Aika ennen aluepolitiikkaa. Pohjoisen kehityshankkeet ja alueiden kehittämisen idea 1950-luvun Suomessa

The dissertation focuses on the recognition of the problems of uneven regional development in Finland in the 1950s, and the way the idea of controlling this development was introduced to Finnish politics. Since it is often stated that Finnish regional policy only began in the mid-1960s, the period at hand is considered to fall in the time before regional policy. However, various ideas, plans and projects of regional development as well as different aims of development were brought forward and discussed already in the 1950s. These give an interesting perspective to the ideas of later regional development. In the 1950s, many Finnish politicians became more conscious of the unavoidable societal change. The need for overall modernisation of the society made it reasonable to expect a growing level of unemployment and eagerness to migration. The uneven distribution of well-being was also feared to cause discontent and political changes. International experience proved interfering in the regional development possible when using the argument of public interest ; the measures taken increased the level of well-being, helped sustain societal balance, and supported national economy. Many of the development projects of the 1950s focused on Northern Finland, the natural resources of which were considered an important reserve and the political climate of which was regarded unstable. After the late 1940s, regional development was discussed frequently both on the national and the regional level. Direct and indirect support was given to less developed areas and the government outlined thorough investigations in order to relieve the regional problem. Towards the end of the decade, the measures taken were already often connected to the idea of equality. In the 1950s the conflicts within and between the largest Finnish political parties significantly affected the decisions of regional development. There are three case studies in this qualitative research based on the narrative method. The case studies clarify the characteristics of the 1950s regional development. In the first one, the representatives of the northern region and the state first discuss the location of a state-run nitrogen fertilizer factory and later the location of a new university. In the second, the aims and perspectives of private entrepreneurs and the state collide due to ideas of statist industrialisation projects and later due to an idea of a tax relief targeting northern industry. In the third case, the main role is given to the changing rural areas, in relation to which societal development and urbanisation were often measured. The regional development of the 1950s laid groundwork for the new, more established regional policy. The early problem solving actions were aimed both at the prevailing situation and the future and thus showed the way for the upcoming actions. Regional development policy existed already before regional policy.

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

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

Paleomagnetic and rock magnetic study with emphasis on the Precambrian intrusions and impact structures in Fennoscandia and South Africa

The importance of supercontinents in our understanding of the geological evolution of the planet Earth has been recently emphasized. The role of paleomagnetism in reconstructing lithospheric blocks in their ancient paleopositions is vital. Paleomagnetism is the only quantitative tool for providing ancient latitudes and azimuthal orientations of continents. It also yields information of content of the geomagnetic field in the past. In order to obtain a continuous record on the positions of continents, dated intrusive rocks are required in temporal progression. This is not always possible due to pulse-like occurrences of dykes. In this work we demonstrate that studies of meteorite impact-related rocks may fill some gaps in the paleomagnetic record. This dissertation is based on paleomagnetic and rock magnetic data obtained from samples of the Jänisjärvi impact structure (Russian Karelia, most recent 40Ar-39Ar age of 682 Ma), the Salla diabase dyke (North Finland, U-Pb 1122 Ma), the Valaam monzodioritic sill (Russian Karelia, U-Pb 1458 Ma), and the Vredefort impact structure (South Africa, 2023 Ma). The paleomagnetic study of Jänisjärvi samples was made in order to obtain a pole for Baltica, which lacks paleomagnetic data from 750 to ca. 600 Ma. The position of Baltica at ca. 700 Ma is relevant in order to verify whether the supercontinent Rodinia was already fragmented. The paleomagnetic study of the Salla dyke was conducted to examine the position of Baltica at the onset of supercontinent Rodinia's formation. The virtual geomagnetic pole (VGP) from Salla dyke provides hints that the Mesoproterozoic Baltica - Laurentia unity in the Hudsonland (Columbia, Nuna) supercontinent assembly may have lasted until 1.12 Ga. Moreover, the new VGP of Salla dyke provides new constraint on the timing of the rotation of Baltica relative to Laurentia (e.g. Gower et al., 1990). A paleomagnetic study of the Valaam sill was carried out in order to shed light into the question of existence of Baltica-Laurentia unity in the supercontinent Hudsonland. Combined with results from dyke complex of the Lake Ladoga region (Schehrbakova et al., 2008) a new robust paleomagnetic pole for Baltica is obtained. This pole places Baltica on a latitude of 10°. This low latitude location is supported also by Mesoproterozoic 1.5 1.3 Ga red-bed sedimentation (for example the Satakunta sandstone). The Vredefort impactite samples provide a well dated (2.02 Ga) pole for the Kaapvaal Craton. Rock magnetic data reveal unusually high Koenigsberger ratios (Q values) in all studied lithologies of the Vredefort dome. The high Q values are now first time also seen in samples from the Johannesburg Dome (ca. 120 km away) where there is no impact evidence. Thus, a direct causative link of high Q values to the Vredefort impact event can be ruled out.

A Decentralized Session Management Framework for Heterogeneous Ad-Hoc and Fixed Networks

Wireless technologies are continuously evolving. Second generation cellular networks have gained worldwide acceptance. Wireless LANs are commonly deployed in corporations or university campuses, and their diffusion in public hotspots is growing. Third generation cellular systems are yet to affirm everywhere; still, there is an impressive amount of research ongoing for deploying beyond 3G systems. These new wireless technologies combine the characteristics of WLAN based and cellular networks to provide increased bandwidth. The common direction where all the efforts in wireless technologies are headed is towards an IP-based communication. Telephony services have been the killer application for cellular systems; their evolution to packet-switched networks is a natural path. Effective IP telephony signaling protocols, such as the Session Initiation Protocol (SIP) and the H 323 protocol are needed to establish IP-based telephony sessions. However, IP telephony is just one service example of IP-based communication. IP-based multimedia sessions are expected to become popular and offer a wider range of communication capabilities than pure telephony. In order to conjoin the advances of the future wireless technologies with the potential of IP-based multimedia communication, the next step would be to obtain ubiquitous communication capabilities. According to this vision, people must be able to communicate also when no support from an infrastructured network is available, needed or desired. In order to achieve ubiquitous communication, end devices must integrate all the capabilities necessary for IP-based distributed and decentralized communication. Such capabilities are currently missing. For example, it is not possible to utilize native IP telephony signaling protocols in a totally decentralized way. This dissertation presents a solution for deploying the SIP protocol in a decentralized fashion without support of infrastructure servers. The proposed solution is mainly designed to fit the needs of decentralized mobile environments, and can be applied to small scale ad-hoc networks or also bigger networks with hundreds of nodes. A framework allowing discovery of SIP users in ad-hoc networks and the establishment of SIP sessions among them, in a fully distributed and secure way, is described and evaluated. Security support allows ad-hoc users to authenticate the sender of a message, and to verify the integrity of a received message. The distributed session management framework has been extended in order to achieve interoperability with the Internet, and the native Internet applications. With limited extensions to the SIP protocol, we have designed and experimentally validated a SIP gateway allowing SIP signaling between ad-hoc networks with private addressing space and native SIP applications in the Internet. The design is completed by an application level relay that permits instant messaging sessions to be established in heterogeneous environments. The resulting framework constitutes a flexible and effective approach for the pervasive deployment of real time applications.

Exploring privacy for ubiquitous computing: Tools, methods and experiments

Ubiquitous computing is about making computers and computerized artefacts a pervasive part of our everyday lifes, bringing more and more activities into the realm of information. The computationalization, informationalization of everyday activities increases not only our reach, efficiency and capabilities but also the amount and kinds of data gathered about us and our activities. In this thesis, I explore how information systems can be constructed so that they handle this personal data in a reasonable manner. The thesis provides two kinds of results: on one hand, tools and methods for both the construction as well as the evaluation of ubiquitous and mobile systems---on the other hand an evaluation of the privacy aspects of a ubiquitous social awareness system. The work emphasises real-world experiments as the most important way to study privacy. Additionally, the state of current information systems as regards data protection is studied. The tools and methods in this thesis consist of three distinct contributions. An algorithm for locationing in cellular networks is proposed that does not require the location information to be revealed beyond the user's terminal. A prototyping platform for the creation of context-aware ubiquitous applications called ContextPhone is described and released as open source. Finally, a set of methodological findings for the use of smartphones in social scientific field research is reported. A central contribution of this thesis are the pragmatic tools that allow other researchers to carry out experiments. The evaluation of the ubiquitous social awareness application ContextContacts covers both the usage of the system in general as well as an analysis of privacy implications. The usage of the system is analyzed in the light of how users make inferences of others based on real-time contextual cues mediated by the system, based on several long-term field studies. The analysis of privacy implications draws together the social psychological theory of self-presentation and research in privacy for ubiquitous computing, deriving a set of design guidelines for such systems. The main findings from these studies can be summarized as follows: The fact that ubiquitous computing systems gather more data about users can be used to not only study the use of such systems in an effort to create better systems but in general to study phenomena previously unstudied, such as the dynamic change of social networks. Systems that let people create new ways of presenting themselves to others can be fun for the users---but the self-presentation requires several thoughtful design decisions that allow the manipulation of the image mediated by the system. Finally, the growing amount of computational resources available to the users can be used to allow them to use the data themselves, rather than just being passive subjects of data gathering.

A Floor Control Server in a Distributed Conference Service

The conferencing systems in IP Multimedia (IM) networks are going through restructuring, accomplished in the near future. One of the changes introduced is the concept of floors and floor control in its current form with matching entity roles. The Binary Floor Control Protocol (BFCP) is a novelty to be exploited in distributed tightly coupled conferencing services. The protocol defines the floor control server (FCS), which implements floor control giving access to shared resources. As the newest tendency is to distribute the conferencing services, the locations of different functionality units play an important role in developing the standards. The floor control server location is not yet single-mindedly fixed in different standardization bodies, and the debate goes on where to place it within the media server, providing the conferencing service. The thesis main objective is to evaluate two distinctive alternatives in respect the Mp interface protocol between the respective nodes, as the interface in relation to floor control is under standardization work at the moment. The thesis gives a straightforward preamble in IMS network, nodes of interest including floor control server and conferencing. Knowledge on several protocols – BFCP, SDP, SIP and H.248 provides an important background for understanding the functionality changes introduced in the Mp interface and therefore introductions on those protocols and how they are connected to the full picture is given. The actual analysis on the impact of the floor control server into the Mp reference point is concluded in relation to the locations, giving basic flows, requirements analysis including a limited implementation proposal on supporting protocol parameters. The overall conclusion of the thesis is that even if both choices are seemingly useful, not one of the locations is clearly the most suitable in the light of this work. The thesis suggests a solution having both possibilities available to be chosen from in separate circumstances, realized with consistent standardization. It is evident, that if the preliminary assumption for the analysis is kept regarding to only one right place for the floor control server, more work is to be done in connected areas to discover the one most appropriate location.

Monopolising Names? : The Protection of Geographical Indications in the European Community

Marketing of goods under geographical names has always been common. Aims to prevent abuse have given rise to separate forms of legal protection for geographical indications (GIs) both nationally and internationally. The European Community (EC) has also gradually enacted its own legal regime to protect geographical indications. The legal protection of GIs has traditionally been based on the idea that geographical origin endows a product exclusive qualities and characteristics. In today s world we are able to replicate almost any prod-uct anywhere, including its qualities and characteristics. One would think that this would preclude protec-tion from most geographical names, yet the number of geographical indications seems to be rising. GIs are no longer what they used to be. In the EC it is no longer required that a product is endowed exclusive characteristics by its geographical origin as long as consumers associate the product with a certain geo-graphical origin. This departure from the traditional protection of GIs is based on the premise that a geographical name extends beyond and exists apart from the product and therefore deserves protection itself. The thesis tries to clearly articulate the underlying reasons, justifications, principles and policies behind the protection of GIs in the EC and then scrutinise the scope and shape of the GI system in the light of its own justifications. The essential questions it attempts to aswer are (1) What is the basis and criteria for granting GI rights? (2) What is the scope of protection afforded to GIs? and (3) Are these both justified in the light of the functions and policies underlying granting and protecting of GIs? Despite the differences, the actual functions of GIs are in many ways identical to those of trade marks. Geographical indications have a limited role as source and quality indicators in allowing consumers to make informed and efficient choices in the market place. In the EC this role is undermined by allowing able room and discretion for uses that are arbitrary. Nevertheless, generic GIs are unable to play this role. The traditional basis for justifying legal protection seems implausible in most case. Qualities and charac-teristics are more likely to be related to transportable skill and manufacturing methods than the actual geographical location of production. Geographical indications are also incapable of protecting culture from market-induced changes. Protection against genericness, against any misuse, imitation and evocation as well as against exploiting the reputation of a GI seem to be there to protect the GI itself. Expanding or strengthening the already existing GI protection or using it to protect generic GIs cannot be justified with arguments on terroir or culture. The conclusion of the writer is that GIs themselves merit protection only in extremely rare cases and usually only the source and origin function of GIs should be protected. The approach should not be any different from one taken in trade mark law. GI protection should not be used as a means to mo-nopolise names. At the end of the day, the scope of GI protection is nevertheless a policy issue.

Small State Cultures of Consensus : State Traditions and Consensus-Seeking in the Neo-Corporatist and Neutrality Policies in Post-1945 Austria and Finland

Austria and Finland are persistently referred to as the “success stories” of post-1945 European history. Notwithstanding their different points of departure, in the course of the Cold War both countries portrayed themselves as small and neutral border-states in the world dictated by superpower politics. By the 1970s, both countries frequently ranked at the top end in various international classifications regarding economic development and well-being in society. This trend continues today. The study takes under scrutiny the concept of consensus which figures centrally in the two national narratives of post-1945 success. Given that the two domestic contexts as such only share few direct links with one another and are more obviously different than similar in terms of their geographical location, historical experiences and politico-cultural traditions, the analogies and variations in the anatomies of the post-1945 “cultures of consensus” provide an interesting topic for a historical comparative and cross-national examination. The main research question concerns the identification and analysis of the conceptual and procedural convergence points of the concepts of the state and consensus. The thesis is divided into six main chapters. After the introduction, the second chapter presents the theoretical framework in more detail by focusing on the key concepts of the study – the state and consensus. Chapter two also introduces the comparative historical and cross-national research angles. Chapter three grounds the key concepts of the state and consensus in the historical contexts of Austria and Finland by discussing the state, the nation and democracy in a longer term comparative perspective. The fourth and fifth chapter present case studies on the two policy fields, the “pillars”, upon which the post-1945 Austrian and Finnish cultures of consensus are argued to have rested. Chapter four deals with neo-corporatist features in the economic policy making and chapter five discusses the building up of domestic consensus regarding the key concepts of neutrality policies in the 1950s and 1960s. The study concludes that it was not consensus as such but the strikingly intense preoccupation with the theme of domestic consensus that cross-cut, in a curiously analogous manner, the policy-making processes studied. The main challenge for the post-1945 architects of Austrian and Finnish cultures of consensus was to find strategies and concepts for consensus-building which would be compatible with the principles of democracy. Discussed at the level of procedures, the most important finding of the study concerns the triangular mechanism of coordination, consultation and cooperation that set into motion and facilitated a new type of search for consensus in both post-war societies. In this triangle, the agency of the state was central, though in varying ways. The new conceptions concerning a small state’s position in the Cold War world also prompted cross-nationally perceivable willingness to reconsider inherited concepts and procedures of the state and the nation. At the same time, the ways of understanding the role of the state and its relation to society remained profoundly different in Austria and Finland and this basic difference was in many ways reflected in the concepts and procedures deployed in the search for consensus and management of domestic conflicts. For more detailed information, please consult the author.

Pathogenicity, functional significance and clinical phenotype of mismatch repair gene MSH2 variants found in cancer patients

DNA ja siinä sijaitsevat geenit ohjaavat kaikkea solujen toimintaa. DNA-molekyyleihin kuitenkin kertyy mutaatioita sekä ympäristön vaikutuksen, että solujen oman toiminnan tuloksena. Mikäli virheitä ei korjata, saattaa tuloksena olla solun muuttuminen syöpäsoluksi. Soluilla onkin käytössä useita DNA-virheiden korjausmekanismeja, joista yksi on ns. mismatch repair (MMR). MMR vastaa DNA:n kahdentumisessa syntyvien virheiden korjauksesta. Periytyvät mutaatiot geeneissä, jotka vastaavat MMR-proteiinien rakentamisesta, aiheuttavat ongelmia DNA:n korjauksessa ja altistavat kantajansa periytyvälle ei-polypoottiselle paksusuolisyöpäoireyhtymälle (hereditary nonpolyposis colorectal cancer, HNPCC). Yleisimmin mutatoituneet MMR-geenit ovat MLH1 ja MSH2. HNPCC periytyy vallitsevasti, eli jo toiselta vanhemmalta peritty geenivirhe altistaa syövälle. MMR-geenivirheen kantaja sairastuu syöpään elämänsä aikana suurella todennäköisyydellä, ja sairastumisikä on vain noin 40 vuotta. Syövälle altistavan geenivirheen löytäminen mutaation kantajilta on hyvin tärkeää, sillä säännöllinen seuranta mahdollistaa kehittymässä olevan kasvaimen havaitsemisen ja poistamisen jo aikaisessa vaiheessa. Tämän on osoitettu alentavan syöpäkuolleisuutta merkittävästi. Varma tieto altistuksen alkuperästä on tärkeä myös niille syöpäsuvun jäsenille, jotka eivät kanna kyseistä mutaatiota. Syövälle altistavien mutaatioiden ohella MMR-geeneistä löydetään säännöllisesti muutoksia, jotka ovat normaalia henkilöiden välistä geneettistä vaihtelua, eikä niiden oleteta lisäävän syöpäaltistusta. Altistavien mutaatioiden erottaminen näistä neutraaleista variaatioista on vaikeaa, mutta välttämätöntä altistuneiden tehokkaan seurannan varmistamiseksi. Tässä väitöskirjassa tutkittiin 18:a MSH2 -geenin mutaatiota. Mutaatiot oli löydetty perheistä, joissa esiintyi paljon syöpiä, mutta niiden vaikutus DNA:n korjaustehoon ja syöpäaltistukseen oli epäselvä. Työssä tutkittiin kunkin mutaation vaikutusta MSH2-proteiinin normaaliin toimintaan, ja tuloksia verrattiin potilaiden ja sukujen kliinisiin tietoihin. Tutkituista mutaatiosta 12 aiheutti puutteita MMR-korjauksessa. Nämä mutaatiot tulkittiin syövälle altistaviksi. Analyyseissä normaalisti toimineet 4 mutaatiota eivät todennäköisesti ole syynä syövän syntyyn kyseisillä perheillä. Tulkinta jätettiin avoimeksi 2 mutaation kohdalla. Tutkimuksesta hyötyivät suoraan kuvattujen mutaatioiden kantajaperheet, joiden geenivirheen syöpäaltistuksesta saatiin tietoa, mahdollistaen perinnöllisyysneuvonnan ja seurannan kohdentamisen sitä tarvitseville. Työ selvensi myös mekanismeja, joilla mutatoitunut MSH2-proteiini voi menettää toimintakykynsä.

Where and how to conserve: Extending the scope of spatial reserve network design

Ongoing habitat loss and fragmentation threaten much of the biodiversity that we know today. As such, conservation efforts are required if we want to protect biodiversity. Conservation budgets are typically tight, making the cost-effective selection of protected areas difficult. Therefore, reserve design methods have been developed to identify sets of sites, that together represent the species of conservation interest in a cost-effective manner. To be able to select reserve networks, data on species distributions is needed. Such data is often incomplete, but species habitat distribution models (SHDMs) can be used to link the occurrence of the species at the surveyed sites to the environmental conditions at these locations (e.g. climatic, vegetation and soil conditions). The probability of the species occurring at unvisited location is next predicted by the model, based on the environmental conditions of those sites. The spatial configuration of reserve networks is important, because habitat loss around reserves can influence the persistence of species inside the network. Since species differ in their requirements for network configuration, the spatial cohesion of networks needs to be species-specific. A way to account for species-specific requirements is to use spatial variables in SHDMs. Spatial SHDMs allow the evaluation of the effect of reserve network configuration on the probability of occurrence of the species inside the network. Even though reserves are important for conservation, they are not the only option available to conservation planners. To enhance or maintain habitat quality, restoration or maintenance measures are sometimes required. As a result, the number of conservation options per site increases. Currently available reserve selection tools do however not offer the ability to handle multiple, alternative options per site. This thesis extends the existing methodology for reserve design, by offering methods to identify cost-effective conservation planning solutions when multiple, alternative conservation options are available per site. Although restoration and maintenance measures are beneficial to certain species, they can be harmful to other species with different requirements. This introduces trade-offs between species when identifying which conservation action is best applied to which site. The thesis describes how the strength of such trade-offs can be identified, which is useful for assessing consequences of conservation decisions regarding species priorities and budget. Furthermore, the results of the thesis indicate that spatial SHDMs can be successfully used to account for species-specific requirements for spatial cohesion - in the reserve selection (single-option) context as well as in the multi-option context. Accounting for the spatial requirements of multiple species and allowing for several conservation options is however complicated, due to trade-offs in species requirements. It is also shown that spatial SHDMs can be successfully used for gaining information on factors that drive a species spatial distribution. Such information is valuable to conservation planning, as better knowledge on species requirements facilitates the design of networks for species persistence. This methods and results described in this thesis aim to improve species probabilities of persistence, by taking better account of species habitat and spatial requirements. Many real-world conservation planning problems are characterised by a variety of conservation options related to protection, restoration and maintenance of habitat. Planning tools therefore need to be able to incorporate multiple conservation options per site, in order to continue the search for cost-effective conservation planning solutions. Simultaneously, the spatial requirements of species need to be considered. The methods described in this thesis offer a starting point for combining these two relevant aspects of conservation planning.

Phylogeny of a taxonomically difficult group and evolution of host location mechanism

The parasitic wasps are one of the largest insect groups and their life histories are remarkably variable. Common to all parasitic wasps is that they kill their hosts, which are usually beetles, butterflies and sometimes spiders. Hosts are often at a larval or pupal stage and live in concealed conditions, such as in plant tissue. Parasitic wasps have two main ways of finding their host. 1) They can detect chemical compounds emitted by damaged plant material or released by larvae living in plant tissue, and 2) detect the larvae by sound vibrations. Even though pupae are immobile and silent, and therefore do not cause vibration, parasitoids have, however, adapted to find passive developmental stages by producing vibration themselves by knocking the substrate with their antennae, and then detecting the echoes with their legs. This echolocation allows a parasitoid to locate its potential hosts that are deeply buried in wood. This study focuses on the relationships of the subfamily Cryptinae (Hymenoptera: Ichneumonidae) and related taxa, and the evolution of host location mechanism. There are no earlier studies of the phylogeny of the Cryptinae, and the position of related taxa are unclear. According to the earlier classification, which is entirely intuitional, the Cryptinae is divided into three tribes: Cryptini, Hemigasterini and Phygadeuontini. Further, these tribes are subdiveded into numerous subtribes. This work, based on molecular characters, shows that the cryptine tribes Cryptini, Phygadeuon¬tini and Hemigasterini come out largely as monophyletic groups, thus agreeing with the earlier classification. The earlier subtribal classification had no support. In addition, it is shown that modified antennal structures are associated with host usage of wood-boring coleopteran hosts. The cryptines have a clear modification series on their antennal tips from a simply tip to a hammer-like structure. The species with strongly modified antennae belong mostly to the tribe Cryptini and they utilise wood-boring beetles as hosts. Also, field observations on insect behaviour support this result.

Individual variation in in vitro efficacy of antiplatelet medication - aspirin and clopidogrel

Antiplatelet medication is known to decrease adverse effects in patients with atherothrombotic disease. However, despite ongoing antiplatelet medication considerable number of patients suffer from atherothrombotic events. The aims of the study were 1) to evaluate the individual variability in platelet functions and compare the usability of different methods in detecting it, 2) to assess variability in efficacy of antiplatelet medication with aspirin (acetylsalicylic acid) or the combination of aspirin and clopidogrel and 3) to investigate the main genetic and clinical variables as well as potential underlying mechanisms of variability in efficacy of antiplatelet medication. In comparisons of different platelet function tests in 19 healthy individuals PFA-100® correlated with traditional methods of measuring platelet function and was thus considered appropriate for testing individual variability in platelet activity. Efficacy of ongoing 100mg aspirin daily was studied in 101 patients with coronary artery disease (CAD). Aspirin response was measured with arachidonic acid (AA)-induced platelet aggregation, which reflects cyclo-oxygenase (COX)-1 dependent thromboxane (Tx) A2 formation, and PFA-100®, which evaluates platelet activation under high shear stress in the presence of collagen and epinephrine. Five percent of patients failed to show inhibition of AA-aggregation and 21% of patients had normal PFA-100® results despite aspirin and were thus considered non-responders to aspirin. Interestingly, the two methods of assessing aspirin efficacy, platelet aggregation and PFA-100®, detected different populations as being aspirin non-responders. It could be postulated that PFA-100® actually measures enhanced platelet function, which is not directly associated with TxA2 inhibition exerted by aspirin. Clopidogrel efficacy was assessed in 50 patients who received a 300mg loading dose of clopidogrel 2.5 h prior to percutaneous coronary intervention (PCI) and in 51 patients who were given a loading dose of 300mg combined with a five day treatment of 75mg clopidogrel daily mimicking ongoing treatment. Clopidogrel response was assessed with ADP-induced aggregations, due to its mechanism of action as an inhibitor of ADP-induced activation. When patients received only a loading dose of clopidogrel prior to PCI, 40% did not gain measurable inhibition of their ADP-induced platelet activity (inhibition of 10% or less). Prolongation of treatment so that all patients had reached a plateau of inhibition exerted by clopidogrel, decreased the incidence of non-responders to 20%. Polymorphisms of COX-1 and GP VI, as well as diabetes and female gender, were associated with decreased in vitro aspirin efficacy. Diabetes also impaired the in vitro efficacy of short-term clopidogrel. Decreased response to clopidogrel was associated with limited inhibition by ARMX, an antagonist of P2Y12-receptor, suggesting the reason for clopidogrel resistance to be receptor-dependent. Conclusions: Considerable numbers of CAD patients were non-responders either to aspirin, clopidogrel or both. In the future, platelet function tests may be helpful to individually select effective and safe antiplatelet medication for these patients.

Prognostic markers in head and neck carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Well-known risk factors include tobacco smoking and alcohol consumption. Overall survival has improved, but is still low especially in developing countries. One reason for this is the often advanced stage of the disease at the time of diagnosis, but also lack of reliable prognostic tools to enable individualized patient treatment to improve outcome. To date, the TNM classification still serves as the best disease evaluation criterion, although it does not take into account the molecular basis of the tumor. The need for surrogate molecular markers for more accurate disease prediction has increased research interests in this field. We investigated the prevalence, physical status, and viral load of human papillomavirus (HPV) in HNSCC to determine the impact of HPV on head and neck carcinogenesis. The prevalence and genotyping of HPV were assessed with an SPF10 PCR microtiter plate-based hybridization assay (DEIA), followed by a line probe-based genotyping assay. More than half of the patients had HPV DNA in their tumor specimens. Oncogenic HPV-16 was the most common type, and coinfections with other oncogenic and benign associated types also existed. HPV-16 viral load was unevenly distributed among different tumor sites; the tonsils harbored significantly greater amounts of virus than other sites. Episomal location of HPV-16 was associated with large tumors, and both integrated and mixed forms of viral DNA were detected. In this series, we could not show that the presence of HPV DNA correlated with survival. In addition, we investigated the prevalence and genotype of HPV in laryngeal carcinoma patients in a prospective Nordic multicenter study based on fresh-frozen laryngeal tumor samples to determine whether the tumors were HPV-associated. These patients were also examined and interviewed at diagnosis for known risk factors, such as tobacco smoking and alcohol consumption, and for several other habituations to elucidate their effects on patient survival. HPV analysis was performed with the same protocols as in the first study. Only 4% of the specimens harbored HPV DNA. Heavy drinking was associated with poor survival. Heavy drinking patients were also younger than nonheavy drinkers and had a more advanced stage of disease at diagnosis. Heavy drinkers had worse oral hygiene than nonheavy drinkers; however, poor oral hygiene did not have prognostic significance. History of chronic laryngitis, gastroesophageal reflux disease, and orogenital sex contacts were rare in this series. To clarify why vocal cord carcinomas seldom metastasize, we determined tumor lymph vessel (LVD) and blood vessel (BVD) densities in HNSCC patients. We used a novel lymphatic vessel endothelial marker (LYVE-1 antibody) to locate the lymphatic vessels in HNSCC samples and CD31 to detect the blood microvessels. We found carcinomas of the vocal cords to harbor less lymphatic and blood microvessels than carcinomas arising from sites other than vocal cords. The lymphatic and blood microvessel densities did not correlate with tumor size. High BVD was strongly correlated with high LVD. Neither BVD nor LVD showed any association with survival in our series. The immune system plays an important role in tumorigenesis, as neoplastic cells have to escape the cytotoxic lymphocytes in order to survive. Several candidate HLA class II alleles have been reported to be prognostic in cervical carcinomas, an epithelial malignancy resembling HNSCC. These alleles may have an impact on head and neck carcinomas as well. We determined HLA-DRB1* and -DQB1* alleles in HNSCC patients. Healthy organ donors served as controls. The Inno-LiPA reverse dot-blot kit was used to identify alleles in patient samples. No single haplotype was found to be predictive of either the risk for head and neck cancer, or the clinical course of the disease. However, alleles observed to be prognostic in cervical carcinomas showed a similar tendency in our series. DRB1*03 was associated with node-negative disease at diagnosis. DRB1*08 and DRB1*13 were associated with early-stage disease; DRB1*04 had a lower risk for tumor relapse; and DQB1*03 and DQB1*0502 were more frequent in controls than in patients. However, these associations reached only borderline significance in our HNSCC patients.

Genetic Variation and Clinical Manifestations in Inflammatory Bowel Disease

Crohn s disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), are characterised by chronic inflammation of the gastrointestinal tract. IBD prevalence in Finland is approximately 3-4 per 1000 inhabitants with a peak incidence in adolescence. The symptoms of IBD include diarrhoea, abdominal pain, fever, and weight loss. The precise aetiology of IBD is unknown but interplay of environmental risk factors and immunologic changes trigger the disease in a genetically susceptible individual. Twin and family studies have provided strong evidence for genetic factors in IBD susceptibility, and genetic factors may be more prominent in CD than UC. The first CD susceptibility gene was identified in 2001. Three common mutations R702W, G908R, and 1007fs of the CARD15/NOD2 gene are shown to associate independently with CD but the magnitude of association varies between different populations. The present study aimed at identifying mutations and genetic variations in IBD susceptibility and candidate genes. In addition, correlation to phenotype was also assessed. One of the main objectives of this study was to evaluate the role of CARD15 in a Finnish CD cohort. 271 CD patients were studied for the three common mutations and the results showed a lower mutation frequency than in other Caucasian populations. Only 16% of the patients carried one of the three mutations. Ileal location as well as stricturing and penetrating behaviour of the disease were associated with occurrence of the mutations. The whole protein coding region of CARD15 was screened for possible Finnish founder mutations. In addition to several sequence variants, five novel mutations (R38M, W355X, P727L, W907R, and R1019X) were identified in five patients. Functional consequences of these novel variants were studied in vitro, and these studies demonstrated a profound impairment of MDP response. Investigation of CARD15 mutation frequency in healthy people across three continents showed a large geographic fluctuation. No simple correlation between mutation frequency and disease incidence was seen in populations studied. The occurrence of double mutant carriers in healthy controls suggested that the penetrance of risk alleles is low. Other main objectives aimed at identifying other genetic variations that are involved in the susceptibility to IBD. We investigated the most plausible IBD candidate genes including TRAF6, SLC22A4, SLC22A5, DLG5, TLR4, TNFRSF1A, ABCB1/MDR1, IL23R, and ATG16L1. The marker for a chromosome 5 risk haplotype and the rare HLA-DRB1*0103 allele were also studied. The study cohort consisted of 699 IBD patients (240 CD and 459 UC), of which 23% had a first-degree relative with IBD. Of the several candidate genes studied, IL23R was associated with CD susceptibility, and TNFRSF1A as well as the HLA-DRB1*0103 allele with UC susceptibility. IL23R variants also showed association with the stricturing phenotype and longer disease duration in CD patients. In addition, TNFRSF1A variants were more common among familial UC and ileocolonic CD. In conclusion, the common CARD15 mutations were shown to account for 16% of CD cases in Finland. Novel CARD15 variants identified in the present study are most likely disease-causing mutations, as judged by the results of in vitro studies. The present study also confirms the IL23R association with CD susceptibility and, in addition, TNFRSF1A and HLA-DRB1*0103 allele association with UC of specific clinical phenotypes.

Distal anterior cerebral artery aneurysms

Objective: Distal anterior cerebral artery (DACA) aneurysms represent about 6% of all intracranial aneurysms. So far, only small series on treatment of these aneurysms have been published. Our aim is to evaluate the anatomic features, microneurosurgical techniques, treatment results, and long-term outcome in patients treated for DACA aneurysms. Patients and methods: We analyzed the clinical and radiological data on 517 consecutive patients diagnosed with DACA aneurysm at two neurosurgical centers serving solely the Southern (Helsinki) and Eastern (Kuopio) Finland in 1936–2007, and used a defined subgroup of the whole study population in each part of the study. Detailed anatomic analysis was performed in 101 consecutive patients from 1998 to 2007. Treatment results were analyzed in 427 patients treated between 1980 to 2005, the era of CT imaging and microneurosurgery. Long-term treatment outcome of ruptured DACA aneurysm(s) was evaluated in 280 patients with a median follow-up of 10 years; no patients were lost to follow-up. Results: DACA aneurysms, found most often (83%) at the A3 segment of the anterior cerebral artery (ACA), were smaller (median 6 mm vs. 8 mm), more frequently associated with multiple aneurysms (35% vs. 18%), and presented more often with intracerebral hematomas (ICHs) (53% vs. 26%) than ruptured aneurysms in general. They were associated with anomalies of the ACA in 23% of the patients. Microsurgical treatment showed similar complication rates (treatment morbidity 15%, treatment mortality 0.4%) as for other ruptured aneurysms. At one year after subarachnoid hemorrhage (SAH), DACA aneurysms had equally favorable outcome (GOS≥4) as other ruptured aneurysms (74% vs. 69%) but their mortality was lower (13% vs. 24%). Factors predicting unfavorable outcome for ruptured DACA aneurysms were advanced age, Hunt&Hess≥3, rebleeding before treatment, ICH, intraventricular hemorrhage, and severe preoperative hydrocephalus. The cumulative relative survival ratio showed 16% excess mortality in patients with ruptured DACA aneurysm during the first three years after SAH compared to the matched general population. From the fourth year onwards, there was no excess mortality during the follow-up. There were four episodes of recurrent SAH, only one due to treated DACA aneurysm, with a 10-year cumulative risk of 1.4%. Conclusions: The special neurovascular features and frequent association with anterior cerebral artery anomalies must be taken into account when planning occlusive treatment of DACA aneurysms. Clipping of DACA aneurysms provides a long-lasting result, with very small rates of rebleeding. After surviving three years from rupture of DACA aneurysm, the long-term survival of these patients becomes similar to that of the matched general population.