347 resultados para bioekonominen analyysi
Resumo:
The aim of this work was to study, whether international fashion trends show in knit designs in Finnish craft magazines and how trends are modified. Women s knitted clothes and accessories in autumn winter season 2005 2006 were analyzed. Future research, trends, fashion, designing and knitting provides theoretical basis for this study. The trend material of this study came from Carlin Women s knitwear winter 2005 2006, which is fashion forecast for Women s knitwear. In addition to the trend book, I selected two international fashion magazines to reinforce this study. Fashion magazines were L´Officiel, 1000 models, Milan New York winter 05/06, No 52, April 2005 and Collezioni Donna, Prêt-à-porter autumn-winter 2005 2006, No 107. Finnish craft magazines in this study were MODA s issues 4/2005, 5/2005, 6/2005 and Novita s issues autumn 2005, winter 2005 and Suuri Käsityölehti s issues 8/2005, 9/2005, 10/2005. For the base of the analyze I took themes from the trend book. From fashion magazines I searched knitwear designs and these designs were sorted out by themes of trend book. To this trend and fashion material I compared knit designs from craft magazines. I analyzed how fashion trends show in knit designs and how they are modified. I also studied what features of trends were shown and which did not appear in knit designs of the craft magazines. For analyzing trend pictures and knit designs in craft magazines I applied qualitative content analysis and image analysis. According to the results of this research, effects of trend can be recognized in knit designs of craft maga-zines, although the fashion trends have been applied very discreetly. Knit designs were very similar re-gardless of magazine. The craft magazine data included approximately as many designs from Novita and MODA. In Suuri Käsityölehti provided only fifth of the designs data. There were also designs in MODA and Suuri Käsityölehti, which were made of Novita s yarns. This research material includes yarns of 15 different yarn manufacturers. Although half of all knit designs were knitted from Novita s yarn. There were 10 different yarns from Novita. Nevertheless Novita s yarn called Aino was the most popular. Finnish craft magazines have not respond to popularity of knitting. Magazines do not provide any novelty designs for knitters. Knit designs in Finnish craft magazines are usually practical basic designs without any innovativeness.
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"I want there now!" Images of the future in the drawings of Ghanaian, British, Finnish and Tanzanian children The aim of the Thesis is to examine what kind of images children aged between 8 and 12 years in Ghana, Great Britain, Finland and Tanzania hold of their future. The study is a qualitative analysis based on data that consists of 214 drawings, digitally photographed and analysed using AtlasTI computer program. The data was coded and divided into " families " whose frequencies were compared in order to maintain results. The assignment was given to the children in the language used in the school and it was similar in each country. The children were introduced to the idea with a set of stimulating questions and after that they were asked to draw and colour with a pen a picture of 1) him/herself as an adult, 2) his/her future home and 3) the people and the animals they think they will be living with. The children were also asked to write down the country and the place they believe to live in their future. They were also encouraged to write down e.g. their dream profession, what they would like to have as hobbies in their adulthood and other important things in their lives. The analysis focuses on the content of the drawings instead of artistic or psychological interpretations. The differences between the drawings from different countries as well as the differences in a single country were significant. The current trends and the experiences children had lived through were present in the drawings. There were no differences in the colour of the skin and the most popular professions were doctor, police and football player. The football was very strongly present in all of the data; almost fourth of the children had either drawn or mentioned football as their future profession or hobby. Different flora was present in 84% of Tanzanian and 70% of Ghanaian drawings compared to the 23% of British and 17% of Finnish drawings. Of all the family forms a dream of the traditional nuclear family could be found among 29% of the drawings. Compared to that a total of 30% wanted either a child of their own without a spouse (15%) or a spouse without a child (15%). Also grandparents, childhood friends, other adults, animals or even space aliens were present and sharing a home with the children in the drawings. Of all children 15% wanted to live totally alone in the future. This was most typical (38%) among the Finnish boys. The cat and the dog were the most popular animals to appear in the drawings. Moving abroad proved to be purely a western phenomenon, dreamed by 57% of the British and 18% of the Finnish children. As results, a negative self-image, violence, lack of expressions of positive feelings and solitude among the Finnish boys in the data were very concerning. Keywords: Images of the future, future studies, future-education, picture analysis
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In this thesis, taking place within the clothing industry of Finland, the impact of the globalisation of the economy on the pattern maker s job was studied and the present day fields of know-how of the job were found out. The thesis answers the questions, what are the characteristics of the patternmaker s job nowadays, and what areas of the know-how in the patternmaker s job form the core know-how, which is repeated in every organisation. Earlier studies of the subject do not exist in Finland. Similar studies have been made in USA (Staples 1993) and in Estonia (2002). Patternmakers who took part in this study were located in the Finnish clothing companies manufacturing or having clothes manufactured in series production, like clothing industry or chain of stores. A methodical triangulation was used in the thesis. In a phenomenological research of experience seven patternmakers were interviewed and in a quantitative research 26 patternmakers filled in a structured questionnaire. The phenomenological analysis has 2 parts. In the first phase using the professional background of the patternmakers, the historical development of the clothing industry for the last 40 years was described. In the second phase of the phenomenological analysis the description of the patternmaker s job was created based on the organisational strategy of the companies nowadays. The analysis of quantitative research material was performed by one-dimensional study of variables, where the variations in the amounts of variables lead to proportional conclusions. As a result of the structured questionnaire, the core know-how of the patternmaker was pointed out. In the thesis, the concept of situationality was used to describe the continuous change in the clothing industry. This explains the continuous requirement of patternmakers commitment to the time and location. The researcher has a background of a patternmaker and she works as a specialist instructor. With the thesis the researcher updates her professional competence. The analysis of the patternmaker s job can be used to update the content of patternmakers education in the vocational schools.
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Knowledge of healthy food does not move alone our food choice. One also needs a piece of tongue evidence that food tastes good. Way to eat is part of our lifestyle. It is important to eat same foods with one`s friend. Aims: The overall aim of this study was to find out how youngsters themselves feel and sense of the school lunch, both food and whole lunch situation. This study has three specific research problems. The research problems are: 1. How the youngsters sense their school lunch events? 2. How the youngsters experience the physical conditions of their school lunch events? 3. How the youngsters think their lunch events could be changed? Methods: The data is collected in spring 2009 from two secondary school at the Kaarina city. The respondents were ninth grader. They were studying optional home economics classes. The number of respondents was 28 pupils. The respondents wrote a story, describing what kind of their school lunch situation should be. The story was based on youngsters own vision of school lunch situations. In this study the material is collected by the narrative method and the stories were analyzed with qualitative content analysis. Results and conclusions: According to the results these youngsters wanted their lunch to be more cosier and also more quiet. School lunches should be the moment when they can eat in peace and at the same talk with their friends in the pleasant surroundings. The food selection should be more varied, including both salad and main food as well as bread.
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The Finnish instrumental education system is said to be one of the bests in the world. Finnish musicians have become famous and they have gained success all over the world. To produce professional musicians has been the main goal of the whole Finnish instrumental education system for a long time. This has meant that playing an instrument as a hobby has been neglected. The focus of this qualitative study is the culture of instrumental education from the view of amateuring. One of the goals is to describe the Finnish context where music lovers grow up and where they construct their identities. The other aim is to give answers to the question “How can we develop the culture of instrumental education to serve also the needs of amateurs?” The data of this study is narrative. It consists of the stories of five amateurs, who were in their thirties. In the analysis I’ve used two different types of analysis: the analysis of narratives and the content analysis. In the analysis of narratives the stories were seen as narrative identities. Because the main focus of this study is the culture of instrumental education, I used the qualitative content analysis to find out some themes or phenomena which should be improved from the view of amateuring. This study has shown that there are many ways to become a music lover. An essential factor in the construction of an identity of a music lover seems to be a society which values the amateuring. In this study music schools weren’t that kind of societies. The present study reveals that to construct the identities of music lovers should be one of the most important aims of the music education. This means for example that, in practice, instrumental studies could be more activating, there should be more music making in groups, and the evaluation should concentrate on the whole learning process.
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The importance of open discussion with the adopted child and his parents about adoption and ethnicity is often emphasized in adoption literature (Kirk 1964; Grotevant 1999; Carli & Dalen 1999). The child should have the possibility of constructing a harmonious view of himself, which consists of his history before adoption, ethnicity and the social environment’s conception of him. The purpose of this study was to examine the Finnish adoptive parents’ supportive role in relation to their child’s adoptive and ethnic identity and the social environment’s disposition to the child as witnessed by the parents. The first research problem was to find out how the parents support their child’s adoptive identity formation. The second problem was to find out if the parents want to support the child’s ethnic identity. The third problem was regarding the environment’s disposition to the child and family. The hypothesis was that Finnish adoptive parents are well aware of the problems of adoption and they have been well selected, so they have the aspirations and skills to help their child with his identity formation. The focus of this study was on Finnish parents who had adopted internationally, from whom 58 answers were obtained. The data was collected with an Internet based questionnaire. The questions were mostly qualitative. The analysis was directed by the theory, so that the analysis units were obtained from the main questions of international adoption and identity formation. The results expressed that the adoptive parents want to support their child’s adoption identity. They accept their child’s questions regarding his history, and that they did not want to conceal any details about their child’s life, even if they felt that it was a sensitive issue for them. The main problem was that there was no information available on the child’s history. Contact with the biological parents was almost impossible because there was hardly any information on them. Instead the parents were in contact with the children’s home because they felt that it had an important role as the child’s former home. The parents felt that the child’s birth culture was of importance and they mainly offered aspects of it informally daily. Parents who stressed their child’s Finnish identity were concerned that their child would not form a feeling of being Finnish. However, the majority wished that their child would have a multicultural identity. The parents felt that the environment regarded the child positively and the possibility of upcoming problems was tackled by discussing them beforehand with the child and environment.
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In recent years girls’ increased violence has been a topical issue. Including the voices of the girls’ themselves engaged to violent offending is therefore essential. The goal for this research was to make sense of girls’ stance toward violence in the project Restless Cinderellas’ discussion group for violent girls. The methodological approach was ethnographic and the data was collected by using the method of participant observation. Girls’ stance toward violence was explored by asking the data following questions: 1. What is the purpose of violent behaviour? 2. Which issues motivate for violence? 3. What alternatives exist for violent behaviour? In a thick description of research material this study also aimed to chart if there was any change in girls’ attitudes due to participation on violence preventative discussion group. The ethnographic data was extensive and consisted of observations, start, - middle, - and end point group discussion records, fieldnotes, self report-questionnaires and feedback documentary. The four girls that participated on this study were 14 -15- years old by the time of research. They came from one elementary school in the capital region. They were chosen to the group based on NFG’s youth workers interview. The girls were allocated to the group by the school’s student welfare group because of their violent behaviour on school time. The analysis was qualitative and the concepts were created through theory triangulation. These concepts were exploited to exam girls’ violent attitudes. The study shows that violence was used to pitch for justice, lesson and respect. The factors that motivated on using violence were experienced insult, betrayal and concatenation of violence. Alternatives for violence were the circle of success and value consciousness. In the dialectics between the research documentaries some changes in girls’ attitudes heaved into sight. However, the study could not show reliable connection between the changes and participation on discussion group.
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The aim of the study was to get acquainted with the activity of Näppärät Mummot, a Lahti-based crafts society, and its importance to the wellness of the members of the group. The selected aim, i.e., analyzing the wellness, largely affected the whole research process and its results. According to earlier studies in the field, different forms of craft and expressional activity promote one's wellness as well as support the work for one's identity. Based on my theoretical knowledge, my research was set out to: 1) form a general view of crafts culture within Näppärät Mummot and 2) find out how recollective craft that promotes wellness is perceived through communality, experiential activity, work for one's identity, and divided as well as undivided craft. Qualitative field work was governed by ethnographic research strategy, according to which I set out to get thoroughly familiar with the society I was studying. The methods I used to collect data were participant observation and thematic interview. I used a field diary for writing down all data I acquired through the observation. The interviewee group was formed by seven members of Näppärät Mummot. An mp3 recorder was used to record the interviews, which I transcribed later. The method for data analysis was qualitative content analysis, for which I used Weft QDA, a qualitative analysis software application. I formed themes that shed light on research tasks from the data using coding and theory-driven analysis. I kept literature and data I collected in cooperation through the whole analysis process. Lastly, drawing from the classes of meaning of therapeutic craft that I sketched by means of summarizing and classifying, I presented the central concepts that describe the main results of the study. The main results were six concepts that describe Näppärät Mummot's crafts culture and recollective craft with its wellness-beneficial effect: 1) autobiographical craft, 2) shared work for one's identity, 3) shared intention for craft, 4) craft as a partner, 5) individual manner of craft, and 6) shared improvement. Craft promoted wellness in many ways. It was used to promote inner life management in difficult times and it also provided sensations of empowerment through pleasure from craft. Expressional, shared craft also served as means of reinforcing one's identity in various ways. Expressional work for one's identity through autobiographical themes of craft represented rearranging one's life through holistic craft. A personal way of doing things also served as expressional action and work for one's identity even with divided craft. Shared work for identities meant reinforcing the identities of the members through discources of craft and interaction with their close ones. What proves the interconnection between communality and craft as well as their shared meaning is that communality motivated the members to work on their craft projects, while craft served as the means of communication between the members: communication through craft was easier than lingual communication. The results can not be generalized to apply to other groups: they are used to describe the versatile means of recollective craft to promote the well-being among the crafts society Näppärät Mummot. However, the results do introduce a new perspective to the social discussion on how cultural activities promote well-being.
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Tutkimuksen päätarkoitus oli hahmottaa verkko-opetuksen arvoja ja arviointia luokanopettajan näkökulmasta. Teoreettisena viitekehyksenä oli mediakasvatus ja didaktiikan käsitys opetus opiskelu oppimisprosessista. Didaktisena perustana käytettiin Kansasen ym. (2000) opettajan pedagogista ajattelua, Lahdeksen (1997) didaktiikan kehämallia sekä Uljensin (1997) opetus opiskelu oppimisprosessia. Lähtökohtana oli luokanopettajan arvioinnin kautta pohtia opetuksen, opiskelun ja oppimisen sekä tieto- ja viestintätekniikan yhtymistä koulukontekstissa. Tutkimuksen pääongelmat olivat: 1) Minkälainen oli luokanopettajan käsitys verkko-opetuksen toteuttamisesta? 2) Miten luokanopettaja arvioi verkko-opetusta? Myös ensimmäistä pääongelmaa lähestyttiin arvojen ja arvioinnin näkökulmasta. Menetelmänä käytettiin teemahaastattelua. Teemahaastattelun teemoja jäsennettiin Gallinin (2001) sosiokulttuurisen verkko-opetuksen arviointimallin sekä Tellan ja Mononen-Aaltosen (2001) mediakasvatuksen monitasomallin avulla. Aineistonkeruussa kahdeksan helsinkiläistä luokanopettajaa vastasivat lyhyeen kyselyyn, jonka jälkeen heitä haastateltiin välittömästi. Laadullisen aineiston analyysissä teemoiteltiin aineisto, ja tämän rinnalla rakennettiin aineistolähtöistä analyysiä. Näiden vuorovaikutuksesta syntyivät tutkimuksen johtopäätökset. Keskeisinä tuloksina tutkimuksessa nähtiin luokanopettajan verkko-opetukseen liittyvien arvojen kaksi eri näkökulmaa: (A) opetus opiskelu oppimismenetelmien ja -tulosten arvonäkökulma sekä (B) ns. kasvatuksellinen ja koulukulttuurin arvonäkökulma. Arvonäkökulmien pohjalta hahmotettiin johtopäätöksissä erilaisia tasoja luokanopettajan opetuksen, opiskelun ja oppimisen arvioinnista, kun tieto- ja viestintätekniikka on mukana prosessissa. Kaksi tasoa tarkennettiin verkko-opetuksen arvioinnin fokuksiksi, jotka olivat (1) teknologinen ja (2) tavoitteinen fokus. Teknologisessa arvioinnin fokuksessa (1) arviointia hallitsee huoli oppilaasta ihmisenä. Arviointi liittyy joko siihen, että oppilaan on opittava perustaidot tieto- ja viestintätekniikassa ja ymmärrettävä Internetin mahdollisuudet, tai siihen, että opettaja pyrkii suojelemaan lapsia Internetin uhkilta ja liialliselta altistumiselta esimerkiksi digitaalisille peleille. Verkko-opetuksen tavoitteinen arvioinnin fokus (2) nojaa siihen, minkälaisia tavoitteita luokanopettaja yleisesti asettaa opetukselleen, vaikka tieto- ja viestintätekniikka ei liittyisikään prosessiin. Fokuksen taustalla on myös mediakasvatuksen näkökulma tieto- ja viestintätekniikan opetuskäyttöön, jolloin keskeistä on, että opetuksen suunnittelu ja arviointi ei lähde teknologiasta käsin vaan didaktiikasta ja peda-gogisista arvoista. Verkko-opetuksen arvioinnin fokusten voidaan nähdä täydentävän toisiaan. Fokusten varioinnissa voidaan puhua luokanopettajan kohdalla todellisesta mediataidosta, joka ulottuu yli ammatillisen pätevyyden aina opettajan henkilökohtaiseen kehittymisen kaareen. Avainsanat: Verkko-opetus, arvot, arviointi, opetus-opiskelu-oppimisprosessi, opettajan pedagoginen ajattelu, tieto- ja viestintätekniikan opetuskäyttö Keywords: Network-Based Education (NBE), values, evaluation, teaching-studying-learning process, teacher's pedagogical thinking, educational use of information and communication technologies (ICT)
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Drug Analysis without Primary Reference Standards: Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material Primary reference standards for new drugs, metabolites, designer drugs or rare substances may not be obtainable within a reasonable period of time or their availability may also be hindered by extensive administrative requirements. Standards are usually costly and may have a limited shelf life. Finally, many compounds are not available commercially and sometimes not at all. A new approach within forensic and clinical drug analysis involves substance identification based on accurate mass measurement by liquid chromatography coupled with time-of-flight mass spectrometry (LC-TOFMS) and quantification by LC coupled with chemiluminescence nitrogen detection (LC-CLND) possessing equimolar response to nitrogen. Formula-based identification relies on the fact that the accurate mass of an ion from a chemical compound corresponds to the elemental composition of that compound. Single-calibrant nitrogen based quantification is feasible with a nitrogen-specific detector since approximately 90% of drugs contain nitrogen. A method was developed for toxicological drug screening in 1 ml urine samples by LC-TOFMS. A large target database of exact monoisotopic masses was constructed, representing the elemental formulae of reference drugs and their metabolites. Identification was based on matching the sample component s measured parameters with those in the database, including accurate mass and retention time, if available. In addition, an algorithm for isotopic pattern match (SigmaFit) was applied. Differences in ion abundance in urine extracts did not affect the mass accuracy or the SigmaFit values. For routine screening practice, a mass tolerance of 10 ppm and a SigmaFit tolerance of 0.03 were established. Seized street drug samples were analysed instantly by LC-TOFMS and LC-CLND, using a dilute and shoot approach. In the quantitative analysis of amphetamine, heroin and cocaine findings, the mean relative difference between the results of LC-CLND and the reference methods was only 11%. In blood specimens, liquid-liquid extraction recoveries for basic lipophilic drugs were first established and the validity of the generic extraction recovery-corrected single-calibrant LC-CLND was then verified with proficiency test samples. The mean accuracy was 24% and 17% for plasma and whole blood samples, respectively, all results falling within the confidence range of the reference concentrations. Further, metabolic ratios for the opioid drug tramadol were determined in a pharmacogenetic study setting. Extraction recovery estimation, based on model compounds with similar physicochemical characteristics, produced clinically feasible results without reference standards.
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Clinical trials have shown that weight reduction with lifestyles can delay or prevent diabetes and reduce blood pressure. An appropriate definition of obesity using anthropometric measures is useful in predicting diabetes and hypertension at the population level. However, there is debate on which of the measures of obesity is best or most strongly associated with diabetes and hypertension and on what are the optimal cut-off values for body mass index (BMI) and waist circumference (WC) in this regard. The aims of the study were 1) to compare the strength of the association for undiagnosed or newly diagnosed diabetes (or hypertension) with anthropometric measures of obesity in people of Asian origin, 2) to detect ethnic differences in the association of undiagnosed diabetes with obesity, 3) to identify ethnic- and sex-specific change point values of BMI and WC for changes in the prevalence of diabetes and 4) to evaluate the ethnic-specific WC cutoff values proposed by the International Diabetes Federation (IDF) in 2005 for central obesity. The study population comprised 28 435 men and 35 198 women, ≥ 25 years of age, from 39 cohorts participating in the DECODA and DECODE studies, including 5 Asian Indian (n = 13 537), 3 Mauritian Indian (n = 4505) and Mauritian Creole (n = 1075), 8 Chinese (n =10 801), 1 Filipino (n = 3841), 7 Japanese (n = 7934), 1 Mongolian (n = 1991), and 14 European (n = 20 979) studies. The prevalence of diabetes, hypertension and central obesity was estimated, using descriptive statistics, and the differences were determined with the χ2 test. The odds ratios (ORs) or coefficients (from the logistic model) and hazard ratios (HRs, from the Cox model to interval censored data) for BMI, WC, waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) were estimated for diabetes and hypertension. The differences between BMI and WC, WHR or WSR were compared, applying paired homogeneity tests (Wald statistics with 1 df). Hierarchical three-level Bayesian change point analysis, adjusting for age, was applied to identify the most likely cut-off/change point values for BMI and WC in association with previously undiagnosed diabetes. The ORs for diabetes in men (women) with BMI, WC, WHR and WSR were 1.52 (1.59), 1.54 (1.70), 1.53 (1.50) and 1.62 (1.70), respectively and the corresponding ORs for hypertension were 1.68 (1.55), 1.66 (1.51), 1.45 (1.28) and 1.63 (1.50). For diabetes the OR for BMI did not differ from that for WC or WHR, but was lower than that for WSR (p = 0.001) in men while in women the ORs were higher for WC and WSR than for BMI (both p < 0.05). Hypertension was more strongly associated with BMI than with WHR in men (p < 0.001) and most strongly with BMI than with WHR (p < 0.001), WSR (p < 0.01) and WC (p < 0.05) in women. The HRs for incidence of diabetes and hypertension did not differ between BMI and the other three central obesity measures in Mauritian Indians and Mauritian Creoles during follow-ups of 5, 6 and 11 years. The prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others, given the same BMI or WC category. The coefficients for diabetes in BMI (kg/m2) were (men/women): 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for Asian Indian, Chinese, Japanese, Mauritian Indian and European (overall homogeneity test: p > 0.05 in men and p < 0.001 in women). Similar results were obtained in WC (cm). Asian Indian women had lower coefficients than women of other ethnicities. The change points for BMI were 29.5, 25.6, 24.0, 24.0 and 21.5 in men and 29.4, 25.2, 24.9, 25.3 and 22.5 (kg/m2) in women of European, Chinese, Mauritian Indian, Japanese, and Asian Indian descent. The change points for WC were 100, 85, 79 and 82 cm in men and 91, 82, 82 and 76 cm in women of European, Chinese, Mauritian Indian, and Asian Indian. The prevalence of central obesity using the 2005 IDF definition was higher in Japanese men but lower in Japanese women than in their Asian counterparts. The prevalence of central obesity was 52 times higher in Japanese men but 0.8 times lower in Japanese women compared to the National Cholesterol Education Programme definition. The findings suggest that both BMI and WC predicted diabetes and hypertension equally well in all ethnic groups. At the same BMI or WC level, the prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others. Ethnic- and sex-specific change points of BMI and WC should be considered in setting diagnostic criteria for obesity to detect undiagnosed or newly diagnosed diabetes.
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Objective and background. Tobacco smoking, pancreatitis and diabetes mellitus are the only known causes of pancreatic cancer, leaving ample room for yet unidentified determinants. This is an empirical study on a Finnish data on occupational exposures and pancreatic cancer risk, and a non-Bayesian and a hierarchical Bayesian meta-analysis of data on occupational factors and pancreatic cancer. Methods. The case-control study analyzed 595 incident cases of pancreatic cancer and 1,622 controls of stomach, colon, and rectum cancer, diagnosed 1984-1987 and known to be dead by 1990 in Finland. The next-of-kin responded to a mail questionnaire on job and medical histories and lifestyles. Meta-analysis of occupational risk factors of pancreatic cancer started off with 1,903 identified studies. The analyses were based on different subsets of that database. Five epidemiologists examined the reports and extracted the pertinent data using a standardized extraction form that covered 20 study descriptors and the relevant relative risk estimates. Random effects meta-analyses were applied for 23 chemical agents. In addition, hierarchical Bayesian models for meta-analysis were applied to the occupational data of 27 job titles using job exposure matrix as a link matrix and estimating the relative risks of pancreatic cancer associated with nine occupational agents. Results. In the case-control study, logistic regressions revealed excess risks of pancreatic cancer associated with occupational exposures to ionizing radiation, nonchlorinated solvents, and pesticides. Chlorinated hydrocarbon solvents and related compounds, used mainly in metal degreasing and dry cleaning, are emerging as likely risk factors of pancreatic cancer in the non-Bayesian and the hierarchical Bayesian meta-analysis. Consistent excess risk was found for insecticides, and a high excess for nickel and nickel compounds in the random effects meta-analysis but not in the hierarchical Bayesian meta-analysis. Conclusions. In this study occupational exposure to chlorinated hydrocarbon solvents and related compounds and insecticides increase risk of pancreatic cancer. Hierarchical Bayesian meta-analysis is applicable when studies addressing the agent(s) under study are lacking or very few, but several studies address job titles with potential exposure to these agents. A job-exposure matrix or a formal expert assessment system is necessary in this situation.
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In genetic epidemiology, population-based disease registries are commonly used to collect genotype or other risk factor information concerning affected subjects and their relatives. This work presents two new approaches for the statistical inference of ascertained data: a conditional and full likelihood approaches for the disease with variable age at onset phenotype using familial data obtained from population-based registry of incident cases. The aim is to obtain statistically reliable estimates of the general population parameters. The statistical analysis of familial data with variable age at onset becomes more complicated when some of the study subjects are non-susceptible, that is to say these subjects never get the disease. A statistical model for a variable age at onset with long-term survivors is proposed for studies of familial aggregation, using latent variable approach, as well as for prospective studies of genetic association studies with candidate genes. In addition, we explore the possibility of a genetic explanation of the observed increase in the incidence of Type 1 diabetes (T1D) in Finland in recent decades and the hypothesis of non-Mendelian transmission of T1D associated genes. Both classical and Bayesian statistical inference were used in the modelling and estimation. Despite the fact that this work contains five studies with different statistical models, they all concern data obtained from nationwide registries of T1D and genetics of T1D. In the analyses of T1D data, non-Mendelian transmission of T1D susceptibility alleles was not observed. In addition, non-Mendelian transmission of T1D susceptibility genes did not make a plausible explanation for the increase in T1D incidence in Finland. Instead, the Human Leucocyte Antigen associations with T1D were confirmed in the population-based analysis, which combines T1D registry information, reference sample of healthy subjects and birth cohort information of the Finnish population. Finally, a substantial familial variation in the susceptibility of T1D nephropathy was observed. The presented studies show the benefits of sophisticated statistical modelling to explore risk factors for complex diseases.
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Intracranial artery aneurysms (IAs) are estimated to be present in 2.3% of the population. A rupture of an IA causes subarachnoid hemorrhage, with up to 50% mortality. The annual low rupture risk of an IA indicates that most IAs never rupture. The current treatment options are invasive and somewhat risky. Thus rupture-prone IAs should be identified and this requires a better understanding of the IA wall pathobiology. Inflammatory cell infiltrations have been found to precede IA rupture, indicating the role of inflammation in IA wall degeneration and rupture. The complement system is a key mediator of inflammation and house-hold processing of injured tissue. This study aimed at identifying the role of complement activation in IA wall degeneration and the complement activators involved and determining how the complement system is regulated in the IA wall. In immunostainings, the end-product of complement activation, the terminal complement complex (TCC), was located mainly in the outer part of the IA wall, in areas that had also sustained loss of cells. In electron microscopy, the area of maximum TCC accumulation contained cellular debris and evidence of both apoptotic and necrotic cell death. Complement activation correlated with IA wall degeneration and rupture, de-endothelialization, and T-cell and CD163-positive macrophage infiltration. The complement system was found to become activated in all IAs by the classical pathway, with recruitment of alternative pathway amplification. Of the potential activators immunoglobulins G and M and oxidatively modified lipids were found in large areas. Lipid accumulation was observed to clearly colocalize with TCC and C-reactive protein. In the luminal parts of the IA wall, complement activation was limited by cellular expression of protectin (CD59) and extracellular matrix-bound inhibitors, C4b binding protein and factor H whereas the outer part of the wall lacked cells expressing protectin as well as matrix-bound factor H. In single nucleotide polymorphism-analysis, age-related macular degeneration-associated factor H Y402H polymorphism did not associate with the presence of IAs or their rupture The data suggest that complement activation and TCC formation are involved in IA wall degeneration and rupture. Complement seems to become activated by more than one specific activator. The association of complement with de-endothelialization and expression of several complement activators indicate a possible role of endothelial dysfunction and/or impaired clearance mechanisms. Impaired complement regulation seems to be associated with increased complement activation in IA walls. These results stress the role of chronic inflammation in IA wall pathobiology and the regulatory role of complement within this process. Imaging inflammation would possibly enhance the diagnostics of rupture-prone IAs, and targeting IA treatment to prevent chronic inflammation might improve IA treatment in the future.
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Infection by Epstein-Barr virus (EBV) occurs in approximately 95% of the world s population. EBV was the first human virus implicated in oncogenesis. Characteristic for EBV primary infection are detectable IgM and IgG antibodies against viral capsid antigen (VCA). During convalescence the VCA IgM disappears while the VCA IgG persists for life. Reactivations of EBV occur both among immunocompromised and immunocompetent individuals. In serological diagnosis, measurement of avidity of VCA IgG separates primary from secondary infections. However, in serodiagnosis of mononucleosis it is quite common to encounter, paradoxically, VCA IgM together with high-avidity VCA IgG, indicating past immunity. We determined the etiology of this phenomenon and found that, among patients with cytomegalovirus (CMV) primary infection a large proportion (23%) showed antibody profiles of EBV reactivation. In contrast, EBV primary infection did not appear to induce immunoreactivation of CMV. EBV-associated post-transplant lymphoproliferative disease (PTLD) is a life threatening complication of allogeneic stem cell or solid organ transplantation. PTLD may present with a diverse spectrum of clinical symptoms and signs. Due to rapidity of PTLD progression especially after stem cell transplantation, the diagnosis must be obtained quickly. Pending timely detection, the evolution of the fatal disease may be halted by reduction of immunosuppression. A promising new PTLD treatment (also in Finland) is based on anti-CD-20 monoclonal antibodies. Diagnosis of PTLD has been demanding because of immunosuppression, blood transfusions and the latent nature of the virus. We set up in 1999 to our knowledge first in Finland for any microbial pathogen a real-time quantitative PCR (qPCR) for detection of EBV DNA in blood serum/plasma. In addition, we set up an in situ hybridisation assay for EBV RNA in tissue sections. In collaboration with a group of haematologists at Helsinki University Central Hospital we retrospectively determined the incidence of PTLD among 257 allogenic stem cell transplantations (SCT) performed during 1994-1999. Post-mortem analysis revealed 18 cases of PTLD. From a subset of PTLD cases (12/18) and a series of corresponding controls (36), consecutive samples of serum were studied by the new EBV-qPCR. All the PTLD patients were positive for EBV-DNA with progressively rising copy numbers. In most PTLD patients EBV DNA became detectable within 70 days of SCT. Of note, the appearance of EBV DNA preceded the PTLD symptoms (fever, lymphadenopathy, atypical lymphocytes). Among the SCT controls, EBV DNA occurred only sporadically, and the EBV-DNA levels remained relatively low. We concluded that EBV qPCR is a highly sensitive (100%) and specific (96%) new diagnostic approach. We also looked for and found risk factors for the development of PTLD. Together with a liver transplantation group at the Transplantation and Liver Surgery Clinic we wanted to clarify how often and how severely do EBV infections occur after liver transplantation. We studied by the EBV qPCR 1284 plasma samples obtained from 105 adult liver transplant recipients. EBV DNA was detected in 14 patients (13%) during the first 12 months. The peak viral loads of 13 asymptomatic patients were relatively low (<6600/ml), and EBV DNA subsided quickly from circulation. Fatal PTLD was diagnosed in one patient. Finally, we wanted to determine the number and clinical significance of EBV infections of various types occurring among a large, retrospective, nonselected cohort of allogenic SCT recipients. We analysed by EBV qPCR 5479 serum samples of 406 SCT recipients obtained during 1988-1999. EBV DNA was seen in 57 (14%) patients, of whom 22 (5%) showed progressively rising and ultimately high levels of EBV DNA (median 54 million /ml). Among the SCT survivors, EBV DNA was transiently detectable in 19 (5%) asymptomatic patients. Thereby, low-level EBV-DNA positivity in serum occurs relatively often after SCT and may subside without specific treatment. However, high molecular copy numbers (>50 000) are diagnostic for life-threatening EBV infection. We furthermore developed a mathematical algorithm for the prediction of development of life-threatening EBV infection.