Biotransformation and endocrine disruptive effects of contaminants in ringed seals - implications for monitoring and risk assessment

Marine mammals are exposed to persistent organic pollutants (POPs), which may be biotransformed to metabolites some of which are highly toxic. Both POPs and their metabolites may lead to adverse health effects, which have been studied using various biomarkers. Changes in endocrine homeostasis have been suggested to be sensitive biomarkers for contaminant-related effects. The overall objective of this doctoral thesis was to investigate biotransformation capacity of POPs and their potential endocrine disruptive effects in two contrasting ringed seal populations from the low contaminated Svalbard area and from the highly contaminated Baltic Sea. Biotransformation capacity was studied by determining the relationships between congener-specific patterns and concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and their hydroxyl (OH)- and/or methylsulfonyl (MeSO₂)-metabolites, and catalytic activities of hepatic xenobiotic-metabolizing phase I and II enzymes. The results suggest that the biotransformation of PCBs, PBDEs and toxaphenes in ringed seals depends on the congener-specific halogen-substitution pattern. Biotransformation products detected in the seals included OH-PCBs, MeSO₂-PCBs and –DDE, pentachlorophenol, 4-OHheptachlorostyrene, and to a minor extent OH-PBDEs. The effects of life history state (moulting and fasting) on contaminant status and potential biomarkers for endocrine disruption, including hormone and vitamin homeostasis, were investigated in the low contaminated ringed seal population from Svalbard. Moulting/fasting status strongly affected thyroid, vitamin A and calcitriol homeostasis, body condition and concentrations of POPs and their OH-metabolites. In contrast, moulting/fasting status was not associated with variations in vitamin E levels. Endocrine disruptive effects on multiple endpoints were investigated in the two contrasting ringed seal populations. The results suggest that thyroid, vitamin A and calcitriol homeostasis may be affected by the exposure of contaminants and/or their metabolites in the Baltic ringed seals. Complex and non-linear relationships were observed between the contaminant levels and the endocrine variables. Positive relationships between circulating free and total thyroid hormone concentration ratios and OH-PCBs suggest that OH-PCBs may mediate the disruption of thyroid hormone transport in plasma. Species differences in thyroid and bone-related effects of contaminants were studied in ringed and grey seals from low contaminated references areas and from the highly contaminated Baltic Sea. The results indicate that these two species living at the same environment approximately at the same trophic level respond in a very different way to contaminant exposure. The results of this thesis suggest that the health status of the Baltic ringed seals has still improved during the last decade. PCB and DDE levels have decreased in these seals and the contaminant-related effects are different today than a decade ago. The health of the Baltic ringed seals is still suggested to be affected by the contaminant exposure. At the present level of the contaminant exposure the Baltic ringed seals seem to be at a zone where their body is able to compensate for the contaminant-mediated endocrine disruption. Based on the results of this thesis, several recommendations that could be applied on monitoring and assessing risk for contaminant effects are provided. Circulating OH-metabolites should be included in monitoring and risk assessment programs due to their high toxic potential. It should be noted that endogenous variables may have complex and highly variable responses to contaminant exposure including non-linear responses. These relationships may be further confounded by life history status. Therefore, it is highly recommended that when using variables related to endocrine homeostasis to investigate/monitor or assess the risk of contaminant effects in seals, the life history status of the animal should be carefully taken into consideration. This applies especially when using thyroid, vitamin A or calcitriolrelated parameters during moulting/fasting period. Extrapolations between species for assessing risk for contaminant effects in phocid seals should be avoided.

Social capital and health : variations, associations and challenges

Although social capital and health have been extensively studied during the last decade, there are still open issues in current empirical research. These concern for instance the measurement of the concept in different contexts, as well as the association between different types of social capital and different dimensions of health. The present thesis addressed these questions. The general aim was to promote the understanding of social capital and health by investigating the oldest old and the two major language groups in Finland, Swedish- and Finnish-speakers. Another aim was to contribute to the discussion on methodological issues in social capital and health research. The present thesis investigated two empirical data sets, Umeå 85+ and Health 2000. The Umeå 85+ study was a cross-sectional study of 163 individuals aged 85, 90, and 95 or older, living in the municipality of Umeå, Sweden, in the year of 2000. The Health 2000 survey was a national study of 8,028 persons aged 30 or above carried out in Finland in 2000-2001. Different indicators of structural (e.g. social contacts) and cognitive (e.g. trust) social capital, as well as health indicators were used as variables in the analyses. The Umeå 85+ data set was analyzed with factor analysis, as well as univariate and multivariate analysis of variance. The Health 2000 data was analyzed with logistic regression techniques. The results showed that the Swedish-speakers in the Finnish data set Health 2000 had consistently higher prevalence of social capital compared to the Finnish-speakers even after controlling for central sociodemographic variables. The results further showed that even if the language group differences in health were small, the Swedishspeakers experienced in general better self-reported health compared with the Finnish-speakers. Common sociodemographic variables could not explain these observed differences in health. The results imply that social capital is often, but not always, associated with health. This was clearly seen in the Umeå 85+ data set where only one health indicator (depressive symptoms) was associated with structural social capital among the oldest old. The results based on the analysis of the Health 2000 survey demonstrated that the cognitive component of social capital was associated with self-rated health and psychological health rather than with participation in social activities and social contacts. In addition, social capital statistically reduced the health advantage especially for Swedish-speaking men, indicating that high prevalence of social capital may promote health. Finally, the present thesis also discussed the issue of methodological challenges faced with when analyzing social capital and health. It was suggested that certain components of social capital such as bonding and bridging social capital may be more relevant than structural and cognitive components when investigating social capital among the two language groups in Finland. The results concerning the oldest old indicated that the structural aspects of social capital probably reflect current living conditions, whereas cognitive social capital reflects attitudes and traits often acquired decades earlier. This is interpreted as an indication of the fact that structural and cognitive social capital are closely related yet empirically two distinctive concepts. Taken together, some components of social capital may be more relevant to study than others depending on which population group and age group is under study. The results also implied that the choice of cut-off point of dichotomization of selfrated health has an impact on the estimated effects of the explanatory variables. When the whole age interval, 35-64 years, was analyzed with logistic regression techniques the choice of cut-off point did not matter for the estimated effects of marital status and educational level. The results changed, however, when the age interval was divided into three shorter intervals. If self-rated health is explored using wide age intervals that do not account for age-dependent covariates there is a risk of drawing misleading conclusions. In conclusion, the results presented in the thesis suggest that the uneven distribution of social capital observed between the two language groups in Finland are of importance when trying to further understand health inequalities that exist between Swedish- and Finnish-speakers in Finland. Although social capital seemed to be relevant to the understanding of health among the oldest old, the meaning of social capital is probably different compared to a less vulnerable age group. This should be noticed in future empirical research. In the present thesis, it was shown that the relationship between social capital and health is complex and multidimensional. Different aspects of social capital seem to be important for different aspects of health. This reduces the possibility to generalize the results and to recommend general policy implementations in this area. An increased methodological awareness regarding social capital as well as health are called for in order to further understand the cfomplex association between them. However, based on the present data and findings social capital is associated with health. To understand individual health one must also consider social aspects of the individuals’ environment such as social capital.

Customer Driven Service Development – Technology-based Care and Services for the Elderly

The objective of this master’s thesis was to examine technology-based smart home devices and services. Topic was approached through basic theories, transaction cost theory and resource-based view in order to build basis for this thesis. Conceptual framework was discussed by means of networks, value networks and service systems which provide a useful framework for service development. The needs of the elderly living at home were discussed in order to find out which technology-based services could be used to satisfy the needs. Segmentation and need data collected previously during proactive home visits was exploited and additionally a survey targeted to experts and professionals of social and health care sector was done to verify the needs. Finally, the results of the survey were analyzed using quality function deployment method to figure out the most important and suitable service offerings for the elderly. As a conclusion of analysis, social media and monitoring services are the most useful technology-based services. However, traditional home services will still maintain their necessity too.

Cultural differences in web-based health information seeking of Finnish and Japanese students

Abstrakti

Implementing gateway monitoring service for infrastructure sensor networks

Wireless sensor networks and its applications have been widely researched and implemented in both commercial and non commercial areas. The usage of wireless sensor network has developed its market from military usage to daily use of human livings. Wireless sensor network applications from monitoring prospect are used in home monitoring, farm fields and habitant monitoring to buildings structural monitoring. As the usage boundaries of wireless sensor networks and its applications are emerging there are definite ongoing research, such as lifetime for wireless sensor network, security of sensor nodes and expanding the applications with modern day scenarios of applications as web services. The main focus in this thesis work is to study and implement monitoring application for infrastructure based sensor network and expand its usability as web service to facilitate mobile clients. The developed application is implemented for wireless sensor nodes information collection and monitoring purpose enabling home or office environment remote monitoring for a user.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Simulation of structural stress history based on dynamic analysis

Modern machine structures are often fabricated by welding. From a fatigue point of view, the structural details and especially, the welded details are the most prone to fatigue damage and failure. Design against fatigue requires information on the fatigue resistance of a structure’s critical details and the stress loads that act on each detail. Even though, dynamic simulation of flexible bodies is already current method for analyzing structures, obtaining the stress history of a structural detail during dynamic simulation is a challenging task; especially when the detail has a complex geometry. In particular, analyzing the stress history of every structural detail within a single finite element model can be overwhelming since the amount of nodal degrees of freedom needed in the model may require an impractical amount of computational effort. The purpose of computer simulation is to reduce amount of prototypes and speed up the product development process. Also, to take operator influence into account, real time models, i.e. simplified and computationally efficient models are required. This in turn, requires stress computation to be efficient if it will be performed during dynamic simulation. The research looks back at the theoretical background of multibody dynamic simulation and finite element method to find suitable parts to form a new approach for efficient stress calculation. This study proposes that, the problem of stress calculation during dynamic simulation can be greatly simplified by using a combination of floating frame of reference formulation with modal superposition and a sub-modeling approach. In practice, the proposed approach can be used to efficiently generate the relevant fatigue assessment stress history for a structural detail during or after dynamic simulation. In this work numerical examples are presented to demonstrate the proposed approach in practice. The results show that approach is applicable and can be used as proposed.

Energy-efficient control strategies for variable speed driven parallel pumping systems based on pump operation point monitoring with frequency converters

The pumping processes requiring wide range of flow are often equipped with parallelconnected centrifugal pumps. In parallel pumping systems, the use of variable speed control allows that the required output for the process can be delivered with a varying number of operated pump units and selected rotational speed references. However, the optimization of the parallel-connected rotational speed controlled pump units often requires adaptive modelling of both parallel pump characteristics and the surrounding system in varying operation conditions. The available information required for the system modelling in typical parallel pumping applications such as waste water treatment and various cooling and water delivery pumping tasks can be limited, and the lack of real-time operation point monitoring often sets limits for accurate energy efficiency optimization. Hence, alternatives for easily implementable control strategies which can be adopted with minimum system data are necessary. This doctoral thesis concentrates on the methods that allow the energy efficient use of variable speed controlled parallel pumps in system scenarios in which the parallel pump units consist of a centrifugal pump, an electric motor, and a frequency converter. Firstly, the suitable operation conditions for variable speed controlled parallel pumps are studied. Secondly, methods for determining the output of each parallel pump unit using characteristic curve-based operation point estimation with frequency converter are discussed. Thirdly, the implementation of the control strategy based on real-time pump operation point estimation and sub-optimization of each parallel pump unit is studied. The findings of the thesis support the idea that the energy efficiency of the pumping can be increased without the installation of new, more efficient components in the systems by simply adopting suitable control strategies. An easily implementable and adaptive control strategy for variable speed controlled parallel pumping systems can be created by utilizing the pump operation point estimation available in modern frequency converters. Hence, additional real-time flow metering, start-up measurements, and detailed system model are unnecessary, and the pumping task can be fulfilled by determining a speed reference for each parallel-pump unit which suggests the energy efficient operation of the pumping system.

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonance

Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.