Corporate Governance Mechanisms and Firm Performance:Evidence from Finland

This paper examines the association between corporate governance attributes and firm performance of Finnish firms during 1990 – 2000. The empirical results suggest that corporate governance matters for firm performance. First, univariate test results indicate that firms characterized by a high (efficient) level of corporate governance have delivered greater stock returns, are higher valued based on the measure of Tobin’s Q, and exhibit higher ratios of cash flow to assets, on average, in comparison to their counterparts characterized by a low (inefficient) level of corporate governance. Second, controlling for a number of well-known determinants of stock returns, we find evidence that firms categorized by inefficient corporate governance have delivered inferior returns to shareholders during the investigation period. Finally, after controlling for several common determinants of firm value, we find that firms characterized by efficient corporate governance have been valued higher during the investigation period, measured by Tobin’s Q.

Factors related to seat belt use : A Turkish case

Seat belts are effective safety devices used to protect car occupants from severe injuries and fatalities during road vehicle accidents. Despite the proven effectiveness of seat belts, seat belt use rates are quite low, especially in developing countries, such as Turkey. The general aim of the present study was to investigate a large variety of factors related to seat belt use among Turkish car occupants using different perspectives and methods and therefore, to contribute to the design of effective seat belt use interventions for increasing seat belt use rates in Turkey. Five sub-studies were conducted within the present study. In the first sub-study, environmental (e.g., road type) and psycho-social factors (e.g., belt use by other car occupants) related to the seat belt use of front-seat occupants were investigated using observation techniques. Being male, of a young age, and traveling on city roads were the main factors negatively related to seat belt use. Furthermore, seat belt use by the drivers and front-seat passengers was highly correlated and a significant predictors of each other. In the second sub-study, the motivations of the car occupants for seat belt use and non-use were investigated using interview techniques. Situational conditions, such as traveling on city roads and for short distances, and not believing in the effectiveness and relevance of seat belt use for safety, were the most frequently reported reasons for not using a seat belt. Safety, habit and avoiding punishment were among the most frequently reported reasons for using a seat belt. In the third sub-study, the Theory of Planned Behavior (TPB) and the Health Belief Model (HBM) were applied to seat belt use using Structural Equation Modeling techniques. The TPB model showed a good fit to the data, whereas the HBM showed a poor fit to the data. Within the TPB model, attitude and subjective norm were significant predictors of intentions to use a seat belt on both urban and rural roads. In the fourth sub-study, seat belt use frequency and motivations for seat belt use among taxi drivers were investigated and compared between free-time and work-time driving using a survey. The results showed that taxi drivers used seat belts more when driving a private car in their free-times compared to when driving a taxi during their work-times. The lack of a legal obligation to use a seat belt in city traffic and fear of being attacked or robbed by the passengers were found as two specific reasons for not using a seat belt when driving a taxi. Lastly, in the fifth sub-study, the relationship of seat belt use to driver and health behaviors was investigated using a survey. Although seat belt use was related both to health and driver behaviors, factor analysis results showed that it grouped with driver behaviors. Based on the results of the sub-studies, a tentative empirical model showing different predictors of seat belt use was proposed. According to the model, safety and normative motivations and perceived physical barriers related to seat belt use are the three important predictors of seat belt use. Keywords: Seat belt use; environmental factors; psycho-social factors; safety and normative motivations; the Theory of Planned Behavior; the Health Belief Model; health behaviors; driver behaviors; front-seat occupants; taxi drivers; Turkey.

Analysis of Heterogeneous IP Traffic in Wireless Environment

Wireless access is expected to play a crucial role in the future of the Internet. The demands of the wireless environment are not always compatible with the assumptions that were made on the era of the wired links. At the same time, new services that take advantage of the advances in many areas of technology are invented. These services include delivery of mass media like television and radio, Internet phone calls, and video conferencing. The network must be able to deliver these services with acceptable performance and quality to the end user. This thesis presents an experimental study to measure the performance of bulk data TCP transfers, streaming audio flows, and HTTP transfers which compete the limited bandwidth of the GPRS/UMTS-like wireless link. The wireless link characteristics are modeled with a wireless network emulator. We analyze how different competing workload types behave with regular TPC and how the active queue management, the Differentiated services (DiffServ), and a combination of TCP enhancements affect the performance and the quality of service. We test on four link types including an error-free link and the links with different Automatic Repeat reQuest (ARQ) persistency. The analysis consists of comparing the resulting performance in different configurations based on defined metrics. We observed that DiffServ and Random Early Detection (RED) with Explicit Congestion Notification (ECN) are useful, and in some conditions necessary, for quality of service and fairness because a long queuing delay and congestion related packet losses cause problems without DiffServ and RED. However, we observed situations, where there is still room for significant improvements if the link-level is aware of the quality of service. Only very error-prone link diminishes the benefits to nil. The combination of TCP enhancements improves performance. These include initial window of four, Control Block Interdependence (CBI) and Forward RTO recovery (F-RTO). The initial window of four helps a later starting TCP flow to start faster but generates congestion under some conditions. CBI prevents slow-start overshoot and balances slow start in the presence of error drops, and F-RTO reduces unnecessary retransmissions successfully.

Adjuvant Arteriovenous Fistula for Infrapopliteal Bypass Patency

A lack of suitable venous graft material or poor outflow is an increasingly encountered situation in peripheral vascular surgery. Prosthetic grafts have clearly worse patency than vein grafts in femorodistal bypass surgery. The use of an adjuvant arteriovenous fistula (av-fistula) at the distal anastomosis has been postulated to improve the flow and thus increase prosthetic graft patency. In theory the adjuvant fistula might have the same effect in a compromised outflow venous bypass. A free flap transfer also augments graft flow and may have a positive effect on an ischaemic limb. The aim of this study was to evaluate the possible benefit of an adjuvant av-fistula and an internal av-fistula within a free flap transfer on the patency and outcome of an infrapopliteal bypass. The effect of the av-fistula on bypass haemodynamics was also assessed along with possible adverse effects. Patients and methods: 1. A prospective randomised multicentre trial comprised 59 patients with critical leg ischaemia and no suitable veins for grafting. Femorocrural polytetrafluoroethylene (PTFE) bypasses with a distal vein cuff, with or without an adjuvant av-fistula, were performed. The outcome was assessed according to graft patency and leg salvage. 2. Haemodynamic measurements were performed to a total of 50 patients from Study I with a prolonged follow-up. 3. Nine critically ischaemic limbs were treated with a modified radial forearm flap transfer in combination with a femorodistal bypass operation. An internal av-fistula was created within the free flap transfer to increase flap artery and bypass graft flow. 4. The effect of a previous free flap transfer on bypass haemodynamics was studied in a case report. 5. In a retrospective multicentre case-control study, 77 infrapopliteal vein bypasses with an adjuvant av-fistula were compared with matched controls without a fistula. The outcome and haemodynamics of the bypasses were recorded. Main results: 1. The groups with and without the av-fistula did not differ as regards prosthetic graft patency or leg salvage. 2. The intra- and postoperative prosthetic graft flow was significantly increased in the patients with the av-fistula. However, this increase did not improve patency. There was no difference in patency between the groups, even in the extended follow-up. 3. The vein graft flow increased significantly after the anastomosis of the radial forearm flap with an internal av-fistula. 4. A previously performed free flap transfer significantly augmented the flow of a poor outflow femoropedal bypass graft. 5. The adjuvant av-fistula increased the venous infrapopliteal bypass flow significantly. The increased flow did not, however, lead to improved graft patency or leg salvage. Conclusion: An adjuvant av-fistula does not improve the patency of a femorocrural PTFE bypass with a distal vein cuff despite the fact that the flow values increased both in the intraoperative measurements and during the immediate postoperative surveillance. The adjuvant av-fistula increased graft flow significantly also in a poor outflow venous bypass, but regardless of this the outcome was no improved. The adjuvant av-fistula rarely caused adverse effects. In a group of diabetic patients, the flow in a vascular bypass graft was augmented by an internal av-fistula within a radial forearm flap and similarly in a patient with a previous free flap transfer, a high intraoperative graft flow was achieved due to the free flap shunt effect.

Heme oxygenase-1 in cardiovascular diseases

Myocardial infarction (MI) and heart failure are major causes of morbidity and mortality worldwide. Treatment of MI involves early restoration of blood flow to limit infarct size and preserve cardiac function. MI leads to left ventricular remodeling, which may eventually progress to heart failure, despite the established pharmacological treatment of the disease. To improve outcome of MI, new strategies for protecting the myocardium against ischemic injury and enhancing the recovery and repair of the infarcted heart are needed. Heme oxygenase-1 (HO-1) is a stress-responsive and cytoprotective enzyme catalyzing the degradation of heme into the biologically active reaction products biliverdin/bilirubin, carbon monoxide (CO) and free iron. HO-1 plays a key role in maintaining cellular homeostasis by its antiapoptotic, anti-inflammatory, antioxidative and proangiogenic properties. The present study aimed, first, at evaluating the role of HO-1 as a cardioprotective and prohealing enzyme in experimental rat models and at investigating the potential mechanisms mediating the beneficial effects of HO-1 in the heart. The second aim was to evaluate the role of HO-1 in 231 critically ill intensive care unit (ICU) patients by investigating the association of HO-1 polymorphisms and HO-1 plasma concentrations with illness severity, organ dysfunction and mortality throughout the study population and in the subgroup of cardiac patients. We observed in an experimental rat MI model, that HO-1 expression was induced in the infarcted rat hearts, especially in the infarct and infarct border areas. In addition, pre-emptive HO-1 induction and CO donor pretreatment promoted recovery and repair of the infarcted hearts by differential mechanisms. CO promoted vasculogenesis and formation of new cardiomyocytes by activating c-kit+ stem/progenitor cells via hypoxia-inducible factor 1 alpha, stromal cell-derived factor 1 alpha (SDF-1a) and vascular endothelial growth factor B, whereas HO-1 promoted angiogenesis possibly via SDF-1a. Furthermore, HO-1 protected the heart in the early phase of infarct healing by increasing survival and proliferation of cardiomyocytes. The antiapoptotic effect of HO-1 persisted in the late phases of infarct healing. HO-1 also modulated the production of extracellular matrix components and reduced perivascular fibrosis. Some of these beneficial effects of HO-1 were mediated by CO, e.g. the antiapoptotic effect. However, CO may also have adverse effects on the heart, since it increased the expression of extracellular matrix components. In isolated perfused rat hearts, HO-1 induction improved the recovery of postischemic cardiac function and abrogated reperfusion-induced ventricular fibrillation, possibly in part via connexin 43. We found that HO-1 plasma levels were increased in all critically ill patients, including cardiac patients, and were associated with the degree of organ dysfunction and disease severity. HO-1 plasma concentrations were also higher in ICU and hospital nonsurvivors than in survivors, and the maximum HO-1 concentration was an independent predictor of hospital mortality. Patients with the HO-1 -413T/GT(L)/+99C haplotype had lower HO-1 plasma concentrations and lower incidence of multiple organ dysfunction. However, HO-1 polymorphisms were not associated with ICU or hospital mortality. The present study shows that HO-1 is induced in response to stress in both experimental animal models and severely ill patients. HO-1 played an important role in the recovery and repair of infarcted rat hearts. HO-1 induction and CO donor pretreatment enhanced cardiac regeneration after MI, and HO-1 may protect against pathological left ventricular remodeling. Furthermore, HO-1 induction potentially may protect against I/R injury and cardiac dysfunction in isolated rat hearts. In critically ill ICU patients, HO-1 plasma levels correlate with the degree of organ dysfunction, disease severity, and mortality, suggesting that HO-1 may be useful as a marker of disease severity and in the assessment of outcome of critically ill patients.

What Determines Stock Option Contract Design?

This paper analyzes factors driving the design of stock option plans for Finnish firms. We examine determinants of the scope of plans, exercise price, target group, and dividend protection. The scope is found to be negatively related to Tobin’s Q and positively related to proxies for monitoring costs. The scope is also greater in broad-based plans, and in plans with dividend protection. Prior stock return is found to be negatively related to the size of the premium (out-of-the-moneyness), whereas dividend protection increases the premium. The results also suggest that investment intensity, cash flow, and monitoring costs are associated with the likelihood of granting premium (out-of-the-money) stock options. Furthermore, the likelihood of granting broad-based plans is increasing in institutional ownership and cash flow constraints, and decreasing in firm size. Broad-based plans are also more likely among firms in growth industries. We find support that the likelihood of dividend protection is decreasing in foreign ownership. In addition, firms paying zero-dividends are less likely to include dividend protection, whereas higher unsystematic risk is associated with a greater likelihood of including dividend protection.

Interactions of natural products with β-lactoglobulins, members of the lipocalin family

Natural products constitute an important source of new drugs. The bioavailability of the drugs depends on their absorption, distribution, metabolism and elimination. To achieve good bioavailability, the drug must be soluble in water, stable in the gastrointestinal tract and palatable. Binding proteins may improve the solubility of drug compounds, masking unwanted properties, such as bad taste, bitterness or toxicity, transporting or protecting these compounds during processing and storage. The focus of this thesis was to study the interactions, including ligand binding and the effect of pH and temperature, of bovine and reindeer β-lactoglobulin (βLG) with such compounds as retinoids, phenolic compounds as well as with compounds from plant extracts, and to investigate the transport properties of the βLG-ligand complex. To examine the binding interactions of different ligands to βLG, new methods were developed. The fluorescence binding method for the evaluation of ligand binding to βLG was miniaturized from a quartz cell to a 96-well plate. A method of ultrafiltration sampling combined with high-performance liquid chromatography was developed to assess the binding of compounds from extracts. The interactions of phenolic compounds or retinoids and βLG were investigated using the 96-well plate method. The majority of flavones, flavonols, flavanones and isoflavones and all of the retinoids included were shown to bind to bovine and reindeer βLG. Phenolic compounds, contrary to retinol, were not released at acidic pH. Those results suggest that βLG may have more binding sites, probably also on the surface of βLG. An extract from Camellia sinensis (L.) O. Kunze (black tea), Urtica dioica L. (nettle) and Piper nigrum (black pepper) were used to evaluate whether βLG could bind compounds from plant extracts. Piperine from P. nigrum was found to bind tightly and rutin from U. dioica weakly to βLG. No components from C. sinensis bound to βLG in our experiment. The uptake and membrane permeation of bovine and reindeer βLG, free and bound with retinol, palmitic acid and cholesterol, were investigated using Caco-2 cell monolayers. Both bovine and reindeer βLG were able to cross the Caco-2 cell membrane. Free and βLG-bound retinol and palmitic acid were transported equally, whereas cholesterol could not cross the Caco-2 cell monolayer free or bound to βLG. Our results showed that βLG can bind different natural product compounds, but cannot enhance transport of retinol, palmitic acid or cholesterol through Caco-2 cells. Despite this, βLG, as a water-soluble binding protein, may improve the solubility of natural compounds, possibly protecting them from early degradation and transporting some of them through the stomach. Furthermore, it may decrease their bad or bitter taste during oral administration of drugs or in food preparations. βLG can also enhance or decrease the health benefits of herbal teas and food preparations by binding compounds from extracts.

The Europeanisation of occupational health services: A study of the impact of EU policies

This study concerns Framework Directive 89/391/EEC on health and safety at work, which encouraged improvements in occupational health services (OHS) for workers in EU member states. Framework Directive 89/391/EEC originally aimed at bringing the same level of occupational health and safety to employees in both the public and private sectors in EU member states. However, the implementation of the framework directive and OHS varies widely among EU member states. Occupational health services have generally been considered an important work-related welfare benefit in EU member states. The purpose of this study was to analyse OHS within the EU context and then analyse the impact of EU policies on OHS implementation as part of the welfare state benefit. The focus is on social, health, and industrial policies within welfare state regimes as well as EU policy-making processes affecting these policies in EU member states. The research tasks were divided into four groups related to the policy, functions, targets,and actors of OHS. The questions related to policy tried to discover the role of OHS in other policies, such as health, social, and labour market policies within the EU. The questions about functions sought to describe the changes, as well as the path dependence, of OHS in EU member states after the framework directive. The questions about targets were based on the general aims of WHO and the ILO in relation to equity, solidarity, universality, and access to OHS. The questions on actors were designed to understand the variety of stakeholders interested in OHS. The actors were supranational (EU, ILO, and WHO), national (ministries, institutes, and professional organisations), and social partners (trade unions and employers organisations). The study data were collected by interviewing 92 people in 15 EU member states, including representatives of ministries, institutions, research,trade unions, employers organisations, and occupational health organisations. Other documents were collected from the Internet,databases, libraries, and conference materials for a systematic review of the policies, strategies, organisation, financing, and monitoring of OHS in EU member states. Different analytical methods were used in the data analysis. The main findings of the study can be summarised as follows. First, occupational health services is a context-dependent phenomenon, which therefore varies according to the development of the welfare state in general, and depends on each country s culture, history, economy, and politics. The views of different stakeholders in EU member states concerning the impact and possibilities of OHS to improve health vary from evidence-based opinions to the sporadic impact of OHS on occupational health. OHS as a concept is vaguely defined by the EU, whereas the ILO defines OHS content. The tasks of OHS began as preventive and protective services for workers. However, they have moved towards multidisciplinary and organisational development as well as the workplace health promotion sphere.Since 1989 OHS has developed differently in different EU member states depending on the starting position of those states, but planning and implementation are crucial phases in the process toward better OHS coverage, equity, and access. Nevertheless, the data used for the planning and legitimisation of OHS activities are mainly based on occupational health data rather than on OHS data. This makes decisions on political or policy grounds inaccurate. OHS is still an evolving concept and benefit for workers, but the Europeanisation of OHS reflects contextual changes, such as the impact of the internal market, competition, and commercialisation on OHS. Stronger cooperation and integration with health, social, and employment services would be an asset for workers, because of new epidemics, an epidemiological shift towards new risks, an ageing labour market, and changes in the labour market. Different methods and approaches are needed in order to study the results of integrated services. In the future, more detailed information will be needed about the actual impact of EU policies on OHS and decision-making processes in order to get OHS into different policies in the EU and its member states. Further results and effects of OHS processes on occupational health need to be analysed more carefully. The adoption of a variety of research strategies and a multidisciplinary approach to understand the influence of different policies on OHS in the EU and its member states would highlight the options and opportunities to improve workers occupational health. Key subject headings: Occupational health services, EU policy, policymaking,framework directive 89/391/EEC

Population structure and evolution in the ant Plagiolepis pygmaea and its two social parasites Plagiolepis xene and Plagiolepis grassei

Social behaviour affects dispersal of animals and is an important modifier of genetic population structures. The female sex is often philopatric, which maintains coancestry within the breeding groups and promotes cooperative behaviours. This enables also inclusive fitness returns from altruism and explains why some individuals sacrifice personal reproduction for the good of others in social insects such as ants. However, reduced dispersal and population substructuring at the level of colonies may also entail inbreeding, loss of genetic diversity, and vulnerability. In addition, the most vulnerable ants are species that are evolved to parasitize colonies of other ants, and which compromise between abilities to disperse and the efficiency to parasitize the host. On the other hand, certain social organisations of ant colonies may facilitate a species to disperse outside its natural range and become a pest. Altogether, knowledge on genetic structuring of ant populations, as well as the evolution of their life histories can contribute to conservation biology and population management. The aim of this thesis was to investigate population structures and phylogenetic evolution of the ant Plagiolepis pygmaea and its two obligatory, workerless social parasites (inquilines) P. xene and P. grassei with genetic markers and DNA sequence data. The results support the general assumption that populations of inquiline parasites are highly fragmented and genetically vulnerable. Comparison of the two parasites suggests that differences in their relative abundance may follow from their interaction with the host, i.e. how well the species is adapted to reproduce in the host colonies. The results also indicate that the most recent free living ancestor to these two parasite species is their common host. This is considered to provide evidence for the controversial issue of sympatric speciation. Further, given that the level of adaptations to parasitic life history depends on the evolutionary time since the free-living ancestor, the results establish a link between species rarity and its evolutionary age. The populations of the host species P. pygmaea displayed significantly reduced dispersal both among the females (queens) and males, and high levels of inbreeding which may enhance worker altruism. In addition, the queens were found to mate with multiple males. Given the high relatedness between the queens and their mates, this occurs probably for non-genetic reasons, e.g. without benefits associated in genetically more diverse offspring. The results hence caution that the contribution of non-genetic factors to the prevailing mating patterns and genetic population structures should not be underestimated.

Prognostic molecular factors and algorithms in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin lymphomas. As DLBCL is characterized by heterogeneous clinical and biological features, its prognosis varies. To date, the International Prognostic Index has been the strongest predictor of outcome for DLBCL patients. However, no biological characters of the disease are taken into account. Gene expression profiling studies have identified two major cell-of-origin phenotypes in DLBCL with different prognoses, the favourable germinal centre B-cell-like (GCB) and the unfavourable activated B-cell-like (ABC) phenotypes. However, results of the prognostic impact of the immunohistochemically defined GCB and non-GCB distinction are controversial. Furthermore, since the addition of the CD20 antibody rituximab to chemotherapy has been established as the standard treatment of DLBCL, all molecular markers need to be evaluated in the post-rituximab era. In this study, we aimed to evaluate the predictive value of immunohistochemically defined cell-of-origin classification in DLBCL patients. The GCB and non-GCB phenotypes were defined according to the Hans algorithm (CD10, BCL6 and MUM1/IRF4) among 90 immunochemotherapy- and 104 chemotherapy-treated DLBCL patients. In the chemotherapy group, we observed a significant difference in survival between GCB and non-GCB patients, with a good and a poor prognosis, respectively. However, in the rituximab group, no prognostic value of the GCB phenotype was observed. Likewise, among 29 high-risk de novo DLBCL patients receiving high-dose chemotherapy and autologous stem cell transplantation, the survival of non-GCB patients was improved, but no difference in outcome was seen between GCB and non-GCB subgroups. Since the results suggested that the Hans algorithm was not applicable in immunochemotherapy-treated DLBCL patients, we aimed to further focus on algorithms based on ABC markers. We examined the modified activated B-cell-like algorithm based (MUM1/IRF4 and FOXP1), as well as a previously reported Muris algorithm (BCL2, CD10 and MUM1/IRF4) among 88 DLBCL patients uniformly treated with immunochemotherapy. Both algorithms distinguished the unfavourable ABC-like subgroup with a significantly inferior failure-free survival relative to the GCB-like DLBCL patients. Similarly, the results of the individual predictive molecular markers transcription factor FOXP1 and anti-apoptotic protein BCL2 have been inconsistent and should be assessed in immunochemotherapy-treated DLBCL patients. The markers were evaluated in a cohort of 117 patients treated with rituximab and chemotherapy. FOXP1 expression could not distinguish between patients, with favourable and those with poor outcomes. In contrast, BCL2-negative DLBCL patients had significantly superior survival relative to BCL2-positive patients. Our results indicate that the immunohistochemically defined cell-of-origin classification in DLBCL has a prognostic impact in the immunochemotherapy era, when the identifying algorithms are based on ABC-associated markers. We also propose that BCL2 negativity is predictive of a favourable outcome. Further investigational efforts are, however, warranted to identify the molecular features of DLBCL that could enable individualized cancer therapy in routine patient care.

Inflammatory and coagulation disturbances in acute pancreatitis

Acute pancreatitis (AP), a common cause of acute abdominal pain, is usually a mild, self-limited disease. However, some 20-30% of patients develop a severe disease manifested by pancreatic necrosis, abscesses or pseudocysts, and/or extrapancreatic complications, such as vital organ failure (OF). Patients with AP develop systemic inflammation, which is considered to play a role in the pathogenesis of multiple organ failure (MOF). OF mimics the condition seen in patients with sepsis, which is characterized by an overwhelming production of inflammatory mediators, activation of the complement system and systemic activation of coagulation, as well as the development of disseminated intravascular coagulation (DIC) syndrome. Vital OF is the major cause of mortality in AP, along with infectious complications. About half of the deaths occur within the first week of hospitalization and thus, early identification of patients likely to develop OF is important. The aim of the present study was to investigate inflammatory and coagulation disturbances in AP and to find inflammatory and coagulation markers for predicting severe AP, and development of OF and fatal outcome. This clinical study consists of four parts. All of patients studied had AP when admitted to Helsinki University Central Hospital. In the first study, 31 patients with severe AP were investigated. Their plasma levels of protein C (PC) and activated protein C (APC), and monocyte HLA-DR expression were studied during the treatment period in the intensive care unit; 13 of these patients developed OF. In the second study, the serum levels of complement regulator protein CD59 were studied in 39 patients during the first week of hospitalization; 12 of them developed OF. In the third study, 165 patients were investigated; their plasma levels of soluble form of the receptor for advanced glycation end products (sRAGE) and high mobility group box 1 (HMGB1) protein were studied during the first 12 days of hos-pitalization; 38 developed OF. In the fourth study, 33 patients were studied on admission to hospital for plasma levels of prothrombin fragment F1+2 and tissue factor pathway inhibitor (TFPI), and thrombin formation capacity by calibrated automated thrombogram (CAT); 9 of them developed OF. Our results showed significant PC deficiency and decreased APC generation in patients with severe AP. The PC pathway defects seemed to be associated with the development of OF. In patients who developed OF, the levels of serum CD59 and plasma sRAGE, but not of HMGB1, were significantly higher than in patients who recovered without OF. The high CD59 levels on admission to the hospital seemed to be predictive for severe AP and OF. The median of the highest sRAGE levels was significantly higher in non-survivors than in survivors. No significant difference between the patient groups was found in the F1+2 levels. The thrombograms of all patients were disturbed in their shape, and in 11 patients the exogenous tissue factor did not trigger thrombin generation at all ( flat curve ). All of the patients that died displayed a flat curve. Free TFPI levels and free/total TFPI ratios were significantly higher in patients with a flat curve than in the others, and these levels were also significantly higher in non-survivors than in survivors. The flat curve in combination with free TFPI seemed to be predictive for a fatal outcome in AP.

Carbon dioxide and methane exchange between a boreal pristine lake and the atmosphere

Lakes serve as sites for terrestrially fixed carbon to be remineralized and transferred back to the atmosphere. Their role in regional carbon cycling is especially important in the Boreal Zone, where lakes can cover up to 20% of the land area. Boreal lakes are often characterized by the presence of a brown water colour, which implies high levels of dissolved organic carbon from the surrounding terrestrial ecosystem, but the load of inorganic carbon from the catchment is largely unknown. Organic carbon is transformed to methane (CH4) and carbon dioxide (CO2) in biological processes that result in lake water gas concentrations that increase above atmospheric equilibrium, thus making boreal lakes as sources of these important greenhouse gases. However, flux estimates are often based on sporadic sampling and modelling and actual flux measurements are scarce. Thus, the detailed temporal flux dynamics of greenhouse gases are still largely unknown. ----- One aim here was to reveal the natural dynamics of CH4 and CO2 concentrations and fluxes in a small boreal lake. The other aim was to test the applicability of a measuring technique for CO2 flux, i.e. the eddy covariance (EC) technique, and a computational method for estimation of primary production and community respiration, both commonly used in terrestrial research, in this lake. Continuous surface water CO2 concentration measurements, also needed in free-water applications to estimate primary production and community respiration, were used over two open water periods in a study of CO2 concentration dynamics. Traditional methods were also used to measure gas concentration and fluxes. The study lake, Valkea-Kotinen, is a small, humic, headwater lake within an old-growth forest catchment with no local anthropogenic disturbance and thus possible changes in gas dynamics reflect the natural variability in lake ecosystems. CH4 accumulated under the ice and in the hypolimnion during summer stratification. The surface water CH4 concentration was always above atmospheric equilibrium and thus the lake was a continuous source of CH4 to the atmosphere. However, the annual CH4 fluxes were small, i.e. 0.11 mol m-2 yr-1, and the timing of fluxes differed from that of other published estimates. The highest fluxes are usually measured in spring after ice melt but in Lake Valkea-Kotinen CH4 was effectively oxidised in spring and highest effluxes occurred in autumn after summer stratification period. CO2 also accumulated under the ice and the hypolimnetic CO2 concentration increased steadily during stratification period. The surface water CO2 concentration was highest in spring and in autumn, whereas during the stable stratification it was sometimes under atmospheric equilibrium. It showed diel, daily and seasonal variation; the diel cycle was clearly driven by light and thus reflected the metabolism of the lacustrine ecosystem. However, the diel cycle was sometimes blurred by injection of hypolimnetic water rich in CO2 and the surface water CO2 concentration was thus controlled by stratification dynamics. The highest CO2 fluxes were measured in spring, autumn and during those hypolimnetic injections causing bursts of CO2 comparable with the spring and autumn fluxes. The annual fluxes averaged 77 (±11 SD) g C m-2 yr-1. In estimating the importance of the lake in recycling terrestrial carbon, the flux was normalized to the catchment area and this normalized flux was compared with net ecosystem production estimates of -50 to 200 g C m-2 yr-1 from unmanaged forests in corresponding temperature and precipitation regimes in the literature. Within this range the flux of Lake Valkea-Kotinen yielded from the increase in source of the surrounding forest by 20% to decrease in sink by 5%. The free water approach gave primary production and community respiration estimates of 5- and 16-fold, respectively, compared with traditional bottle incubations during a 5-day testing period in autumn. The results are in parallel with findings in the literature. Both methods adopted from the terrestrial community also proved useful in lake studies. A large percentage of the EC data was rejected, due to the unfulfilled prerequisites of the method. However, the amount of data accepted remained large compared with what would be feasible with traditional methods. Use of the EC method revealed underestimation of the widely used gas exchange model and suggests simultaneous measurements of actual turbulence at the water surface with comparison of the different gas flux methods to revise the parameterization of the gas transfer velocity used in the models.

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.

Lumettoman maan routaolojen mallintaminen ja ennustettavuus muuttuvassa ilmastossa

Raportissa on arvioitu ilmastonmuutoksen vaikutusta Suomen maaperän talviaikaiseen jäätymiseen lämpösummien perusteella. Laskelmat kuvaavat roudan paksuutta nimenomaisesti lumettomilla alueilla, esimerkiksi teillä, joilta satanut lumi aurataan pois. Luonnossa lämpöä eristävän lumipeitteen alla routaa on ohuemmin kuin tällaisilla lumettomilla alueilla. Toisaalta luonnollisessa ympäristössä paikalliset erot korostuvat johtuen mm. maalajeista ja kasvillisuudesta. Roudan paksuudet laskettiin ensin perusjakson 1971–2000 ilmasto-oloissa talviaikaisten säähavaintotietoihin pohjautuvien lämpötilojen perusteella. Sen jälkeen laskelmat toistettiin kolmelle tulevalle ajanjaksolle (2010–2039, 2040–2069 ja 2070–2099) kohottamalla lämpötiloja ilmastonmuutosmallien ennustamalla tavalla. Laskelman pohjana käytettiin 19 ilmastomallin A1B-skenaarioajojen keskimäärin simuloimaa lämpötilan muutosta. Tulosten herkkyyden arvioimiseksi joitakin laskelmia tehtiin myös tätä selvästi heikompaa ja voimakkaampaa lämpenemisarviota käyttäen. A1B-skenaarion mukaisen lämpötilan nousun toteutuessa nykyisiä mallituloksia vastaavasti routakerros ohenee sadan vuoden aikana Pohjois-Suomessa 30–40 %, suuressa osassa maan keski- ja eteläosissa 50–70 %. Jo lähivuosikymmeninä roudan ennustetaan ohentuvan 10–30 %, saaristossa enemmän. Mikäli lämpeneminen toteutuisi voimakkaimman tarkastellun vaihtoehdon mukaisesti, roudan syvyys pienenisi tätäkin enemmän. Roudan paksuuden vuosienvälistä vaihtelua ja sen muuttumista tulevaisuudessa pyrittiin myös arvioimaan. Leutoina talvina routa ohenee enemmän kuin normaaleina tai ankarina pakkastalvina. Päivittäistä sään vaihtelua simuloineen säägeneraattorin tuottamassa aineistoissa esiintyi kuitenkin liian vähän hyvin alhaisia ja hyvin korkeita lämpötiloja. Siksi näitten lämpötilatietojen pohjalta laskettu roudan paksuuskin ilmeisesti vaihtelee liian vähän vuodesta toiseen. Kelirikkotilanteita voi esiintyä myös kesken routakauden, jos useamman päivän suojasää ja samanaikainen runsas vesisade pääsevät sulattamaan maata. Tällaiset routakauden aikana sattuvat säätilat näyttävätkin yleistyvän lähivuosikymmeninä. Vuosisadan loppua kohti ne sen sijaan maan eteläosissa jälleen vähenevät, koska routakausi lyhenee oleellisesti. Tulevia vuosikymmeniä koskevien ilmastonmuutosennusteiden ohella routaa ja kelirikon esiintymistä on periaatteessa mahdollista ennustaa myös lähiaikojen sääennusteita hyödyntäen. Pitkät, viikkojen tai kuukausien mittaiset sääennusteet eivät tosin ole ainakaan vielä erityisen luotettavia, mutta myös lyhyemmistä ennusteista voisi olla hyötyä mm. tienpitoa suunniteltaessa.