgAD) belongs to the group of primary antibody deficiencies characterised by reduced levels of immunoglobulins. IgAD co-occurs often with coeliac disease. Renal transplantation is needed in the end stage kidney diseases. Transplantation causes strong immune response which is tried to suppress with drugs. All these conditions are multifactorial with complex genetic background and multiple environmental factors affecting the outcome. We have screened ICOS for polymorphisms by sequencing the exon regions. We detected 11 new variants and determined their frequencies in Finnish population. We have measured linkage disequilibrium on the 2q33 region in Finnish as well as other European populations and observed conserved haplotypes. We analysed genetic association and linkage of the co-stimulatory receptor gene region aiming to study if it is a common risk locus for immune diseases. The 2q33 region was replicated to be linked to coeliac disease in Finnish population and CTLA4-ICOS haplotypes were found to be associated with CD and IgAD being the first non-HLA risk locus common for CD and immunodeficiencies. We also showed association between ICOS and the outcome of kidney transplantation. Our results suggest new evidence for CTLA4-ICOS gene region to be involved in susceptibility of coeliac disease. The earlier published contradictory association results can be explained by involvement of both CTLA4 and ICOS in disease susceptibility. The pattern of variants acting together rather than a single polymorphism may confer the disease risk. These genes may predispose also to immunodeficiencies as well as decreased graft survival and delayed graft function. Consequently, the present study indicates that like the well established HLA locus, the co-stimulatory receptor genes predispose to variety of immune disorders.

Evaluation of methods and applications for behavioural profiling of transgenic mice

During the last 10-15 years interest in mouse behavioural analysis has evolved considerably. The driving force is development in molecular biological techniques that allow manipulation of the mouse genome by changing the expression of genes. Therefore, with some limitations it is possible to study how genes participate in regulation of physiological functions and to create models explaining genetic contribution to various pathological conditions. The first aim of our study was to establish a framework for behavioural phenotyping of genetically modified mice. We established comprehensive battery of tests for the initial screening of mutant mice. These included tests for exploratory and locomotor activity, emotional behaviour, sensory functions, and cognitive performance. Our interest was in the behavioural patterns of common background strains used for genetic manipulations in mice. Additionally we studied the behavioural effect of sex differences, test history, and individual housing. Our findings highlight the importance of careful consideration of genetic background for analysis of mutant mice. It was evident that some backgrounds may mask or modify the behavioural phenotype of mutants and thereby lead to false positive or negative findings. Moreover, there is no universal strain that is equally suitable for all tests, and using different backgrounds allows one to address possible phenotype modifying factors. We discovered that previous experience affected performance in several tasks. The most sensitive traits were the exploratory and emotional behaviour, as well as motor and nociceptive functions. Therefore, it may be essential to repeat some of the tests in naïve animals for assuring the phenotype. Social isolation for a long time period had strong effects on exploratory behaviour, but also on learning and memory. All experiments revealed significant interactions between strain and environmental factors (test history or housing condition) indicating genotype-dependent effects of environmental manipulations. Several mutant line analyses utilize this information. For example, we studied mice overexpressing as well as those lacking extracellular matrix protein heparin-binding growth-associated molecule (HB-GAM), and mice lacking N-syndecan (a receptor for HB-GAM). All mutant mice appeared to be fertile and healthy, without any apparent neurological or sensory defects. The lack of HB-GAM and N-syndecan, however, significantly reduced the learning capacity of the mice. On the other hand, overexpression of HB-GAM resulted in facilitated learning. Moreover, HB-GAM knockout mice displayed higher anxiety-like behaviour, whereas anxiety was reduced in HB-GAM overexpressing mice. Changes in hippocampal plasticity accompanied the behavioural phenotypes. We conclude that HB-GAM and N-syndecan are involved in the modulation of synaptic plasticity in hippocampus and play a role in regulation of anxiety- and learning-related behaviour.