Long-term effects of fenofibrate on lipoproteins and surrogate markers of macrovascular and microvascular disease in people with type 2 diabetes

Background and aims. Diabetic dyslipidemia is a highly atherogenic triad of increased triglycerides, decreased HDL cholesterol, and small dense LDL. Fibrates have a beneficial effect on diabetic dyslipidemia, and they have reduced cardiovascular events in randomized trials. Fenofibrate has reduced albuminuria and markers of low-grade inflammation and endothelial dysfunction. The present studies were undertaken to characterize the alterations of VLDL and LDL subclasses and to investigate the binding of LDL to arterial wall in type 2 diabetes. Further purpose was to elucidate the effects of fenofibrate on several lipoprotein subclasses, augmentation index (AIx), carotid intima-media thickness (IMT), and renal function. Subjects. 239 type 2 diabetic subjects were recruited among participants of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study at the Helsinki centre. The patients were randomized to fenofibrate (200mg/d) or placebo for 5 years. Additionally, a healthy control group (N = 93) was recruited. Results. VLDL1 triglycerides increased in similar proportion to total triglycerides in type 2 diabetic patients and control subjects. Despite the increase in total apoCIII levels, VLDL apoCIII was decreased in diabetic patients. Enrichment of LDL with apoCIII induced a small increase in binding of LDL to arterial wall proteoglycan. Intrinsic characteristics of diabetic LDL, rather than levels of apoCIII, were responsible for increased proteoglycan binding of diabetic LDL with high apoCIII. Fenofibrate reduced triglycerides, increased LDL size, and shifted HDL subclasses towards smaller particles with no change in levels of HDL cholesterol. High levels of homocysteine were associated with lower increase of HDL cholesterol and apoA-I during fenofibrate treatment. Long-term fenofibrate treatment did not improve IMT, AIx, inflammation, or endothelial function. Fenofibrate decreased creatinine clearance and estimated glomerular filtration rate. No effect on albuminuria was seen with fenofibrate. Instead, Cystatin C was increased during fenofibrate treatment. Conclusions. 1) Elevation of VLDL 1 triglycerides was the major determinant of plasma triglyceride concentration in control subjects and type 2 diabetic patients. 2) LDL with high apoCIII showed multiple atherogenic properties, that were only partially mediated by apoCIII per se in type 2 diabetes 3) Fenofibrate demonstrated no effect on surrogate markers of atherosclerosis. 4) Fenofibrate had no effect on albuminuria and the observed decrease in markers of renal function could complicate the clinical surveillance of the patients. 5) Fenofibrate can be used to treat severe hypertriglyceridemia or in combination therapy with statins, but not to increase HDL levels.

Short- and long-term consequences of food resources on Ural owl Strix uralensis reproduction

Life-history theory states that although natural selection would favour a maximisation of both reproductive output and life-span, such a combination can not be achieved in any living organism. According to life-history theory the reason for the fact that not all traits can be maximised simultaneously is that different traits compete with each other for resources. These relationships between traits that constrain the simultaneous evolution of two or more traits are called trade-offs. Therefore, during different life-stages an individual needs to optimise its allocation of resources to life-history components such as growth, reproduction and survival. Resource limitation acts on these traits and therefore investment in one trait, e.g. reproduction, reduces the resources available for investment in another trait, e.g. residual reproduction or survival. In this thesis I study how food resources during different stages of the breeding event affect reproductive decisions in the Ural owl (Strix uralensis) and the consequences of these decisions on parents and offspring. The Ural owl is a suitable study species for such studies in natural populations since they are long-lived, site-tenacious, and feed on voles. The vole populations in Fennoscandia fluctuate in three- to four-year cycles, which create a variable food environment for the Ural owls to cope with. The thesis gives new insight in reproductive costs and their consequences in natural animal populations with emphasis on underlying physiological mechanisms. I found that supplementary fed Ural owl parents invest supplemented food resources during breeding in own self-maintenance instead of allocating those resources to offspring growth. This investment in own maintenance instead of improving current reproduction had carry-over effects to the following year in terms of increased reproductive output. Therefore, I found evidence that reduced reproductive costs improves future reproductive performance. Furthermore, I found evidence for the underlying mechanism behind this carry-over effect of supplementary food on fecundity. The supplementary-fed parents reduced their feeding investment in the offspring compared to controls, which enabled the fed female parents to invest the surplus resources in parasite resistance. Fed female parents had lower blood parasite loads than control females and this effect lasted until the following year when also reproductive output was increased. Hence, increased investment in parasite resistance when resources are plentiful has the potential to mediate positive carry-over effects on future reproduction. I further found that this carry-over effect was only present when potentials for future reproduction were good. The thesis also provides new knowledge on resource limitation on maternal effects. I found that increased resources prior to egg laying improve the condition and health of Ural owl females and enable them to allocate more resources to reproduction than control females. These additional resources are not allocated to increase the number of offspring, but instead to improve the quality of each offspring. Fed Ural owl females increased the size of their eggs and allocated more health improving immunological components into the eggs. Furthermore, the increased egg size had long-lasting effects on offspring growth, as offspring from larger eggs were heavier at fledging. Limiting resources can have different short- and long-term consequences on reproductive decisions that affect both offspring number and quality. In long-lived organisms, such as the Ural owl, it appears to be beneficial in terms of fitness to invest in long breeding life-span instead of additional investment in current reproduction. In Ural owls, females can influence the phenotypic quality of the offspring by transferring additional resources to the eggs that can have long-lasting effects on growth.

Given and News : Media discourse and the construction of community on national days

National anniversaries such as independence days demand precise coordination in order to make citizens change their routines to forego work and spend the day at rest or at festivities that provide social focus and spectacle. The complex social construction of national days is taken for granted and operates as a given in the news media, which are the main agents responsible for coordinating these planned disruptions of normal routines. This study examines the language used in the news to construct the rather unnatural idea of national days and to align people in observing them. The data for the study consist of news stories about the Fourth of July in the New York Times, sampled over 150 years and are supplemented by material from other sources and other countries. The study is multidimensional, applying concepts from pragmatics (speech acts, politeness, information structure), systemic functional linguistics (the interpersonal metafunction and the Appraisal framework) and cognitive linguistics (frames, metaphor) as well as journalism and communications to arrive at an interdisciplinary understanding of how resources for meaning are used by writers and readers of the news stories. The analysis shows that on national anniversaries, nations tend to be metaphorized as persons having birthdays, to whom politeness should be shown. The face of the nation is to be respected in the sense of identifying the nation's interests as one's own (positive face) and speaking of citizen responsibilities rather than rights (negative face). Resources are available for both positive and negative evaluations of events and participants and the newspaper deftly changes footings (Goffman 1981) to demonstrate the required politeness while also heteroglossically allowing for a certain amount of disattention and even protest - within limits, for state holidays are almost never construed as Bakhtinian festivals, as they tend to reaffirm the hierarchy rather than invert it. Celebrations are evaluated mainly for impressiveness, and for the essentially contested quality of appropriateness, which covers norms of predictability, size, audience response, aesthetics, and explicit reference to the past. Events may also be negatively evaluated as dull ("banal") or inauthentic ("hoopla"). Audiences are evaluated chiefly in terms of their enthusiasm, or production of appropriate displays for emotional response, for national days are supposed to be occasions of flooding-out of nationalistic feeling. By making these evaluations, the newspaper reinforces its powerful position as an independent critic, while at the same time playing an active role in the construction and reproduction of emotional order embodied in "the nation's birthday." As an occasion for mobilization and demonstrations of power, national days may be seen to stand to war in the relation of play to fighting (Bateson 1955). Evidence from the newspaper's coverage of recent conflicts is adduced to support this analysis. In the course of the investigation, methods are developed for analyzing large collections of newspaper content, particularly topical soft news and feature materials that have hitherto been considered less influential and worthy of study than so-called hard news. In his work on evaluation in newspaper stories, White (1998) proposed that the classic hard news story is focused on an event that threatens the social order, but news of holidays and celebrations in general does not fit this pattern, in fact its central event is a reproduction of the social order. Thus in the system of news values (Galtung and Ruge 1965), national holiday news draws on "ground" news values such as continuity and predictability rather than "figure" news values such as negativity and surprise. It is argued that this ground helps form a necessary space for hard news to be seen as important, similar to the way in which the information structure of language is seen to rely on the regular alternation of given and new information (Chafe 1994).

Stand structural dynamics on pristine and managed boreal peatlands

The objectives of this study were to investigate the stand structure and succession dynamics in Scots pine (Pinus sylvestris L.) stands on pristine peatlands and in Scots pine and Norway spruce (Picea abies (L.) Karst.) dominated stands on drained peatlands. Furthermore, my focus was on characterising how the inherent and environmental factors and the intermediate thinnings modify the stand structure and succession. For pristine peatlands, the study was based on inventorial stand data, while for drained peatlands, longitudinal data from repeatedly measured stands were utilised. The studied sites covered the most common peatland site types in Finland. They were classified into two categories according to the ecohydrological properties related to microsite variation and nutrient levels within sites. Tree DBH and age distributions in relation to climate and site type were used to study the stand dynamics on pristine sites. On drained sites, the Weibull function was used to parameterise the DBH distributions and mixed linear models were constructed to characterise the impacts of different ecological factors on stand dynamics. On pristine peatlands, both climate and the ecohydrology of the site proved to be crucial factors determining the stand structure and its dynamics. Irrespective of the vegetation succession, enhanced site productivity and increased stand stocking they significantly affected the stand dynamics also on drained sites. On the most stocked sites on pristine peatlands the inter-tree competition seemed to also be a significant factor modifying stand dynamics. Tree age and size diversity increased with stand age, but levelled out in the long term. After drainage, the stand structural unevenness increased due to the regeneration and/or ingrowth of the trees. This increase was more pronounced on sparsely forested composite sites than on more fully stocked genuine forested sites in Scots pine stands, which further undergo the formation of birch and spruce undergrowth beneath the overstory as succession proceeds. At 20-30 years after drainage the structural heterogeneity started to decrease, indicating increased inter-tree competition, which increased the mortality of suppressed trees within stand. Peatland stands are more dynamic than anticipated and are generally not characterized by a balanced, self-perpetuating structure. On pristine sites, various successional pathways are possible, whereas on drained sites the succession has more uniform trend. Typically, stand succession proceeds without any distinct developmental stages on pristine peatlands, whereas on drained peatlands, at least three distinct stages could be identified. Thinnings had only little impact on the stand succession. The new information on stand dynamics may be utilised, e.g. in forest management planning to facilitate the allocation of the growth resources to the desired crop component by appropriate silvicultural treatments, as well as assist in assessing the effects of the climate change on the forested boreal peatlands.

Effects of dietary phosphorus and calcium-to-phosphorus ratio on calcium and bone metabolism in healthy 20- to 43-year-old Finnish women

Dietary habits have changed during the past decades towards an increasing consumption of processed foods, which has notably increased not only total dietary phosphorus (P) intake, but also intake of P from phosphate additives. While the intake of calcium (Ca) in many Western countries remains below recommended levels (800 mg/d), the usual daily P intake in a typical Western diet exceeds by 2- to 3-fold the dietary guidelines (600 mg/d). The effects of high P intake in healthy humans have been investigated seldom. In this thesis healthy 20- to 43-year-old women were studied. In the first controlled study (n = 14), we examined the effects of P doses, and in a cross-sectional study (n = 147) the associations of habitual P intakes with Ca and bone metabolism. In this same cross-sectional study, we also investigated whether differences exist between dietary P originating from natural P sources and phosphate additives. The second controlled study (n = 12) investigated whether by increasing the Ca intake, the effects of a high P intake could be reduced. The associations of habitual dietary calcium-to-phosphorus ratios (Ca:P ratio) with Ca and bone metabolism were determined in a cross-sectional study design (n = 147). In the controlled study, the oral intake of P doses (495, 745, 1245 and 1995 mg/d) with a low Ca intake (250 mg/d) increased serum parathyroid hormone (S-PTH) concentration in a dose-dependent manner. In addition, the highest P dose decreased serum ionized calcium (S-iCa) concentration and bone formation and increased bone resorption. In the second controlled study with a dietary P intake of 1850 mg/d, by increasing the Ca intake from 480 mg/d to 1080 mg/d and then to 1680 mg/d, the S-PTH concentration decreased, the S-iCa concentration increased and bone resorption decreased dose-dependently. However, not even the highest Ca intake could counteract the effect of high dietary P on bone formation, as indicated by unchanged bone formation activity. In the cross-sectional studies, a higher habitual dietary P intake (>1650 mg/d) was associated with lower S-iCa and higher S-PTH concentrations. The consumption of phosphate additive-containing foods was associated with a higher S-PTH concentration. Moreover, habitual low dietary Ca:P ratios (≤0.50, molar ratio) were associated with higher S-PTH concentrations and 24-h urinary Ca excretions, suggesting that low dietary Ca:P ratios may interfere with homeostasis of Ca metabolism and increase bone resorption. In summary, excessive dietary P intake in healthy Finnish women seems to be detrimental to Ca and bone metabolism, especially when dietary Ca intake is low. The results indicate that by increasing dietary Ca intake to the recommended level, the negative effects of high P intake could be diminished, but not totally prevented. These findings imply that phosphate additives may be more harmful than natural P. Thus, reduction of an excessively high dietary P intake is also beneficial for healthy individuals.

Substance flow analysis in Finland : Four case studies on N and P flows

Nitrogen (N) and phosphorus (P) are essential elements for all living organisms. However, in excess, they contribute to several environmental problems such as aquatic and terrestrial eutrophication. Globally, human action has multiplied the volume of N and P cycling since the onset of industrialization. The multiplication is a result of intensified agriculture, increased energy consumption and population growth. Industrial ecology (IE) is a discipline, in which human interaction with the ecosystems is investigated using a systems analytical approach. The main idea behind IE is that industrial systems resemble ecosystems, and, like them, industrial systems can then be described using material, energy and information flows and stocks. Industrial systems are dependent on the resources provided by the biosphere, and these two cannot be separated from each other. When studying substance flows, the aims of the research from the viewpoint of IE can be, for instance, to elucidate the ways how the cycles of a certain substance could be more closed and how the flows of a certain substance could be decreased per unit of production (= dematerialization). In Finland, N and P are studied widely in different ecosystems and environmental emissions. A holistic picture comparing different societal systems is, however, lacking. In this thesis, flows of N and P were examined in Finland using substance flow analysis (SFA) in the following four subsystems: I) forest industry and use of wood fuels, II) food production and consumption, III) energy, and IV) municipal waste. A detailed analysis at the end of the 1990s was performed. Furthermore, historical development of the N and P flows was investigated in the energy system (III) and the municipal waste system (IV). The main research sources were official statistics, literature, monitoring data, and expert knowledge. The aim was to identify and quantify the main flows of N and P in Finland in the four subsystems studied. Furthermore, the aim was to elucidate whether the nutrient systems are cyclic or linear, and to identify how these systems could be more efficient in the use and cycling of N and P. A final aim was to discuss how this type of an analysis can be used to support decision-making on environmental problems and solutions. Of the four subsystems, the food production and consumption system and the energy system created the largest N flows in Finland. For the creation of P flows, the food production and consumption system (Paper II) was clearly the largest, followed by the forest industry and use of wood fuels and the energy system. The contribution of Finland to N and P flows on a global scale is low, but when compared on a per capita basis, we are one of the largest producers of these flows, with relatively high energy and meat consumption being the main reasons. Analysis revealed the openness of all four systems. The openness is due to the high degree of internationality of the Finnish markets, the large-scale use of synthetic fertilizers and energy resources and the low recycling rate of many waste fractions. Reduction in the use of fuels and synthetic fertilizers, reorganization of the structure of energy production, reduced human intake of nutrients and technological development are crucial in diminishing the N and P flows. To enhance nutrient recycling and replace inorganic fertilizers, recycling of such wastes as wood ash and sludge could be promoted. SFA is not usually sufficiently detailed to allow specific recommendations for decision-making to be made, but it does yield useful information about the relative magnitude of the flows and may reveal unexpected losses. Sustainable development is a widely accepted target for all human action. SFA is one method that can help to analyse how effective different efforts are in leading to a more sustainable society. SFA's strength is that it allows a holistic picture of different natural and societal systems to be drawn. Furthermore, when the environmental impact of a certain flow is known, the method can be used to prioritize environmental policy efforts.

Effects of turbidity on feeding and distribution of fish

In aquatic systems, the ability of both the predator and prey to detect each other may be impaired by turbidity. This could lead to significant changes in the trophic interactions in the food web of lakes. Most fish use their vision for predation and the location of prey can be highly influenced by light level and clarity of the water environment. Turbidity is an optical property of water that causes light to be scattered and absorbed by particles and molecules. Turbidity is highly variable in lakes, due to seasonal changes in suspended sediments, algal blooms and wind-driven suspension of sediments especially in shallow waters. There is evidence that human activity has increased erosion leading to increased turbidity in aquatic systems. Turbidity could also play a significant role in distribution of fish. Turbidity could act as a cover for small fish and reduce predation risk. Diel horizontal migration by fish is common in shallow lakes and is considered as consequences of either optimal foraging behaviour for food or as a trade-off between foraging and predator avoidance. In turbid lakes, diel horizontal migration patterns could differ since turbidity can act as a refuge itself and affect the predator-prey interactions. Laboratory experiments were conducted with perch (Perca fluviatilis L.) and white bream (Abramis björkna (L.)) to clarify the effects of turbidity on their feeding. Additionally to clarify the effects of turbidity on predator preying on different types of prey, pikeperch larvae (Sander lucioperca (L.)), Daphnia pulex (Leydig), Sida crystallina (O.F. Müller), and Chaoborus flavicans (Meigen) were used as prey in different experiments. To clarify the role of turbidity in distribution and diel horizontal migration of perch, roach (Rutilus rutilus (L.)) and white bream, field studies were conducted in shallow turbid lakes. A clear and a turbid shallow lake were compared to investigate distribution of perch and roach in these two lakes in a 15-year study period. Feeding efficiency of perch and white bream was not significantly affected with increasing clay turbidity up to 50 NTU. The perch experiments with pikeperch larvae suggested that clay turbidity could act as a refuge especially at turbidity levels higher than 50 NTU. Perch experiments with different prey types suggested that pikeperch larvae probably use turbidity as a refuge better compared to Daphnia. Increase in turbidity probably has stronger affect on perch predating on plant-attached prey. The main findings of the thesis show that turbidity can play a significant role in distribution of fish. Perch and roach could use turbidity as refuge when macrophytes disappear while small perch may also use high turbidity as refuge when macrophytes are present. Floating-leaved macrophytes are probably good refuges for small fish in clay-turbid lakes and provide a certain level of turbidity and not too complex structure for refuge. The results give light to the predator-prey interactions in turbid environments. Turbidity of water should be taken in to account when studying the diel horizontal migrations and distribution of fish in shallow lakes.

Significant effects of Pgi genotype and body reserves on lifespan in the Glanville fritillary butterfly

Individuals with a particular variant of the gene phosphoglucose isomerase (Pgi ) have been shown to have superior dispersal capacity and fecundity in the Glanville fritillary butterfly (Melitaea cinxia), raising questions about the mechanisms that maintain polymorphism in this gene in the field. Here, we investigate how variation in the Pgi genotype affects female and male life history under controlled conditions. The most striking effect is the longer lifespan of genotypes with high dispersal capacity, especially in nonreproducing females. Butterflies use body reserves for somatic maintenance and reproduction, but <br/>different resources (in thorax versus abdomen) are used under dissimilar conditions, with some interactions with the Pgi genotype. These results indicate life-history trade-offs that involve resource allocation and genotype!environment interactions, and these trade-offs are likely to contribute to the maintenance of Pgi polymorphism in the natural populations.

Captured by conventions : On objectivity and factuality in international news agency discourse

The thesis explores the discourse of two global news agencies, the Associated Press (AP) and Reuters, which together with the French AFP are generally regarded as the world s leading news distributors. A glance at the guidelines given by AP and Reuters to their journalists shows that these two news agencies make a lot of effort to strive for objectivity the well-known journalistic ideal, which, however, is an almost indefinable concept. In journalism textbooks definitions of objectivity often contain various components: detachment, nonpartisanship, facticity, balance, etc. AP and Reuters, too, in their guidelines, present several other ideals besides objectivity , viz., reliability, accuracy, balance, freedom from bias, precise sourcing, reporting the truth, and so on. Other central concepts connected to objectivity are neutrality and impartiality. However, objectivity is, undoubtedly, the term that is most often mentioned when the ethics of journalism is discussed, acting as a kind of umbrella term for several related journalistic ideals. It can even encompass the other concept that is relevant for this study, that of factuality. These two intertwined concepts are extremely complex; paradoxically, it is easier to show evidence of the lack of objectivity or factuality than of their existence. I argue that when journalists conform to the deep-rooted conventions of objective news reporting, facts may be blurred, and the language becomes vague and ambiguous. As global distributors of news, AP and Reuters have had an influential role in creating and reinforcing conventions of (at least English-language) news writing. These conventions can be seen to work at various levels of news reporting: the ideological (e.g., defining what is regarded as newsworthy, or who is responsible), structural (e.g., the well-known inverted pyramid model), and stylistic (e.g., presupposing that in hard news reports, the journalist s voice should be backgrounded). On the basis of my case studies, I have found four central conventions to be worthy of closer examination: the conventional structure of news reports, the importance of newsworthiness, the tactics of impersonalisation which tends to blur news actors responsibility, and the routines of presenting emotions. My linguistic analyses draw mainly on M.A.K. Halliday s Systemic Functional Grammar, on notions of transitivity, ergativity, nominalisation and grammatical metaphor. The Appraisal framework, too, has provided useful tools for my analyses. The thesis includes six case studies dealing with the following topics: metaphors in political reporting, terrorism discourse, terrorism fears, emotions more generally, unnamed sources as rhetorical constructs, and responsibility in the convention of attribution.

Effects of gender, and SLCO1B1 and CYP7A1 polymorphisms on plasma bile acids in humans and the pharmacokinetics of therapeutic ursodeoxycholic acid

Bile acids are important steroid-derived molecules essential for fat absorption in the small intestine. They are produced in the liver and secreted into the bile. Bile acids are transported by bile flow to the small intestine, where they aid the digestion of lipids. Most bile acids are reabsorbed in the small intestine and return to the liver through the portal vein. The whole recycling process is referred to as the enterohepatic circulation, during which only a small amount of bile acids are removed from the body via faeces. The enterohepatic circulation of bile acids involves the delicate coordination of a number of bile acid transporters expressed in the liver and the small intestine. Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family, member 1B1 (SLCO1B1) gene, mediates the sodium independent hepatocellular uptake of bile acids. Two common SNPs in the SLCO1B1 gene are well known to affect the transport activity of OATP1B1. Moreover, bile acid synthesis is an important elimination route for cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production. The aim of this thesis was to investigate the effects of SLCO1B1 polymorphism on the fasting plasma levels of individual endogenous bile acids and a bile acid synthesis marker, and the pharmacokinetics of exogenously administered ursodeoxycholic acid (UDCA). Furthermore, the effects of CYP7A1 genetic polymorphism and gender on the fasting plasma concentrations of individual endogenous bile acids and the bile acid synthesis marker were evaluated. Firstly, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of bile acids was developed (Study I). A retrospective study examined the effects of SLCO1B1 genetic polymorphism on the fasting plasma concentrations of individual bile acids and a bile acid synthesis marker in 65 healthy subjects (Study II). In another retrospective study with 143 healthy individuals, the effects of CYP7A1 genetic polymorphism and gender as well as SLCO1B1 polymorphism on the fasting plasma levels of individual bile acids and the bile acid synthesis marker were investigated (Study III). The effects of SLCO1B1 polymorphism on the pharmacokinetics of exogenously administered UDCA were evaluated in a prospective genotype panel study including 27 healthy volunteers (Study IV). A robust, sensitive and simple HPLC-MS/MS method was developed for the simultaneous determination of 16 individual bile acids in human plasma. The method validation parameters for all the analytes met the requirements of the FDA (Food and Drug Administration) bioanalytical guidelines. This HPLC-MS/MS method was applied in Studies II-IV. In Study II, the fasting plasma concentrations of several bile acids and the bile acid synthesis marker seemed to be affected by SLCO1B1 genetic polymorphism, but these findings were not replicated in Study III with a larger sample size. Moreover, SLCO1B1 polymorphism had no effect on the pharmacokinetic parameters of exogenously administered UDCA. Furthermore, no consistent association was observed between CYP7A1 genetic polymorphism and the fasting plasma concentrations of individual bile acids or the bile acid synthesis marker. In contrast, gender had a major effect on the fasting plasma concentrations of several bile acids and also total bile acids. In conclusion, gender, but not SLCO1B1 or CYP7A1 polymorphisms, has a major effect on the fasting plasma concentrations of individual bile acids. Moreover, the common genetic polymorphism of CYP7A1 is unlikely to influence the activity of CYP7A1 under normal physiological conditions. OATP1B1 does not play an important role in the in vivo disposition of exogenously administered UDCA.

META-NORD: Towards Sharing of Language Resources in Nordic and Baltic Countries

This paper introduces the META-NORD project which develops Nordic and Baltic part of the European open language resource infrastructure. META-NORD works on assembling, linking across languages, and making widely available the basic language resources used by developers, professionals and researchers to build specific products and applications. The goals of the project, overall approach and specific focus lines on wordnets, terminology resources and treebanks are described. Moreover, results achieved in first five months of the project, i.e. language whitepapers, metadata specification and IPR, are presented.