Spirometric studies on the adult general population of Helsinki : bronchodilation responses, determinants, and intrasession repeatability of FEV1, FEV6, FVC, and forced expiratory time

Spirometry is the most widely used lung function test in the world. It is fundamental in diagnostic and functional evaluation of various pulmonary diseases. In the studies described in this thesis, the spirometric assessment of reversibility of bronchial obstruction, its determinants, and variation features are described in a general population sample from Helsinki, Finland. This study is a part of the FinEsS study, which is a collaborative study of clinical epidemiology of respiratory health between Finland (Fin), Estonia (Es), and Sweden (S). Asthma and chronic obstructive pulmonary disease (COPD) constitute the two major obstructive airways diseases. The prevalence of asthma has increased, with around 6% of the population in Helsinki reporting physician-diagnosed asthma. The main cause of COPD is smoking with changes in smoking habits in the population affecting its prevalence with a delay. Whereas airway obstruction in asthma is by definition reversible, COPD is characterized by fixed obstruction. Cough and sputum production, the first symptoms of COPD, are often misinterpreted for smokers cough and not recognized as first signs of a chronic illness. Therefore COPD is widely underdiagnosed. More extensive use of spirometry in primary care is advocated to focus smoking cessation interventions on populations at risk. The use of forced expiratory volume in six seconds (FEV6) instead of forced vital capacity (FVC) has been suggested to enable office spirometry to be used in earlier detection of airflow limitation. Despite being a widely accepted standard method of assessment of lung function, the methodology and interpretation of spirometry are constantly developing. In 2005, the ATS/ERS Task Force issued a joint statement which endorsed the 12% and 200 ml thresholds for significant change in forced expiratory volume in one second (FEV1) or FVC during bronchodilation testing, but included the notion that in cases where only FVC improves it should be verified that this is not caused by a longer exhalation time in post-bronchodilator spirometry. This elicited new interest in the assessment of forced expiratory time (FET), a spirometric variable not usually reported or used in assessment. In this population sample, we examined FET and found it to be on average 10.7 (SD 4.3) s and to increase with ageing and airflow limitation in spirometry. The intrasession repeatability of FET was the poorest of the spirometric variables assessed. Based on the intrasession repeatability, a limit for significant change of 3 s was suggested for FET during bronchodilation testing. FEV6 was found to perform equally well as FVC in the population and in a subgroup of subjects with airways obstruction. In the bronchodilation test, decreases were frequently observed in FEV1 and particularly in FVC. The limit of significant increase based on the 95th percentile of the population sample was 9% for FEV1 and 6% for FEV6 and FVC; these are slightly lower than the current limits for single bronchodilation tests (ATS/ERS guidelines). FEV6 was proven as a valid alternative to FVC also in the bronchodilation test and would remove the need to control duration of exhalation during the spirometric bronchodilation test.

X-ray scattering and diffraction enhanced imaging studies of in vitro breast tissues

This thesis is a study of the x-ray scattering properties of tissues and tumours of the breast. Clinical radiography is based on the absorption of the x-rays when passing right through the human body and gives information about the densities of the tissues. Besides being absorbed, x-rays may change their direction within the tissues due to elastic scattering or even to refraction. The phenomenon of scattering is a nuisance to radiography in general, and to mammography in particular, because it reduces the quality of the images. However, scattered x-rays bear very useful information about the structure of the tissues at the supra-molecular level. Some pathologies, like breast cancer, produce alterations to the structures of the tissues, being especially evident in collagen-rich tissues. On the other hand, the change of direction due to refraction of the x-rays on the tissue boundaries can be mapped. The diffraction enhanced imaging (DEI) technique uses a perfect crystal to convert the angular deviations of the x-rays into intensity variations, which can be recorded as images. This technique is of especial interest in the cases were the densities of the tissues are very similar (like in mammography) and the absorption images do not offer enough contrast. This thesis explores the structural differences existing in healthy and pathological collagen in breast tissue samples by the small-angle x-ray scattering (SAXS) technique and compares these differences with the morphological information found in the DEI images and the histo-pathology of the same samples. Several breast tissue samples were studied by SAXS technique in the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Scattering patterns of the different tissues of the breast were acquired and compared with the histology of the samples. The scattering signals from adipose tissue (fat), connective tissue (collagen) and necrotic tissue were identified. Moreover, a clear distinction could be done between the scattering signals from healthy collagen and from collagen from an invasive tumour. Scattering from collagen is very characteristic. It includes several scattering peaks and scattering features that carry information about the size and the spacing of the collagen fibrils in the tissues. It was found that the collagen fibrils in invaded tumours were thinner and had a d-spacing length 0,7% longer that fibrils from healthy tumours. The scattering signals from the breast tissues were compared with the histology by building colour-coded maps across the samples. They were also imaged with the DEI technique. There was a total agreement between the scattering maps, the morphological features seen in the images and the information of the histo- pathological examination. The thesis demonstrates that the x-ray scattering signal can be used to characterize tissues and that it carries important information about the pathological state of the breast tissues, thus showing the potential of the SAXS technique as a possible diagnostic tool for breast cancer.

Primordial Isocurvature Perturbation in Light of CMB and LSS Data

The increased accuracy in the cosmological observations, especially in the measurements of the comic microwave background, allow us to study the primordial perturbations in grater detail. In this thesis, we allow the possibility for a correlated isocurvature perturbations alongside the usual adiabatic perturbations. Thus far the simplest six parameter \Lambda CDM model has been able to accommodate all the observational data rather well. However, we find that the 3-year WMAP data and the 2006 Boomerang data favour a nonzero nonadiabatic contribution to the CMB angular power sprctrum. This is primordial isocurvature perturbation that is positively correlated with the primordial curvature perturbation. Compared with the adiabatic \Lambda CMD model we have four additional parameters describing the increased complexity if the primordial perturbations. Our best-fit model has a 4% nonadiabatic contribution to the CMB temperature variance and the fit is improved by \Delta\chi^2 = 9.7. We can attribute this preference for isocurvature to a feature in the peak structure of the angular power spectrum, namely, the widths of the second and third acoustic peak. Along the way, we have improved our analysis methods by identifying some issues with the parametrisation of the primordial perturbation spectra and suggesting ways to handle these. Due to the improvements, the convergence of our Markov chains is improved. The change of parametrisation has an effect on the MCMC analysis because of the change in priors. We have checked our results against this and find only marginal differences between our parametrisation.

Swedish advertising language in Finland mirrored by the newspaper advertisements of the Stockmanns department store during the 20th century

The advertising business is often said to favour a modern, innovative language use. This is a statement not easily verified. Newspaper ads are in fact the genre of written language that linguists have paid the least attention to. People writing texts for newspaper ads are individuals representing contemporary language use. Advertisements representing different periods therefore diverge not only regarding the change of style and form advertising undergoes over time, but changes in the language itself also reflect the continuous process of alteration in a speech community. Advertisements and marketing material on the whole, are also read by many individuals who otherwise are not accustomed to reading at all. The marketing manager, the copywriter and the Art Director, in other words, produce texts that unconsciously function as language models. Changes are not created by, or urged on by linguistic expertise, but by ordinary users confronting other ordinary users. From a sociolinguistic perspective the widely diffused advertising language is therefore a most influential factor.

Reklamsvenska i Finland speglad genom varuhuset Stockmanns tidningsannonser under det 20e seklet - Swedish Advertising Language in Finland Mirrored by the Newspaper Advertisements of the Stockmanns Department Store during the 20th Century

Reklam sägs använda ett modernt, gärna ett nyskapande språk. Detta är ett påstående som inte så lätt kan verifieras. Tidningsannonsen är troligen den skriftspråksgenre som har fått minst uppmärksamhet av språkforskare. De som skriver texten i en tidningsannons är personer som representerar det samtida språkbruket. Annonser som representerar olika tidsepoker skiljer sig därför från varandra inte bara genom att annonsen förändras i fråga om stil och form. Annonsens språk avspeglar också den språkliga förändringsprocess som kontinuerligt pågår i varje språksamhälle. Annonser, och marknadsföringsmaterial över huvud taget, läses också av många människor som i övrigt läser mycket litet eller kanske inte alls. Marknadsföraren, reklamskribenten (copywriter) och AD:n producerar m.a.o. texter som på ett omedvetet sätt kommer att vara språkmodeller för sina läsare. Förändringar i språket kreeras inte och drivs inte på av språkforskare, utan av vanliga språkbrukare i interaktion med andra språkbrukare. Sett ur ett sociolingvistiskt perspektiv har det vitt spridda reklamspråket därför inflytande på språket i samhället. Syftet med det reklamspråksprojekt som presenteras i föreliggande rapport är att analysera hur och när förändringar i svenskan som uppträder i Sverige dyker upp i annonser som skrivs på svenska i Finland. Reklam på svenska Finland under 1900-talet står i fokus, och tidningsannonser för Stockmanns varuhus i Helsingfors utgör primärmaterialet. Tidningsannonser för varuhuset Nordiska Kompaniet (NK) i Stockholm under motsvarande tid tjänar som jämförelsematerial. I denna rapport presenteras projektets syfte, de uppställda forskningsfrågorna, och resonemanget illustreras med exempel ur projektmaterialet. Rapporten innehåller också en beskrivning av projektets reklamdatabas och basfakta om material och metoder. -

Elämänmuutoksen, jännityksen ja asiantuntijuuden representointi Veikkaus Oy:n mainonnassa vuosina 1970— 2006

Aim of this master's thesis paper for consumer economics, is to research gambling advertisements in Finland over a period of 35 years, from 1970 to 2006. Veikkaus Oy (later Veikkaus), was founded in 1940, as one of the three licensed gambling organizations in Finland. Material for the current research comprised 1494 advertisements published by Veikkaus in newspapers and magazines at that time. Veikkaus has the exclusive licence to organize lotto games, sport games, instant games and other draw games in Finland. The other two operators, The Finnish Slot Machine Association RAY and Fintoto (on-track horse betting), were not included in the current analysis. This study has been completed according to research contract and grand by the Finnish Foundation for Gaming Research (Pelitoiminnan tutkimussäätiö). In general, advertisements reflect surrounding culture and time, and their message is built on stratified meanings, symbols and codes. Advertising draws the viewer's attention, introduces the advertised subject, and finally, affects the individual's consumption habits. However, advertisements not only work on individual level, but also influence public perception of the advertised product. Firstly, in order to assess gambling as a phenomenon, this paper discusses gambling as consumer behaviour, and also reviews history of gambling in Finland. Winning is a major feature of gambling, and dreaming about positive change of life is a centre of most gambling ads. However, perceived excitement through risk of losing can also be featured in gambling ads. Secondly, this study utilizes Veikkaus’ large advertising archives, were advertising data is analyzed by content analysis and the semiotic analysis. Two methods have been employed to support analyzing outcome in a synergistic way. Content analysis helps to achieve accuracy and comprehensiveness. Semiotic analysis allows deeper and more sensitive analysis to emerged findings and occurrences. It is important to understand the advertised product, as advertising is bound to the culture and time. Hence, to analyze advertising, it is important to understand the environment where the ads appear. Content analysis of Veikkaus data discovered the main gambling and principal advertisement style for each.period. Interestingly, nearly half of Veikkaus’ advertisements promoted topic other than “just winning the bet”. Games of change, like Lotto, typically advertised indirectly represented dreams about winning. In the category of skill gambling, features were represented as investment, and the excitement of sporting expertise was emphasized. In addition, there were a number of gambling ads that emphasize social responsibility of Veikkaus as a government guided organization. Semiotic methods were employed to further elaborate on findings of content analysis. Dreaming in the advertisements was represented by the product of symbols, (e.g. cars and homes) that were found to have significance connection with each other. Thus, advertising represents change of life obtained by the winning. Interestingly, gambling ads promoting jackpots were often representing religious symbolisms. Ads promoting social responsibility were found to be the most common during economical depression of the 90’s. Deeper analysis showed that at that time, advertisements frequently represented depression-related meanings, such as unemployment and bank loans. Skill gaming ads were often represented by sports expertise – late 90’s, their number started sky rocketing, and continued increasing until 2006 (when this study ended). One may conclude that sport betting draws its meanings from the relevant consumer culture, and from the rules and features of the betted sport.

Temperature-Sensitive Src-Transformed Mdck Cells nn 3d Cultures as a Model of Malignant Transformation of Epithelial Cells

The equilibrium between cell proliferation, differentiation, and apoptosis is crucial for maintaining homeostasis in epithelial tissues. In order for the epithelium to function properly, individual cells must gain normal structural and functional polarity. The junctional proteins have an important role both in binding the cells together and in taking part in cell signaling. Cadherins form adherens junctions. Cadherins initiate the polarization process by first recognizing and binding the neighboring cells together, and then guiding the formation of tight junctions. Tight junctions form a barrier in dividing the plasma membranes to apical and basolateral membrane domains. In glandular tissues, single layered and polarized epithelium is folded into tubes or spheres, in which the basal side of the epithelial layer faces the outer basal membrane, and the apical side the lumen. In carcinogenesis, the differentiated architecture of an epithelial layer is disrupted. Filling of the luminal space is a hallmark of early epithelial tumors in tubular and glandular structures. In order for the transformed tumor cells to populate the lumen, enhanced proliferation as well as inhibition of apoptosis is required. Most advances in cancer biology have been achieved by using two-dimensional (2D) cell culture models, in which the cells are cultured on flat surfaces as monolayers. However, the 2D cultures are limited in their capacity to recapitulate the structural and functional features of tubular structures and to represent cell growth and differentiation in vivo. The development of three-dimensional (3D) cell culture methods enables the cells to grow and to be studied in a more natural environment. Despite the wide use of 2D cell culture models and the development of novel 3D culture methods, it is not clear how the change of the dimensionality of culture conditions alters the polarization and transformation process and the molecular mechanisms behind them. Src is a well-known oncogene. It is found in focal and adherens junctions of cultured cells. Active src disrupts cell-cell junctions and interferes with cell-matrix binding. It promotes cell motility and survival. Src transformation in 2D disrupts adherens junctions and the fibroblastic phenotype of the cells. In 3D, the adherens junctions are weakened, and in glandular structures, the lumen is filled with nonpolarized vital cells. Madin-Darby canine kidney (MDCK) cells are an epithelial cell type commonly used as a model for cell polarization. Its-src-transformed variants are useful model systems for analyzing the changes in cell morphology, and they play a role in src-induced malignant transformation. This study investigates src-transformed cells in 3D cell cultures as a model for malignant transformation. The following questions were posed. Firstly: What is the role of the composition and stiffness of the extracellular matrix (ECM) on the polarization and transformation of ts v-src MDCK cells in 3D cell cultures? Secondly: How do the culture conditions affect gene expression? What is the effect of v-src transformation in 2D and in 3D cell models? How does the shift from 2D to 3D affect cell polarity and gene expression? Thirdly: What is the role of survivin and its regulator phosphatase and tensin homolog protein (PTEN) in cell polarization and transformation, and in determining cell fate? How does their expression correlate with impaired mitochondrial function in transformed cells? In order to answer the above questions, novel methods of culturing and monitoring cells had to be created: novel 3D methods of culturing epithelial cells were engineered, enabling real time monitoring of a polarization and transformation process, and functional testing of 3D cell cultures. Novel 3D cell culture models and imaging techniques were created for the study. Attention was focused especially on confocal microscopy and live-cell imaging. Src-transformation disturbed the polarization of the epithelium by disrupting cell adhesion, and sensitized the cells to their environment. With active src, the morphology of the cell cluster depended on the composition and stiffness of the matrix. Gene expression studies revealed a broader impact of src transformation than mere continuous activity of src-kinase. In 2D cultures, src transformation altered the expression of immunological, actin cytoskeleton and extracellular matrix (ECM). In 3D, the genes regulating cell division, inhibition of apoptosis, cell metabolism, mitochondrial function, actin cytoskeleton and mechano-sensing proteins were altered. Surprisingly, changing the culture conditions from 2D to 3D affected also gene expression considerably. The microarray hit survivin, an inhibitor of apoptosis, played a crucial role in the survival and proliferation of src-transformed cells.