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.

Novel word learning ability in chronic post-stroke aphasia : variability and modality effects

Novel word learning has been rarely studied in people with aphasia (PWA), although it can provide a relatively pure measure of their learning potential, and thereby contribute to the development of effective aphasia treatment methods. The main aim of the present thesis was to explore the capacity of PWA for associative learning of word–referent pairings and cognitive-linguistic factors related to it. More specifically, the thesis examined learning and long-term maintenance of the learned pairings, the role of lexical-semantic abilities in learning as well as acquisition of phonological versus semantic information in associative novel word learning. Furthermore, the effect of modality on associative novel word learning and the neural underpinnings of successful learning were explored. The learning experiments utilized the Ancient Farming Equipment (AFE) paradigm that employs drawings of unfamiliar referents and their unfamiliar names. Case studies of Finnishand English-speaking people with chronic aphasia (n = 6) were conducted in the investigation. The learning results of PWA were compared to those of healthy control participants, and active production of the novel words and their semantic definitions was used as learning outcome measures. PWA learned novel word–novel referent pairings, but the variation between individuals was very wide, from more modest outcomes (Studies I–II) up to levels on a par with healthy individuals (Studies III–IV). In incidental learning of semantic definitions, none of the PWA reached the performance level of the healthy control participants. Some PWA maintained part of the learning outcomes up to months post-training, and one individual showed full maintenance of the novel words at six months post-training (Study IV). Intact lexical-semantic processing skills promoted learning in PWA (Studies I–II) but poor phonological short-term memory capacities did not rule out novel word learning. In two PWA with successful learning and long-term maintenance of novel word–novel referent pairings, learning relied on orthographic input while auditory input led to significantly inferior learning outcomes (Studies III–IV). In one of these individuals, this previously undetected modalityspecific learning ability was successfully translated into training with familiar but inaccessible everyday words (Study IV). Functional magnetic resonance imaging revealed that this individual had a disconnected dorsal speech processing pathway in the left hemisphere, but a right-hemispheric neural network mediated successful novel word learning via reading. Finally, the results of Study III suggested that the cognitive-linguistic profile may not always predict the optimal learning channel for an individual with aphasia. Small-scale learning probes seem therefore useful in revealing functional learning channels in post-stroke aphasia.

Study of the advancement of innovations in communications industry. Case study: Russian Post Company

This study attempted to provide a project based on the already tested and successful results of foreign business which can help to contain the final price of innovation on desired levels. The research will attempt to dig out most of available information related to aforementioned definitions and thus completing theoretical background. Next author will explain used methodology and the process of evidence collection. After that the study will show the analysis of collected data in order to obtain results which are going to be compared with stated objectives in the final part. The conclusion of the research and proposed possibilities for additional work will be given in the last part. For this study author has chosen the qualitative model because it performs very well for analysis of small scale of data. The case study method was used because it gave author an opportunity to make an in-depth analysis of the collected information about particular organization so it became possible to analyze system's details in comparison. The results have been early considered valid and applicable to other studies. As the result thesis has proposed undertakings which reflect researches aimed on solving problems with provision of services and development of communications. In addition thesis has proposed formulation of database of postal service for Russian Post when (by request) customer possess an account where he or she can access postal services via PC or info table in postal office and order delivery of postal products which will be given private identification code. Project's payoff period has been calculated as well.

Acute exposure to lead increases myocardial contractility independent of hypertension development

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetateiv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

VEGF receptor expression decreases during lung development in congenital diaphragmatic hernia induced by nitrofen

Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.

Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of β cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, β-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-β cells within the pancreas to β cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase β-cell mass. However, their clinical significance is yet to be determined. Hypothetically, β cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for β-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native β cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of β-cell mass restoration for diabetes mellitus therapy: β-cell regeneration and β-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Post-transaction brand and model line-up integration in the automotive industry: Case studies of European companies as target of acquisitions by Chinese and Indian multinational corporations

Corporations practice company acquisitions in order to create shareholder’s value. During the last few decades, the companies in emerging markets have become active in the acquisition business. During the last decade, large and significant acquisitions have occurred especially in automotive industry. While domestic markets have become too competitive and companies are lacking required capabilities, they seek possibilities to expand into Western markets by attaining valuable assets through acquisitions of developed country corporations. This study discusses the issues and characteristics of these acquisitions through case studies. The purpose of this study was to identify the acquisition motives and strategies for post-transaction brand and product integration as well as analyze the effect of the motives to the integration strategy. The cases chosen for the research were Chinese Geely acquiring Swedish Volvo in 2010 and Indian Tata Motors buying British Jaguar Land Rover in 2008. The main topics were chosen according to their significance for companies in automotive industry as well as those are most visible parts for consumers. The study is based on qualitative case study methods, analyzing secondary data from academic papers and news articles as well as companies’ own announcements e.g. stock exchange and press releases. The study finds that the companies in the cases mainly possessed asset-seeking and market-seeking motives. In addition, the findings refer to rather minimal post-acquisition brand and product integration strategies. Mainly the parent companies left the target company autonomous to make their own business strategies and decisions. The most noticeable integrations were in the product development and production processes. Through restructuring the product architectures, the companies were able to share components and technology between product families and brands, which results in cutting down costs and in increase of profitability and efficiency. In the Geely- Volvo case, the strategy focused more on component sharing and product development know-how, whereas in Tata Motors-Jaguar Land Rover case, the main actions were to cut down costs through component sharing and combine production and distribution networks especially in Asian markets. However, it was evident that in both cases the integration and technology sharing were executed cautiously to prevent on harming the valuable image of the luxury brand. This study has concluded that the asset-seeking motives have significant influence on the posttransaction brand and model line-up integration strategies. By taking a cautious approach in acquiring assets, such as luxury brand, the companies in the cases have implemented a successful post-acquisition strategy and managed to create value for the shareholders at least in short-term. Yritykset harjoittavat yritysostoja luodakseen osakkeenomistajille lisäarvoa. Viimeisten muutamien vuosikymmenien aikana yritykset kehittyvissä maissa ovat myös aktivoituneet yritysostoissa. Viimeisen vuosikymmenen aikana erityisesti autoteollisuudessa on esiintynyt suuria ja merkittäviä yritysostoja. Koska kilpailu kotimaan markkinoilla on kiristynyt ja yritykset ovat vailla vaadittavia valmiuksia, ne etsivät mahdollisuuksiaan laajentaa länsimaisiin markkinoihin hankkimalla arvokkaita etuja kehittyneiden maiden yrityksistä yritysostojen avulla. Tämä tutkimus pohtii näiden yritysostojen olennaisia kysymyksiä ja ominaisuuksia casetutkimuksien kautta. Tutkimuksen tarkoitus oli tunnistaa sekä yritysostojen motiiveja ja brändi- ja mallisto-integraation strategioita että analysoida kyseisten motiivien vaikutusta integraatiostrategiaan. Tapaus-tutkimuksiksi valittiin kiinalaisen Geelyn yritysosto ruotsalaisesta Volvosta vuonna 2010 ja intialaisen Tata Motorsin yritysosto englantilaisesta Jaguar Land Roverista vuonna 2008. Tutkimus on kvalitatiivinen case-tutkimus ja siinä analysoidaan toissijaista tietoa sekä akateemisten ja uutisartikkeleiden että yritysten omien ilmoitusten, kuten pörssi- ja lehdistötiedotteiden, kautta. Tutkimuksen tulokset osoittavat, että tutkittujen yritysten toiminnat perustuivat motiiveihin, joita ajoivat etujen and uusien markkinoiden tarve. Sen lisäksi tutkimustulokset osoittivat, että yritysoston jälkeinen brändi- ja mallisto-integraatio pidettiin minimaalisena. Pääasiallisesti kohdeyrityksille jätettiin autonomia tehdä omat liikkeenjohdolliset päätökset yritysstrategioihin liittyen. Huomattavimmat integraatiot koskivat tuotekehityksellisiä ja tuotannollisia prosesseja. Kehittämällä uudelleen tuotearkkitehtuureja, yritykset pystyivät jakamaan komponentteja ja teknologiaa tuoteperheiden ja brändien välillä. Tämä mahdollisti kustannusleikkauksia sekä kannattavuuden ja tehokkuuden parantamista. Geely-Volvo –tapauksessa integraatiostrategia keskittyi komponenttien jakamiseen yhteisten tuotearkkitehtuurien avulla ja tuotekehityksen ammattitaitoon, kun taas Tata Motors-JLR –tapauksessa päätoiminnat olivat kustannuksien leikkaus sekä tuotannon ja jakeluverkoston yhdistäminen erityisesti Aasian maissa. Yhteistä yrityskaupoissa oli, että brändi- ja mallisto-integraatio sekä teknologian jakaminen suoritettiin varoen ehkäistäkseen arvokkaiden luksus-brändien tuotekuvan vahingoittamista. Tutkimuksen lopputulokset osoittavat, että yrityskaupan motiiveilla on huomattava vaikutus brändija mallisto-integraation strategiaan. Toteuttamalla varovaista lähestymistapaa luksus-brändin hankinnassa ja integraatiossa, yritykset ovat onnistuneet luomaan lisäarvoa osakkeenomistajille vähintään lyhyellä aikavälillä.

Building-up influence: post-war industrialization in the State of Minas Gerais, Brazil

This paper examines the post-War industrialization process in the Brazilian State of Minas Gerais, focusing on one of its desirable outcomes, namely the capacity to generate growth through the impact of strong input-output linkages. This process is placed into historical perspective considering the ideas that permeate the economic development debate throughout the period of analysis. Changes in the regional economic structure are assessed through the use of three input-output tables for the years of 1953, 1980 and 1995. By adopting the fields of influence methodology as the analytical core, it is shown that the efforts towards the creation of a more integrated regional economy have generated stronger influence of the targeted sectors (metal products, transportation equipment, chemical, and services). However, structural changes also contributed to strengthen leakage in the system originated in traditional economic activities.

Development of hypogene and supergene alteration and copper mineralization patterns, Sar Cheshmeh porphyry copper deposits, Iran /

The formation of the Sar Cheshmeh porphyry Cu-Mo deposit is related to the culmination of calc-alkaline igneous activity in the Kerman region. The deposit comprises a suite of Late Cenozoic intrusive sub-volcanic and extrusive rocks emplaced into a folded series of Eocene andesitic lavas and pyroclastic sediments. The earliest stage of magmatism was emplacement of a large granodiorite stock about 29 m.y.b.p. This was followed by intrusion of two separate porphyritic bodies at 15 (Sar Cheshrneh porphyry) and 12 m.y.b.p. (Late porphyry) and a series of sub-volcanic dikes between 12 and 9 m.y.b.p. Magmatic activity terminated with multi-phase extrusion of a Pelean dacitic dome complex between 10 and 2.8 m.y.b.p. The country rocks and the earlier porphyritic intrusions are pervasively altered to biotite-rich potassium silicate (metasomatic and hydrothermal) sericite-clay, phyllic and chlorite-clay, argillic assemblages. These grade outwards to an extensive propylitic zone. Within the ore body, the later intra-. and post-mineral dikes only reach the propylitic grade. At least three different sets of quartz veins are present, including a sericite-chlorite-quartz set which locally retrogrades pervasive secondary biotite to sericite. In the hypogene zone, metasomatic and hydrothermal alteration is related to all stages of magmatism but copper mineralization and veining are restricted to a period of 15 to 9 m.y.b.p.related to the early intrusive phases. The copper mineralization and silicate alteration do not fit a simple annular ring model but have been greatly modified by, 1. The existence of an ititial, outer ring, of metasomatic alteration overprinted by an inner.ring of hydrothermal alteration and, 2. later extensive dilating effects of intra- and post-mineral dikes. The hydrothermal clay mineral assemblage in the hypogene zone is illite-chlorite-kaolinite-smectite (beidellite). Preliminary studies indicate that the amount of each of these clays varies vertically and that hydrothermal zonation of clay minerals is possible. However, these minerals alter to illite-kaolinite assemblages in the supergene sulfide zone and to more kaolinite-rich assemblages in the supergene leached zone. Hydrothermal biotite breaks down readily in the supergene zone and is not well preserved in surface outcrops. The distribution of copper minerals in the supergene sulfide enrichment zone is only partly related to rock type being more dependent on topography and the availability of fractures.

The effects of computer assisted interactive fiction on the development of reading comprehension in grade five students

This study was undertaken in order to determine the effects of playing computer based text adventure games on the reading comprehension gains of students. Forty-five grade five students from one elementary school were randomly assigned to experimental and control groups, and were tested with regard to ability, achievement and reading skills. An experimental treatment, consisting of playing computer based interactive fiction games of the student's choice for fifteen minutes each day over an eight-week period, was administered. A comparison treatment engaged the control group in sustained silent reading of materials of the student's choice for an equal period of time. Following the experimental period all students were post-tested with an alternate form of the pre-test in reading skills, and gain scores were analysed. It was found that there were no significant differences in the gain scores of the experimental and control groups for overall reading comprehenSion, but the experimental group showed greater gains than the control group in the structural analysis reading sub-skill. Extreme variance in the data made generalization very difficult, but the findings indicated a potential for computer based interactive fiction as a useful tool for developing reading sl

The development, assessment, and implementation of an evaluation of the EMPOWER Program at shelters for abused women /

The development, assessment, and implementation of a program evaluation instrument was carried out to evaluate the impact and efficacy of the EMPOWER Program. This intervention was created to educate residents at a shelter for abused women with an anticipated outcome of prevention. Participants included the staff and residents at 2 shelters in Southern Ontario. Client pre, post and follow-up measures were obtained and analyzed statistically and using keyword content analysis. A single staff measure was obtained and summarized using keyword content analysis. Qualitative results were suggestive of important change in participants. All women in the post and follow-up measures believed their participation in the EMPOWER Program provided them with the knowledge, skills, and confidence to avoid abusive relationships in the fliture. This transformational impact was repeatedly expressed in both resident and staff feedback. Limitations of this research, as well as suggestions for future study were discussed.

An exploration of the impact of a mandatory quality assurance program on the staff nurse's commitment to professional development /

This study explored experiences in relation to the impact of the College of Nurses of Ontario's (CNO's) mandatory Quality Assurance (QA) program on registered nurses (RNs) working in a clinical setting of an acute care hospital. A qualitative descriptive research design was used and data collection was done in 2 stages. First, a survey with open-ended questions was given to 45 nurses. Second, 8 respondents from the survey were interviewed using a semistructured format. Data were obtained from 2 groups-diploma-prepared and post diploma-prepared RNs. Findings demonstrated that the CNO's QA program had varying influences on the RNs' learning paths, and these differences appeared to be related to the educational background of the individual. The diploma-prepared nurses reported that their commitment to professional development was influenced by their level of internal motivation, the pressures associated with time, and the need for a strong external motivator, namely the obligation of management to conduct formal performance appraisals. They further reported that the QA program played a part in positively altering their commitment to continuing education. The post-diploma baccalaureate nurses reported that the QA program played a positive role in influencing their ongoing learning, along with their level of internal motivation, the work and health care environment, and the element of professionalism. Several implications for nursing practice, theory, and fiirther research also became evident.

Economic security & reconstruction: utility, history and practice in post-conflict environments

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999 P65 D53 2007

Effect of a high fat maternal diet on body composition and bone development in male offspring

Direct high fat (HF) feeding has adverse effects on body composition and bone development in rodents. However, it is unclear whether maternal HF feeding has similar effects in male rat offspring. The objectives of this thesis were to determine if maternal HF feeding altered body composition, plasma hormones, bone development, and bone fatty acid composition in male offspring at weaning and 3 months of age. Maternal HF feeding increased bone mass and altered femur fatty acid composition at weaning, without differences in fat mass, lean mass, plasma hormones, or bone mass (femur or lumbar vertebrae). However, early differences did not persist at 3 months of age or contribute to lower bone strength – following consumption of a control diet post-weaning. These findings suggest that maternal HF feeding can alter body composition and bone development in weanling male offspring, without long-lasting effects if a healthy control diet is consumed post-weaning.

Impact of a Youth Development Camp on Participants’ Skills, Attitudes, and Views Towards Science and Scientific Inquiry

This mixed-methods research study sought to determine the impact of an informal science camp—the Youth Science Inquiry Development Camp (YSIDC)—on participants’ science inquiry skills, through self-assessment, as well as their views and attitudes towards science and scientific inquiry. Pre and post data were collected using quantitative surveys (SPSI, CARS), a qualitative survey (VOSI-E), interviews, and researcher’s observations. Paired sample t-tests from the quantitative surveys revealed that the YSIDC positively impacted participants’ science inquiry skills and attitudes towards science. Interviews supported these findings and provided contextual reasons for these impacts. Implications from this research would suggest that informal and formal educational institutions can increase science inquiry skills and promote positive views and attitudes towards science and scientific inquiry by using non-competitive cooperative learning strategies with a mixture of guided and open inquiry. Suggested directions for further research include measuring science inquiry skills directly and conducting longitudinal studies to determine the lasting effects of informal and formal science programs.