De lapidibus viventibus, I. Pet. II:5

Invokaatio: I.N.J.

Striatal and extrastriatal dopamine D2/3 receptors studied with [11C]raclopride and high-resolution PET

The human striatum is a heterogeneous structure representing a major part of the dopamine (DA) system’s basal ganglia input and output. Positron emission tomography (PET) is a powerful tool for imaging DA neurotransmission. However, PET measurements suffer from bias caused by the low spatial resolution, especially when imaging small, D2/3 -rich structures such as the ventral striatum (VST). The brain dedicated high-resolution PET scanner, ECAT HRRT (Siemens Medical Solutions, Knoxville, TN, USA) has superior resolution capabilities than its predecessors. In the quantification of striatal D2/3 binding, the in vivo highly selective D2/3 antagonist [11C] raclopride is recognized as a well-validated tracer. The aim of this thesis was to use a traditional test-retest setting to evaluate the feasibility of utilizing the HRRT scanner for exploring not only small brain regions such as the VST but also low density D2/3 areas such as cortex. It was demonstrated that the measurement of striatal D2/3 binding was very reliable, even when studying small brain structures or prolonging the scanning interval. Furthermore, the cortical test-retest parameters displayed good to moderate reproducibility. For the first time in vivo, it was revealed that there are significant divergent rostrocaudal gradients of [11C]raclopride binding in striatal subregions. These results indicate that high-resolution [11C]raclopride PET is very reliable and its improved sensitivity means that it should be possible to detect the often very subtle changes occurring in DA transmission. Another major advantage is the possibility to measure simultaneously striatal and cortical areas. The divergent gradients of D2/3 binding may have functional significance and the average distribution binding could serve as the basis for a future database. Key words: dopamine, PET, HRRT, [11C]raclopride, striatum, VST, gradients, test-retest.

Evaluation of the quality of pet foods using fast techniques and official methods

This paper was designed to evaluate the rancidity of 18 pet food samples using the Diamed FATS kits and official AOCS methods for the quantification of free fatty acids, peroxide value and concentrations of malonaldehyde and alkenal in the lipid extracted. Although expiration dates have passed, the samples presented good quality evidencing little oxidative rancidity. The results of this study suggest that the Brazilian pet food market is replete with products of excellent quality due to the competitiveness of this market sector.

A method to determine volatile contaminants in polyethylene terephthalate (PET) packages by HDC-GC-FID and its application to post-consumer materials

A simple and low cost method to determine volatile contaminants in post-consumer recycled PET flakes was developed and validated by Headspace Dynamic Concentration and Gas Chromatography-Flame Ionization Detection (HDC-GC-FID). The analytical parameters evaluated by using surrogates include: correlation coefficient, detection limit, quantification limit, accuracy, intra-assay precision, and inter-assay precision. In order to compare the efficiency of the proposed method to recognized automated techniques, post-consumer PET packaging samples collected in Brazil were used. GC-MS was used to confirm the identity of the substances identified in the PET packaging. Some of the identified contaminants were estimated in the post-consumer material at concentrations higher than 220 ng.g-1. The findings in this work corroborate data available in the scientific literature pointing out the suitability of the proposed analytical method.

The alpha2C-adrenoceptor as a neuropsychiatric drug tar-get - PET studies in human subjects

Positron emission tomography imaging has both academic and applied uses in revealing the distribution and density of different molecular targets in the central nervous system. Following the significant progress made with the dopamine D2 receptor, advances have been made in developing PET tracers to allow analysis of receptor occupancy of many other receptor types as well as evaluating changes in endogenous synaptic transmitter concentrations of transmitters e.g. serotonin and noradrenaline. Noradrenergic receptors are divided into α1-, α2- and β-adrenoceptor subfamilies, in humans each of which is composed of three receptor subtypes. The α2-adrenoceptors have an important presynaptic auto-inhibitory function on noradrenaline release but they also have postsynaptic roles in modulating the release of other neurotransmitters, such as serotonin and dopamine. One of the subtypes, the α2C-adrenoceptor, has been detected at distinct locations in the central nervous system, most notably the dorsal striatum. Several serious neurological conditions causing dementia, Alzheimer’s disease and Parkinson’s disease have been linked to disturbed noradrenergic signaling. Furthermore, altered noradrenergic signaling has also been implicated in conditions like ADHD, depression, anxiety and schizophrenia. In order to benefit future research into these central nervous system disorders as well as being useful in the clinical development of drugs affecting brain noradrenergic neurotransmission, validation work of a novel tracer for positron emission tomography studies in humans was performed. Altogether 85 PET imaging experiments were performed during four separate clinical trials. The repeatability of [11C]ORM-13070 binding was tested in healthy individuals, followed by a study to evaluate the dose-dependent displacement of [11C]ORM-13070 from α2C-adrenoceptors by a competing ligand, and the final two studies examined the sensitivity of [11C]ORM-13070 binding to reflect changes in endogenous noradrenaline levels. The repeatability of [11C]ORM-13070 binding was very high. The binding properties of the tracer allowed for a reliable estimation of α2C-AR occupancy by using the reference tissue ratio method with low test-retest variability. [11C]ORM-13070 was dose-dependently displaced from its specific binding sites by the subtype-nonselective α2-adrenoceptor antagonist atipamezole, and thus it proved suitable for use in clinical drug development of novel α2C-adrenoceptor ligands e.g. to determine the best doses and dosing intervals for clinical trials. Convincing experimental evidence was gained to support the suitability of [11C]ORM-13070 for detecting an increase in endogenous synaptic noradrenaline in the human brain. Tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, although statistical significance was not reached. Thus, the investigation was unable to fully validate [11C]ORM-13070 for the detection of pharmacologically evoked reductions in noradrenaline levels.

Cool Cats Don’t Dig the Squares” - The New York Times ja beat-sukupolvi, opiskelijamellakat ja hipit vuosina 1952-1969

Beat-sukupolvi, opiskelijoiden poliittinen aktiivisuus ja hipit olivat tunnettuja ilmiöitä Yhdysvalloissa 1950- ja 1960-luvuilla. Ilmiöillä oli paljon yhteistä ja ne vaikuttivat toisiinsa merkittävästi. Tätä yhteyttä ei aina tuoda esiin. Tämä tutkielma tuo esiin sen, miten The New York Times kirjoitti ilmiöistä. Tutkimus kertoo myös, miten The New York Times yhdistää ilmiöt keskenään. Sen lisäksi tulee esiin The New York Timesin näkemys ilmiöiden taustoista suhteessa nuorisokulttuuriin. Tutkimuksen kohteena on The New York Timesin lehtiartikkeleita vuosilta 1952-1969. Tutkimuksen pääkysymykset ovat: Miten The New York Times suhtautui beat-sukupolveen ja nuorisokulttuurin muutokseen? Miten The New York Times suhtautui yliopisto-opiskelijoihin ja heidän suhteeseensa nuorisokulttuurin muutokseen sekä miten The New York Times näkee hippien muuttavan yhteiskuntaa? Ensimmäistä pääkysymystä tarkastelen kahden alakysymyksen kautta: Miten beat-sukupolven synty esitetään The New York Timesissa, ja toisaalta millaisen kuvan The New York Times antaa beat-sukupolven vaikutuksesta nuorisoon? Toista pääkysymystä käsittelen kysymällä: Miten The New York Times näki nuorten poliittisen vaikuttavuuden nousun ja miten lehti suhtautui ajanjakson yliopistomellakoihin?. Kolmannessa luvussa tarkastelen pääkysymystä kysymällä: Keitä hipit olivat, ja olivatko hipit poliittisesti aktiivisia vai ei? Tutkimuksesta selviää, että The New York Times pyrkii kuvaamaan ilmiöitä mahdollisimman objektiivisesti. Lehti antaa ilmiöitä kuvatessa asioihin hyvin perehtyneiden henkilöiden esittää ilmiö. Sen jälkeen lehti antaa lukijoiden ja muiden asiantuntijoiden kommentoida. The New York Times näkee näiden ilmiöiden yhteyden ja se tulee voimakkaasti esille laajoissa artikkeleissa. Lyhyemmissä uutisissa yhteyttä ei aina näe, ja terminologia on yleistävämpi, tekstin eri tarkoitusperän takia. Kaiken kaikkiaan The New York Times tuo esiin mahdollisimman vähän moralisoivaa kuvaa ilmiöistä ja tuo esiin niiden keskinäisiä suhteita. Tuloksista näkee, että The New York Times on arvoiltaan vapaamielinen lehti, joka uutisoi, näiden aiheiden perusteella, kattavasti koko Yhdysvaltoja koskevista tapahtumista.

EXPLOITING SCENARIO PLANNING FOR STRATEGIC ASSESSMENT OF THE EXTERNAL BUSINESS ENVIRONMENT Future insights of the European pet food sector

The purpose of this study is to explore how scenarios can be exploited in strategic assessment of the external business environment. One of the key challenges for managers worldwide is to adapt their businesses to the ever-changing business environment. As the companies’ external business environment is constantly presenting new opportunities and threats, it is extremely important that companies continuously monitor the possible changes happening around it. As the speed of change rises, assessing the future has become more and more vital. The study was conducted as an exploratory research and the research strategy was influenced by scenario planning and case study strategy. The study examined the European pet food sector from the future point of view. Qualitative study was chosen as research approach and empirical data was collected primarily by seven expert interviews. The secondary data about the sector was applied as complementary empirical data. In the theoretical part of the research it was discovered that nowadays, traditional analysis frameworks are ill-suited for strategic assessment of the external business environment. This is why a self-created combination framework for analysis was employed both as study’s theoretical framework and analysis technique. Furthermore, the framework formed the base for interview questions. Both in theoretical and the empirical part of the study it was found that today, in strategic assessment of the external business environment, besides setting focus on the current situation, it is important to concentrate also on the future. The traditional analysis frameworks offer a good starting point for collecting relevant data but they do not encourage conducting a deeper analysis. By adding characteristics from scenario planning to these more traditional tools, a new analysis framework was created, which ensured the more comprehensive analysis. By understanding the interconnections between discovered phenomena and changes, and by recognizing uncertainties, the user is helped to reflect the environment more profoundly. The contributions of the study are both theoretical and managerial. A new analysis framework strives to answer to the current needs for strategic assessment of external business environment and the framework was tested in the context of European pet food sector. When it comes to managerial contributions, the importance lies in understanding the future. Managers must take future into account and understand that future includes various possibilities which all must be reflected