Novel Mass Spectrometric Analysis Methods for Anabolic Androgenic Steroids in Sports Drug Testing

The feasibility of different modern analytical techniques for the mass spectrometric detection of anabolic androgenic steroids (AAS) in human urine was examined in order to enhance the prevalent analytics and to find reasonable strategies for effective sports drug testing. A comparative study of the sensitivity and specificity between gas chromatography (GC) combined with low (LRMS) and high resolution mass spectrometry (HRMS) in screening of AAS was carried out with four metabolites of methandienone. Measurements were done in selected ion monitoring mode with HRMS using a mass resolution of 5000. With HRMS the detection limits were considerably lower than with LRMS, enabling detection of steroids at low 0.2-0.5 ng/ml levels. However, also with HRMS, the biological background hampered the detection of some steroids. The applicability of liquid-phase microextraction (LPME) was studied with metabolites of fluoxymesterone, 4-chlorodehydromethyltestosterone, stanozolol and danazol. Factors affecting the extraction process were studied and a novel LPME method with in-fiber silylation was developed and validated for GC/MS analysis of the danazol metabolite. The method allowed precise, selective and sensitive analysis of the metabolite and enabled simultaneous filtration, extraction, enrichment and derivatization of the analyte from urine without any other steps in sample preparation. Liquid chromatographic/tandem mass spectrometric (LC/MS/MS) methods utilizing electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) were developed and applied for detection of oxandrolone and metabolites of stanozolol and 4-chlorodehydromethyltestosterone in urine. All methods exhibited high sensitivity and specificity. ESI showed, however, the best applicability, and a LC/ESI-MS/MS method for routine screening of nine 17-alkyl-substituted AAS was thus developed enabling fast and precise measurement of all analytes with detection limits below 2 ng/ml. The potential of chemometrics to resolve complex GC/MS data was demonstrated with samples prepared for AAS screening. Acquired full scan spectral data (m/z 40-700) were processed by the OSCAR algorithm (Optimization by Stepwise Constraints of Alternating Regression). The deconvolution process was able to dig out from a GC/MS run more than the double number of components as compared with the number of visible chromatographic peaks. Severely overlapping components, as well as components hidden in the chromatographic background could be isolated successfully. All studied techniques proved to be useful analytical tools to improve detection of AAS in urine. Superiority of different procedures is, however, compound-dependent and different techniques complement each other.

Preliminary phonological analysis of the Limi dialect of Humla Bhotia

The purpose of this research was to analyse the phonological system of the Limi dialect of Humla Bhotia. Humla Bhotia is a Tibeto-Burman language that is spoken by approximately 4000 5000 people in the far northwestern Humla province of the Kingdom of Nepal. The language has not previously been the subject of analysis. The data base for this thesis was collected on two different dialects of Humla Bhotia in Kathmandu, the capital of Nepal, from February to May 2000. I had three language informants who speak Humla Bhotia as their mother tongue. One of the informants speaks the Upper Humla dialect and the other two informants speak the Limi dialect. In this thesis I have concentrated on the phonology of the dialect of Limi but occasionally I also make reference to the Upper Humla dialect. The Limi data base consists of 600 words elicited in isolation, sentences where words have been checked for consonantal and pitch variation, and five texts comprising 117 sentences. Firstly, I have studied the geographical location, population and dialects of Humla Bhotia. Five dialects were identified: Limi, Upper Humla, La Yakba, Nyinba and Humli Khyampa. Information on the dialect areas is based on the accounts of seven mother tongue speakers of the language and on Nancy Levine s (1988) anthropological research of the ethnic group Nyinba. Secondly, I have analysed the phonological system of Limi from the viewpoint of American stucturalism much along the lines followed by Pike 1966 [1947] ja 1967 [1948]. In defining the prosodic elements I have also used acoustic analysis. In the Limi dialect there are 7 vowel phonemes. No vowel clusters occur within the same syllable. In this preliminary analysis 29 contrastive plosives, 8 affricates and 5 6 fricatives were found. The data also revealed 4 nasal phonemes, two rhotic phonemes, one lateral phoneme and two central approximants. Further research is however called for to check the phonemic status of these segments. Four contrastive prosodic elements were encountered: nasalisation, length, phonation type and pitch movement. There are two contrastive types of phonation: tense and lax. Many words were found with a third type of phonation, modal phonation. How modal phonation relates to the prosodic system is unclear at this stage and is therefore left for further research to determine. There are two contrastive pitch movement tonemes: a rising toneme and falling toneme. The falling toneme occurs in free variation with a level pitch contour. Rising appears to be linked with lax phonation and falling with tense phonation.

A Touch of Red : Archaeological and Ethnographic Approaches to Interpreting Finnish Rock Paintings

Approximately 125 prehistoric rock paintings have been found in the modern territory of Finland. The paintings were done with red ochre and are almost without exception located on steep lakeshore cliffs associated with ancient water routes. Most of the sites are found in the central and eastern parts of the country, especially on the shores of Lakes Päijänne and Saimaa. Using shore displacement chronology, the art has been dated to ca. 5000 – 1500 BC. It was thus created mainly during the Stone Age and can be associated with the so-called ‘Comb Ware’ cultures of the Subneolithic period. The range of motifs is rather limited, consisting mainly of schematic depictions of stick-figure humans, elks, boats, handprints and geometric signs. Few paintings include any evidence of narrative scenes, making their interpretation a rather difficult task. In Finnish archaeological literature, the paintings have traditionally been associated with ’sympathetic’ hunting magic, or the belief that the ritual shooting of the painted animals would increase hunting luck. Some writers have also suggested totemistic and shamanistic readings of the art. This dissertation is a critical review of the interpretations offered of Finnish rock art and an exploration of the potentials of archaeological and ethnographic research in increasing our knowledge of its meaning. Methods used include ’formal’ approaches such as archaeological excavation, landscape analysis and the application of neuropsychological research to the study of rock art, as well as ethnographically ’informed’ approaches that make use of Saami and Baltic Finnish ethnohistorical sources in interpretation. In conclusion, it is argued that although North European hunter-gatherer rock art is often thought to lie beyond the reach of ‘informed’ knowledge, the exceptional continuity of prehistoric settlement in Finland validates the informed approach in the interpretation of Finnish rock paintings. The art can be confidently associated with shamanism of the kind still practiced by the Saami of Northern Fennoscandia in the historical period. Evidence of similar shamanistic practices, concepts and cosmology are also found in traditional Finnish-Karelian epic poetry. Previous readings of the art based on ‘hunting magic’ and totemism are rejected. Most of the paintings appear to depict experiences of falling into a trance, of shamanic metamorphosis and trance journeys, and of ‘spirit helper’ beings comparable to those employed by the Saami shaman (noaidi). As demonstrated by the results of an excavation at the rock painting of Valkeisaari, the painted cliffs themselves find a close parallel in the Saami cult of the 'sieidi', or sacred cliffs and boulders worshipped as expressing a supernatural power. Like the Saami, the prehistoric inhabitants of the Finnish Lake Region seem to have believed that certain cliffs were ’alive’ and inhabited by the spirit helpers of the shaman. The rock paintings can thus be associated with shamanic vision quests, and the making of ‘art’ with an effort to socialize the other members of the community, especially the ritual specialists, with trance visions. However, the paintings were not merely to be looked at. The red ochre handprints pressed on images of elks, as well as the fact that many paintings appear ’smeared’, indicate that they were also to be touched – perhaps in order to tap into the supernatural potency inherent in the cliff and in the paintings of spirit animals.

Archaeology of wings : Birds and people in the Baltic Sea region during the Stone Age

The prominent roles of birds, often mentioned in historical sources, are not well reflected in archaeological research. Absence or scarcity of bird bones in archaeological assemblages has been often seen as indication of a minor role of birds in the prehistoric economy or ideology, or explained by taphonomic loss. Few studies exist where birds form the basis for extensive archaeological interpretation. In this doctoral dissertation bird bone material from various Stone Age sites in the Baltic Sea region is investigated. The study period is approximately 7000-3400 BP, comprising mainly Neolithic cultures. The settlement material comes from Finland, Åland, Gotland, Saaremaa and Hiiumaa. Osteological materials are used for studying the economic and cultural importance of birds, fowling methods and principal fowling seasons. The bones were identified and earlier identifications partially checked with help of a reference material of modern skeletons. Fracture analysis was used in order to study the deposition history of bones at Ajvide settlement site. Birds in burials at two large cemeteries, Ajvide on Gotland and Zvejnieki in northern Latvia were investigated in order to study the roles of birds in burial practices. My study reveals that the economic importance of birds is at least seasonally often more prominent than usually thought, and varies greatly in different areas. Fowling has been most important in coastal areas, and especially during the breeding season. Waterbirds and grouse species were generally the most important groups in Finnish Stone Age economy. The identified species composition shows much resemblance to contemporary hunting with species such as the mallard and capercaillie commonly found. Burial materials and additional archaeological evidence from Gotland, Latvia and some other parts of northern Europe indicate that birds –e.g., jay, whooper swan, ducks – have been socially and ideologically important for the studied groups (indicating a place in the belief system, e.g. clan totemism). The burial finds indicate that some common ideas about waterbirds (perhaps as messengers or spirit helpers) might have existed in the northern European Stone Age.

Fumarate Hydratase and Succinate Dehydrogenase in Neoplasia

Germline mutations in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell cancer (HLRCC). FH is a nuclear encoded enzyme which functions in the Krebs tricarboxylic acid cycle, and homozygous mutation in FH lead to severe developmental defects. Both uterine and cutaneous leiomyomas are components of the HLRCC phenotype. Most of these tumours show loss of the wild-type allele and, also, the mutations reduce FH enzyme activity, which indicate that FH is a tumour suppressor gene. The renal cell cancers associated with HLRCC are of rare papillary type 2 histology. Other genes involved in the Krebs cycle, which are also implicated in neoplasia are 3 of the 4 subunits encoding succinate dehydrogenase (SDH); mutations in SHDB, SDHC, and SDHD predispose to paraganglioma and phaeochromocytoma. Although uterine leiomyomas (or fibroids) are very common, the estimations of affected women ranging from 25% to 77%, not much is known about their genetic background. Cytogenetic studies have revealed that rearrangements involving chromosomes 6, 7, 12 and 14 are most commonly seen in fibroids. Deletions on the long arm of chromosome 7 have been reported to be involved in about 17 to 34 % of leiomyomas and the small commonly deleted region on 7q22 suggests that there might be an underlying tumour suppressor gene in that region. The purpose of this study was to investigate the genetic mechanisms behind the development of tumours associated with HLRCC, both renal cell cancer and uterine fibroids. Firstly, a database search at the Finnish cancer registry was conducted in order to identify new families with early-onset RCC and to test if the family history was compatible with HLRCC. Secondly, sporadic uterine fibroids were tested for deletions on 7q in order to define the minimal deleted 7q-region, followed by mutation analysis of the candidate genes. Thirdly, oligonucleotide chips were utilised to study the global gene expression profiles of uterine fibroids in order to test whether 7q-deletions and FH mutations significantly affected fibroid biology. In the screen for early-onset RCC, 214 families were identified. Subsequently, the pedigrees were constructed and clinical data obtained. One of the index cases (RCC at the age of 28) had a mother who had been diagnosed with a heart tumour, which in further investigation turned out to be a paraganglioma. This lead to an alternative hypothesis that SDH, instead of FH, could be involved. SDHA, SDHB, SDHC and SDHD were sequenced from these individuals; a germline SDHB R27X mutation was detected with loss of the wild-type allele in both tumours. These results suggest that germline mutations in the SDHB gene predispose to early-onset RCC establishing a novel form of hereditary RCC. This has immediate clinical implications in the surveillance of patients suffering from early-onset RCC and phaeochromocytoma/paraganglioma. For the studies on sporadic uterine fibroids, a set of 166 fibroids from 51 individuals were collected. The 7q LOH mapping defined a commonly deleted region of about 3.2 mega bases in 11 of the 166 tumours. The deletion was consistent with previously reported allelotyping studies of leiomyomas and it therefore suggested the presence of a tumour suppressor gene in the deleted region. Furthermore, the high-resolution aCGH-chip analysis refined the deleted region to only 2.79Mb. When combined with previous data, the commonly deleted region was only 2.3Mb. The mutation screening of the known genes within the commonly deleted region did not reveal pathogenic mutations, however. The expression microarray analysis revealed that FH-deficient fibroids, both sporadic and familial, had their distinct gene expression profile as they formed their own group in the unsupervised clustering. On the other hand, the presence or absence of 7q-deletions did not significantly alter the global gene expression pattern of fibroids, suggesting that these two groups do not have different biological backgrounds. Multiple differentially expressed genes were identified between FH wild-type and FH-mutant fibroids, and the most significant increase was seen in the expression of carbohydrate metabolism-related and hypoxia inducible factor (HIF) target genes.

A matter of taste : genetic and environmental influences on responses to sweetness

Diet is a major player in the maintenance of health and onset of many diseases of public health importance. The food choice is known to be largely influenced by sensory preferences. However, in many cases it is unclear whether these preferences and dietary behaviors are innate or acquired. The aim of this thesis work was to study the extent to which the individual differences in dietary responses, especially in liking for sweet taste, are influenced by genetic factors. Several traits measuring the responses to sweetness and other dietary variables were applied in four studies: in British (TwinsUK) and Finnish (FinnTwin12 and FinnTwin16) twin studies and in a Finnish migraine family study. All the subjects were adults and they participated in chemosensory measurements (taste and smell tests) and filled in food behavior questionnaires. Further, it was studied, whether the correlations among the variables are mediated by genetic or environmental factors and where in the genome the genes influencing the heritable traits are located. A study of young adult Finnish twins (FinnTwin16, n=4388) revealed that around 40% of the food use is attributable to genetic factors and that the common, childhood environment does not affect the food use even shortly after moving from the parents home. Both the family study (n=146) and the twin studies (British twins, n=663) showed that around half of the variation in the liking for sweetness is inherited. The same result was obtained both by the chemosensory measurements (heritability 41-49%) and the questionnaire variables (heritability 31-54%). By contrast, the intensity perception of sweetness or the responses to saltiness were not influenced by genetic factors. Further, a locus influencing the use-frequency of sweet foods was identified on chromosome 16p. A closer examination of the relationships among the variables based on 663 British twins revealed that several genetic and environmental correlations exist among the different measures of liking for sweetness. However, these correlations were not very strong (range 0.06-0.55) implying that the instruments used measure slightly different aspects of the phenomenon. In addition, the assessment of the associations among responses to fatty foods, dieting behaviors, and body mass index in twin populations (TwinsUK n=1027 and FinnTwin12 n=299) showed that the dieting behaviors (cognitive restraint, uncontrolled eating, and emotional eating) mediate the relationship between obesity and diet. In conclusion, the work increased the understanding of the background variables of human eating behavior. Genetic effects were shown to underlie the variation of many dietary traits, such as liking for sweet taste, use of sweet foods, and dieting behaviors. However, the responses to salty taste were shown to be mainly determined by environmental factors and thus should more easily be modifiable by dietary education, exposure, and learning than sweet taste preferences. Although additional studies are needed to characterize the genetic element located on chromosome 16 that influences the use-frequency of sweet foods, the results underline the importance of inherited factors on human eating behavior.

Environmental change and anthropogenic impact on lake sediments during the Holocene in the Finnish - Karelian inland area

This thesis discusses the prehistoric human disturbance during the Holocene by means of case studies using detailed high-resolution pollen analysis from lake sediment. The four lakes studied are situated between 61o 40' and 61o 50' latitudes in the Finnish Karelian inland area and vary between 2.4 and 28.8 ha in size. The existence of Early Metal Age population was one important question. Another study question concerned the development of grazing, and the relationship between slash-and-burn cultivation and permanent field cultivation. The results were presented as pollen percentages and pollen concentrations (grains cm 3). Accumulation values (grains cm 2 yr 1) were calculated for Lake Nautajärvi and Lake Orijärvi sediment, where the sediment accumulation rate was precisely determined. Sediment properties were determined using loss-on-ignition (LOI) and magnetic susceptibility (k). Dating methods used include both conventional and AMS 14C determinations, paleomagnetic dating and varve choronology. The isolation of Lake Kirjavalampi on the northern shore of Lake Ladoga took place ca. 1460 1300 BC. The long sediment cores from Finland, Lake Kirkkolampi and Lake Orijärvi in southeastern Finland and Lake Nautajärvi in south central Finland all extended back to the Early Holocene and were isolated from the Baltic basin ca. 9600 BC, 8600 BC and 7675 BC, respectively. In the long sediment cores, the expansion of Alnus was visible between 7200 - 6840 BC. The spread of Tilia was dated in Lake Kirkkolampi to 6600 BC, in Lake Orijärvi to 5000 BC and at Lake Nautajärvi to 4600 BC. Picea is present locally in Lake Kirkkolampi from 4340 BC, in Lake Orijärvi from 6520 BC and in Lake Nautajärvi from 3500 BC onwards. The first modifications in the pollen data, apparently connected to anthropogenic impacts, were dated to the beginning of the Early Metal Period, 1880 1600 BC. Anthropogenic activity became clear in all the study sites by the end of the Early Metal Period, between 500 BC AD 300. According to Secale pollen, slash-and-burn cultivation was practised around the eastern study lakes from AD 300 600 onwards, and at the study site in central Finland from AD 880 onwards. The overall human impact, however, remained low in the studied sites until the Late Iron Age. Increasing human activity, including an increase in fire frequency was detected from AD 800 900 onwards in the study sites in eastern Finland. In Lake Kirkkolampi, this included cultivation on permanent fields, but in Lake Orijärvi, permanent field cultivation became visible as late as AD 1220, even when the macrofossil data demonstrated the onset of cultivation on permanent fields as early as the 7th century AD. On the northern shore of Lake Ladoga, local activity became visible from ca. AD 1260 onwards and at Lake Nautajärvi, sediment the local occupation was traceable from 1420 AD onwards. The highest values of Secale pollen were recorded both in Lake Orijärvi and Lake Kirjavalampi between ca. AD 1700 1900, and could be associated with the most intensive period of slash-and-burn from AD 1750 to 1850 in eastern Finland.

Irritable bowel syndrome in the general population : epidemiology, comorbidity and societal costs

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterised by abdominal pain and abnormal bowel function. It is associated with a high rate of healthcare consumption and significant health care costs. The prevalence and economic burden of IBS in Finland has not been studied before. The aims of this study were to assess the prevalence of IBS according to various diagnostic criteria and to study the rates of psychiatric and somatic comorbidity in IBS. In addition, health care consumption and societal costs of IBS were to be evaluated. Methods: The study was a two-phase postal survey. Questionnaire I identifying IBS by Manning 2 (at least two of the six Manning symptoms), Manning 3 (at least three Manning symptoms), Rome I, and Rome II criteria, was mailed to a random sample of 5 000 working age subjects. It also covered extra-GI symptoms such as headache, back pain, and depression. Questionnaire II, covering rates of physician visits, and use of GI medication, was sent to subjects fulfilling Manning 2 or Rome II IBS criteria in Questionnaire I. Results: The response rate was 73% and 86% for questionnaires I and II. The prevalence of IBS was 15.9%, 9.6%, 5.6%, and 5.1% according to Manning 2, Manning 3, Rome I, and Rome II criteria. Of those meeting Rome II criteria, 97% also met Manning 2 criteria. Presence of severe abdominal pain was more often reported by subjects meeting either of the Rome criteria than those meeting either of the Manning criteria. Presence of depression, anxiety, and several somatic symptoms was more common among subjects meeting any IBS criterion than by controls. Of subjects with depressive symptoms, 11.6% met Rome II IBS criteria compared to 3.7% of those with no depressiveness. Subjects meeting any IBS criteria made more physician visits than controls. Intensity of GI symptoms and presence of dyspeptic symptoms were the strongest predictors of GI consultations. Presence of dyspeptic symptoms and a history of abdominal pain in childhood also predicted non-GI visits. Annual GI related individual costs were higher in the Rome II group (497 ) than in the Manning 2 group (295 ). Direct expenses of GI symptoms and non GI physician visits ranged between 98M for Rome II and 230M for Manning 2 criteria. Conclusions: The prevalence of IBS varies substantially depending on the criteria applied. Rome II criteria are more restrictive than Manning 2, and they identify an IBS population with more severe GI symptoms, more frequent health care use, and higher individual health care costs. Subjects with IBS demonstrate high rates of psychiatric and somatic comorbidity regardless of health care seeking status. Perceived symptom severity rather than psychiatric comorbidity predicts health care seeking for GI symptoms. IBS incurs considerable medical costs. The direct GI and non-GI costs are equivalent to up to 5% of outpatient health care and medicine costs in Finland. A more integral approach to IBS by physicians, accounting also for comorbid conditions, may produce a more favourable course in IBS patients and reduce health care expenditures.

Long-term results of operative treatment for Hirschsprung's disease and internal anal sphincter achalasia

The aim of the study was to evaluate long-term results of operative treatment for Hirschsprung's disease(HD) and internal anal sphincter achalasia. Fecal continence and quality of life were evaluated by a questionnaire in 100 adult patients who had undergone surgery for HD, during 1950-75. Fecal continence was evaluated using a numerical scoring described by Holschneider. Fifty-four of the 100 patients underwent clinical examination, rigid sigmoidoscopy and manometric evaluation. In anorectal manometry basal resting pressure(BRP)and maximal squeeze pressure(MSP) were measured and voluntary sphincter force(VSF) was calculated by subtracting the BRP from MSP. The results of operative treatment for adult HD were compared with the results of the patients operated in childhood. In adult HD the symptoms are such mild that the patients attain adolescence or even adulthood. The patients with HD and cartilage-hair-hypoplasia were specifically evaluated. The outcome of the patients with internal anal sphincter achalasia operated on by myectomy was evaluated by a questionnaire and continence was evaluated using a numerical scoring described by Holschneider. Of the 100 patients operated on for HD 38 patients had completely normal bowel habits. A normal or good continence score was found in 91 our of 100 patients. Nine patients had fair continence. One of the patients with fair continence had Down's syndrome and two were mentally retarded for other reasons. Only one patient suffered from constipation. In anorectal manometry the difference in BRP between patients with normal and good continence was statistically significant, whereas the difference between good and fair continence groups was not statistically significant. The differences on MSP and VSF between patient groups with different continence outcome were not statistically significant. The differences between patient groups and normal controls were statistically significant in BRP and MSP. In VSF there was not statistically significant difference between the patients and the normal controls. The VSF reflects the working power of the muscles including external sphincter, levator ani and gluteal muscles. The patients operated at adult age had as good continence as patients operated in childhood. The patients with HD and cartilage-hair-hypoplasia had much more morbidity and mortality than non-cartilage-hair-hypoplasia HD patients. The mortality was as high as 38%. In patients with internal anal sphincter achalasia the constipation was cured or alleviated by myectomy whereas a significant number suffered from soiling-related social problems.

Itämafia : Uhkakuvapolitiikka, rikosilmiöt ja kulttuuriset merkitykset

The Eastern Mafia Threat policy, crime phenomena, and cultural meanings An interdisciplinary research on the crime phenomena and the threat policy relating to the organized crime and the mafia of Russia and Estonia is based on 151 expert interviews, statistics, documents, research literature, and press material. The main part of the material consists of interviews of the Finnish, Estonian and Russian police authorities specialized in the problem of organized crime, and the reports on the crime situation drawn up in the Finnish diplomatic representations in Tallinn and St Petersburg. The interviews have been gathered in the years 1996-2001. The main theoretical tools of the research are constructivist research on social problems, and political psychology. Definitional processes of social problems and cultural semantic structures behind them are identified in the analysis and connected to the analysis of the crime cases. Both in the Anglo-American and Russian cultural frames there appears an inflated and exaggerated talk, according to which the mafia rules everything in Russia and is spreading everywhere. There is the traditional anti-Semitic paranoia in the core of this cultural symbiosis produced by Russian legal nihilism, the theory of totalitarianism of Sovietology, and the inertia of Russian anti-capitalism. To equate the Sicilian Mafia with Russia is an anachronism, since no empirical proof of systematic uncontrolled violence or absolute power vacuum in Russia can be found. In the Anglo-American policy of threat images, "the Russian mafia" was seen as a commodified conspiracy theory, which the police, the media, and the research took advantage of, blurring the line between fact and fiction. In Finland, the evolution of the policy of threat images proceeded in three phases: Initially, extensive rolling of refugees and criminals from Russia to Finland was emphasized in the beginning of the 1990's. In the second phase, the eastern mafia was said to infiltrate all over Finnish society and administration. Finland was, however, found immune to this kind of spreading. In the third phase, in the 21st century, the organized crime of Finland was said to be lead from abroad. In Finland, the policy of threat images was especially canalised to moral panics connected to "eastern prostitution". In Estonia, the policy of threat images emphasized the crime organized by the Russian authorities and politicians in order to weaken Estonia. In Russia, the policy of threat images emphasized the total criminalizing of society caused by criminal capitalism. In every country, the policy of threat images was affected by a so-called large-group identity, a term by Vamik Volkan, in which a so-called chosen trauma caused a political paranoia of an outer and inner danger. In Finland, procuring, car theft, and narcotics crimes were at their widest arranged by the Finnish often with the help of the Estonians. The Russians had no influence in the most serious violent crimes in Finland, although the number of assassinations were at least 5, 000 in Russia in the 1990's. In Russia, the assassinations were on one hand connected to marital problems, on the other hand to the pursuit of public attention and a hoped-for effect by the aid of the murder of an influential person. In the white-collar crime phenomena between Finland and Russia, the Finnish state and Finnish corporations gained remarkable benefit of the frauds aimed at the states of the Soviet Union and Russia in 1980's-21st century. The situation of Estonia was very difficult compared to that of Russia in the 1990's, which was manifested in the stagnation of the Estonian police and judicial authorities, the crimes of the police and the voluntary paramilitary organization, bomb explosions, the rebellion called "the jaeger crisis" in the voluntary paramilitary organization, and the "blood autumn" of Eastern Virumaa, in other words terror. The situation of Estonia had a powerful effect on the crime situation of Finland and on the security of the Finnish diplomats. In the continuum of the Finnish policy of threat images, Russia and the Russians were, however, presented as a source of a marked danger.

Rannansiirtyminen ja ihmisen toimintaympäristön muutos Mätäjokilaakson alueella esihistoriallisella ajalla

In this thesis, I study the changing ladscape and human environment of the Mätäjoki Valley, West-Helsinki, using reconstructions and predictive modelling. The study is a part of a larger project funded by the city of Helsinki aming to map the past of the Mätäjoki Valley. The changes in landscape from an archipelago in the Ancylus Lake to a river valley are studied from 10000 to 2000 years ago. Alongside shore displacement, we look at the changing environment from human perspective and predict the location of dwelling sitesat various times. As a result, two map series were produced that show how the landscape changed and where inhabitance is predicted. To back them up, we have also looked at what previous research says about the history of the waterways, climate, vegetation and archaeology. The changing landscape of the river valley is reconstructed using GIS methods. For this purpose, new laser point data set was used and at the same time tested in the context landscape modelling. Dwelling sites were modeled with logistic regression analysis. The spatial predictive model combines data on the locations of the known dwelling sites, environmental factors and shore displacement data. The predictions were visualised into raster maps that show the predictions for inhabitance 3000 and 5000 years ago. The aim of these maps was to help archaeologists map potential spots for human activity. The produced landscape reconstructions clarified previous shore displacement studies of the Mätäjoki region and provided new information on the location of shoreline. From the shore displacement history of the Mätäjoki Valley arise the following stages: 1. The northernmost hills of the Mätäjoki Valley rose from Ancylus Lake approximately 10000 years ago. Shore displacement was fast during the following thousand years. 2. The area was an archipelago with a relatively steady shoreline 9000 7000 years ago. 8000 years ago the shoreline drew back in the middle and southern parts of the river valley because of the transgression of the Litorina Sea. 3. Mätäjoki was a sheltered bay of the Litorina Sea 6000 5000 years ago. The Vantaanjoki River started to flow into the Mätäjoki Valley approximately 5000 years ago. 4. The sediment plains in the southern part of the river valley rose from the sea rather quickly 5000 3000 years ago. Salt water still pushed its way into the southermost part of the valley 4000 years ago. 5. The shoreline proceeded to Pitäjänmäki rapids where it stayed at least a thousand years 3000 2000 years ago. The predictive models managed to predict the locations of dwelling sites moderately well. The most accurate predictions were found on the eastern shore and Malminkartano area. Of the environment variables sand and aspect of slope were found to have the best predictive power. From the results of this study we can conclude that the Mätäjoki Valley has been a favorable location to live especially 6000 5000 years ago when the climate was mild and vegetation lush. The laser point data set used here works best in shore displacement studies located in rural areas or if further specific palaeogeographic or hydrologic analysis in the research area is not needed.

PERFECT Stroke : PERFormance, Effectiveness, and Costs of treatment episodes in Stroke

Stroke is a major cause of death and disability, incurs significant costs to healthcare systems, and inflicts severe burden to the whole society. Stroke care in Finland has been described in several population-based studies between 1967 and 1998, but not since. In the PERFECT Stroke study presented here, a system for monitoring the Performance, Effectiveness, and Costs of Treatment episodes in Stroke was developed in Finland. Existing nationwide administrative registries were linked at individual patient level with personal identification numbers to depict whole episodes of care, from acute stroke, through rehabilitation, until the patients went home, were admitted to permanent institutional care, or died. For comparisons in time and between providers, patient case-mix was adjusted for. The PERFECT Stroke database includes 104 899 first-ever stroke patients over the years 1999 to 2008, of whom 79% had ischemic stroke (IS), 14% intracerebral hemorrhage (ICH), and 7% subarachnoid hemorrhage (SAH). A 18% decrease in the age and sex adjusted incidence of stroke was observed over the study period, 1.8% improvement annually. All-cause 1-year case-fatality rate improved from 28.6% to 24.6%, or 0.5% annually. The expected median lifetime after stroke increased by 2 years for IS patients, to 7 years and 7 months, and by 1 year for ICH patients, to 4 years 5 months. No change could be seen in median SAH patient survival, >10 years. Stroke prevalence was 82 000, 1.5% of total population of Finland, in 2008. Modern stroke center care was shown to be associated with a decrease in both death and risk of institutional care of stroke patients. Number needed to treat to prevent these poor outcomes at one year from stroke was 32 (95% confidence intervals 26 to 42). Despite improvements over the study period, more than a third of Finnish stroke patients did not have access to stroke center care. The mean first-year healthcare cost of a stroke patient was ~20 000 , and among survivors ~10 000 annually thereafter. Only part of this cost was incurred by stroke, as the same patients cost ~5000 over the year prior to stroke. Total lifetime costs after first-ever stroke were ~85 000 . A total of 1.1 Billion , 7% of all healthcare expenditure, is used in the treatment of stroke patients annually. Despite a rapidly aging population, the number of new stroke patients is decreasing, and the patients are more likely to survive. This is explained in part by stroke center care, which is effective, and should be made available for all stroke patients. It is possible, in a suitable setting with high-quality administrative registries and a common identifier, to avoid the huge workload and associated costs of setting up a conventional stroke registry, and still acquire a fairly comprehensive dataset on stroke care and outcome.

Accurate mass-based analysis in human sport doping control : Application of liquid chromatography - time-of-flight mass spectrometry

Human sport doping control analysis is a complex and challenging task for anti-doping laboratories. The List of Prohibited Substances and Methods, updated annually by World Anti-Doping Agency (WADA), consists of hundreds of chemically and pharmacologically different low and high molecular weight compounds. This poses a considerable challenge for laboratories to analyze for them all in a limited amount of time from a limited sample aliquot. The continuous expansion of the Prohibited List obliges laboratories to keep their analytical methods updated and to research new available methodologies. In this thesis, an accurate mass-based analysis employing liquid chromatography - time-of-flight mass spectrometry (LC-TOFMS) was developed and validated to improve the power of doping control analysis. New analytical methods were developed utilizing the high mass accuracy and high information content obtained by TOFMS to generate comprehensive and generic screening procedures. The suitability of LC-TOFMS for comprehensive screening was demonstrated for the first time in the field with mass accuracies better than 1 mDa. Further attention was given to generic sample preparation, an essential part of screening analysis, to rationalize the whole work flow and minimize the need for several separate sample preparation methods. Utilizing both positive and negative ionization allowed the detection of almost 200 prohibited substances. Automatic data processing produced a Microsoft Excel based report highlighting the entries fulfilling the criteria of the reverse data base search (retention time (RT), mass accuracy, isotope match). The quantitative performance of LC-TOFMS was demonstrated with morphine, codeine and their intact glucuronide conjugates. After a straightforward sample preparation the compounds were analyzed directly without the need for hydrolysis, solvent transfer, evaporation or reconstitution. The hydrophilic interaction technique (HILIC) provided good chromatographic separation, which was critical for the morphine glucuronide isomers. A wide linear range (50-5000 ng/ml) with good precision (RSD<10%) and accuracy (±10%) was obtained, showing comparable or better performance to other methods used. In-source collision-induced dissociation (ISCID) allowed confirmation analysis with three diagnostic ions with a median mass accuracy of 1.08 mDa and repeatable ion ratios fulfilling WADA s identification criteria. The suitability of LC-TOFMS for screening of high molecular weight doping agents was demonstrated with plasma volume expanders (PVE), namely dextran and hydroxyethylstarch (HES). Specificity of the assay was improved, since interfering matrix compounds were removed by size exclusion chromatography (SEC). ISCID produced three characteristic ions with an excellent mean mass accuracy of 0.82 mDa at physiological concentration levels. In summary, by combining TOFMS with a proper sample preparation and chromatographic separation, the technique can be utilized extensively in doping control laboratories for comprehensive screening of chemically different low and high molecular weight compounds, for quantification of threshold substances and even for confirmation. LC-TOFMS rationalized the work flow in doping control laboratories by simplifying the screening scheme, expediting reporting and minimizing the analysis costs. Therefore LC-TOFMS can be exploited widely in doping control, and the need for several separate analysis techniques is reduced.