From statin efficacy to everyday effectiveness: Studying the gap in between.

Statins are indicated for preventing cardiovascular disease events. Patients with diabetes have a risk of major cardiovascular events double the risk of their peers without diabetes. Thus, clinical treatment guidelines recommend statins for the management of diabetic dyslipidemia. The evidence base for statin use in cardiovascular disease derives from the randomized controlled statin trials designed to prove statin efficacy under ideal conditions, among a homogenous study population meeting strict trial eligibility criteria. This thesis was implemented as four pharmacoepidemiological statin studies using register data on realworld statin users. The overall purpose was to evaluate the trends, patterns and effectiveness of statin use in everyday life. More specifically, nationwide secular trends in statin use in Finland were analysed, especially among patient groups which had been underrepresented in the statin trials. Furthermore, the benchmarking statin trials in diabetes, the Heart Protection Study and the Collaborative Atorvastatin Diabetes Study, were evaluated for their representativeness for real-world diabetes care with the emphasis placed on adherence to statin use. The association between good adherence and the incidence of major cardiovascular events in the real-world was further investigated in diabetes. These studies demonstrate that statin initiations increased from 1995 to 2005 in Finland. The increase was most pronounced among those aged at least 75 years and was observed already before the publication of rigorous trial data conducted in elderly subjects. Thus, statins seem to have been initiated in clinical practice also going beyond the strict trial eligibility criteria. Nonetheless, low adherence to statin use among the real-world patients with diabetes was found not only to limit the representativeness of the trials for clinical care but also to attenuate in all likelihood their benefits in the real-world. In fact, good adherence to statin use was found to associate with a decreased risk for major cardiovascular events in patients with diabetes. In conclusion, these studies highlight the importance of good adherence to statin use in clinical practice in order to obtain the full therapeutic value demonstrated in the statin trials. Simply increasing the number of statin users will not alone suffice in sharing our common resources appropriately.

Implementatiоn оf Sustainability-Оriented Innоvatiоns in Business - Studying Оrganizatiоnal and External Capabilities: Evidence frоm Pоland

The cоncept оf sustainability-оriented innоvatiоn is recent and still under researched. The aim оf the Thesis is tо cоntribute tо the field and investigate hоw dо cоmpanies оperating in Pоland apply sustainability-оriented innоvatiоn (SОI) tо their cоre business activities, what are the differences between variоus business fоrms оf оrganizatiоn in terms оf SОI, and what type оf capabilities facilitate implementatiоn оf SОI. Given early stage оf empirical research оn sustainability-оriented innоvatiоn, an explоratоry-descriptive case study research strategy was taken applying qualitative methоds. 6 interviews with managers and CEОs оf 4 cоmpanies lоcated in Warsaw were cоnducted. In additiоn, twо academic expert panels with specialists frоm University оf Lоdz and Lappeenranta University оf Technоlоgy were carried оut in оrder tо suppоrt the findings. The study fоund оut that in case оf cоmpanies which purpоse is tо create pоsitive impact and develоp sustainable prоducts оr services by using innоvative apprоaches, SОI activities are embedded in оrganizatiоnal culture and prоcess sо that it is difficult tо differentiate between main business activities and SОI. In the оther twо cases SОI practices were in line with cоre business activities thus reflected the main оperatiоns and were determined as a part оf CSR strategy. Activities are industry specific and are cоntingent upоn resоurces and capabilities pоssessed. Amоng list оf success factоrs management suppоrt, CEО’s persоnal values, dedicated and mоtivated team, investments in research and develоpment, оrganizatiоnal culture, nоn-hierarchical cоmmunicatiоns channels, empоwerment оf emplоyees, prоvisiоn оf time and space fоr failures were identified as key оrganizatiоnal capabilities facilitating integratiоn оf SОI practices. Whereas market demand, NGОs’ pressure, regulatiоns enfоrced, access tо external funding, netwоrking and cооperating present external оr cоllabоrative capabilities suppоrting implementatiоn оf sustainability оriented innоvatiоn in cоmpanies. SОI takes a systemic apprоach that drives the transfоrmatiоn tо becоme sustainable business embedding and integrating sоcial, envirоnmental and ecоnоmic value creatiоn tоgether.

STUDYING ABERRANT METHYLATION AND miRNA PROFILING FOR THE DETECTION OF LUNG CANCER BIOMARKERS

Lung cancer is a major chronic disease responsible for the highest mortality rate, among other types of cancer, and represents 29% of all deaths in Canada. The clinical diagnosis of lung carcinoma still requires a standard diagnostic approach, as there are no symptoms in its early stage. Therefore, it is usually diagnosed at a later stage, when the survival rate is low. With the recent advancement in molecular biology and biotechnology, a molecular biomarker approach for the diagnosis of early lung cancer seems to be a potential option. In this study, we aimed to investigate and standardize a promising Lung ,Cancer Biomarker by studying the aberrant methylation of two tumour suppressor genes, namely RASSFIA and RAR-B, and the miRNA profiling of four . commonly deregulated miRNA (miR-199a-3p, miR-182, miR-lOO and miR-221). Four lung cancer cell lines were used (two SCLC and two NSCLC), with comparisons being made with normal lung cell lines. Our results, we found that none of these genes were methylated. We then evaluated TP53, and found the promoter of this gene to be methylated in the cancer cell lines, as compared to the normal cell lines, indicating gene inactivation. We carried out miRNA profiling of the cancer cell lines and reported that 80 miRNAs are deregulated in lung cancer cell lines as compared to the normal cell lines. Our study was the first of its kind to indicate that hsa-mir-4301, hsa-mir-4707-5p and hsa-mir-4497 (newly discovered miRNAs) are deregulated in lung cancer cell lines. We also investigated miR-199a-3p, mir-lOO and miR-182, and found that miR-199a -3p and mir-l00 were down-regulated in cancer lines, whereas miR-182 was up-regulated in the cancer cell lines. In the final part of the study we observed that mir-221 could be a putative biomarker to distinguish between the two types of lung cancer because it was down-regulated in SCLC, and up-regulated in the NSCLC cell lines. In conclusion, we found four miRNA molecular biomarkers that possibly could be used in the early diagnosis of the lung cancer. More studies are still required with larger numbers of samples to effectively establish these as molecular biomarkers for the diagnosis of lung cancer

Non-invasive investigation of the response to oxidative stress in living cardiomyocytes by studying mitochondrial NAD(P)H

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Studying the cytomechanic aspects of pollen tube growth behavior using Lab-On-Chip technology

L'élongation cellulaire de cellules cultivant bout comme hyphae fongueux, inculquez hairs, des tubes de pollen et des neurones, est limité au bout de la cellule, qui permet à ces cellules d'envahir l'encerclement substrate et atteindre une cible. Les cellules cultivant bout d'équipement sont entourées par le mur polysaccharide rigide qui régule la croissance et l'élongation de ces cellules, un mécanisme qui est radicalement différent des cellules non-walled. La compréhension du règlement du mur de cellule les propriétés mécaniques dans le contrôle de la croissance et du fonctionnement cellulaire du tube de pollen, une cellule rapidement grandissante d'équipement, est le but de ce projet. Le tube de pollen porte des spermatozoïdes du grain de pollen à l'ovule pour la fertilisation et sur sa voie du stigmate vers l'ovaire le tube de pollen envahit physiquement le stylar le tissu émettant de la fleur. Pour atteindre sa cible il doit aussi changer sa direction de croissance les temps multiples. Pour évaluer la conduite de tubes de pollen grandissants, un dans le système expérimental vitro basé sur la technologie de laboratoire-sur-fragment (LOC) et MEMS (les systèmes micro-électromécaniques) ont été conçus. En utilisant ces artifices nous avons mesuré une variété de propriétés physiques caractérisant le tube de pollen de Camélia, comme la croissance la croissance accélérée, envahissante et dilatant la force. Dans une des organisations expérimentales les tubes ont été exposés aux ouvertures en forme de fente faites de l'élastique PDMS (polydimethylsiloxane) la matière nous permettant de mesurer la force qu'un tube de pollen exerce pour dilater la croissance substrate. Cette capacité d'invasion est essentielle pour les tubes de pollen de leur permettre d'entrer dans les espaces intercellulaires étroits dans les tissus pistillar. Dans d'autres essais nous avons utilisé l'organisation microfluidic pour évaluer si les tubes de pollen peuvent s'allonger dans l'air et s'ils ont une mémoire directionnelle. Une des applications auxquelles le laboratoire s'intéresse est l'enquête de processus intracellulaires comme le mouvement d'organelles fluorescemment étiqueté ou les macromolécules pendant que les tubes de pollen grandissent dans les artifices LOC. Pour prouver que les artifices sont compatibles avec la microscopie optique à haute résolution et la microscopie de fluorescence, j'ai utilisé le colorant de styryl FM1-43 pour étiqueter le système endomembrane de tubes de pollen de cognassier du Japon de Camélia. L'observation du cône de vésicule, une agrégation d'endocytic et les vésicules exocytic dans le cytoplasme apical du bout de tube de pollen, n'a pas posé de problèmes des tubes de pollen trouvés dans le LOC. Pourtant, le colorant particulier en question a adhéré au sidewalls du LOC microfluidic le réseau, en faisant l'observation de tubes de pollen près du difficile sidewalls à cause du signal extrêmement fluorescent du mur. Cette propriété du colorant pourrait être utile de refléter la géométrie de réseau en faisant marcher dans le mode de fluorescence.

Studying Your Own Country. Social Scientific Knowledge For Our Times and Places; Presidential Address to the Canadian Political Science Association, St Catharines, May 28, 2014

Political science is both a generalizing and an anchored, nationally defined, discipline. Too often, the first perspective tends to crowd out the latter, because it appears more prestigious, objective, or scientific. Behind the international/national dichotomy, there are indeed rival conceptions of social science, and important ontological, epistemological and methodological assumptions. This article discusses these assumptions and stresses the critical contribution of idiographic, single-outcome studies, the importance of producing relevant, usable knowledge, and the distinctive implications of studying one’s own country, where a scholar is also a citizen, involved in more encompassing national conversations. The aim is not to reject the generalizing, international perspective, or even the comparative approach, but rather to reaffirm the importance of maintaining as well, and in fact celebrating, the production of social scientific knowledge directly relevant for our own times and places.

A fiber optic smart sensor for studying the setting characteristics of various grades of cement

A simple, effective and inexpensive fiber optic sensor for investigating the setting characteristics of various grades of cement is described. A finite length of unsheathed multimode optical fiber laid inside the cement mix, is subjected to stress during the setting process. The microbends created on the fiber due to this stress directly influence the intensity of light propagating through the fiber. Continuous monitoring of such variations in the light output transmitted through the fiber gives a clear measure of the setting characteristics of the cement mix, thus providing a simple and elegant technique of great practical importance in the field of civil engineering. The smart fiber optic sensor described above can be incorporated into a building during the construction process itself so that continuous monitoring of the deterioration process for the entire life time of the building can be carried out.

Model Development and Validation for Studying Consumer Preferences of Car Owners

Globalization and liberalization, with the entry of many prominent foreign manufacturers, changed the automobile scenario in India, since early 1990‟s. Manufacturers such as Ford, General Motors, Honda, Toyota, Suzuki, Hyundai, Renault, Mitsubishi, Benz, BMW, Volkswagen and Nissan set up their manufacturing units in India in joint venture with their Indian counterpart companies, by making use of the Foreign Direct Investment policy of the Government of India, These manufacturers started capturing the hearts of Indian car customers with their choice of technological and innovative product features, with quality and reliability. With the multiplicity of choices available to the Indian passenger car buyers, it drastically changed the way the car purchase scenario in India and particularly in the State of Kerala. This transformed the automobile scene from a sellers‟ market to buyers‟ market. Car customers started developing their own personal preferences and purchasing patterns, which were hitherto unknown in the Indian automobile segment. The main purpose of this paper is to come up with the identification of possible parameters and a framework development, that influence the consumer purchase behaviour patterns of passenger car owners in the State of Kerala, so that further research could be done, based on the framework and the identified parameters

Conceptualisation Of Model For Studying Consumer Purchase Behaviour Of Passenger Cars

Automobile Industry in India is influenced by the presence of national and multi-national manufacturers. The presence of many manufacturers and brands in the state provides many choices to the customer. The current market for car manufacturers has been transformed from a monopoly of one or two manufacturers in the seventies to oligopoly of many manufacturers in the current marketing scenario. The main objective of the research paper is to explore and conceptualize various parameters and develop a model, which influence the purchase patterns of passenger cars in the State of Kerala. Thus, the main purpose of this paper is to come up with a model, which shall facilitate further study on the consumer purchase behaviour patterns of passenger car owners in the State of Kerala, India. The author intends to undertake further quantitative analysis to verify and validate the model so developed. The main methods used for this paper are secondary research on available material, depth interview of car dealers, car financing agencies and car owners in the city of Cochin, in Kerala State in India. The depth interviews were conducted with the use of prepared questionnaire for car dealers, car customers and car financing agencies. The findings resulted in the identification of the parameters that influence the consumer purchase behaviour of passenger cars and the formulation of the model, which will be the basis for the further research of the author. The paper will be of tremendous value to the existing and new car manufacturers both indigenous and foreign, to formalize and strategies their policies towards an effective marketing strategy, so as to market their models in the State, which is known for its high literacy, consumerism and higher educational penetration

An explanatory model of the intention to continue studying among nontraditional university students

Resumen tomado de la publicación

Improving computer interaction for older people - studying mouse clicks

Interactions using a standard computer mouse can be particularly difficult for novice and older adult users. Tasks that involve positioning the mouse over a target and double-clicking to initiate some action can be a real challenge for many users. Hence, this paper describes a study that investigates the double-click interactions of older and younger adults and presents data that can help inform the development of methods of assistance. Twelve older adults (mean age = 63.9 years) and 12 younger adults (mean age = 20.8 years) performed click and double-click target selections with a computer mouse. Initial results show that older users make approximately twice as many errors as younger users when attempting double-clicks. For both age groups, the largest proportion of errors was due to difficulties with keeping the cursor steady between button presses. Compared with younger adults, older adults experienced more difficulties with performing two button presses within a required time interval. Understanding these interactions better is a step towards improving accessibility, and may provide some suggestions for future directions of research in this area.

Studying the Human Gut Microbiota in the Trans-Omics Era - Focus on Metagenomics and Metabonomics

The human gut microbiota comprises a diverse microbial consortium closely co-evolved with the human genome and diet. The importance of the gut microbiota in regulating human health and disease has however been largely overlooked due to the inaccessibility of the intestinal habitat, the complexity of the gut microbiota itself and the fact that many of its members resist cultivation and are in fact new to science. However, with the emergence of 16S rRNA molecular tools and "post-genomics" high resolution technologies for examining microorganisms as they occur in nature without the need for prior laboratory culture, this limited view of the gut microbiota is rapidly changing. This review will discuss the application of molecular microbiological tools to study the human gut microbiota in a culture independent manner. Genomics or metagenomics approaches have a tremendous capability to generate compositional data and to measure the metabolic potential encoded by the combined genomes of the gut microbiota. Another post-genomics approach, metabonomics, has the capacity to measure the metabolic kinetic or flux of metabolites through an ecosystem at a particular point in time or over a time course. Metabonomics thus derives data on the function of the gut microbiota in situ and how it responds to different environmental stimuli e. g. substrates like prebiotics, antibiotics and other drugs and in response to disease. Recently these two culture independent, high resolution approaches have been combined into a single "transgenomic" approach which allows correlation of changes in metabolite profiles within human biofluids with microbiota compositional metagenomic data. Such approaches are providing novel insight into the composition, function and evolution of our gut microbiota.

A family of promoter probe vectors incorporating autofluorescent and chromogenic reporter proteins for studying gene expression in Gram-negative bacteria

A series of promoter probe vectors for use in Gram-negative bacteria has been made in two broad-host-range vectors, pOT (pBBR replicon) and pJP2 (incP replicon). Reporter fusions can be made to gfpUV, gfprnut3.1, unstable gfpmut3.1 variants (LAA, LVA, AAV and ASV), gfp+, dsRed2, dsRedT3, dsRedT4, mRFP1, gusA or lacZ. The two vector families, pOT and pJP2, are compatible with one another and share the same polylinker for facile interchange of promoter regions. Vectors based on pJP2 have the advantage of being ultra-stable in the environment due to the presence of the parABCDE genes. As a confirmation of their usefulness, the dicarboxylic acid transport system promoter (dctA(p)) was cloned into a pOT (pRU1097)- and a pJP2 (pRU1156)-based vector and shown to be expressed by Rhizobium leguminosarum in infection threads of vetch. This indicates the presence of dicarboxylates at the earliest stages of nodule formation.