Early Life Intestinal Microbiota in Health and in Atopic Eczema

Decrease in microbial contacts in affluent societies is considered to lie behind the rise in allergic and other chronic inflammatory diseases during the last decades. Indeed, deviations in the intestinal microbiota composition and diversity have been associated with several diseases, such as atopic eczema. However, there is no consensus yet on what would constitute a beneficial or harmful microbiota. The aim of this thesis was to study the microbiota development in healthy infants and to characterize intestinal microbiota signatures associated with disease status and severity in infants with atopic eczema. The methodological aim was to compare and optimize methods for DNA extraction from fecal samples to be used in high-throughput microbiota analyses. It was confirmed that the most critical step in successful microbial DNA extraction from fecal samples is the mechanical cell lysis procedure. Based on this finding, an efficient semi-automated extraction process was developed that can be scaled for use in high-throughput platforms such as phylogenetic microarray used in this series of studies. By analyzing a longitudinal motherchild cohort for 3 years it was observed that the microbiota development is a gradual process, where some bacterial groups reach the degree of adult-type pattern earlier than others. During the breast-feeding period, the microbiota appeared to be relatively simple, while major diversification was found to start during the weaning process. By the age of 3 years, the child’s microbiota composition started to resemble that of an adult, but the bacterial diversity has still not reached the full diversity, indicating that the microbiota maturation extends beyond this age. In addition, at three years of age, the child’s microbiota was more similar to mother’s microbiota than to microbiota of nonrelated women.In infants with atopic eczema, a high total microbiota diversity and abundance of butyrate-producing bacteria was found to correlate with mild symptoms at 6 months. At 18 months, infants with mild eczema had significantly higher microbiota diversity and aberrant microbiota composition when compared to healthy controls at the same age. In conclusion, the comprehensive phylogenetic microarray analysis of early life microbiota shows the synergetic effect of vertical transmission and shared environment on the intestinal microbiota development. By the age of three years, the compositional development of intestinal microbiota is close to adult level, but the microbiota diversification continues beyond this age. In addition, specific microbiota signatures are associated with the existence and severity of atopic eczema and intestinal microbiota seems to have a role in alleviating the symptoms of this disease.

Machine vision measurement system for paper printability assessments

This work had two primary objectives: 1) to produce a working prototype for automated printability assessment and 2) to perform a study of available machine vision and other necessary hardware solutions. The three printability testing methods, IGT Picking,He¬liotest, and mottling, considered in this work have several different requirements and the task was to produce a single automated testing system suitable for all methods. A system was designed and built and its performance was tested using the Heliotest. Working proto¬types are important tools for implementing theoretical methods into practical systems and testing and demonstrating the methodsin real life conditions. The system was found to be sufficient for the Heliotest method. Further testing and possible modifications related to other two test methods were left for future works. A short study of available systems and solutions concerning image acquisition of machine vision was performed. The theoretical part of this study includes lighting systems, optical systems and image acquisition tools, mainly cameras and the underlying physical aspects for each portion.

Conventional and novel cardiovascular risk factors in young Finns and their associations with structural and functional vascular changes of subclinical atherosclerosis. The Cardiovascular Risk in Young Finns Study

Background: Atherosclerosis begins in early life progressing from asymptomatic to symptomatic as we age. Although substantial progress has been made in identifying the determinants of atherosclerosis in middle to older age adults at increased cardiovascular risk, there is lack of data examining determinants and prediction of atherosclerosis in young adults. Aims: The current study was designed to investigate levels of cardiovascular risk factors in young adults, subclinical measures of atherosclerosis, and prediction of subclinical arterial changes with conventional risk factor measures and novel metabolic profiling of serum samples. Subjects and Methods: This thesis utilised data from the follow-ups performed in 2001 and 2007 in the Cardiovascular Risk in Young Finns study, a Finnish population-based prospective cohort study that examined 2,204 subjects who were aged 30-45 years in 2007. Subclinical atherosclerosis was studied using noninvasive ultrasound measurements of carotid intima-media thickness (IMT), carotid arterial distensibility (CDist) and brachial flow-mediated dilation (FMD). Measurements included conventional risk factors and metabolic profiling using highthroughput nuclear magnetic resonance (NMR) methods that provided data on 42 lipid markers and 16 circulating metabolites. Results: Trends in lipids were favourable between 2001 and 2007, whereas waist circumference, fasting glucose, and blood pressure levels increased. To study the stability of noninvasive ultrasound markers, 6-year tracking (the likelihood to maintain the original fractile over time) in 6 years was examined. IMT tracked more strongly than CDist and FMD. Cardiovascular risk scores (Framingham, SCORE, Finrisk, Reynolds and PROCAM) predicted subclinical atherosclerosis equally. Lipoprotein subclass testing did not improve the prediction of subclinical atherosclerosis over and above conventional risk factors. However, circulating metabolites improved risk stratification. Tyrosine and docosahexaenoic acid were found to be novel biomarkers of high IMT. Conclusions: Prediction of cardiovascular risk in young Finnish adults can be performed with any of the existing risk scores. The addition of metabonomics to risk stratification improves prediction of subclinical changes and enables more accurate targeting of prevention at an early stage.

Metabolic syndrome in young adults – prevalence, childhood predictors and association with subclinical atherosclerosis

Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, insulin resistance, impaired glucose tolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing worldwide in all age groups. MetS is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. Aims: The aim of the present study was to investigate the prevalence, secular trends and childhood predictors of MetS in young adults. Furthermore, the relations between MetS and subclinical atherosclerosis were studied and whether apolipoproteins (apo) B and A-I, C-reactive protein (CRP) and type II secretory phospholipase A2 (sPLA2) were associated with MetS, and to what extent the atherogenicity of MetS was explained by these factors. Participants and Methods: The present thesis is part of the large scale population-based, prospective study, the Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980 and included 3,596 participants aged 3-18 years. Carotid and brachial ultrasound studies were performed for 2,283 of these participants in 2001 and 2,200 of these participants in 2007. Results: The overall prevalence of MetS in young adults aged 24-39 years in 2001 was 10-15 % and 6 years later in 30-45 year-old adults it was 15-23 % depending on the MetS definition used. Between the years 1986 and 2001, MetS prevalence increased from 1.0 % to 7.5 % (p<0.0001) in 24-year-old participants that was mostly driven by the increased central obesity. Participants with MetS had increased carotid intima-media thickness (cIMT) and decreased carotid elasticity compared to those without the syndrome. Impaired brachial flow-mediated dilatation (FMD) was not related to MetS but it modified the relationship between MetS and cIMT (P for interaction 0.023). High levels of apoB, CRP, sPLA2 and low levels of apoA-I associated with MetS in young adults. In prospective analysis both MetS and high apoB predicted (P<0.0001) incident high cIMT, defined as cIMT>90th percentile and/or plaque. The association between MetS and incident high cIMT was attenuated by ~40 % after adjustment with apoB. Conclusions: MetS is common in young adults and increases with age. Screening for risk factors, especially obesity, at an early life stage could help identify children and adolescents at increased risk of developing MetS and cardiovascular disease later in life. MetS identifies a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MetS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis. In addition, the atherogenicity of MetS in this population assessed by incident high cIMT appears to be substantially mediated by elevated apoB.

Pelillistäminen menetelmänä julkisen liikenteen käytön lisäämisessä

Joukkoliikenteen suosio hiipuu vähitellen, käyttö aste laskee. Tätä ongelmaa lähdimme ratkaisemaan sovelluksen ja pelillistämis menetelmän avulla. Menetelmää hyödyntäen tavoitteena oli luoda sovellus joka koukuttaa käyttäjän sovelluksen käyttöön ja sitä kautta joukkoliikenteen käyttöön. Pyrimme pysäyttämään joukkoliikenteen käyttöasteen laskun tai jopa kääntämään sen kasvuun. Varsinaista tulosta ei tällä työllä saatu, sillä aika ei vain riittänyt sovelluksen testaamiseen käytännössä. Pelillistämis menetelmiä kun tutkii ja vertaa sovellustamme niihin, niin sovelluksellamme on hyvä mahdollisuudet toimia joukkoliikenteen käytön lisäämisen työkaluna.

Supporting knowledge creation and sharing in the early phases of the strategic innovation process

The driving forces of technology and globalization continuously transform the business landscape in a way which undermines the existing strategies and innovations of organizations. The challenge for organizations is to establish such conditions where they are able to create new knowledge for innovative business ideas in interaction between other organizations and individuals. Innovation processes continuously need new external stimulations and seek new ideas, new information and knowledge locating more and more outside traditional organizational boundaries. In several studies, the early phases of the innovation process have been considered as the most critical ones. During these phases, the innovation process can emerge or conclude. External knowledge acquirement and utilization are noticed to be important at this stage of the innovation process giving information about the development of future markets and needs for new innovative businessideas. To make it possible, new methods and approaches to manage proactive knowledge creation and sharing activities are needed. In this study, knowledge creation and sharing in the early phases of the innovation process has been studied, and the understanding of knowledge management in the innovation process in an open and collaborative context advanced. Furthermore, the innovation management methods in this study are combined in a novel way to establish an open innovation process and tested in real-life cases. For these purposes two complementary and sequentially applied group work methods - the heuristic scenario method and the idea generation process - are examined by focusing the research on the support of the open knowledge creation and sharing process. The research objective of this thesis concerns two doctrines: the innovation management including the knowledge management, and the futures research concerning the scenario paradigm. This thesis also applies the group decision support system (GDSS) in the idea generation process to utilize the converged knowledge during the scenario process.