The brain serotonin transporter binding in young adults; methodological considerations and association with Bulimia Nervosa and acquired obesity

The neurotransmitter serotonin (5-HT) modulates many functions important for life, e.g., appetite and body temperature, and controls development of the neural system. Disturbed 5-HT function has been implicated in mood, anxiety and eating disorders. The serotonin transporter (SERT) controls the amount of effective 5-HT by removing it from the extracellular space. Radionuclide imaging methods single photon emission tomography (SPET) and positron emission tomography (PET) enable studies on the brain SERTs. This thesis concentrated on both methodological and clinical aspects of the brain SERT imaging using SPET. The first study compared the repeatability of automated and manual methods for definition of volumes of interest (VOIs) in SERT images. The second study investigated within-subject seasonal variation of SERT binding in healthy young adults in two brain regions, the midbrain and thalamus. The third study investigated the association of the midbrain and thalamic SERT binding with Bulimia Nervosa (BN) in female twins. The fourth study investigated the association of the midbrain and hypothalamic/thalamic SERT binding and body mass index (BMI) in monozygotic (MZ) twin pairs. Two radioligands for SERT imaging were used: [123I]ADAM (studies I-III) and [123I]nor-beta-CIT (study IV). Study subjects included young adult MZ and dizygotic (DZ) twins screened from the FinnTwin16 twin cohort (studies I-IV) and healthy young adult men recruited for study II. The first study validated the use of an automated brain template in the analyses of [123I]ADAM images and proved automated VOI definition more reproducible than manual VOI definition. The second study found no systematic within-subject variation in SERT binding between scans done in summer and winter in either of the investigated brain regions. The third study found similar SERT binding between BN women (including purging and non-purging probands), their unaffected female co-twins and other healthy women in both brain regions; in post hoc analyses, a subgroup of purging BN women had significantly higher SERT binding in the midbrain as compared to all healthy women. In the fourth study, MZ twin pairs were divided into twins with higher BMI and co-twins with lower BMI; twins with higher BMI were found to have higher SERT binding in the hypothalamus/thalamus than their leaner co-twins. Our results allow the following conclusions: 1) No systematic seasonal variation exists in the midbrain and thalamus between SERT binding in summer and winter. 2) In a population-based sample, BN does not associate with altered SERT status, but alterations are possible in purging BN women. 3) The higher SERT binding in MZ twins with higher BMIs as compared to their leaner co-twins suggests non-genetic association between acquired obesity and the brain 5-HT system, which may have implications on feeding behavior and satiety.

Didactical reconstructions for organizing knowledge in physics teacher education

Physics teachers are in a key position to form the attitudes and conceptions of future generations toward science and technology, as well as to educate future generations of scientists. Therefore, good teacher education is one of the key areas of physics departments education program. This dissertation is a contribution to the research-based development of high quality physics teacher education, designed to meet three central challenges of good teaching. The first challenge relates to the organization of physics content knowledge. The second challenge, connected to the first one, is to understand the role of experiments and models in (re)constructing the content knowledge of physics for purposes of teaching. The third challenge is to provide for pre-service physics teachers opportunities and resources for reflecting on or assessing their knowledge and experience about physics and physics education. This dissertation demonstrates how these challenges can be met when the content knowledge of physics, the relevant epistemological aspects of physics and the pedagogical knowledge of teaching and learning physics are combined. The theoretical part of this dissertation is concerned with designing two didactical reconstructions for purposes of physics teacher education: the didactical reconstruction of processes (DRoP) and the didactical reconstruction of structures (DRoS). This part starts with taking into account the required professional competencies of physics teachers, the pedagogical aspects of teaching and learning, and the benefits of the graphical ways of representing knowledge. Then it continues with the conceptual and philosophical analysis of physics, especially with the analysis of experiments and models role in constructing knowledge. This analysis is condensed in the form of the epistemological reconstruction of knowledge justification. Finally, these two parts are combined in the designing and production of the DRoP and DRoS. The DRoP captures the knowledge formation of physical concepts and laws in concise and simplified form while still retaining authenticity from the processes of how concepts have been formed. The DRoS is used for representing the structural knowledge of physics, the connections between physical concepts, quantities and laws, to varying extents. Both DRoP and DRoS are represented in graphical form by means of flow charts consisting of nodes and directed links connecting the nodes. The empirical part discusses two case studies that show how the three challenges are met through the use of DRoP and DRoS and how the outcomes of teaching solutions based on them are evaluated. The research approach is qualitative; it aims at the in-depth evaluation and understanding about the usefulness of the didactical reconstructions. The data, which were collected from the advanced course for prospective physics teachers during 20012006, consisted of DRoP and DRoS flow charts made by students and student interviews. The first case study discusses how student teachers used DRoP flow charts to understand the process of forming knowledge about the law of electromagnetic induction. The second case study discusses how student teachers learned to understand the development of physical quantities as related to the temperature concept by using DRoS flow charts. In both studies, the attention is focused on the use of DRoP and DRoS to organize knowledge and on the role of experiments and models in this organization process. The results show that students understanding about physics knowledge production improved and their knowledge became more organized and coherent. It is shown that the flow charts and the didactical reconstructions behind them had an important role in gaining these positive learning results. On the basis of the results reported here, the designed learning tools have been adopted as a standard part of the teaching solutions used in the physics teacher education courses in the Department of Physics, University of Helsinki.

Historical considerations and evolution of the forest policies for small woodlot owners of Quebec.

XVIII IUFRO World Congress, Ljubljana 1986.

Development of radiosynthesis methods for 18F-labelled radiopharmaceuticals : General considerations and production of a dopamine transporter radioligand

Positron emission tomography (PET) is a molecular imaging technique that utilises radiopharmaceuticals (radiotracers) labelled with a positron-emitting radionuclide, such as fluorine-18 (18F). Development of a new radiotracer requires an appropriate radiosynthesis method: the most common of which with 18F is nucleophilic substitution with [18F]fluoride ion. The success of the labelling reaction is dependent on various factors such as the reactivity of [18F]fluoride, the structure of the target compound in addition to the chosen solvent. The overall radiosynthesis procedure must be optimised in terms of radiochemical yield and quality of the final product. Therefore, both quantitative and qualitative radioanalytical methods are essential in developing radiosynthesis methods. Furthermore, biological properties of the tracer candidate need to be evaluated by various pre-clinical studies in animal models. In this work, the feasibility of various nucleophilic 18F-fluorination strategies were studied and a labelling method for a novel radiotracer, N-3-[18F]fluoropropyl-2beta-carbomethoxy-3beta-4-fluorophenyl)nortropane ([18F]beta-CFT-FP), was optimised. The effect of solvent was studied by labelling a series of model compounds, 4-(R1-methyl)benzyl R2-benzoates. 18F-Fluorination reactions were carried out both in polar aprotic and protic solvents (tertiary alcohols). Assessment of the 18F-fluorinated products was studied by mass spectrometry (MS) in addition to conventional radiochromatographic methods, using radiosynthesis of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) as a model reaction. Labelling of [18F]beta-CFT-FP was studied using two 18F-fluoroalkylation reagents, [18F]fluoropropyl bromide and [18F]fluoropropyl tosylate, as well as by direct 18F-fluorination of sulfonate ester precursor. Subsequently, the suitability of [18F]beta-CFT-FP for imaging dopamine transporter (DAT) was evaluated by determining its biodistribution in rats. The results showed that protic solvents can be useful co-solvents in aliphatic 18F-fluorinations, especially in the labelling of sulfonate esters. Aromatic 18F-fluorination was not promoted in tert-alcohols. Sensitivity of the ion trap MS was sufficient for the qualitative analysis of the 18F-labelled products; p-[18F]MPPF was identified from the isolated product fraction with a mass-to-charge (m/z) ratio of 435 (i.e. protonated molecule [M+H]+). [18F]beta-CFT-FP was produced most efficiently via [18F]fluoropropyl tosylate, leading to sufficient radiochemical yield and specific radioactivity for PET studies. The ex vivo studies in rats showed fast kinetics as well as the specific uptake of [18F]beta-CFT-FP to the DAT rich brain regions. Thus, it was concluded that [18F]beta-CFT-FP has potential as a radiotracer for imaging DAT by PET.