PET and MR imaging in Parkinson’s disease patients with cognitive impairment. A study of dopaminergic dysfunction, amyloid deposition, cortical hypometabolism and brain atrophy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by a severe loss of substantia nigra dopaminergic neurons leading to dopamine depletion in the striatum. PD affects movement, producing motor symptoms such as rigidity, tremor and bradykinesia. Non-motor symptoms include autonomic dysfunction, neurobehavioral problems and cognitive impairment, which may lead to dementia. The pathophysiological basis of cognitive impairment and dementia in PD is unclear. The aim of this thesis was to study the pathophysiological basis of cognitive impairment and dementia in PD. We evaluated the relation between frontostriatal dopaminergic dysfunction and the cognitive symptoms in PD patients with [18F]Fdopa PET. We also combined [C]PIB and [¹⁸F]FDG PET and magnetic resonance imaging in PD patients with and without dementia. In addition, we analysed subregional striatal [¹⁸F]Fdopa PET data to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. The impaired dopaminergic function of the frontostriatal regions was related to the impairment in cognitive functions, such as memory and cognitive processing in PD patients. PD patients with dementia showed an impaired glucose metabolism but not amyloid deposition in the cortical brain regions, and the hypometabolism was associated with the degree of cognitive impairment. PD patients had atrophy, both in the prefrontal cortex and in the hippocampus, and the hippocampal atrophy was related to impaired memory. A single 15-min scan 75 min after a tracer injection seemed to be sufficient for separating patients with PD from healthy controls in a clinical research environment. In conclusion, the occurrence of cognitive impairment and dementia in PD seems to be multifactorial and relates to changes, such as reduced dopaminergic activity, hypometabolism, brain atrophy and rarely to amyloid accumulation.

Natural history of celiac disease-associated antibodies and progression to overt disease in children at increased genetic risk

Background: Celiac disease is a lifelong, gluten-sensitive, autoimmune-mediated chronic enteropathy, tightly associated with risk alleles at the HLA class II genes. Aims: This study was carried out as a part of the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Project. The first aim was to study the natural history of celiac disease-associated antibodies before the diagnosis of celiac disease was made. The second aim was to describe when and in which order celiac disease-associated and type 1 diabetes-associated antibodies appeared in children with genetic risk for both diseases. Subjects and Methods: Antibodies against tissue transglutaminase (TGA) and other celiac disease-associated antibodies were measured in serum samples collected at 3- to 12-month intervals of children at genetic risk for celiac disease who participated in the DIPP project. Celiac disease was confirmed by duodenal biopsy. Type 1 diabetes-associated antibodies were measured in all samples that had been collected. Overt disease was diagnosed according to World Health Organization criteria. Follow-up continued until a diagnosis of type 1 diabetes or until the end of a defined follow-up period. Results: TGA appeared in children at genetic risk for celiac disease only after the first year of life, but anti-gliadin antibodies often emerged significantly earlier, at age 6 months. The data show that spontaneous disappearance of celiac disease-associated antibodies, transient or persisting, is a common phenomenon, at least in prepubertal children. In children with genetic susceptibility to type 1 diabetes and celiac disease, celiac disease-associated antibodies usually develop earlier than the type 1 diabetes-associated antibodies. Conclusions: The transient nature of celiac disease-associated antibodies emphasizes the significance of establishing seropositivity repeatedly in screening detected celiac disease before gastroscopy and duodenal biopsy are considered and emphasized the importance of duodenal biopsy for diagnosing celiac disease.

Integrating environmental education in primary school education in Tanzania : teachers’ perceptions and teaching practices

The study focuses on primary school teachers’ perceptions of environmental education, its integration into primary school education and teachers’ teaching practices in Tanzania. The thesis is based on empirical research. The theoretical underpinnings of the study are based on Palmer’s (1998) model of environmental education. According to the model, meaningful environmental education should include education about, in or through and for the environment. The study is supported by national and international literature from research done on environmental education and education for sustainable development and policy statements. The study is qualitative in nature, adopting phenomenography and phenomenology as points of departure. The empirical data was collected from four primary schools in Morogoro region in Tanzania. The study sample consisted of 31 primary school teachers. Data was collected through interviews and lesson observations. According to the results of the study, primary school teachers expressed variations in their perceptions of environmental education and education for sustainable development. Most of the teachers focused on the aspect of knowledge acquisition. According to Tanzanian education and training policy, environmental education has to be integrated into all subjects. Although there is environmental education in the primary school curriculum, it is not integrated on an equal footing in all subjects. Some subjects like science, social studies and geography have more environmental content than other subjects. Teachers claim that the approach used to integrate environmental education into the school curriculum was not favoured because many claimed that what is to be taught as environmental education in the various subjects is not shown clearly. As a result, many teachers suggested that to ensure that it is taught properly it should be included in the curriculum as an independent subject or as specific topics. The study revealed that teachers’ teaching practices in integrating environmental education varied from one subject to another. Although most of the teachers said that they used participatory methods, lesson observations showed that they limited themselves to question and answer and group discussion. However, the teachers faced a number of barriers in the teaching of environmental education, some of which include lack of teaching and learning resources, time and large class size. The role of teachers in the implementation of environmental education in developing an environmentally literate citizenry is of great significance. The responsibility of the government in developing a curriculum with clear goals and content, developing teachers’ capacity in the teaching of environmental education and provision of teaching and learning materials needs to be taken seriously by the government in educational plans and programs.

Translational models of coronary artery disease, myocardial infarction and heart failure. Development, validation and in vivo imaging studies using positron emission tomography

Coronary artery disease is an atherosclerotic disease, which leads to narrowing of coronary arteries, deteriorated myocardial blood flow and myocardial ischaemia. In acute myocardial infarction, a prolonged period of myocardial ischaemia leads to myocardial necrosis. Necrotic myocardium is replaced with scar tissue. Myocardial infarction results in various changes in cardiac structure and function over time that results in “adverse remodelling”. This remodelling may result in a progressive worsening of cardiac function and development of chronic heart failure. In this thesis, we developed and validated three different large animal models of coronary artery disease, myocardial ischaemia and infarction for translational studies. In the first study the coronary artery disease model had both induced diabetes and hypercholesterolemia. In the second study myocardial ischaemia and infarction were caused by a surgical method and in the third study by catheterisation. For model characterisation, we used non-invasive positron emission tomography (PET) methods for measurement of myocardial perfusion, oxidative metabolism and glucose utilisation. Additionally, cardiac function was measured by echocardiography and computed tomography. To study the metabolic changes that occur during atherosclerosis, a hypercholesterolemic and diabetic model was used with [18F] fluorodeoxyglucose ([18F]FDG) PET-imaging technology. Coronary occlusion models were used to evaluate metabolic and structural changes in the heart and the cardioprotective effects of levosimendan during post-infarction cardiac remodelling. Large animal models were used in testing of novel radiopharmaceuticals for myocardial perfusion imaging. In the coronary artery disease model, we observed atherosclerotic lesions that were associated with focally increased [18F]FDG uptake. In heart failure models, chronic myocardial infarction led to the worsening of systolic function, cardiac remodelling and decreased efficiency of cardiac pumping function. Levosimendan therapy reduced post-infarction myocardial infarct size and improved cardiac function. The novel 68Ga-labeled radiopharmaceuticals tested in this study were not successful for the determination of myocardial blood flow. In conclusion, diabetes and hypercholesterolemia lead to the development of early phase atherosclerotic lesions. Coronary artery occlusion produced considerable myocardial ischaemia and later infarction following myocardial remodelling. The experimental models evaluated in these studies will enable further studies concerning disease mechanisms, new radiopharmaceuticals and interventions in coronary artery disease and heart failure.

Feasibility Study and Market Review of Small Scale Bioenergy Heating Plants in North-West Russia

The paper is focused on feasibility study and market review of small scale bioenergy heating plants in the Russian North-West region. The main focus is effective and competitive usage of low-grade wood for heating purposes in the region. As example of economical feasibility estimation it was chosen the project of reconstruction of small scale boiler plant in Leningrad region that Brofta Oy is planning to implement the nearest time. It includes calculation the payback time with and without interest, the estimation of probable investments, the evaluation of possible risks and research on the potential of small scale heating plants projects. Calculations show that the profitability of this kind of projects is high, but payback time is not very short, because of high level of initial investments. Though, the development of small scale bioenergy heating plants in the region is considered to be the best way to solve the problems of heat supply in small settlements using own biomass resources.

Towards the Best A++ Rating Productivity of Research and Teaching in Finnish Universities

Tämän tutkimusraportin suomenkielinen versio on osoitteessa: http://urn.fi/URN:ISBN:978-951-29-4509-2

Limits of Meritocracy. How Fields of Study and Gender Segregation Affect Social Stratification in Finland

This dissertation critically reviews the idea of meritocracy from both a theoretical and an empirical perspective. Based on a discussion of classical texts of social philosophy and sociology, it is argued that meritocracy as a concept for social stratification is best compatible with the sociological tradition of status attainment research: both frame social inequality in primarily individualistic terms, centring on the role of ascribed (e.g., gender, social background) and achieved (e.g., educational qualifications) characteristics for determining individuals’ socioeconomic rewards. This theoretical argument introduces the research problem at the core of this dissertation: to what extent can the individualistic conception of social stratification be maintained empirically? Fields of study and their interaction with educational attainment levels play a prominent role in the analysis of this question. Drawing on sociological versions of segmented labour market theory, it is assumed that fields of study may channel individuals into heterogeneous political-economic contexts on the labour market, which potentially modify the socioeconomic benefit individuals derive from their qualification levels. The focus on fields of study may also highlight economic differentials between men and women that derive from the persisting segregation of men’s and women’s occupational and educational specializations rather than direct gender discrimination on the labour market. The quantitative analyses in this dissertation consist of three research articles, which are based primarily on Finnish data, but occasionally extend the view to other European countries. The data sources include register-based macro- and microdata as well as survey data. Article I examines the extent and the patterns of gender segregation within the Finnish educational system between 1981 and 2005. The results show that differences between men’s and women’s field specializations have for the most part remained stable during this period, with particularly high levels of gender segregation observed at lower educational levels. The focus in Article II rests on the effects of gender-segregated fields of study on higher education graduates’ occupational status. It is shown that fields of study matter for accessing professional jobs and avoiding low-skilled positions in Finland: at the early career stage, particularly polytechnic graduates from female-dominated fields are less likely to work in professional positions. Finnish university graduates from male-dominated fields were more likely than their peers with different specializations to work as professionals, yet they also faced a greater risk of being sorted into lowskilled jobs if they failed to make use of this advantage. Article III proceeded to analyse the joint impact of educational qualification levels and fields of study on young adults’ median earnings in Finland between 1985 and 2005. The results show that qualification levels do not confer a consistent benefit in the process of earnings stratification. Advanced qualifications raise median earnings most clearly among individuals specializing in the same field of study. When comparing individuals with different field specializations, on the other hand, higher-level qualifications do not necessarily lead to higher median earnings. Overall, the findings of this dissertation reveal a heterogeneous effect of education for achieving social positions, which challenges individual-centred, meritocratic accounts of social stratification and underlines the problematic lack of structural and institutional dimensions in the dominant account of social status attainment.