Analyzing changes in macro-level drivers of country-specific emissions : The role of consumption, technology and trade

Industrial ecology is an important field of sustainability science. It can be applied to study environmental problems in a policy relevant manner. Industrial ecology uses ecosystem analogy; it aims at closing the loop of materials and substances and at the same time reducing resource consumption and environmental emissions. Emissions from human activities are related to human interference in material cycles. Carbon (C), nitrogen (N) and phosphorus (P) are essential elements for all living organisms, but in excess have negative environmental impacts, such as climate change (CO2, CH4 N2O), acidification (NOx) and eutrophication (N, P). Several indirect macro-level drivers affect emissions change. Population and affluence (GDP/capita) often act as upward drivers for emissions. Technology, as emissions per service used, and consumption, as economic intensity of use, may act as drivers resulting in a reduction in emissions. In addition, the development of country-specific emissions is affected by international trade. The aim of this study was to analyse changes in emissions as affected by macro-level drivers in different European case studies. ImPACT decomposition analysis (IPAT identity) was applied as a method in papers I III. The macro-level perspective was applied to evaluate CO2 emission reduction targets (paper II) and the sharing of greenhouse gas emission reduction targets (paper IV) in the European Union (EU27) up to the year 2020. Data for the study were mainly gathered from official statistics. In all cases, the results were discussed from an environmental policy perspective. The development of nitrogen oxide (NOx) emissions was analysed in the Finnish energy sector during a long time period, 1950 2003 (paper I). Finnish emissions of NOx began to decrease in the 1980s as the progress in technology in terms of NOx/energy curbed the impact of the growth in affluence and population. Carbon dioxide (CO2) emissions related to energy use during 1993 2004 (paper II) were analysed by country and region within the European Union. Considering energy-based CO2 emissions in the European Union, dematerialization and decarbonisation did occur, but not sufficiently to offset population growth and the rapidly increasing affluence during 1993 2004. The development of nitrogen and phosphorus load from aquaculture in relation to salmonid consumption in Finland during 1980 2007 was examined, including international trade in the analysis (paper III). A regional environmental issue, eutrophication of the Baltic Sea, and a marginal, yet locally important source of nutrients was used as a case. Nutrient emissions from Finnish aquaculture decreased from the 1990s onwards: although population, affluence and salmonid consumption steadily increased, aquaculture technology improved and the relative share of imported salmonids increased. According to the sustainability challenge in industrial ecology, the environmental impact of the growing population size and affluence should be compensated by improvements in technology (emissions/service used) and with dematerialisation. In the studied cases, the emission intensity of energy production could be lowered for NOx by cleaning the exhaust gases. Reorganization of the structure of energy production as well as technological innovations will be essential in lowering the emissions of both CO2 and NOx. Regarding the intensity of energy use, making the combustion of fuels more efficient and reducing energy use are essential. In reducing nutrient emissions from Finnish aquaculture to the Baltic Sea (paper III) through technology, limits of biological and physical properties of cultured fish, among others, will eventually be faced. Regarding consumption, salmonids are preferred to many other protein sources. Regarding trade, increasing the proportion of imports will outsource the impacts. Besides improving technology and dematerialization, other viewpoints may also be needed. Reducing the total amount of nutrients cycling in energy systems and eventually contributing to NOx emissions needs to be emphasized. Considering aquaculture emissions, nutrient cycles can be partly closed through using local fish as feed replacing imported feed. In particular, the reduction of CO2 emissions in the future is a very challenging task when considering the necessary rates of dematerialisation and decarbonisation (paper II). Climate change mitigation may have to focus on other greenhouse gases than CO2 and on the potential role of biomass as a carbon sink, among others. The global population is growing and scaling up the environmental impact. Population issues and growing affluence must be considered when discussing emission reductions. Climate policy has only very recently had an influence on emissions, and strong actions are now called for climate change mitigation. Environmental policies in general must cover all the regions related to production and impacts in order to avoid outsourcing of emissions and leakage effects. The macro-level drivers affecting changes in emissions can be identified with the ImPACT framework. Statistics for generally known macro-indicators are currently relatively well available for different countries, and the method is transparent. In the papers included in this study, a similar method was successfully applied in different types of case studies. Using transparent macro-level figures and a simple top-down approach are also appropriate in evaluating and setting international emission reduction targets, as demonstrated in papers II and IV. The projected rates of population and affluence growth are especially worth consideration in setting targets. However, sensitivities in calculations must be carefully acknowledged. In the basic form of the ImPACT model, the economic intensity of consumption and emission intensity of use are included. In seeking to examine consumption but also international trade in more detail, imports were included in paper III. This example demonstrates well how outsourcing of production influences domestic emissions. Country-specific production-based emissions have often been used in similar decomposition analyses. Nevertheless, trade-related issues must not be ignored.

Obstetric and gynaecological aspects of HIV infection

The purpose of the present study was to examine the outcome of pregnancies among HIV-infected women in Helsinki, use of the levonorgestrel-releasing intrauterine system (LNG-IUS) among HIV-infected women and the prevalence and risk factors of cytological and histologically proven cervical lesions in this population. Between 1993 and 2003 a total of 45 HIV-infected women delivered 52 singleton infants. HIV infection was diagnosed during pregnancy in 40% of the mothers. Seventeen of the mothers received antiretroviral (ARV) medication prior to pregnancy and in 34 cases, the medication was started during pregnancy. A good virological response (i.e. HIV RNA load <1000/mL during the last trimester) to ARV medication was achieved in 36/40 (90%) of the patients in whom HI viral load measurements were performed. Of the infants, 92% were born at term, and their mean (±SD) birth weight was 3350±395 g. The Caesarean section rate was low, 25%. All newborns received ARV medication and none of the infants born to mothers with pre-delivery diagnosis of maternal HIV infection were infected. The safety and advantages of the LNG-IUS were studied prospectively (n=12) and retrospectively (n=6). The LNG-IUS was well tolerated and no cases of PID or pregnancy were noted. Menstrual bleeding was reduced significantly during use of the LNG-IUS; this was associated with a slight increase in haemoglobin levels. Serum oestradiol concentrations remained in the follicular range in all subjects. The key finding was that genital shedding of HIV RNA did not change after the insertion of the LNG-IUS. The mean annual prevalence of low-grade squamous intraepithelial lesions (SIL) was 15% and that of high-grade SIL was 5% among 108 systematically followed HIV-infected women during 1989 2003. A reduced CD4 lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection, use of ARV medication and HI viral load were not. The cumulative risk of any type of SIL was 17% after one year and 48% after five years among patients with initially normal Pap smears. The risk of developing SIL was associated with young age and a high initial HI viral load. During the follow-up 51 subjects (n=153) displayed cervical intraepithelial neoplasia (CIN), (16% CIN1 and 18% CIN 2-3). Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN. Both nulliparity (p<0.01) and bacterial vaginosis (p<0.04) emerged as significant risk factors of CIN. In conclusion, a combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV. Use of the LNG-IUS is safe among HIV-infected women and cervicovaginal shedding of HIV RNA is not affected by use of the LNG-IUS. The risk of cervical pre-malignant lesions is high among HIV-infected women despite systematic follow-up.

The paribhasas arthavadgrahane nanarthakasya, laksanapratipadoktayoh pratipadoktasyaiva grahanam and ekadesavikrtam ananyavat : Studies on some Metarules in Paninian system

In his grammatical treatise, the Astadhyayi, Panini includes sutras that state guiding rules for the right interpretation and application of his other directly grammatical sutras. These sutras are called paribhasas. In addition to these paribhasas, the various commentaries on Panini frequently invoke supplementary paribhasas which are not stated explicitly in his Astadhyayi. These paribhasas have been a subject of study since early times after Panini and have also occupied modern scholars on Panini s grammar. In regard to most of them, it remains unsettled even today whether they are used in the Astadhyayi, where they apply, what is their role, and whether they are necessary in arriving at the desired grammatical form. Some scholars go even further and argue that none of such paribhasas were intended by Panini. This study aims to settle this question by dealing with three such of these paribhasas individually considering all the information available in the commentaries in their regard and examining the cases in which, according to commentaries, the paribhasas apply. I select the paribhasas arthavadgrahane nanarthakasya, laksanapratipadoktayoh pratipadoktasyaiva grahanam and ekadesavikrtam ananyavat, which are all considered nyayasiddha or lokanyayasiddha; they express logical and obvious principles which are found in daily life. On this basis, Paniniyas explain why Panini did not mention them in the Astadhyayi. I discuss each paribhasa separately and all the issues it involves. I present and explain the cases where the specified paribhasas are invoked in the major commentaries, the Mahabhasya, the Kasika and the Siddhantakaumudi and the arguments found in the commentaries concerning these cases. If available, I supply other solutions to the difficulties for which these paribhasas are invoked. The study aims to make the issue of these paribhasas clearer, which will help us to reach a solution to the key question, that is, whether Panini has presupposed them in his Astadhyayi. My study shows that Panini has presupposed the paribhasa ekadesavikrtam ananyavat (or a similar principle). He also may have used the paribhasa arthavadgrahane nanarthakasya (or a similar principle) as this paribhasa does not lead to undesired results. As for the paribhasa laksanapratipadoktayoh pratipadoktasyaiva grahanam (or a similar principle), the original scope of this paribhasa was clearly extended by later Paniniyas. Moreover, their interpretation of this paribhasa conflicts with Panini s procedure. If Panini has used this paribhasa, he has used it in a very limited way.

Convex-transitive Banach spaces and their hyperplanes

The topic of this dissertation is the geometric and isometric theory of Banach spaces. This work is motivated by the known Banach-Mazur rotation problem, which asks whether each transitive separable Banach space is isometrically a Hilbert space. A Banach space X is said to be transitive if the isometry group of X acts transitively on the unit sphere of X. In fact, some weaker symmetry conditions than transitivity are studied in the dissertation. One such condition is an almost isometric version of transitivity. Another investigated condition is convex-transitivity, which requires that the closed convex hull of the orbit of any point of the unit sphere under the rotation group is the whole unit ball. Following the tradition developed around the rotation problem, some contemporary problems are studied. Namely, we attempt to characterize Hilbert spaces by using convex-transitivity together with the existence of a 1-dimensional bicontractive projection on the space, and some mild geometric assumptions. The convex-transitivity of some vector-valued function spaces is studied as well. The thesis also touches convex-transitivity of Banach lattices and resembling geometric cases.

The effects of habitat edges and trampling intensity on vegetation in urban forests

Although changes in urban forest vegetation have been documented in previous Finnish studies, the reasons for these changes have not been studied explicitly. Especially, the consequences of forest fragmentation, i.e. the fact that forest edges receive more solar radiation, wind and air-borne nutrients than interiors have been ignored. In order to limit the change in urban forest vegetation we need to know why it occurs. Therefore, the effects of edges and recreational use of urban forests on vegetation were investigated together in this thesis to reveal the relative strengths of these effects and to provide recommendations for forest management. Data were collected in the greater Helsinki area (in the cities of Helsinki, Vantaa and Espoo, and in the municipalities of Sipoo and Tuusula) and in the Lahti region (in the city of Lahti and in the municipality of Hollola) by means of systematic and randomized vegetation and soil sampling and tree measurements. Sample plots were placed from the forest edges to the interiors to investigate the effects of forest edges, and on paths of different levels of wear and off these paths to investigate the effects of trampling. The natural vegetation of mesic and sub-xeric forest site types studied was sensitive both to the effects of the edge and to trampling. The abundances of dwarf shrubs and bryophytes decreased, while light- and nitrogen-demanding herbs and grasses - and especially Sorbus aucuparia – were favoured at the edges and next to the paths. Results indicated that typical forest site types at the edges are changing toward more nitrophilic vegetation communities. Covers of the most abundant forest species decreased considerably – even tens of percentages – from interiors to the edges indicating strong edge effects. These effects penetrated at least up to 50 m from the forest edges into the interiors, especially at south to west facing open edges. The effects of trampling were pronounced on paths and even low levels of trampling decreased the abundances of certain species considerably. The effects of trampling extended up to 8 m from path edges. Results showed that the fragmentation of urban forest remnants into small and narrow patches should be avoided in order to maintain natural forest understorey vegetation in the urban setting. Thus, urban forest fragments left within urban development should be at least 3 ha in size, and as circular as possible. Where the preservation of representative original forest interior vegetation is a management aim, closed edges with conifers can act as an effective barrier against solar radiation, wind and urban load, thereby restricting the effects of the edge. Tree volume at the edge should be at least 225-250 m3 ha-1 and the proportion of conifers (especially spruce) 80% or more of the tree species composition. Closed, spruce-dominated edges may also prevent the excessive growth of S. aucuparia saplings at urban forest edges. In addition, closed edges may guide people’s movements to the maintained paths, thus preventing the spontaneous creation of dense path networks. In urban areas the effects of edges and trampling on biodiversity may be considerable, and are important to consider when the aim of management is to prevent the development of homogeneous herb-grass dominated vegetation communities, as was observed at the investigated edges.

Health-Related Quality of Life, Costs and Treatment of Inflammatory Rheumatic Diseases in Routine Practice : With special emphasis on biological drugs

Rheumatoid arthritis (RA) and other chronic inflammatory joint diseases already begin to affect patients health-related quality of life (HRQoL) in the earliest phases of these diseases. In treatment of inflammatory joint diseases, the last two decades have seen new strategies and treatment options introduced. Treatment is started at an earlier phase; combinations of disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroids are used; and in refractory cases new drugs such as tumour necrosis factor (TNF) inhibitors or other biologicals can be started. In patients with new referrals to the Department of Rheumatology of the Helsinki University Central Hospital, we evaluated the 15D and the Stanford Health Assessment Questionnaire (HAQ) results at baseline and approximately 8 months after their first visit. Altogether the analysis included 295 patients with various rheumatic diseases. The mean baseline 15D score (0.822, SD 0.114) was significantly lower than for the age-matched general population (0.903, SD 0.098). Patients with osteoarthritis (OA) and spondyloarthropathies (SPA) reported the poorest HRQoL. In patients with RA and reactive arthritis (ReA) the HRQoL improved in a statistically significant manner during the 8-month follow-up. In addition, a clinically important change appeared in patients with systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. In a study of 97 RA patients treated either with etanercept or adalimumab, we assessed their HRQoL with the RAND 36-Item Health Survey 1.0 (RAND-36) questionnaire. We also analysed changes in clinical parameters and the HAQ. With etanercept and adalimumab, the values of all domains in the RAND-36 questionnaire increased during the first 3 months. The efficacy of each in improving HRQoL was statistically significant, and the drug effects were comparable. Compared to Finnish age- and sex-matched general population values, the HRQoL of the RA patients was significantly lower at baseline and, despite the improvement, remained lower also at follow-up. Our RA patients had long-standing and severe disease that can explain the low HRQoL also at follow-up. In a pharmacoeconomic study of patients treated with infliximab we evaluated medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment. Clinical and economic data for 96 patients with different arthritis diagnoses showed, in all patients, significantly improved clinical and laboratory variables. However, the medical costs increased significantly during the second period by 12 015 (95% confidence interval, 6 496 to 18 076). Only a minimal decrease in work disability costs occurred mean decrease 130 (-1 268 to 1 072). In a study involving a switch from infliximab to etanercept, we investigated the clinical outcome in 49 patients with RA. Reasons for switching were in 42% failure to respond by American College of Rheumatology (ACR) 50% criteria; in 12% adverse event; and in 46% non-medical reasons although the patients had responded to infliximab. The Disease Activity Score with 28 joints examined (DAS28) allowed us to measure patients disease activity and compare outcome between groups based on the reason for switching. In the patients in whom infliximab was switched to etanercept for nonmedical reasons, etanercept continued to suppress disease activity effectively, and 1-year drug survival for etanercept was 77% (95% CI, 62 to 97). In patients in the infliximab failure and adverse event groups, DAS28 values improved significantly during etanercept therapy. However, the 1-year drug survival of etanercept was only 43% (95% CI, 26 to 70) and 50% (95% CI, 33 to 100), respectively. Although the HRQoL of patients with inflammatory joint diseases is significantly lower than that of the general population, use of early and aggressive treatment strategies including TNF-inhibitors can improve patients HRQoL effectively. Further research is needed in finding new treatment strategies for those patients who fail to respond or lose their response to TNF-inhibitors.

Total Hip and Knee Arthoplasty for Osteoarthritis : Factors Related to the Early Outcome of Surgery

Some perioperative clinical factors related to the primary cemented arthroplasty operation for osteoarthritis of the hip or knee joint are studied and discussed in this thesis. In a randomized, double-blind study, 39 patients were divided into two groups: one receiving tranexamic acid and the other not receiving it. Tranexamic acid was given in a dose of 10 mg/kg before the operation and twice thereafter, at 8-hour intervals. Total blood loss was smaller in the tranexamic acid group than in the control group. No thromboembolic complications were noticed. In a prospective, randomized study, 58 patients with hip arthroplasty and 39 patients with knee arthroplasty were divided into groups with postoperative closed-suction drainage and without drainage. There was no difference in healing of the wounds, postoperative blood transfusions, complications or range of motion. As a result of this study, the use of drains is no longer recommended. In a randomised study the effectiveness of a femoral nerve block (25 patients) was compared with other methods of pain control (24 patients) on the first postoperative day after total knee arthroplasty. The femoral block consisted of a single injection administered at patients´ bedside during the surgeon´s hospital rounds. Femoral block patients reported less pain and required half of the amount of oxycodone. Additional femoral block or continued epidural analgesia was required more frequently by the control group patients. Pain management with femoral blocks resulted in less work for nursing staff. In a retrospective study of 422 total hip and knee arthroplasty cases the C-reactive protein levels and clinical course were examined. After hip and knee arthroplasty the maximal C-reactive protein values are seen on the second and third postoperative days, after which the level decreases rapidly. There is no difference between patients with cemented or uncemented prostheses. Major postoperative complications may cause a further increase in C-reactive protein levels at one and two weeks. In-hospital and outpatient postoperative control radiographs of 200 hip and knee arthroplasties were reviewed retrospectively. If postoperative radiographs are of good quality, there seems to be no need for early repetitive radiographs. The quality and safety of follow-up is not compromised by limiting follow-up radiographs to those with clinical indications. Exposure of the patients and the staff to radiation is reduced. Reading of the radiographs by only the treating orthopaedic surgeon is enough. These factors may seem separate from each other, but linking them together may help the treating orthopaedic surgeon to adequate patient care strategy. Notable savings can be achieved.

Prognostic markers in head and neck carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Well-known risk factors include tobacco smoking and alcohol consumption. Overall survival has improved, but is still low especially in developing countries. One reason for this is the often advanced stage of the disease at the time of diagnosis, but also lack of reliable prognostic tools to enable individualized patient treatment to improve outcome. To date, the TNM classification still serves as the best disease evaluation criterion, although it does not take into account the molecular basis of the tumor. The need for surrogate molecular markers for more accurate disease prediction has increased research interests in this field. We investigated the prevalence, physical status, and viral load of human papillomavirus (HPV) in HNSCC to determine the impact of HPV on head and neck carcinogenesis. The prevalence and genotyping of HPV were assessed with an SPF10 PCR microtiter plate-based hybridization assay (DEIA), followed by a line probe-based genotyping assay. More than half of the patients had HPV DNA in their tumor specimens. Oncogenic HPV-16 was the most common type, and coinfections with other oncogenic and benign associated types also existed. HPV-16 viral load was unevenly distributed among different tumor sites; the tonsils harbored significantly greater amounts of virus than other sites. Episomal location of HPV-16 was associated with large tumors, and both integrated and mixed forms of viral DNA were detected. In this series, we could not show that the presence of HPV DNA correlated with survival. In addition, we investigated the prevalence and genotype of HPV in laryngeal carcinoma patients in a prospective Nordic multicenter study based on fresh-frozen laryngeal tumor samples to determine whether the tumors were HPV-associated. These patients were also examined and interviewed at diagnosis for known risk factors, such as tobacco smoking and alcohol consumption, and for several other habituations to elucidate their effects on patient survival. HPV analysis was performed with the same protocols as in the first study. Only 4% of the specimens harbored HPV DNA. Heavy drinking was associated with poor survival. Heavy drinking patients were also younger than nonheavy drinkers and had a more advanced stage of disease at diagnosis. Heavy drinkers had worse oral hygiene than nonheavy drinkers; however, poor oral hygiene did not have prognostic significance. History of chronic laryngitis, gastroesophageal reflux disease, and orogenital sex contacts were rare in this series. To clarify why vocal cord carcinomas seldom metastasize, we determined tumor lymph vessel (LVD) and blood vessel (BVD) densities in HNSCC patients. We used a novel lymphatic vessel endothelial marker (LYVE-1 antibody) to locate the lymphatic vessels in HNSCC samples and CD31 to detect the blood microvessels. We found carcinomas of the vocal cords to harbor less lymphatic and blood microvessels than carcinomas arising from sites other than vocal cords. The lymphatic and blood microvessel densities did not correlate with tumor size. High BVD was strongly correlated with high LVD. Neither BVD nor LVD showed any association with survival in our series. The immune system plays an important role in tumorigenesis, as neoplastic cells have to escape the cytotoxic lymphocytes in order to survive. Several candidate HLA class II alleles have been reported to be prognostic in cervical carcinomas, an epithelial malignancy resembling HNSCC. These alleles may have an impact on head and neck carcinomas as well. We determined HLA-DRB1* and -DQB1* alleles in HNSCC patients. Healthy organ donors served as controls. The Inno-LiPA reverse dot-blot kit was used to identify alleles in patient samples. No single haplotype was found to be predictive of either the risk for head and neck cancer, or the clinical course of the disease. However, alleles observed to be prognostic in cervical carcinomas showed a similar tendency in our series. DRB1*03 was associated with node-negative disease at diagnosis. DRB1*08 and DRB1*13 were associated with early-stage disease; DRB1*04 had a lower risk for tumor relapse; and DQB1*03 and DQB1*0502 were more frequent in controls than in patients. However, these associations reached only borderline significance in our HNSCC patients.

CHEK2 in Breast and Colorectal Cancer

Breast and colorectal cancers, are common types of cancer, with over two million newly diagnosed cases annually worldwide. Cancer is a genetic disease and defects in DNA integrity restoring functions make a significant contribution to cancer risk. CHEK2 is a checkpoint kinase functioning as a regulator of cell cycle checkpoints, apoptosis, and DNA repair in response to DNA double-strand breaks. The aim of this study was to evaluate the role of CHEK2 in breast cancer predisposition in Finnish breast cancer families and in breast cancer risk at the population level. We were interested in the clinical and biological characteristics of the breast tumors associated with the CHEK2 germline mutations or aberrant CHEK2 protein expression and the effect on survival of patients with these CHEK2 defects. We also assessed the role of CHEK2 mutations, namely 1100delC and I157T, in colorectal cancer susceptibility in Finland. CHEK2 I157T was found to be a low-penetrance breast cancer susceptibility allele, conferring a 1.4-fold risk for carriers. Reduced or absent CHEK2 protein expression was observed in one-fifth of breast tumors from patients unselected for family history, implying that defective CHEK2 signaling contributes to tumorigenesis. Reduction in CHEK2 expression was more common in tumors with larger diameter and ER expression, but with regard to other tumor characteristics and prognosis of a patient no association was observed. Results from comparison of CHEK2 1100delC carrier tumors with noncarrier tumors were in line with the findings from the CHEK2 expression study. Tumors from CHEK2 1100delC carriers were more often of higher grade than tumors from noncarriers, and they also tended to be ER-positive more often, although generally 1100delC status does not seem to radically affect the tumor characteristics. Our results suggest that CHEK2 1100delC may not be a susceptibility allele for CRC, although a very small effect cannot be excluded. Furthermore, CHEK2 1100delC is equally frequent in HBCC (hereditary breast and colorectal cancer) phenotype families and in breast cancer families. Over 1000 CRC cases were screened for CHEK2 I157T, and a significantly higher frequency of I157T was observed among both familial and sporadic CRC cases. The relation of CHEK2 I157T with familial CRC has not been studied previously. CHEK2 I157T seems to be a susceptibility allele for both familial and sporadic CRC, conferring a 1.5-fold risk for carriers of this variant. CHEK2 I157T has been proposed to have a role as a multiple cancer susceptibility allele, which is supported by our results since we observed a trend towards higher frequency of the variant among cases with multiple primary tumors or those with a family history of cancer. During the last five years CHEK2 has established its role as an important cancer susceptibility gene. It has become apparent that CHEK2 is a low-penetrance susceptibility gene for several cancer types, significantly contributing to familial cancer risk as well as to cancer risk at the population level.

Occupational Rhinitis : Diagnosis and Health-related Quality of Life

Occupational rhinitis is mainly caused by work environment and not by stimuli encountered outside the workplace. It differs from rhinitis that is worsened by, but not mainly caused by, workplace exposures. Occupational rhinitis can develop in response to allergens, inhaled irritants, or corrosive gases. The thesis evaluated the use of challenge tests in occupational rhinitis diagnostics, studied the long-term health-related quality of life among allergic occupational rhinitis patients, and the allergens of wheat grain among occupational respiratory allergy patients. The diagnosed occupational rhinitis was mainly allergic rhinitis, which was caused by occupational agents, most commonly flours and animal allergens. The non-IgE-mediated rhinitis reactions were less frequent and caused more often asthma than rhinitis. Both nasal challenges and inhalation challenges were found to be safe tests. The inhalation challenge tests had considerably resource-intensive methodology. However, the evaluation of nasal symptoms and signs together with bronchial reactions saved time and expense compared with the organization of multiple individual challenges. The scoring criteria used matched well with the weighted amount of discharge ≥ 0.2 g and in most cases gave comparable results. The challenge tests are valuable tools when there is uncertainty whether the patient's exposure should be reduced or discontinued. It was found that continuing exposure decreases health-related quality of life among patients with allergic occupational rhinitis despite of rhinitis medications, still approximately ten years after the diagnosis. Health-related quality of life among occupational rhinitis patients without any longer occupational exposure was mainly similar than that of the healthy controls. This highlights the importance of the reduction and cessation of occupational exposure. To achieve this, 17% of occupational rhinitis patients had been re-educated. Alpha-amylase inhibitors, lipid transfer protein 2G, thaumatin -like protein, and peroxidase I were found to be relevant allergens in Finnish patients with occupational respiratory wheat allergy. Of these allergens, thaumatin-like protein and lipid transfer protein 2G were found as new allergens associated with baker's rhinitis and asthma. The knowledge of the new clinically relevant proteins can be used in the future in the development of better standardized diagnostic preparations.

Evaluation and modelling of the spatial and temporal variability of particulate matter in urban areas

This thesis contains three subject areas concerning particulate matter in urban area air quality: 1) Analysis of the measured concentrations of particulate matter mass concentrations in the Helsinki Metropolitan Area (HMA) in different locations in relation to traffic sources, and at different times of year and day. 2) The evolution of traffic exhaust originated particulate matter number concentrations and sizes in local street scale are studied by a combination of a dispersion model and an aerosol process model. 3) Some situations of high particulate matter concentrations are analysed with regard to their meteorological origins, especially temperature inversion situations, in the HMA and three other European cities. The prediction of the occurrence of meteorological conditions conducive to elevated particulate matter concentrations in the studied cities is examined. The performance of current numerical weather forecasting models in the case of air pollution episode situations is considered. The study of the ambient measurements revealed clear diurnal variation of the PM10 concentrations in the HMA measurement sites, irrespective of the year and the season of the year. The diurnal variation of local vehicular traffic flows seemed to have no substantial correlation with the PM2.5 concentrations, indicating that the PM10 concentrations were originated mainly from local vehicular traffic (direct emissions and suspension), while the PM2.5 concentrations were mostly of regionally and long-range transported origin. The modelling study of traffic exhaust dispersion and transformation showed that the number concentrations of particles originating from street traffic exhaust undergo a substantial change during the first tens of seconds after being emitted from the vehicle tailpipe. The dilution process was shown to dominate total number concentrations. Minimal effect of both condensation and coagulation was seen in the Aitken mode number concentrations. The included air pollution episodes were chosen on the basis of occurrence in either winter or spring, and having at least partly local origin. In the HMA, air pollution episodes were shown to be linked to predominantly stable atmospheric conditions with high atmospheric pressure and low wind speeds in conjunction with relatively low ambient temperatures. For the other European cities studied, the best meteorological predictors for the elevated concentrations of PM10 were shown to be temporal (hourly) evolutions of temperature inversions, stable atmospheric stability and in some cases, wind speed. Concerning the weather prediction during particulate matter related air pollution episodes, the use of the studied models were found to overpredict pollutant dispersion, leading to underprediction of pollutant concentration levels.

Immigrant Associations in the Metropolitan Area of Finland : Forms of Mobilisation, Participation and Representation

This study examines the role of immigrant associations in the societal and political integration of immigrants into Finnish society. The societal focus is on the ability of immigrant associations to mobilise their ethnic group members to participate in the socio-economic, cultural and political domains of Finnish society and in certain cases even beyond. The political integrative aims are the opportunities of immigrant associations to participate and represent the interests of their ethnic group in local and national policy making. This study focuses on associations in the Metropolitan Area of Finland, (Espoo, Helsinki and Vantaa).The qualitative research consisted of 71 interviews conducted with members of immigrant associations and civil servants. These interviews were mainly semi-structured, including some additional open-ended questions. Additional data consisted of documents, planning reports and of follow-up enquiries. -- In the analysis of the data I categorised thirty-two immigrant associations according to the activity forms and the description of the goals by the members. The four categories consisted of integrative, societal, ethno-cultural and transnational immigrant associations. Most of the immigrant associations belonged to the integrative category (15 of 32 associations). On the one hand the aims of these associations are to provide access for their ethnic group members into Finnish society, while on the other to strengthen the ethnic identity of their members by organising ethno-cultural activities. The societal associations only focused on activities with the objective of including immigrants into the Finnish labour market and educational system. The goal of ethno-cultural associations was to strengthen the ethnic identity of their ethnic group members. The transnational associations aimed at improving the living conditions of women and children in the members' country of origin. The possibilities for immigrant associations to mobilise their members depends partly on external financing. Subsidies have been allocated for societal activities in particular. There remains a risk of the crowding out of ethno-cultural activities: something which has already taken place in several European countries. Immigrant associations aim to strengthen the identity of immigrants mainly by organising social and ethno-cultural activities. Another important target was to provide peer support and therapy courses. Additionally, immigrant women's associations offer assistance to women who have encountered violence by providing counselling and in some cases access to shelter. The data showed that there is an ever growing need to pay heed to the well-being of women, children and elderly immigrants. The participation of immigrant associations in the municipalities' integrative issues takes place mainly through cooperative projects. Until the end of the 1990s there had not been much cooperation. The problem with the projects was that they had mainly been managed by civil servants, whereas members from immigrant associations had remained in a more passive position. Representation of immigrant associations in councils has been fairly weak. Immigrant associations are included in the multicultural councils of Espoo and Vantaa, but only in the planning stages. The municipality of Helsinki does not include immigrant associations due to the large number of organisations which causes problems in finding fair, democratic representation. At the national level, the ‘Advisory Board for Ethnic Relations’ – ETNO didn’t chose its members based on membership of ethnic associations, but based on belongingness to one of the larger language groups spoken by the foreign population in Finland. Since ETNO’s third period (2005-2007), the representatives of immigrant associations and ethnic minority groups have been chosen from proposed candidates. Key words: immigrant associations, integration, mobilisation, participation, representation, the Metropolitan area of Finland, immigrant (women), civil servants

The effects of abiotic and biotic factors on somatic embryogenesis and seedlings of Pinus sylvestris (L.)

Somatic embryogenesis (SE) is an asexual form of plant propagation that occurs in nature and mimics many of the events of sexual reproduction. Pinus sylvestris (L.) is an important source of timber in Northern Eurasia but it is recalcitrant to somatic embryogenesis. Several factors important for the success of the P. sylvestris embryogenic cultures have not been thoroughly investigated. In this study, we examined the effects of parental genotypes on the SE in P. sylvestris, the involvement of the gaseous plant growth regulator, ethylene in SE, and also biotic effects on somatic embryos as well as on seedlings. We tested parental effects on immature embryo initiation for different media, storage periods, and on the maturation process. Maternal effects were found to be crucial for SE in the absence of paternal effects. No maternal-paternal interaction was observed at any stage of somatic embryo production. Additionally the role of ethylene at different developmental stages of SE was investigated. Two ACC synthase genes, PsACS1 and PsACS2, were isolated and characterized. PsACS1 was expressed during the proliferation stage in all tested genotypes, whereas PsACS2 was only expressed in somatic embryos of each genotype. Ethylene production in embryos at stage 3 was significantly higher than the other stages. In a parallel study, the response of somatic embryos to fungal elicitors was investigated. Three fungi, a mutualistic ectomycorrhizal (ECM) fungus (Suillus bovinus), a weak Scots pine pathogen (Heterobasidion parviporum) and a strong pathogen (H. annosum) were used. The gene expression patterns for embryos exposed to the H. parviporum elicitor were found to be similar to that documented for S. bovinus among the tested genes. By contrast somatic embryos exposed to the H. annosum elicitor had a different pattern of regulation which was marked by a delayed response, and in some cases death of the embryos. Furthermore, interaction without direct contact between P. sylvestris seedlings and microbes (mutualistic and pathogenic fungus, cyanobacterium) were investigated. Several novel genes expressed in seedlings treated with ECM fungus were isolated which suggested that physical contact is not necessary for elicitation of host responses. The results suggest that somatic embryos and seedlings of P. sylvestris are genetically well equipped to respond to fungal elicitor/exudates and could serve as a suitable model for reproducible molecular studies in conifer tree patho- and symbiotic systems.

Wood and fiber properties of Norway spruce and its suitability for thermomechanical pulping.

In the first part of the study, the selected wood and fiber properties were investigated in terms of their occurrence and variation in wood, as well as their relevance from the perspective of thermomechanical pulping process and related end-products. It was concluded that the most important factors were the fiber dimensions, juvenile wood content, and in some cases, the content of heartwood being associated with extremely dry wood with low permeability in spruce. With respect to the above properties, the following three pulpwood assortments of which pulping potential was assumed to vary were formed: wood from regeneration cuttings, first-thinnings wood, and sawmill chips. In the experimental part of the study the average wood and fiber characteristics and their variation were determined for each raw material group prior to pulping. Subsequently, each assortment - equaling about 1500 m3 roundwood - was pulped separately for a 24 h period, at constant process conditions. The properties of obtained newsgrade thermomechanical pulps were then determined. Thermomechanical pulping (TMP) from sawmill chips had the highest proportion of long fibers, smallest proportion of fines, and had generally the coarsest and longest fibers. TMP from first-thinnings wood was just the opposite, whereas that from regeneration cuttings fell in between the above two extremes. High proportion of dry heartwood in wood originating from regeneration cuttings produced a slightly elevated shives content. However, no differences were found in pulp specific energy consumption. The obtained pulp tear index was clearly best in TMP made from sawmill chips and poorest in pulp from first-thinnings wood, which had generally inferior strength properties. No dramatical differences in any of the strength properties were found between pulp from sawmill residual wood and regeneration cuttings. Pulp optical properties were superior in TMP from first-thinnings. Unexpectedly, no noticeable differences, which could be explained with fiber morphology, were found in sheet density, bulk, air permeance or roughness between the three pulps. The most important wood quality factors in this study were the fiber length, fiber cross-sectional dimensions and percentage juvenile wood. Differences found in the quality of TMP manufactured from the above spruce assortments suggest that they could be segregated and pulped separately to obtain specific product characteristics, i.e., for instance tailor-made end-products, and to minimize unnecessary variation in the raw material quality, and hence, pulp quality.

Genomic alterations in Myeloproliferative Neoplasms and Myelodysplastic Syndromes

Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders whose etiology and molecular pathogenesis are poorly understood. During the past decade, enormous developments in microarray technology and bioinformatics methods have made it possible to mine novel molecular alterations in a large number of malignancies, including MPN and MDS, which has facilitated the detection of new prognostic, predictive and therapeutic biomarkers for disease stratification. By applying novel microarray techniques, we profiled copy number alterations and microRNA (miRNA) expression changes in bone marrow aspirate and blood samples. In addition, we set up and validated an miRNA expression test for bone marrow core biopsies in order to utilize the large archive material available in many laboratories. We also tested JAK2 mutation status and compare it with the in vitro growth pattern of hematologic progenitors cells. In the study focusing on 100 MPN cases, we detected a Janus kinase 2 (JAK2) mutation in 71 cases. We observed spontaneous erythroid colony growth in all mutation-positive cases in addition to nine mutation negative cases. Interestingly, seven JAK2V167F negative ET cases showed spontaneous megakaryocyte colony formation, one case of which also harbored a myeloproliferative leukemia virus oncogene (MPL) mutation. We studied copy number alterations in 35 MPN and 37 MDS cases by using oligonucleotide-based array comparative hybridization (array CGH). Only one essential thrombocythemia (ET) case presented copy number alterations in chromosomes 1q and 13q. In contrast, MDS cases were characterized by numerous novel cryptic chromosomal aberrations with the most common copy number losses at 5q21.3q33.1 and 7q22.1q33, while the most common copy number gain was trisomy 8. As for the study of the bone marrow core biopsy samples, we showed that even though these samples were embedded in paraffin and underwent decalcification, they were reliable sources of miRNA and suitable for array expression analysis. Further, when studying the miRNA expression profiles of the 19 MDS cases, we found that, compared to controls, two miRNAs (one human Epstein-Barr virus (miR-BART13) miRNA and one human (has-miR-671-5p) miRNA) were downregulated, whereas two other miRNAs (hsa-miR-720 and hsa-miR-21) were upregulated. However, we could find no correlation between copy number alterations and microRNA expression when integrating these two data. This thesis brings to light new information about genomic changes implicated in the development of MPN and MDS, and also underlines the power of applying genome-wide array screening techniques in neoplasias. Rapid advances in molecular techniques and the integration of different genomic data will enable the discovery of the biological contexts of many complex disorders, including myeloid neoplasias.