Adipose tissue inflammation, liver fat and insulin resistance in humans

BACKGROUND: Obesity is closely associated with insulin resistance, which is a pathophysiologic condition contributing to the important co-morbidities of obesity, such as the metabolic syndrome and type 2 diabetes mellitus. In obese subjects, adipose tissue is characterized by inflammation (macrophage infiltration, increased expression insulin resistance genes and decreased expression of insulin sensitivity genes). Increased liver fat, without excessive alcohol consumption, is defined as non-alcoholic fatty liver disease (NAFLD) and also associated with obesity and insulin resistance. It is unknown whether and how insulin resistance is associated with altered expression of adipocytokines (adipose tissue-derived signaling molecules), and whether adipose tissue inflammation and NAFLD coexist independent of obesity. Genetic factors could explain variation in liver fat independent of obesity but the heritability of NAFLD is unknown. AIMS: To determine whether acute regulation of adipocytokine expression by insulin in adipose tissue is altered in obesity. To investigate the relationship between adipose tissue inflammation and liver fat content independent of obesity. To assess the heritability of serum alanine aminotransferase (ALT) activity, a surrogate marker of liver fat. METHODS: 55 healthy normal-weight and obese volunteers were recruited. Subcutaneous adipose tissue biopsies were obtained for measurement of gene expression before and during 6 hours of euglycemic hyperinsulinemia. Liver fat content was measured by proton magnetic resonance spectroscopy, and adipose tissue inflammation was assessed by gene expression, immunohistochemistry and lipidomics analysis. Genetic factors contributing to serum ALT activity were determined in 313 twins by statistical heritability modeling. RESULTS: During insulin infusion the expression of insulin sensitivity genes remains unchanged, while the expression of insulin resistance genes increases in obese/insulin-resistant subjects compared to insulin-sensitive subjects. Adipose tissue inflammation is associated with liver fat content independent of obesity. Adipose tissue of subjects with high liver fat content is characterized infiltrated macrophages and increased expression of inflammatory genes, as well as by increased concentrations of ceramides compared to equally obese subjects with normal liver fat. A significant heritability for serum ALT activity was verified. CONCLUSIONS: Effects of insulin infusion on adipose tissue gene expression in obese/insulin-resistant subjects are not only characterized by hyporesponse of insulin sensitivity genes but also by hyperresponse of insulin resistance and inflammatory genes. This suggests that in obesity, the impaired insulin action contributes or self-perpetuates alterations in adipocytokine expression in adipose tissue. Adipose tissue inflammation is increased in subjects with high liver fat compared to equally obese subjects with normal liver fat content. Concentrations of ceramides, the putative mediators of insulin resistance, are increased in adipose tissue in subjects with high liver fat. Genetic factors contribute significantly to variation in serum ALT activity, a surrogate marker of liver fat. These data imply that adipose tissue inflammation and increased liver fat content are closely interrelated, and determine insulin resistance even independent of obesity.

Inhibition of Thrombin in Cardiac Surgery : experiments in a porcine model

Cardiac surgery involving cardiopulmonary bypass (CPB) induces activation of inflammation and coagulation systems and is associated with ischemia-reperfusion injury (I/R injury)in various organs including the myocardium, lungs, and intestine. I/R injury is manifested as organ dysfunction. Thrombin, the key enzyme of coagulation , plays a cenral role also in inflammation and contributes to regulation of apoptosis as well. The general aim of this thesis was to evaluate the potential of thrombin inhibition in reducing the adverse effects of I/R injury in myocardium, lungs, and intestine associated with the use of CPB and cardiac surgery. Forty five pigs were used for the studies. Two randomized blinded studies were performed. Animals underwent 75 min of normothermic CPB, 60 min of aortic clamping, and 120 min of reperfusion period. Twenty animals received iv. recombinant hirudin, a selective and effective inbitor of thrombin, or placebo. In a similar setting, twenty animals received an iv-bolus (250 IU/kg) of antithrombin (AT) or placebo. An additional group of 5 animals received 500 IU/kg in an open label setting to test dose response. Generation of thrombin (TAT), coagulation status (ACT), and hemodynamics were measured. Intramucosal pH and pCO2 were measured from the luminal surface of ileum using tonometry simultaneusly with arterial gas analysis. In addition, myocardial, lung, and intestinal biopsies were taken to quantitate leukocyte infiltration (MPO), for histological evaluation, and detection of apoptosis (TUNEL, caspase 3). In conclusion, our data suggest that r-hirudin may be an effective inhibitor of reperfusion induced thrombin generation in addition to being a direct inhibitor of preformed thrombin. Overall, the results suggest that inhibition of thrombin, beyond what is needed for efficient anticoagulation by heparin, has beneficial effects on myocardial I/R injury and hemodynamics during cardiac surgery and CPB. We showed that infusion of the thrombin inhibitor r-hirudin during reperfusion was associated with attenuated post ischemia left ventricular dysfunction and decreased systemic vascular resistance. Consequently microvascular flow was improved during ischemia-reperfusion injury. Improved recovery of myocardium during the post-ischemic reperfusion period was associated with significantly less cardiomyocyte apoptosis and with a trend in anti-inflammatory effects. Thus, inhibition of reperfusion induced thrombin may offer beneficial effects by mechanisms other than direct anticoagulant effects. AT, in doses with a significant anticoagulant effect, did not alleviate myocardial I/R injury in terms of myocardial recovery, histological inflammatory changes or post-ischemic troponin T release. Instead, AT attenuated reperfusion induced increase in pulmonary pressure after CPB. Taken the clinical significance of postoperative pulmonary hemodynamics in patients undergoing cardiopulmonary bypass, the potential positive regulatory role of AT and clinical implications needs to be studied further. Inflammatory response in the gut wall proved to be poorly associated with perturbed mucosal perfusion and the animals with the least neutrophil tissue sequestration and I/R related histological alterations tended to have the most progressive mucosal hypoperfusion. Thus, mechanisms of low-flow reperfusion injury during CPB can differ from the mechanisms seen in total ischemia reperfusion injury.

Tactile processing in human somatosensory and auditory cortices

Tactile sensation plays an important role in everyday life. While the somatosensory system has been studied extensively, the majority of information has come from studies using animal models. Recent development of high-resolution anatomical and functional imaging techniques has enabled the non-invasive study of human somatosensory cortex and thalamus. This thesis provides new insights into the functional organization of the human brain areas involved in tactile processing using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). The thesis also demonstrates certain optimizations of MEG and fMRI methods. Tactile digit stimulation elicited stimulus-specific responses in a number of brain areas. Contralateral activation was observed in somatosensory thalamus (Study II), primary somatosensory cortex (SI; I, III, IV), and post-auditory belt area (III). Bilateral activation was observed in secondary somatosensory cortex (SII; II, III, IV). Ipsilateral activation was found in the post-central gyrus (area 2 of SI cortex; IV). In addition, phasic deactivation was observed within ipsilateral SI cortex and bilateral primary motor cortex (IV). Detailed investigation of the tactile responses demonstrated that the arrangement of distal-proximal finger representations in area 3b of SI in humans is similar to that found in monkeys (I). An optimized MEG approach was sufficient to resolve such fine detail in functional organization. The SII region appeared to contain double representations for fingers and toes (II). The detection of activations in the SII region and thalamus improved at the individual and group levels when cardiac-gated fMRI was used (II). Better detection of body part representations at the individual level is an important improvement, because identification of individual representations is crucial for studying brain plasticity in somatosensory areas. The posterior auditory belt area demonstrated responses to both auditory and tactile stimuli (III), implicating this area as a physiological substrate for the auditory-tactile interaction observed in earlier psychophysical studies. Comparison of different smoothing parameters (III) demonstrated that proper evaluation of co-activation should be based on individual subject analysis with minimal or no smoothing. Tactile input consistently influenced area 3b of the human ipsilateral SI cortex (IV). The observed phasic negative fMRI response is proposed to result from interhemispheric inhibition via trans-callosal connections. This thesis contributes to a growing body of human data suggesting that processing of tactile stimuli involves multiple brain areas, with different spatial patterns of cortical activation for different stimuli.

CHEK2 in Breast and Colorectal Cancer

Breast and colorectal cancers, are common types of cancer, with over two million newly diagnosed cases annually worldwide. Cancer is a genetic disease and defects in DNA integrity restoring functions make a significant contribution to cancer risk. CHEK2 is a checkpoint kinase functioning as a regulator of cell cycle checkpoints, apoptosis, and DNA repair in response to DNA double-strand breaks. The aim of this study was to evaluate the role of CHEK2 in breast cancer predisposition in Finnish breast cancer families and in breast cancer risk at the population level. We were interested in the clinical and biological characteristics of the breast tumors associated with the CHEK2 germline mutations or aberrant CHEK2 protein expression and the effect on survival of patients with these CHEK2 defects. We also assessed the role of CHEK2 mutations, namely 1100delC and I157T, in colorectal cancer susceptibility in Finland. CHEK2 I157T was found to be a low-penetrance breast cancer susceptibility allele, conferring a 1.4-fold risk for carriers. Reduced or absent CHEK2 protein expression was observed in one-fifth of breast tumors from patients unselected for family history, implying that defective CHEK2 signaling contributes to tumorigenesis. Reduction in CHEK2 expression was more common in tumors with larger diameter and ER expression, but with regard to other tumor characteristics and prognosis of a patient no association was observed. Results from comparison of CHEK2 1100delC carrier tumors with noncarrier tumors were in line with the findings from the CHEK2 expression study. Tumors from CHEK2 1100delC carriers were more often of higher grade than tumors from noncarriers, and they also tended to be ER-positive more often, although generally 1100delC status does not seem to radically affect the tumor characteristics. Our results suggest that CHEK2 1100delC may not be a susceptibility allele for CRC, although a very small effect cannot be excluded. Furthermore, CHEK2 1100delC is equally frequent in HBCC (hereditary breast and colorectal cancer) phenotype families and in breast cancer families. Over 1000 CRC cases were screened for CHEK2 I157T, and a significantly higher frequency of I157T was observed among both familial and sporadic CRC cases. The relation of CHEK2 I157T with familial CRC has not been studied previously. CHEK2 I157T seems to be a susceptibility allele for both familial and sporadic CRC, conferring a 1.5-fold risk for carriers of this variant. CHEK2 I157T has been proposed to have a role as a multiple cancer susceptibility allele, which is supported by our results since we observed a trend towards higher frequency of the variant among cases with multiple primary tumors or those with a family history of cancer. During the last five years CHEK2 has established its role as an important cancer susceptibility gene. It has become apparent that CHEK2 is a low-penetrance susceptibility gene for several cancer types, significantly contributing to familial cancer risk as well as to cancer risk at the population level.

Effects of SLCO1B1 polymorphism on the pharmacokinetics of the oral antidiabetic drugs repaglinide, nateglinide, rosiglitazone, and pioglitazone

Organic anion-transporting polypeptide 1B1 (OATP1B1), encoded by the SLCO1B1 gene, is an influx transporter expressed on the sinusoidal membrane of human hepatocytes. The common c.521T>C (p.Val174Ala) single-nucleotide polymorphism (SNP) of the SLCO1B1 gene has been associated with reduced OATP1B1 transport activity in vitro and increased plasma concentrations of several of its substrate drugs in vivo in humans. Another common SNP of the SLCO1B1 gene, c.388A>G (p.Asn130Asp), defining the SLCO1B1*1B (c.388G-c.521T) haplotype, has been associated with increased OATP1B1 transport activity in vitro. The aim of this thesis was to investigate the role of SLCO1B1 polymorphism in the pharmacokinetics of the oral antidiabetic drugs repaglinide, nateglinide, rosiglitazone, and pioglitazone. Furthermore, the effect of the SLCO1B1 c.521T>C SNP on the extent of interaction between gemfibrozil and repaglinide as well as the role of the SLCO1B1 c.521T>C SNP in the potential interaction between atorvastatin and repaglinide were evaluated. Five crossover studies with 2-4 phases were carried out, with 20-32 healthy volunteers in each study. The effects of the SLCO1B1 c.521T>C SNP on single doses of repaglinide, nateglinide, rosiglitazone, and pioglitazone were investigated in Studies I and V. In Study II, the effects of the c.521T>C SNP on repaglinide pharmacokinetics were investigated in a dose-escalation study, with repaglinide doses ranging from 0.25 to 2 mg. The effects of the SLCO1B1*1B/*1B genotype on repaglinide and nateglinide pharmacokinetics were investigated in Study III. In Study IV, the interactions of gemfibrozil and atorvastatin with repaglinide were evaluated in relation to the c.521T>C SNP. Plasma samples were collected for drug concentration determinations. The pharmacodynamics of repaglinide and nateglinide was assessed by measuring blood glucose concentrations. The mean area under the plasma repaglinide concentration-time curve (AUC) was ~70% larger in SLCO1B1 c.521CC participants than in c.521TT participants (P ≤ 0.001), but no differences existed in the pharmacokinetics of nateglinide, rosiglitazone, and pioglitazone between the two genotype groups. In the dose-escalation study, the AUC of repaglinide was 60-110% (P ≤ 0.001) larger in c.521CC participants than in c.521TT participants after different repaglinide doses. Moreover, the AUC of repaglinide increased linearly with repaglinide dose in both genotype groups (r > 0.88, P 0.001). The AUC of repaglinide was ~30% lower in SLCO1B1*1B/*1B participants than in SLCO1B1*1A/*1A (c.388AA-c.521TT) participants (P = 0.007), but no differences existed in the AUC of nateglinide between the two genotype groups. In the drug-drug interaction study, the mean increase in the repaglinide AUC by gemfibrozil was ~50% (P = 0.002) larger in c.521CC participants than in c.521TT participants, but the relative (7-8-fold) increases in the repaglinide AUC did not differ significantly between the genotype groups. In c.521TT participants, atorvastatin increased repaglinide peak plasma concentration and AUC by ~40% (P = 0.001) and ~20% (P = 0.033), respectively. In each study, after repaglinide administration, there was a tendency towards lower blood glucose concentrations in c.521CC participants than in c.521TT participants. In conclusion, the SLCO1B1 c.521CC genotype is associated with increased and the SLCO1B1*1B/*1B genotype with decreased plasma concentrations of repaglinide, consistent with reduced and enhanced hepatic uptake, respectively. Inhibition of OATP1B1 plays a limited role in the interaction between gemfibrozil and repaglinide. Atorvastatin slightly raises plasma repaglinide concentrations, probably by inhibiting OATP1B1. The findings on the effect of SLCO1B1 polymorphism on the pharmacokinetics of the drugs studied suggest that in vivo in humans OATP1B1 significantly contributes to the hepatic uptake of repaglinide, but not to that of nateglinide, rosiglitazone, or pioglitazone. SLCO1B1 polymorphism may be associated with clinically significant differences in blood glucose-lowering response to repaglinide, but probably has no effect on the response to nateglinide, rosiglitazone, or pioglitazone.

Studies on orographic effects in a numerical weather prediction model

Numerical models, used for atmospheric research, weather prediction and climate simulation, describe the state of the atmosphere over the heterogeneous surface of the Earth. Several fundamental properties of atmospheric models depend on orography, i.e. on the average elevation of land over a model area. The higher is the models' resolution, the more the details of orography directly influence the simulated atmospheric processes. This sets new requirements for the accuracy of the model formulations with respect to the spatially varying orography. Orography is always averaged, representing the surface elevation within the horizontal resolution of the model. In order to remove the smallest scales and steepest slopes, the continuous spectrum of orography is normally filtered (truncated) even more, typically beyond a few gridlengths of the model. This means, that in the numerical weather prediction (NWP) models, there will always be subgridscale orography effects, which cannot be explicitly resolved by numerical integration of the basic equations, but require parametrization. In the subgrid-scale, different physical processes contribute in different scales. The parametrized processes interact with the resolved-scale processes and with each other. This study contributes to building of a consistent, scale-dependent system of orography-related parametrizations for the High Resolution Limited Area Model (HIRLAM). The system comprises schemes for handling the effects of mesoscale (MSO) and small-scale (SSO) orographic effects on the simulated flow and a scheme of orographic effects on the surface-level radiation fluxes. Representation of orography, scale-dependencies of the simulated processes and interactions between the parametrized and resolved processes are discussed. From the high-resolution digital elevation data, orographic parameters are derived for both momentum and radiation flux parametrizations. Tools for diagnostics and validation are developed and presented. The parametrization schemes applied, developed and validated in this study, are currently being implemented into the reference version of HIRLAM.

Human Rights in Action

In the post-World War II era human rights have emerged as an enormous global phenomenon. In Finland human rights have particularly in the 1990s moved from the periphery to the center of public policy making and political rhetoric. Human rights education is commonly viewed as the decisive vehicle for emancipating individuals of oppressive societal structures and rendering them conscious of the equal value of others; both core ideals of the abstract discourse. Yet little empirical research has been conducted on how these goals are realized in practice. These factors provide the background for the present study which, by combining anthropological insights with critical legal theory, has analyzed the educational activities of a Scandinavian and Nordic network of human rights experts and PhD students in 2002-2005. This material has been complemented by data from the proceedings of UN human rights treaty bodies, hearings organized by the Finnish Foreign Ministry, the analysis of different human rights documents as well as the manner human rights are talked of in the Finnish media. As the human rights phenomenon has expanded, human rights experts have acquired widespread societal influence. The content of human rights remains, nevertheless, ambiguous: on the one hand they are law, on the other, part of a moral discourse. By educating laymen on what human rights are, experts act both as intermediaries and activists who expand the scope of rights and simultaneously exert increasing political influence. In the educational activities of the analyzed network these roles were visible in the rhetorics of legality and legitimacy . Among experts both of these rhetorics are subject to ongoing professional controversy, yet in the network they are presented as undisputable facts. This contributes to the impression that human rights knowledge is uncontested. This study demonstrates how the network s activities embody and strengthen a conception of expertise as located in specific, structurally determined individuals. Simultaneously its conception of learning emphasizes the adoption of knowledge by students, emphasizing the power of experts over them. The majority of the network s experts are Nordic males, whereas its students are predominantly Nordic females and males from East-European and developing countries. Contrary to the ideals of the discourse the network s activities do not create dialogue, but instead repeat power structures which are themselves problematic.

Sukupolvien ongelma : Tutkielmia sukupolven käsitteestä, sukupolvitietoisuudesta ja suurista ikäluokista

The aims of the thesis are (1) to present a systematic evaluation of generation and its relevance as a sociological concept, (2) to reflect on how generational consciousness, i.e. generation as an object of collective identification that has social significance, can emerge and take shape, (3) to analyze empirically the generational experiences and consciousness of one specific generation, namely Finnish baby boomers (b. 1945 1950). The thesis contributes to the discussion on the social (as distinct from its genealogical) meaning of the concept of generation, launched by Karl Mannheim s classic Das Problem der Generationen (1928), in which the central idea is that a certain group of people is bonded together by a shared experience and that this bonding can result in a distinct self-consciousness. The thesis is comprised of six original articles and an extensive summarizing chapter. In the empirical articles, the baby boomers are studied on the basis of nationally representative survey data (N = 2628) and narrative life-story interviews (N = 38). In the article that discusses the connection of generations and social movements, the analysis is based on the member survey of Attac Finland (N = 1096). Three main themes were clarified in the thesis. (1) In the social sense the concept of generation is a modern, problematic, and ultimately a political concept. It served the interests of the intellectuals who developed the concept in the early 20th century and provided them, as an alternative to the concept of social class, a new way of think about social change and progress. The concept of generation is always coupled with the concept of Zeitgeist or some other controversial way of defining what is essential, i.e. what creates generations, in a given culture. Thus generation is, as a product of definition and classification struggles, a contested concept. The concept also clearly implies elitist connotations; the idea of some kind of vanguard (the elite) that represents an entire generation by proclaiming itself as its spokesman automatically creates a counterpart, namely the others in the peer group who are thought to be represented (the masses). (2) Generational consciousness cannot emerge as a result of any kind of automatic process or endogenously; it must be made. There has to be somebody who represents the generation in order for that generation to exist in people s minds and as an object of identification; generational experiences and their meanings must be articulated. Hence, social generations are, in a fundamental manner, discursively constructed. The articulations of generational experiences (speeches, writings, manifests, labels etc.) can be called as the discursive dimension of social generations, and through this notion, how public discourse shapes people s generational consciousness can be seen. Another important element in the process is collective memory, as generational consciousness often takes form only retrospectively. (3) Finnish baby boomers are not a united or homogeneous generation but are divided into many smaller sections with specific generational experiences and consciousnesses. The content of the generational consciousness of the baby boomers is heavily politically charged. A salient dividing line inside the age group is formed by individual attitudes towards so-called 1960s radicalism. Identification with the 1960s generation functions today as a positive self-definition of a certain small leftist elite group, and the values and characteristics usually connected with the idea of the 1960s generation do not represent the whole age group. On the contrary, among some of the members of the baby boomers, the generational identification is still directed by the experience of how traditional values were disgraced in the 1960s. As objects of identification, the neutral term baby boomers and the charged 1960s generation are totally different things, and therefore they should not be used as synonyms. Although the significance of the group of the 1960s generation is often overestimated, they are however special with respect to generational consciousness because they have presented themselves as the voice of the entire generation. Their generational interpretations have spread through the media with the help of certain iconic images of the generation insomuch that 1960s radicalism has become an indirect generational experience for other parts of the baby boom cohort as well.

Work Stress in the Nursing Profession : An Evaluation of Organizational Causal Attribution

The goal of this study was to examine the role of organizational causal attribution in understanding the relation of work stressors (work-role overload, excessive role responsibility, and unpleasant physical environment) and personal resources (social support and cognitive coping) to such organizational-attitudinal outcomes as work engagement, turnover intention, and organizational identification. In some analyses, cognitive coping was also treated as an organizational outcome. Causal attribution was conceptualized in terms of four dimensions: internality-externality, attributing the cause of one’s successes and failures to oneself, as opposed to external factors, stability (thinking that the cause of one’s successes and failures is stable over time), globality (perceiving the cause to be operative on many areas of one’s life), and controllability (believing that one can control the causes of one’s successes and failures). Several hypotheses were derived from Karasek’s (1989) Job Demands–Control (JD-C) model and from the Job Demands–Resources (JD-R) model (Demerouti, Bakker, Nachreiner & Schaufeli, 2001). Based on the JD-C model, a number of moderation effects were predicted, stating that the strength of the association of work stressors with the outcome variables (e.g. turnover intentions) varies as a function of the causal attribution; for example, unpleasant work environment is more strongly associated with turnover intention among those with an external locus of causality than among those with an internal locuse of causality. From the JD-R model, a number of hypotheses on the mediation model were derived. They were based on two processes posited by the model: an energy-draining process in which work stressors along with a mediating effect of causal attribution for failures deplete the nurses’ energy, leading to turnover intention, and a motivational process in which personal resources along with a mediating effect of causal attribution for successes foster the nurses’ engagement in their work, leading to higher organizational identification and to decreased intention to leave the nursing job. For instance, it was expected that the relationship between work stressors and turnover intention could be explained (mediated) by a tendency to attribute one’s work failures to stable causes. The data were collected from among Finnish hospital nurses using e-questionnaires. Overall 934 nurses responded the questionnaires. Work stressors and personal resources were measured by five scales derived from the Occupational Stress Inventory-Revised (Osipow, 1998). Causal attribution was measured using the Occupational Attributional Style Questionnaire (Furnham, 2004). Work engagement was assessed through the Utrecht Work Engagement Scale (Schaufeli & al., 2002), turnover intention by the Van Veldhoven & Meijman (1994) scale, and organizational identification by the Mael & Ashforth (1992) measure. The results provided support for the function of causal attribution in the overall work stress process. Findings related to the moderation model can be divided into three main findings. First, external locus of causality along with job level moderated the relationship between work overload and cognitive coping. Hence, this interaction was evidenced only among nurses in non-supervisory positions. Second, external locus of causality and job level together moderated the relationship between physical environment and turnover intention. An opposite pattern of interaction was found for this interaction: among nurses, externality exacerbated the effect of perceived unpleasantness of the physical environment on turnover intention, whereas among supervisors internality produced the same effect. Third, job level also disclosed a moderation effect for controllability attribution over the relationship between physical environment and cognitive coping. Findings related to the mediation model for the energetic process indicated that the partial model in which work stressors have also a direct effect on turnover intention fitted the data better. In the mediation model for the motivational process, an intermediate mediation effect in which the effects of personal resources on turnover intention went through two mediators (e.g., causal dimensions and organizational identification) fitted the data better. All dimensions of causal attribution appeared to follow a somewhat unique pattern of mediation effect not only for energetic but also for motivational processes. Overall findings on mediation models partly supported the two simultaneous underlying processes proposed by the JD-R model. While in the energetic process the dimension of externality mediated the relationship between stressors and turnover partially, all the dimensions of causal attribution appeared to entail significant mediator effects in the motivational process. The general findings supported the moderation effect and the mediation effect of causal attribution in the work stress process. The study contributes to several research traditions, including the interaction approach, the JD-C, and the JD-R models. However, many potential functions of organizational causal attribution are yet to be evaluated by relevant academic and organizational research. Keywords: organizational causal attribution, optimistic / pessimistic attributional style, work stressors, organisational stress process, stressors in nursing profession, hospital nursing, JD-R model, personal resources, turnover intention, work engagement, organizational identification.

Communicative and Anticipatory Decision-making Supported by Bayesian Networks

The purpose of this research is to draw up a clear construction of an anticipatory communicative decision-making process and a successful implementation of a Bayesian application that can be used as an anticipatory communicative decision-making support system. This study is a decision-oriented and constructive research project, and it includes examples of simulated situations. As a basis for further methodological discussion about different approaches to management research, in this research, a decision-oriented approach is used, which is based on mathematics and logic, and it is intended to develop problem solving methods. The approach is theoretical and characteristic of normative management science research. Also, the approach of this study is constructive. An essential part of the constructive approach is to tie the problem to its solution with theoretical knowledge. Firstly, the basic definitions and behaviours of an anticipatory management and managerial communication are provided. These descriptions include discussions of the research environment and formed management processes. These issues define and explain the background to further research. Secondly, it is processed to managerial communication and anticipatory decision-making based on preparation, problem solution, and solution search, which are also related to risk management analysis. After that, a solution to the decision-making support application is formed, using four different Bayesian methods, as follows: the Bayesian network, the influence diagram, the qualitative probabilistic network, and the time critical dynamic network. The purpose of the discussion is not to discuss different theories but to explain the theories which are being implemented. Finally, an application of Bayesian networks to the research problem is presented. The usefulness of the prepared model in examining a problem and the represented results of research is shown. The theoretical contribution includes definitions and a model of anticipatory decision-making. The main theoretical contribution of this study has been to develop a process for anticipatory decision-making that includes management with communication, problem-solving, and the improvement of knowledge. The practical contribution includes a Bayesian Decision Support Model, which is based on Bayesian influenced diagrams. The main contributions of this research are two developed processes, one for anticipatory decision-making, and the other to produce a model of a Bayesian network for anticipatory decision-making. In summary, this research contributes to decision-making support by being one of the few publicly available academic descriptions of the anticipatory decision support system, by representing a Bayesian model that is grounded on firm theoretical discussion, by publishing algorithms suitable for decision-making support, and by defining the idea of anticipatory decision-making for a parallel version. Finally, according to the results of research, an analysis of anticipatory management for planned decision-making is presented, which is based on observation of environment, analysis of weak signals, and alternatives to creative problem solving and communication.

Water in Action : Encounters among 2- to 3-Year-Old Children, Adults, and Water in Day Care

In line with cultural psychology and developmental theory, a single case approach is applied to construct knowledge on how children s interaction emerge interlinked to historical, social, cultural, and material context. The study focuses on the negotiation of constraints and meaning construction among 2-to 3-year-old children, a preschool teacher, and the researcher in settings with water. Water as an element offers a special case of cultural canalization: adults selectively monitor and guide children s access to it. The work follows the socio-cultural tradition in psychology, particularly the co-constructivist theory of human development and the Network of Meanings perspective developed at the University of São Paulo. Valsiner s concepts of Zone of Free Movement and Zone of Promoted Action are applied together with studies where interactions are seen as spaces of construction where negotiation of constraints for actions, emotions, and conceptions occur. The corpus was derived at a Finnish municipal day care centre. During a seven months period, children s actions were video recorded in small groups twice a month. The teacher and the researcher were present. Four sessions with two children were chosen for qualitative microanalysis; the analysis also addressed the transformations during the months covered by the study. Moreover, the data derivation was analyzed reflectively. The narrowed down arenas for actions were continuously negotiated among the participants both nonverbally and verbally. The adults expectations and intentions were materialized in the arrangements of the setting canalizing the possibilities for actions. Children s co-regulated actions emerged in relation to the adults presence, re-structuring attempts, and the constraints of the setting. Children co-constructed novel movements and meanings in relation to the initiatives and objects offered. Gestures, postures, and verbalizations emerged from the initially random movements and became constructed to have specific meanings and functions; meaning construction became abbreviated. The participants attempted to make sense of the ambiguous (explicit and implicit) intentions and fuzzy boundaries of promoted and possible actions: individualized yet overlapping features were continuously negotiated by all the participants. Throughout the months, children s actions increasingly corresponded adults (re-defined) conceptions of water researchers as an emerging group culture. Water became an instrument and a context for co-regulations. The study contributes to discussions on children as participants in cultural canalization and emphasizes the need for analysis in early childhood education practices on the implicit and explicit constraint structures for actions.

Homeowners' Associations in Russia after the 2005 Housing Reform

The thesis examines homeowners associations as a part of the large-scale housing reform, implemented in Russia since 2005. The reform transferred housing management from the public sector to the private sector and to the citizens responsibility. The reform is a continuation to the privatisation of the housing stock that was started in Russia in the beginning of the 1990s, aiming to build a market-oriented housing sector in the country. The reform makes a fundamental change to the Soviet system, in which ownership along with management and maintenance of housing were monopolised by the state. Homeowners are now responsible for the management of the common areas in privatised houses, which is often realised by establishing a homeowners association. Homeowners associations are examined by using the so-called common-pool resource regime approach, with the main question being the ways in which taking care of common property collectively succeeds in practice. The study is based on interview data of St. Petersburg s homeowners associations. Using the common-pool resource theory the study demonstrates why implementation of the housing reform has not succeeded as expected. Certain elements that characterise a successful common-pool resource regime do not fulfill sufficiently in St. Petersburg s homeowners associations. Firstly, free-riding, that is, withdrawal from the association s joint decision-making and not making the housing payments is common, as effective sanctions to prevent it are missing in the legislation. That is, eviction or expelling a non-paying member from the association is not possible. Secondly, ownership of the land plot and common areas of the house, such as basements and attics, are often disputed between the associations and authorities. In the Soviet era, these common areas were public property along with the apartments, but in privatised houses they should, according to the legislation, belong to the associations property. Thirdly, solution of disputes between the associations and authorities and within the associations is difficult, as the court system tends to be bureaucratic and inefficient. In addition to the common-pool resource approach, the study also examines how social capital contributes to the associations effectiveness and democratic governance. The study finds that although homeowners associations have increased cooperation and tightened social relations between neighbours, social capital has not been able to prevent free-riding. The study shows that unlike it is often claimed, the so-called Soviet mentality , that is, residents passiveness and unwillingness to participate, is not the most important obstacle to the reform. Instead, the reform is impeded most of all by imperfect institutional arrangements and local authorities that prevent the associations from working as independent, self-governing associations.

From environmental concerns towards sustainable food provisioning. : Material flow and food consumption scenario studies on sustainability of agri-food systems

Agriculture is an economic activity that heavily relies on the availability of natural resources. Through its role in food production agriculture is a major factor affecting public welfare and health, and its indirect contribution to gross domestic product and employment is significant. Agriculture also contributes to numerous ecosystem services through management of rural areas. However, the environmental impact of agriculture is considerable and reaches far beyond the agroecosystems. The questions related to farming for food production are, thus, manifold and of great public concern. Improving environmental performance of agriculture and sustainability of food production, sustainabilizing food production, calls for application of wide range of expertise knowledge. This study falls within the field of agro-ecology, with interphases to food systems and sustainability research and exploits the methods typical of industrial ecology. The research in these fields extends from multidisciplinary to interdisciplinary and transdisciplinary, a holistic approach being the key tenet. The methods of industrial ecology have been applied extensively to explore the interaction between human economic activity and resource use. Specifically, the material flow approach (MFA) has established its position through application of systematic environmental and economic accounting statistics. However, very few studies have applied MFA specifically to agriculture. The MFA approach was used in this thesis in such a context in Finland. The focus of this study is the ecological sustainability of primary production. The aim was to explore the possibilities of assessing ecological sustainability of agriculture by using two different approaches. In the first approach the MFA-methods from industrial ecology were applied to agriculture, whereas the other is based on the food consumption scenarios. The two approaches were used in order to capture some of the impacts of dietary changes and of changes in production mode on the environment. The methods were applied at levels ranging from national to sector and local levels. Through the supply-demand approach, the viewpoint changed between that of food production to that of food consumption. The main data sources were official statistics complemented with published research results and expertise appraisals. MFA approach was used to define the system boundaries, to quantify the material flows and to construct eco-efficiency indicators for agriculture. The results were further elaborated for an input-output model that was used to analyse the food flux in Finland and to determine its relationship to the economy-wide physical and monetary flows. The methods based on food consumption scenarios were applied at regional and local level for assessing feasibility and environmental impacts of relocalising food production. The approach was also used for quantification and source allocation of greenhouse gas (GHG) emissions of primary production. GHG assessment provided, thus, a means of crosschecking the results obtained by using the two different approaches. MFA data as such or expressed as eco-efficiency indicators, are useful in describing the overall development. However, the data are not sufficiently detailed for identifying the hot spots of environmental sustainability. Eco-efficiency indicators should not be bluntly used in environmental assessment: the carrying capacity of the nature, the potential exhaustion of non-renewable natural resources and the possible rebound effect need also to be accounted for when striving towards improved eco-efficiency. The input-output model is suitable for nationwide economy analyses and it shows the distribution of monetary and material flows among the various sectors. Environmental impact can be captured only at a very general level in terms of total material requirement, gaseous emissions, energy consumption and agricultural land use. Improving environmental performance of food production requires more detailed and more local information. The approach based on food consumption scenarios can be applied at regional or local scales. Based on various diet options the method accounts for the feasibility of re-localising food production and environmental impacts of such re-localisation in terms of nutrient balances, gaseous emissions, agricultural energy consumption, agricultural land use and diversity of crop cultivation. The approach is applicable anywhere, but the calculation parameters need to be adjusted so as to comply with the specific circumstances. The food consumption scenario approach, thus, pays attention to the variability of production circumstances, and may provide some environmental information that is locally relevant. The approaches based on the input-output model and on food consumption scenarios represent small steps towards more holistic systemic thinking. However, neither one alone nor the two together provide sufficient information for sustainabilizing food production. Environmental performance of food production should be assessed together with the other criteria of sustainable food provisioning. This requires evaluation and integration of research results from many different disciplines in the context of a specified geographic area. Foodshed area that comprises both the rural hinterlands of food production and the population centres of food consumption is suggested to represent a suitable areal extent for such research. Finding a balance between the various aspects of sustainability is a matter of optimal trade-off. The balance cannot be universally determined, but the assessment methods and the actual measures depend on what the bottlenecks of sustainability are in the area concerned. These have to be agreed upon among the actors of the area

Leuconostoc spoilage of refrigerated, packaged foods

Leuconostoc spp. are lactic acid bacteria (LAB) implicated in food spoilage, especially on refrigerated, modified atmosphere packaged (MAP) meats. The overall aim of this thesis was to learn more about Leuconostoc spp. as food spoilage organisms with a focus on commercial products where LAB spoilage is considered a problem and the main factor limiting shelf-life. Therefore, we aimed to identify Leuconostoc spp. involved in food spoilage, as well as to characterise the spoilage reactions they caused and their contamination sources during poultry meat processing. In addition, we examined the distribution of strains of Leuconostoc gasicomitatum in different food commodities. Finally, we analysed the genome content of L. gasicomitatum LMG 18811 with a special focus on metabolic pathways related to food spoilage. The findings show that Leuconostoc gelidum and L.gasicomitatum were responsible for the discoloration and off-odours developed in beef steaks. Together with Leuconostoc mesenteroides, these Leuconostoc spp., also cause spoilage of vegetable sausages. In contrast, we showed that Leuconostoc spp. are not important for the shelf-life or quality of non-marinated broiler products although, in marinated broiler fillet products, Leuconostoc spp., L.gasicomitatum in particular, are considered spoilage organisms. Furthermore, the findings of the contamination survey we carried out in a poultry processing plant indicated that spoilage Leuconostoc spp. are derived from the processing environment rather than from the broilers, and that air movement distributes psychrotrophic spoilage LAB, including leuconostocs, and has an important role in meat contamination during poultry processing. Pulsed-field gel electrophoresis (PFGE) based genotyping of L. gasicomitatum strains demonstrated that certain genotypes are common in various meat products. In contrast, genotypes associated with meat were not recovered in vegetable-based sources. This suggests that these two food categories either become contaminated with, or favour the growth of different genotypes. Furthermore, the results indicated that the meat processing environment contributes to L. gasicomitatum contamination as certain genotypes were repeatedly identified from products of the same processing plant. Finally, the sequenced and annotated genome of L.gasicomitatum LMG 18811 allowed us to identify the metabolic pathways and reactions resulting in food spoilage.

Profligate Descent : The Cultural Transformations of Evolutionary Narrative

This dissertation traces a set of historical transformations the Darwinian evolutionary narrative has undergone toward the end of the twentieth century, especially as reflected in Anglo-American popular science books and novels. The study has three objectives. First, it seeks to understand the organizing logic of evolutionary narratives and the role that assumptions about gender and sexuality play in that logic. Second, it asks what kinds of cultural anxieties evolutionary theory raises and how evolutionary narratives negotiate them. Third, it examines the possibilities and limits of narrative transformation both as a historical phenomenon and as a theoretical question. This interdisciplinary dissertation is situated at the intersection of science studies, cultural studies, literary studies, and gender studies. Its understanding of science as a cultural practice that both emerges from and contributes to cultural expectations and institutional structures follows the tradition of science studies. Its focus on the question of popular appeal and the mechanisms of cultural change arises from cultural studies. Its view of narrative as a structural phenomenon is grounded in literary studies in general and feminist narrative theory in particular. Its understanding of gender and sexuality as implicated in discourses of epistemic authority builds on the view of gender and sexuality as contingent cultural categories central to gender studies. The primary material consists of over 25 British and American popular science books and novels, published roughly between 1990 and 2005. In order to highlight historical transformations, these texts are read in the context of Darwin s The Origin of Species and The Descent of Man, on the one hand, and such sociobiological classics as E. O. Wilson s On Human Nature and Richard Dawkins s The Selfish Gene, on the other. The research method combines feminist narrative analysis with cultural and historical contextualization, emphasizing discursive abruptions, recurrent narrative patterns, and underlying continuities. The dissertation demonstrates that the relationship between Darwin s evolutionary narrative and late twentieth-century evolutionary narratives is characterized by reemphasis, omissions, and continuous rewriting. In particular, contemporary evolutionary discourse extends the role assigned to reproduction both sexual and narrative in Darwin s writing, generating a narrative logic that imagines the desire to reproduce as the driving force of evolution and posits the reproductive sex act as the endlessly repeated narrative event that keeps the story going. The study argues that the popular appeal of evolutionary accounts of gender, sexuality, and human nature may arise, to an extent, from this reproductive narrative dynamic. This narrative dynamic, however, is not logically invulnerable. Since the continuation of the evolutionary narrative relies on successful reproduction, the possibility of reproductive failure poses a constant risk to narrative futurity, arousing cultural anxieties that evolutionary narratives need to address. The study argues that evolutionary narratives appease such anxieties by evoking a range of cultural narratives, especially romantic, religious, and national narratives. Furthermore, the study shows that the event-based logic of evolutionary narratives privileges observable acts over emotions, pleasures, identities, and desires, thus engendering a set of conceptual exclusions that limits the imaginative scope of evolution as a cultural narrative.