Drug epidemiology, interactions and pharmacogenetics : A post-mortem database study

Use of adverse drug combinations, abuse of medicinal drugs and substance abuse are considerable social problems that are difficult to study. Prescription database studies might fail to incorporate factors like use of over-the-counter drugs and patient compliance, and spontaneous reporting databases suffer from underreporting. Substance abuse and smoking studies might be impeded by poor participation activity and reliability. The Forensic Toxicology Unit at the University of Helsinki is the only laboratory in Finland that performs forensic toxicology related to cause-of-death investigations comprising the analysis of over 6000 medico-legal cases yearly. The analysis repertoire covers most commonly used drugs and drugs of abuse, and the ensuing database contains also background information and information extracted from the final death certificate. In this thesis, the data stored in this comprehensive post-mortem toxicology database was combined with additional metabolite and genotype analyses that were performed to complete the profile of selected cases. The incidence of drug combinations possessing serious adverse drug interactions was generally low (0.71%), but it was notable for the two individually studied drugs, a common anticoagulant warfarin (33%) and a new generation antidepressant venlafaxine (46%). Serotonin toxicity and adverse cardiovascular effects were the most prominent possible adverse outcomes. However, the specific role of the suspected adverse drug combinations was rarely recognized in the death certificates. The frequency of bleeds was observed to be elevated when paracetamol and warfarin were used concomitantly. Pharmacogenetic factors did not play a major role in fatalities related to venlafaxine, but the presence of interacting drugs was more common in cases showing high venlafaxine concentrations. Nicotine findings in deceased young adults were roughly three times more prevalent than the smoking frequency estimation of living population. Contrary to previous studies, no difference in the proportion of suicides was observed between nicotine users and non-nicotine users. However, findings of abused substances, including abused prescription drugs, were more common in the nicotine users group than in the non-nicotine users group. The results of the thesis are important for forensic and clinical medicine, as well as for public health. The possibility of drug interactions and pharmacogenetic issues should be taken into account in cause-of-death investigations, especially in unclear cases, medical malpractice suspicions and cases where toxicological findings are scarce. Post-mortem toxicological epidemiology is a new field of research that can help to reveal problems in drug use and prescription practises.

Modern diagnosis of Epstein-Barr virus infections and post-transplant lymphoproliferative disease

Infection by Epstein-Barr virus (EBV) occurs in approximately 95% of the world s population. EBV was the first human virus implicated in oncogenesis. Characteristic for EBV primary infection are detectable IgM and IgG antibodies against viral capsid antigen (VCA). During convalescence the VCA IgM disappears while the VCA IgG persists for life. Reactivations of EBV occur both among immunocompromised and immunocompetent individuals. In serological diagnosis, measurement of avidity of VCA IgG separates primary from secondary infections. However, in serodiagnosis of mononucleosis it is quite common to encounter, paradoxically, VCA IgM together with high-avidity VCA IgG, indicating past immunity. We determined the etiology of this phenomenon and found that, among patients with cytomegalovirus (CMV) primary infection a large proportion (23%) showed antibody profiles of EBV reactivation. In contrast, EBV primary infection did not appear to induce immunoreactivation of CMV. EBV-associated post-transplant lymphoproliferative disease (PTLD) is a life threatening complication of allogeneic stem cell or solid organ transplantation. PTLD may present with a diverse spectrum of clinical symptoms and signs. Due to rapidity of PTLD progression especially after stem cell transplantation, the diagnosis must be obtained quickly. Pending timely detection, the evolution of the fatal disease may be halted by reduction of immunosuppression. A promising new PTLD treatment (also in Finland) is based on anti-CD-20 monoclonal antibodies. Diagnosis of PTLD has been demanding because of immunosuppression, blood transfusions and the latent nature of the virus. We set up in 1999 to our knowledge first in Finland for any microbial pathogen a real-time quantitative PCR (qPCR) for detection of EBV DNA in blood serum/plasma. In addition, we set up an in situ hybridisation assay for EBV RNA in tissue sections. In collaboration with a group of haematologists at Helsinki University Central Hospital we retrospectively determined the incidence of PTLD among 257 allogenic stem cell transplantations (SCT) performed during 1994-1999. Post-mortem analysis revealed 18 cases of PTLD. From a subset of PTLD cases (12/18) and a series of corresponding controls (36), consecutive samples of serum were studied by the new EBV-qPCR. All the PTLD patients were positive for EBV-DNA with progressively rising copy numbers. In most PTLD patients EBV DNA became detectable within 70 days of SCT. Of note, the appearance of EBV DNA preceded the PTLD symptoms (fever, lymphadenopathy, atypical lymphocytes). Among the SCT controls, EBV DNA occurred only sporadically, and the EBV-DNA levels remained relatively low. We concluded that EBV qPCR is a highly sensitive (100%) and specific (96%) new diagnostic approach. We also looked for and found risk factors for the development of PTLD. Together with a liver transplantation group at the Transplantation and Liver Surgery Clinic we wanted to clarify how often and how severely do EBV infections occur after liver transplantation. We studied by the EBV qPCR 1284 plasma samples obtained from 105 adult liver transplant recipients. EBV DNA was detected in 14 patients (13%) during the first 12 months. The peak viral loads of 13 asymptomatic patients were relatively low (<6600/ml), and EBV DNA subsided quickly from circulation. Fatal PTLD was diagnosed in one patient. Finally, we wanted to determine the number and clinical significance of EBV infections of various types occurring among a large, retrospective, nonselected cohort of allogenic SCT recipients. We analysed by EBV qPCR 5479 serum samples of 406 SCT recipients obtained during 1988-1999. EBV DNA was seen in 57 (14%) patients, of whom 22 (5%) showed progressively rising and ultimately high levels of EBV DNA (median 54 million /ml). Among the SCT survivors, EBV DNA was transiently detectable in 19 (5%) asymptomatic patients. Thereby, low-level EBV-DNA positivity in serum occurs relatively often after SCT and may subside without specific treatment. However, high molecular copy numbers (>50 000) are diagnostic for life-threatening EBV infection. We furthermore developed a mathematical algorithm for the prediction of development of life-threatening EBV infection.

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease

Neural stem cell characteristics affected by oncogenic pathways and in a human motoneuron disease Stem cells provide the self-renewing cell pool for developing or regenerating organs. The mechanisms underlying the decisions of a stem or progenitor cell to either self-renew and maintain multipotentiality or alternatively to differentiate are incompletely understood. In this thesis work, I have approached this question by investigating the role of the proto-oncogene Myc in the regulatory functions of neural progenitor cell (NPC) self-renewal, proliferation and differentiation. By using a retroviral transduction technique to create overexpression models in embryonic NPCs cultured as neurospheres, I show that activated levels of Myc increase NPC self-renewal. Furthermore, several mechanisms that regulate the activity of Myc were identified. Myc induced self-renewal is signalled through binding to the transcription factor Miz-1 as shown by the inhibited capacity of a Myc mutant (MycV394D), deficient in binding to Miz-1, to increase self-renewal in NPCs. Furthermore, overexpression of the newly identified proto-oncogene CIP2A recapitulates the effects of Myc overexpression in NPCs. Also the expression levels and in vivo expression patterns of Myc and CIP2A were linked together. CIP2A stabilizes Myc protein levels in several cancer types by inhibiting its degradation and our results suggest the same function for CIP2A in NPCs. Our results also support the conception of self-renewal and proliferation being two separately regulated cellular functions. Finally, I suggest that Myc regulates NPC self-renewal by influencing the way stem and progenitor cells react to the environmental cues that normally dictate the cellular identity of tissues containing self-renewing cells. Neurosphere cultures were also utilised in order to characterise functional defects in a human disease. Neural stem cell cultures obtained post-mortem from foetuses of lethal congenital contracture syndrome (LCCS) were used to reveal possible cell autonomous differentiation defects of patient NPCs. However, LCCS derived NPCs were able to differentiate normally in vitro although several transcriptional differences were identified by using microarray analysis. Proliferation rate of the patient NPCs was also increased as compared to NPCs of age-matched control foetuses.

Amyloid diseases at old age : a pathological, epidemiological, and genetic study

Along with the increased life span of individuals, the burden of old age-associated diseases has inevitably increased. Alzheimer s disease (AD), probably the most well known geriatric disease, belongs to the old age-associated amyloid diseases. The purpose of this study was to investigate the frequency, genetic and health-associated risk factors, mutual association, and amyloid proteins in two old age-associated amyloid disorders senile systemic amyloidosis (SSA) and cerebral amyloid angiopathy (CAA) as part of the prospective population-based Vantaa 85+ autopsy study on a Finnish population aged 85 years or more (Studies I-III), completed with a case report on a patient with advanced AGel amyloidosis (Study IV). The numbers of patients investigated in the studies (I-III) were 256, 74, and 63, respectively. The diagnosis and grading of amyloid were based upon histological examination of tissue samples obtained post mortem and stained with Congo red. The amyloid fibril and associated proteins were characterized by immunohistochemical staining methods. The genotype frequencies of 20 polymorphisms in 9 genes and information on health-associated risk factors in subjects with and without SSA and CAA were compared. In a Finnish population ≥ 95 years of age, SSA and CAA occurred in 36% and 49% of the subjects, respectively. In total, two-thirds of these very elderly individuals had SSA, CAA, or both. However, in only 14% of the population these two conditions co-occurred. In subjects 85 years or older, the prevalence of SSA was 25%. In this population, SSA was associated with age at the time of death (p=0.002), myocardial infarctions (MIs; p=0.004), the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (α2M) gene (p=0.042) and with the H2 haplotype of the tau gene (p=0.016). In contrast, the presence of CAA was strongly associated with APOE e4 (p=0.0003), with histopathological AD (p=0.0005), and with clinical dementia (p=0.01) in both e4+ (p=0.02) and e4- (p=0.06) individuals. Apart from demonstrating the amyloid fibril proteins, complement proteins 3d (C3d) and 9 (C9) were detected in the amyloid deposits of CAA and AGel amyloidosis, and α2M protein was found in fibrous scar tissue close to SSA. In conclusion, this first population based study on SSA shows that both SSA and CAA are common in very elderly individuals. Old age, MIs, the exon 24 polymorphism of the α2M gene, and H1/H2 polymorphism of the tau gene associate with SSA while clinical dementia and APOE ε4 genotype associate with CAA. The high prevalence of CAA, combined with its association with clinical dementia independent of APOE genotype, neuropathological AD, or SSA, also highlights its clinical significance in the very aged, among which the serious end stage complications of CAA, namely multiple infarctions and hemorrhages, are rare. The report on a patient having advanced AGel amyloidosis added knowledge on the disease and showed that this generally benign condition occasionally may lead to death. Further studies are warranted to confirm the findings in other populations. Also, the role of α2M and tau in the pathogenesis of SSA and the involvement of complement in the process of amyloid beta (Aβ) protein elimination from the brain remain to be clarified. Finally, the high prevalence of SSA in the elderly raises the need for prospective clinical studies to define its clinical significance.

Glycogen debranching enzyme activity in the muscles of meat producing animals

Muscle glycogen exists in two forms: low molecular weight pro-glycogen and high molecular weight macro-glycogen. The degradation of glycogen to glucose 1 phosphate and free glucose is catalysed by glycogen phosphorylase together with glycogen debranching enzyme (GDE). The process in which glycogen is broken down via anaerobic pathways to lactate, results in the acidification of the muscles and has a great influence on meat quality. Thus, the overall aim of this thesis was to characterise the post mortem action of GDE in muscles of meat production animals (pigs, cattle and chickens). Interest was focused on the differences in GDE activity between fast twitch glycolytic muscles and slow twitch oxidative muscles. The effects of pH, temperature, RN genotype (PRKAG3 gene), and of time post mortem on GDE activity were also investigated. This thesis showed that there are differences in GDE activity between animal species and between different muscles of an animal. It was shown that in pigs and cattle, higher GDE activity and phosphorylase activity exists in the fast twitch glycolytic muscles than in slow twitch oxidative muscles of the same animal. Thus, the high activity of these enzymes enables a faster rate of glycogenolysis in glycolytic M. longissimus dorsi compared to oxidative M. masseter. In chicken muscles, the GDE activity was low compared to pig or cattle muscles. Furthermore, the GDE activity in the glycolytic M. pectoralis superficialis was lower than in more oxidative M. quadriceps femoris despite the high phosphorylase activity in the former. The relative ratios between phosphorylase and GDE activity were higher in fast twitch glycolytic muscles than in slow twitch oxidative muscles of all studied animals. This suggests that the relatively low GDE activity compared to the phosphorylase activity in fast twitch glycolytic muscles may be a protection mechanism in living muscle against a very fast pH decrease. Chilling significantly decreased GDE activity and below 15 C porcine GDE was almost inactive. The effect of pH on GDE activity was only minor at the range normally found in post mortem muscles (pH 7.4 to 5.0). The GDE activity remained level for several hours after slaughter. During the first hours post mortem, GDE activity was similar in RN- carrier pigs and in wild type pigs. However, the GDE activity declined faster in M. longissimus dorsi from wild type pigs than in the RN carrier pigs, the difference between genotypes was significant after 24 h post mortem. Pro-glycogen and macro-glycogen contents were higher, pH decrease was faster and ultimate pH was lower in RN- carrier pigs than in wild type pigs. In the RN- carriers, the prolonged high GDE activity level may enable an extended pH decrease and lower ultimate pH in their muscles. In conclusion, GDE is not the main factor determining the rate or the extent of post mortem glycogenolysis, but under certain conditions, such as in very fast chilling, the inhibition of GDE activity in meat may reduce the rate of pH decrease and result in higher ultimate pH. The rate and extent of pH decrease affects several meat quality traits.

F-18 Labelling Synthesis, Radioanalysis and Evaluation of A Dopamine Transporter and A Hypoxia Tracer

Positron emission tomography (PET) is an imaging technique in which radioactive positron-emitting tracers are used to study biochemical and physiological functions in humans and in animal experiments. The use of PET imaging has increased rapidly in recent years, as have special requirements in the fields of neurology and oncology for the development of syntheses for new, more specific and selective radiotracers. Synthesis development and automation are necessary when high amounts of radioactivity are needed for multiple PET studies. In addition, preclinical studies using experimental animal models are necessary for evaluating the suitability of new PET tracers for humans. For purification and analysing the labelled end-product, an effective radioanalytical method combined with an optimal radioactivity detection technique is of great importance. In this study, a fluorine-18 labelling synthesis method for two tracers was developed and optimized, and the usefulness of these tracers for possible prospective human studies was evaluated. N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP) is a candidate PET tracer for the dopamine transporter (DAT), and 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([18F]FMISO) is a well-known hypoxia marker for hypoxic but viable cells in tumours. The methodological aim of this thesis was to evaluate the status of thin-layer chromatography (TLC) combined with proper radioactivity detection measurement systems as a radioanalytical method. Three different detection methods of radioactivity were compared: radioactivity scanning, film autoradiography, and digital photostimulated luminescence (PSL) autoradiography. The fluorine-18 labelling synthesis for [18F]β-CFT-FP was developed and carbon-11 labelled [11C]β-CFT-FP was used to study the specificity of β-CFT-FP for the DAT sites in human post-mortem brain slices. These in vitro studies showed that β-CFT-FP binds to the caudate-putamen, an area rich of DAT. The synthesis of fluorine-18 labelled [18F]FMISO was optimized, and the tracer was prepared using an automated system with good and reproducible yields. In preclinical studies, the action of the radiation sensitizer estramustine phosphate on the radiation treatment and uptake of [18F]FMISO was evaluated, with results of great importance for later human studies. The methodological part of this thesis showed that radioTLC is the method of choice when combined with an appropriate radioactivity detection technique. Digital PSL autoradiography proved to be the most appropriate when compared to the radioactivity scanning and film autoradiography methods. The very high sensitivity, good resolution, and wide dynamic range of digital PSL autoradiography are its advantages in detection of β-emitting radiolabelled substances.

Cultural differences and postmerger problems: Misconceptions and cognitive simplifications.

Researchers and practitioners have increasingly explained post-merger organizational problems with cultural differences, especially in the context of cross-border mergers and acquisitions. It is suggested here that cultural differences have great explanatory power in the context of post-merger change processes. There are, however, problems with a number of superficial cultural conceptions that are common in research in this area and in managerial rhetoric. This critical article provocatively delineates misconceptions widely held by researchers and practitioners in this field, which not only disregard cultural differentiation, fragmentation, inconsistencies and ambiguities, but further, illustrate a lack of understanding of cultural permeability and embeddedness in the environment, an overemphasis on abstract values and lack of attention to organizational practices, an overemphasis on initial structural differences and lack of attention to the new cultural layer, a lack of recognition of the political dimensions and a failure to recognize cultural differences as sources of value and learning. In this article, the theoretical problems associated with these misconceptions are examined and new conceptual perspectives suggested. The risks at stake for decision makers are also discussed.

Dental identification and aspects of medico-legal investigations of the Finnish victims of the Sumatra-Andaman earthquake on 26 December 2004

Tsunami waves of the Sumatra-Andaman earthquake on 26 December 2004 claimed approximately 230 000 lives and started the biggest identification operation in Interpol's history. The aim of this study was to resolve methods of the identification and results received. The viewpoint is mainly that of forensic odontology, but also includes other means of identification and results of the medico-legal examination performed in Finland. Of the 5395 victims in Thailand, approximately 2 400 were foreigners from 36 nations including 177 Finnish nationals. Additionally, a Finnish woman perished in Sri Lanka and a severely injured man after the evacuation in a hospital. The final numbers of missing persons and dead bodies registered in the Information Management Centre in Phuket,Thailand, were 3 574 ante-mortem (AM) and 3 681 post-mortem (PM) files. The number of identifications by December 2006 was 3 271 or 89% of the victims registered. Of Finnish victims, 172 have been identified in Thailand and 163 repatriated to Finland. One adult and four children are still missing. For AM data, a list of Finnish missing persons including 178 names was published on 30 December 2004. By February 2005 all useful dental AM data were available. Five persons on the list living in Finland lacked records. Based on the AM database, for the children under age 18 years (n=60) dental identification could be established for 12 (20%). The estimated number for adults (n=112) was 96 (86%). The final identification rate, based on PM examinations in Finland, was 14 (25%) for children (n= 56) and 98 (90%) for adults (n= 109). The number of Finnish victims identified by dental methods, 112 (68%), was high compared to all examined in Thailand (43%). DNA was applied for 26 Finnish children and for 6 adults, fingerprints for 24 and 7, respectively. In 12 cases two methods were applied. Every victim (n=165) underwent in Finland a medico-legal investigation including an autopsy with sampling specimens for DNA, the toxicological and histological investigation. Digital radiographs and computed tomography were taken of the whole body to verify autopsy findings and bring out changes caused by trauma, autolysis, and sampling for DNA in Thailand. Data for identification purposes were also noted. Submersion was the cause of death for 101 of 109 adults (92.7%), and trauma for 8 (7.3%). Injuries were 33 times contributing factors for submersion and 3 times for trauma-based death. Submersion was the cause of death for 51 (92.7%) children and trauma for 4 (7.3%). Injuries were in 3 cases contributing factors in submersion and once in trauma-based death. The success of the dental identification of Finnish victims is mainly based on careful registration of dental records, and on an education program from 1999 in forensic odontology.

Monumenttikuvista elämyskuviin : Helsinki matkaesitteiden kuvituksessa 1895 - 2005

The purpose of this study is to define how Helsinki has been presented in the pictures of tourist brochures and how their illustration has changed over time. Attention is also paid to the values and meanings that the pictures mediate, as well as their historical and societal connections. The pictures are approached as representations selectively interpreting and illustrating the reality of Helsinki, while constructing mental images of it. An iconological framework structures the study. It proceeds from the description and classification of the physical features towards an analysis of time- and culture-specific meanings. The emergence of meanings and their historical and cultural underpinnings are examined from the perspectives of humanistic geography, semiotics and constructionism. In the analysis attention is paid to the discourses, myths and ideologies that underlie the representations. Information on the physical features of the pictures and their changes is collected with a content analysis. The classified data consists of 1377 photographs. These pictures are collected from 75 tourist brochures of Helsinki that have been published between 1895 and 2005. The deeper meanings of the pictures are studied qualitatively, by paying attention to the mental images that the content elements and visual effects evoke. Research studies, contemporary literature and the texts of the tourist brochures are utilised in the interpretation of the meanings. There has been a permanent core to objects of the pictures during the entire study period. It has consisted mainly of sights that are located close to the Senate and Market Squares. In addition, marine elements have been popular. The area of Helsinki represented in the brochures has extended from the Senate Square towards Töölö Bay. Pictures of monumental buildings and statues have been complemented with snapshots and portraits. In the beginning of the 20th century, brochures were mainly produced for the travelling, educated elite. The style of the pictures was declaratory and educative. They aimed at medating an objective image of the reality that prevailed in Helsinki. In practice, the pictures were connected to a patriotic ideology and the corresponding myth of Finnishness. In the second half of the 20th century the improvement of the standard of living led to a democratisation of consumers and an increase in the tourism demand. Local culture and the everyday life of "ordinary" people became popular themes in the pictures. A new welfare ideology manifested itself in the people of the local residential areas, for instance. The increase in the cultural diversity has led to the recognition of new target groups, expecially since the 1980s. The human figures in the pictures have started to function as objects of identification and a means of constructing mental images. A pronounced emphasis on experience and individuality in the illustration of the tourist brochures mirrors the post-modern change and a new ideology based on consumption. The construction and consumption of the pictures in the tourist brochures is governed by the conventions of representation and interpretaion that are typical of the genre of tourist brochures. The pictures emphasize the perceived positive characteristics of Helsinki and thus construct a skewed view of the reality. However, consumers can knowingly use the pictures as a means of dreaming and detaching themselves from their everyday reality.

Post-industrial Intervention : An Activity-Theoretical Expedition Tracing the Proximal Development of Forms of Conducting Interventions

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Elite Bargaining and the Evolution of Centre-Periphery Relations in Post-Soviet Russia : A Comparative Analysis

This work is concerned with presenting a modified theoretical approach to the study of centre-periphery relations in the Russian Federation. In the widely accepted scientific discourse, the Russian federal system under the Yeltsin Administration (1991-2000) was asymmetrical; largely owing to the varying amount of structural autonomy distributed among the federation s 89 constituent units. While providing an improved understanding as to which political and socio-economic structures contributed to federal asymmetry, it is felt that associated large N-studies have underemphasised the role played by actor agency in re-shaping Russian federal institutions. It is the main task of this thesis to reintroduce /re-emphasise the importance of actor agency as a major contributing element of institutional change in the Russian federal system. By focusing on the strategic agency of regional elites simultaneously within regional and federal contexts, the thesis adopts the position that political, ethnic and socio-economic structural factors alone cannot fully determine the extent to which regional leaders were successful in their pursuit of economic and political pay-offs from the institutionally weakened federal centre. Furthermore, this work hypothesises that under conditions of federal institutional uncertainty, it is the ability of regional leaders to simultaneously interpret various mutable structural conditions then translate them into plausible strategies which accounts for the regions ability to extract variable amounts of economic and political pay-offs from the Russian federal system. The thesis finds that while the hypothesis is accurate in its theoretical assumptions, several key conclusions provide paths for further inquiry posed by the initial research question. First, without reliable information or stable institutions to guide their actions, both regional and federal elites were forced into ad-hoc decision-making in order to maintain their core strategic focus: political survival. Second, instead of attributing asymmetry to either actor agency or structural factors exclusively, the empirical data shows that both agency and structures interact symbiotically in the strategic formulation process, thus accounting for the sub-optimal nature of several of the actions taken in the adopted cases. Third, as actor agency and structural factors mutate over time, so, too do the perceived payoffs from elite competition. In the case of the Russian federal system, the stronger the federal centre became, the less likely it was that regional leaders could extract the high degree of economic and political pay-offs that they clamoured for earlier in the Yeltsin period. Finally, traditional approaches to the study of federal systems which focus on institutions as measures of federalism are not fully applicable in the Russian case precisely because the institutions themselves were a secondary point of contention between competing elites. Institutional equilibriums between the regions and Moscow were struck only when highly personalised elite preferences were satisfied. Therefore the Russian federal system is the product of short-term, institutional solutions suited to elite survival strategies developed under conditions of economic, political and social uncertainty.

Psychosocial processes of health behaviour change in a lifestyle intervention : Influences of gender, socioeconomic status and personality

Background: The onset of many chronic diseases such as type 2 diabetes can be delayed or prevented by changes in diet, physical activity and obesity. Known predictors of successful behaviour change include psychosocial factors such as selfefficacy, action and coping planning, and social support. However, gender and socioeconomic differences in these psychosocial mechanisms underlying health behaviour change have not been examined, despite well-documented sociodemographic differences in lifestyle-related mortality and morbidity. Additionally, although stable personality traits (such as dispositional optimism or pessimism and gender-role orientation: agency and communion) are related to health and health behaviour, to date they have rarely been studied in the context of health behaviour interventions. These personality traits might contribute to health behaviour change independently of the more modifiable domain-specific psychosocial factors, or indirectly through them, or moderated by them. The aims were to examine in an intervention setting: (1) whether changes (during the three-month intervention) in psychological determinants (self-efficacy beliefs, action planning and coping planning) predict changes in exercise and diet behaviours over three months and 12 months, (2) the universality assumption of behaviour change theories, i.e. whether preintervention levels and changes in psychosocial determinants are similar among genders and socioeconomic groups, and whether they predict changes in behaviour in a similar way in these groups, (3) whether the personality traits optimism, pessimism, agency and communion predict changes in abdominal obesity, and the nature of their interplay with modifiable and domain-specific psychosocial factors (self-efficacy and social support). Methods: Finnish men and women (N = 385) aged 50 65 years who were at an increased risk for type 2 diabetes were recruited from health care centres to participate in the GOod Ageing in Lahti Region (GOAL) Lifestyle Implementation Trial. The programme aimed to improve participants lifestyle (physical activity, eating) and decrease their overweight. The measurements of self-efficacy, planning, social support and dispositional optimism/pessimism were conducted pre-intervention at baseline (T1) and after the intensive phase of the intervention at three months (T2), and the measurements of exercise at T1, T2 and 12 months (T3) and healthy eating at T1 and T3. Waist circumference, an indicator of abdominal obesity, was measured at T1 and at oneyear (T3) and three-year (T4) follow-ups. Agency and communion were measured at T4 with the Personal Attributes Questionnaire (PAQ). Results: (1) Increases in self-efficacy and planning were associated with three-month increases in exercise (Study I). Moreover, both the post-intervention level and three-month increases (during the intervention) in self-efficacy in dealing with barriers predicted the 12-month increase in exercise, and a high postintervention level of coping plans predicted the 12-month decrease in dietary fat (Study II). One- and three-year waist circumference reductions were predicted by the initial three-month increase in self-efficacy (Studies III, IV). (2) Post-intervention at three months, women had formed more action plans for changing their exercise routines and received less social support for behaviour change than men had. The effects of adoption self-efficacy were similar but change in planning played a less significant role among men (Study I). Examining the effects of socioeconomic status (SES), psychosocial determinants at baseline and their changes during the intervention yielded largely similar results. Exercise barriers self-efficacy was enhanced slightly less among those with low SES. Psychosocial determinants predicted behaviour similarly across all SES groups (Study II). (3) Dispositional optimism and pessimism were unrelated to waist circumference change, directly or indirectly, and they did not influence changes in self-efficacy (Study III). Agency predicted 12-month waist circumference reduction among women. High communion coupled with high social support was associated with waist circumference reduction. However, the only significant predictor of three-year waist circumference reduction was an increase in health-related self-efficacy during the intervention (Study IV). Conclusions: Interventions should focus on improving participants self-efficacy early on in the intervention as well as prompting action and coping planning for health behaviour change. Such changes are likely to be similarly effective among intervention participants regardless of gender and educational level. Agentic orientation may operate via helping women to be less affected by the demands of the self-sacrificing female role and enabling them to assertively focus on their own goals. The earlier mixed results regarding the role of social support in behaviour change may be in part explained by personality traits such as communion.

On the discursive construction of success/failure in narratives of post-merger integration

This article concentrates on the discursive constmction of success and failure in narratives of post-merger integration. Drawing on extensive interview material from eight Finnish-Swedish mergers and acquisitions, the empirical analysis leads to distinguishing four types of discourse — 'rationalistic', 'cultural', 'role-bound' and 'individualistic' — that narrators employ in recounting their experiences. In particular, the empirical material illustrates how the discursive frameworks enable specific (di.scursive) strategies and moves for (re)framing the success/failure, justification/legitimization of one's own actions, and (re)constniction of responsibility when dealing with socio-psychological pressures associated with success/failtire. The analysis also suggests that, as a result of making use of these discursive strategies and moves, success stories are likely to lead to overly optimistic or, in the case of failure stories, overly pessimistic views on the management's ability to control these change processes. Tliese findings imply that we should take the discursive elements that both constrain our descriptions and explanations seriously, and provide opportunities for more or less intentional (re)interpretations of postmerger integration or other organizational change processes.