Topographical, structural and geophysical characterization of fracture zones: implications for groundwater flow and vulnerability

The main objective of this study is to evaluate selected geophysical, structural and topographic methods on regional, local, and tunnel and borehole scales, as indicators of the properties of fracture zones or fractures relevant to groundwater flow. Such information serves, for example, groundwater exploration and prediction of the risk of groundwater inflow in underground construction. This study aims to address how the features detected by these methods link to groundwater flow in qualitative and semi-quantitative terms and how well the methods reveal properties of fracturing affecting groundwater flow in the studied sites. The investigated areas are: (1) the Päijänne Tunnel for water-conveyance whose study serves as a verification of structures identified on regional and local scales; (2) the Oitti fuel spill site, to telescope across scales and compare geometries of structural assessment; and (3) Leppävirta, where fracturing and hydrogeological environment have been studied on the scale of a drilled well. The methods applied in this study include: the interpretation of lineaments from topographic data and their comparison with aeromagnetic data; the analysis of geological structures mapped in the Päijänne Tunnel; borehole video surveying; groundwater inflow measurements; groundwater level observations; and information on the tunnel s deterioration as demonstrated by block falls. The study combined geological and geotechnical information on relevant factors governing groundwater inflow into a tunnel and indicators of fracturing, as well as environmental datasets as overlays for spatial analysis using GIS. Geophysical borehole logging and fluid logging were used in Leppävirta to compare the responses of different methods to fracturing and other geological features on the scale of a drilled well. Results from some of the geophysical measurements of boreholes were affected by the large diameter (gamma radiation) or uneven surface (caliper) of these structures. However, different anomalies indicating more fractured upper part of the bedrock traversed by well HN4 in Leppävirta suggest that several methods can be used for detecting fracturing. Fracture trends appear to align similarly on different scales in the zone of the Päijänne Tunnel. For example, similarities of patterns were found between the regional magnetic trends, correlating with orientations of topographic lineaments interpreted as expressions of fracture zones. The same structural orientations as those of the larger structures on local or regional scales were observed in the tunnel, even though a match could not be made in every case. The size and orientation of the observation space (patch of terrain at the surface, tunnel section, or borehole), the characterization method, with its typical sensitivity, and the characteristics of the location, influence the identification of the fracture pattern. Through due consideration of the influence of the sampling geometry and by utilizing complementary fracture characterization methods in tandem, some of the complexities of the relationship between fracturing and groundwater flow can be addressed. The flow connections demonstrated by the response of the groundwater level in monitoring wells to pressure decrease in the tunnel and the transport of MTBE through fractures in bedrock in Oitti, highlight the importance of protecting the tunnel water from a risk of contamination. In general, the largest values of drawdown occurred in monitoring wells closest to the tunnel and/or close to the topographically interpreted fracture zones. It seems that, to some degree, the rate of inflow shows a positive correlation with the level of reinforcement, as both are connected with the fracturing in the bedrock. The following geological features increased the vulnerability of tunnel sections to pollution, especially when several factors affected the same locations: (1) fractured bedrock, particularly with associated groundwater inflow; (2) thin or permeable overburden above fractured rock; (3) a hydraulically conductive layer underneath the surface soil; and (4) a relatively thin bedrock roof above the tunnel. The observed anisotropy of the geological media should ideally be taken into account in the assessment of vulnerability of tunnel sections and eventually for directing protective measures.

Risk factors for open angle glaucoma; a clinical and molecular genetic study

Glaucoma, optic neuropathy with excavation in the optic nerve head and corresponding visual field defect, is one of the leading causes for blindness worldwide. However, visual disability can often be avoided or delayed if the disease is diagnosed at an early stage. Therefore, recognising the risk factors for development and progression of glaucoma may prevent further damage. The purpose of the present study was to evaluate factors associated with visual disability caused by glaucoma and the genetic features of two risk factors, exfoliation syndrome (ES) and a positive family history of glaucoma. The present study material consisted of three study groups 1) deceased glaucoma patients from the Ekenäs practice 2) glaucoma families from the Ekenäs region and 3) population based families with and without exfoliation syndrome from Kökar Island. For the retrospective study, 106 patients with open angle glaucoma (OAG) were identified. At the last visit, 17 patients were visually impaired. Blindness induced by glaucoma was found in one or both eyes in 16 patients and in both eyes in six patients. The cumulative incidence of glaucoma caused blindness for one eye was 6% at 5 years, 9% at 10 years, and 15% at 15 years from initialising the treatment. The factors associated with blindness caused by glaucoma were an advanced stage of glaucoma at diagnosis, fluctuation in intraocular pressure during treatment, the presence of exfoliation syndrome, and poor patient compliance. A cross-sectional population based study performed in 1960-1962 on Kökar Island and the same population was followed until 2002. In total 965 subjects (530 over 50 years) have been examined at least once. The prevalence of exfoliation syndrome (ES) was 18% among subjects older than 50 years. Seventy-five of all 78 ES-positives belonged to the same extended pedigree. According to the segregation and family analysis, exfoliation syndrome seemed to be inherited as an autosomal dominant trait with reduced penetrance. The penetrance was more reduced for males, but the risk for glaucoma was higher in males than in females. To find the gene or genes associated with exfoliation syndrome, a genome wide scan was performed for 64 members (28 ES affected and 36 controls) of the Kökar pedigree. A promising result was found: the highest two-point LOD score of 3.45 (θ=0.04) in chromosome18q12.1-21.33. The presence of mutations in glaucoma genes TIGR/MYOC (myocilin) and OPTN (optineurin) was analysed in eight glaucoma families from the Ekenäs region. An inheritance pattern resembling autosomal dominant mode was detected in all these families. Primary open angle glaucoma or exfoliation glaucoma was found in 35% of 136 family members and 28% were suspected to have glaucoma. No mutations were detected in these families.

Laboratory analyses for evaluation of platelet disorders and platelet concentrates

High quality of platelet analytics requires specialized knowledge and skills. It was applied to analyze platelet activation and aggregation responses in a prospective controlled study of patients with Finnish type of amyloidosis. The 20 patients with AGel amyloidosis displayed a delayed and more profound platelet shape change than healthy siblings and healthy volunteers, which may be related to altered fragmentation of mutated gelsolin during platelet activation. Alterations in platelet shape change have not been reported in association with platelet disorders. In the rare Bernard-Soulier syndrome with Asn45Ser mutation of glycoprotein (GP) IX, the diagnostic defect in the expression of GPIb-IX-V complex was characterized in seven Finnish patients, also an internationally exceptionally large patient series. When measuring thrombopoietin in serial samples of amniotic fluid and cord blood of 15 pregnant women with confirmed or suspected fetal alloimmune thrombocytopenia, the lower limit of detection could be extended. The results approved that thrombopoietin is present already in amniotic fluid. The application of various non-invasive means for diagnosing thrombocytopenia (TP) revealed that techniques for estimating the proportion of young, i.e. large platelets, such as direct measurement of reticulated platelets and the mean platelet size, would be useful for evaluating platelet kinetics in a given patient. Due to different kinetics between thrombopoietin and increase of young platelets in circulation, these measurements may have most predictive value when measured from simultaneous samples. Platelet autoantibodies were present not only in isolated autoimmune TP but also in patients without TP where disappearance of platelets might be compensated by increased production. The autoantibodies may also persist after TP has been cured. Simultaneous demonstration of increased young platelets (or increased mean platelet volume) in peripheral blood and the presence of platelet associated IgG specificities to major glycoproteins (GPIb-IX and GPIIb-IIIa) may be considered diagnostic for autoimmune TP. Measurement of a soluble marker as a sign of thrombin activation and proceeding deterioration of platelet components was applied to analyze the alterations under several stress factors (storage, transportation and lack of continuous shaking under controlled conditions) of platelet products. The GPV measured as a soluble factor in platelet storage medium showed good correlation with an array of other measurements commonly applied in characterization of stored platelets. The benefits of measuring soluble analyte in a quantitative assay were evident.

Essential Thrombocythaemia : Diagnosis, Prognostic Aspects, and the Outcome of Finnish patients

Essential thrombocythaemia (ET) is a myeloproliferative disease (MPD) characterized by thrombocytosis, i.e. a constant elevation of platelet count. Thrombocytosis may appear in MPDs (ET, polycythaemia vera, chronic myeloid leukaemia, myelofibrosis) and as a reactive phenomenon. The differential diagnosis of thrombocytosis is important, because the clinical course, need of therapy, and prognosis are different in patients with MPDs and in those with reactive thrombocytosis. ET patients may remain asymptomatic for years, but serious thrombohaemorrhagic and pregnancy-related complications may occur. The complications are difficult to predict. The aims of the present study were to evaluate the diagnostic findings, clinical course, and prognostic factors of ET. The present retrospective study consists of 170 ET patients. Two thirds had a platelet count < 1000 x 109/l. The diagnosis was supported by an increased number of megakaryocytes with an abnormal morphology in a bone marrow aspirate, aggregation defects in platelet function studies, and the presence of spontaneous erythroid and/or megakaryocytic colony formation in in vitro cultures of haematopoietic progenitors. About 70 % of the patients had spontaneous colony formation, while about 30 % had a normal growth pattern. Only a fifth of the patients remained asymptomatic. Half had a major thrombohaemorrhagic complication. The proportion of the patients suffering from thrombosis was as high as 45 %. About a fifth had major bleedings. Half of the patients had microvascular symptoms. Age over 60 years increased the risk of major bleedings, but the occurrence of thrombotic complications was similar in all age groups. Male gender, smoking in female patients, the presence of any spontaneous colony formation, and the presence of spontaneous megakaryocytic colony formation in younger patients were identified as risk factors for thrombosis. Pregnant ET patients had an increased risk of complications. Forty-five per cent of the pregnancies were complicated and 38 % of them ended in stillbirth. Treatment with acetylsalicylic acid alone or in combination with platelet lowering drugs improved the outcome of the pregnancy. The present findings about risk factors in ET as well as treatment outcome in the pregnancies of ET patients should be taken into account when planning treatment strategies for Finnish patients.

Basement membrane and provisional matrix components (collagen type IV, laminins and von Willebrand factor) in rheumatoid arthritis and Sjögren s syndrome

The aim of this study was twofold- Firstly, to determine the composition of the type IV collagen which are the major components of the basement membrane (BM), in the synovial lining of the rheumatoid arthritis (RA) patient and in the BM in the labial salivary gland of the Sjögrens syndrome (SS) patient. Secondly, this thesis aimed to investigate the role of the BM component laminin α4 and laminin α5 in the migration of neutrophils from the blood vessels thorough the synovial lining layer into synovial fluid and the presence of vWF in the microvasculature of labial salivary gland in SS. Our studies showed that certain α chains type IV collagen are low in RA compared to control synovial linings, while laminin α5 exhibited a pattern of low expression regions at the synovial lining interface towards the joint cavity and fluid. Also, high numbers of macrophage-like lining cells containing MMP-9 were found in the lining. MMP-9 was also found in the synovial fluid. Collagen α1/2 (IV) mRNA was found to be present in high amount compared to the other α(IV) chains and also showed intense labelling in immunohistochemical staining in normal and SS patients. In healthy glands α5(IV) and α6(IV) chains were found to be continuous around ducts but discontinuous around acini. The α5(IV) and α6(IV) mRNAs were present in LSG explants and HSG cell line, while in SS these chains seemed to be absent or appear only in patches around the ductal BM and tended to be absent around acini in immunohistochemical staining, indicating that their synthesis and/or degradation seemed to be locally regulated around acinar cells. The provisional matrix component vWF serves as a marker of vascular damage. Microvasculature in SS showed signs of focal damage which in turn might impair arteriolar feeding, capillary transudation and venular drainage of blood. However, capillary density was not decreased but rather increased, perhaps as a result of angiogenesis compensatory to microvascular damage. Microvascular involvement of LSG may contribute to the pathogenesis of this syndrome. This twofold approach allows us to understand the intricate relation between the ECM components and the immunopathological changes that occur during the pathogenesis of these inflammatory rheumatic disease processes. Also notably this study highlights the importance of maintaining a healthy ECM to prevent the progression or possibly allow reversal of the disease to a considerable level. Furthermore, it can be speculated that a healthy BM could quarantine the inflamed region or in case of cancer cells barricade the movement of malignant cells thereby preventing further spread to the surrounding areas. This understanding can be further applied to design appropriate drugs which act specifically to maintain a proper BM/BM like intercellular matrix composition.

The influence of school smoking policy and school prevention programs on the smoking behaviour of high school students in Prince Edward Island, Canada

The aim of the study was to examine the influence of school smoking policy and school smoking prevention programs on the smoking behaviour of students in high schools in Prince Edward Island using the School Health Action Planning Evaluation System (SHAPES). A total sample included 13,131 observations of students in grades 10-12 in ten high schools in Prince Edward Island over three waves of data collection (1999, 2000, and 2001). Changes in prevalence of smoking and factors influencing smoking behaviour were analyzed using descriptive statistics and Chi-Square tests. Multi-level logistic regression analyses were used to examine how both school and student characteristics were associated with smoking behaviour (I, II, III, IV). Since students were located within schools, a basic 2-level nested structure was used in which individual students (level 1) were nested within schools (level 2). For grade 12 students, the combination of both school policies and programs was not associated with the risk of smoking and the presence of the new policy was not associated with decreased risk of smoking, unless there were clear rules in place (I). For the grade 10 study, (II) schools with both policies and programs were not associated with decreased risk of smoking. However, the smoking behaviour of older students (grade 12) at a school was associated with younger students’ (grade 10) smoking behaviour. Students first enrolled in a high school in grade 9, rather than grade 10, were at increased risk of occasional smoking. For students who transitioned from grade 10 to 12 (III), close friends smoking had a substantial influence on smoking behaviour for both males and females (III). Having one or more close friends who smoke (Odds Ratio (OR) = 37.46; 95% CI = 19.39 to 72.36), one or more smokers in the home (OR = 2.35; 95% CI = 1.67 to 3.30) and seeing teachers and staff smoking on or near school property (OR=1.78; 95% CI = 1.13 to 2.80), were strongly associated with increased risk of smoking for grade 12 students. Smoking behaviour increased for both junior (Group 1) and senior (Group 2) students (IV). Group 1 students indicated a greater decrease in smoking behaviour and factors influencing smoking behaviour compared to those of Group 2. Students overestimating the percentage of youth their age who smoke was strongly associated with increased likelihood of smoking. Smoking rates showed a decreasing trend (1999, 2000, and 2001). However, policies and programs alone were not successful in influencing smoking behaviour of youth. Rather, factors within the students and schools contextual environment influenced smoking behaviour. Comprehensive approaches are required for school-based tobacco prevention interventions. Keywords: schools, policy, programs, smoking prevention, adolescents Subject Terms: school-based programming, public health, health promotion

Studies of electronic structure by x-ray Raman and emission spectroscopy: applications to MgB2 superconductors and high pressure physics

X-ray Raman scattering and x-ray emission spectroscopies were used to study the electronic properties and phase transitions in several condensed matter systems. The experimental work, carried out at the European Synchrotron Radiation Facility, was complemented by theoretical calculations of the x-ray spectra and of the electronic structure. The electronic structure of MgB2 at the Fermi level is dominated by the boron σ and π bands. The high density of states provided by these bands is the key feature of the electronic structure contributing to the high critical temperature of superconductivity in MgB2. The electronic structure of MgB2 can be modified by atomic substitutions, which introduce extra electrons or holes into the bands. X ray Raman scattering was used to probe the interesting σ and π band hole states in pure and aluminum substituted MgB2. A method for determining the final state density of electron states from experimental x-ray Raman scattering spectra was examined and applied to the experimental data on both pure MgB2 and on Mg(0.83)Al(0.17)B2. The extracted final state density of electron states for the pure and aluminum substituted samples revealed clear substitution induced changes in the σ and π bands. The experimental work was supported by theoretical calculations of the electronic structure and x-ray Raman spectra. X-ray emission at the metal Kβ line was applied to the studies of pressure and temperature induced spin state transitions in transition metal oxides. The experimental studies were complemented by cluster multiplet calculations of the electronic structure and emission spectra. In LaCoO3 evidence for the appearance of an intermediate spin state was found and the presence of a pressure induced spin transition was confirmed. Pressure induced changes in the electronic structure of transition metal monoxides were studied experimentally and were analyzed using the cluster multiplet approach. The effects of hybridization, bandwidth and crystal field splitting in stabilizing the high pressure spin state were discussed. Emission spectroscopy at the Kβ line was also applied to FeCO3 and a pressure induced iron spin state transition was discovered.

Components of fractionated stallion seminal plasma and the effects of seminal plasma on sperm longevity

Seminal plasma (SP) is the fluid portion of semen, secreted by the epididymides and the accessory glands before and during ejaculation. The stallion s ejaculate is a series of jets that differ in sperm concentration, semen volume and biochemical composition. Before the actual ejaculation, a clear and watery pre-sperm fluid is secreted. The first three jets form the sperm-rich fractions, and contain ¾ of the total number of sperm. The semen volume and sperm concentration in each of the jets decrease towards the end of the ejaculation, and the last jets are sperm-poor fractions with a low sperm concentration. The aims of these studies were to examine the effects of the different SP fractions, and the presence of SP, on sperm survival during storage. Pre-sperm fluid, and semen fractions with a high (sperm-rich) and low (sperm-poor) sperm concentration were collected in five experiments. The levels of selected enzymes, electrolytes and proteins in different SP fractions were determined. These studies also aimed at assessing the individual variation in the levels of the selected SP components and in the effects of SP on spermatozoa. The association between the components of SP and semen quality, sperm longevity, and fertility was examined with a stepwise linear regression analysis. Compared to samples containing SP during storage, centrifugation and the subsequent removal of SP reduced sperm motility parameters during 24 h of cooled storage in all SP fractions, but sperm membrane integrity was not affected. Some of the measured post-thaw motility parameters were also higher in samples containing SP compared to samples stored without SP. In contrast, the proportion of DNA-damaged spermatozoa was greater in the samples stored with SP than those without SP, and this effect was seen in both sperm-rich and sperm-poor fractions. There were no differences in DNA integrity between fractions stored with SP, but the sperm-rich fraction showed less DNA damage than the sperm-poor fraction after SP removal. The differences between fractions in sperm motility after cooled storage were non-significant. The levels of alkaline phosphatase, acid phosphatase and β-glucuronidase were higher in the sperm-rich fractions compared to the sperm-poor fractions, while the concentrations of calcium and magnesium were higher in sperm-poor fractions than in sperm-rich fractions. The concentrations of sodium and chloride were highest in pre-sperm fluid. In the sperm-poor fraction, the level of potassium was associated with the maintenance of sperm motility during storage. The levels of alkaline and acid phosphatase were associated with sperm concentration and the total number of spermatozoa in the ejaculates. None of the measured SP components were correlated to the first cycle pregnancy rate. In summary, the removal of SP improved DNA integrity after cooled storage compared with samples containing SP. There were no differences in the maintenance of sperm motility between the sperm-rich and sperm-poor fractions and whole ejaculates during cooled storage, irrespective of the presence of SP. The lowest rate of DNA damage was found in the sperm-rich fractions stored without SP. In practice, the results presented in this thesis support the use of individual modifications of semen processing techniques for cooled transported semen from subfertile stallions.

Poststroke survival and ischemic stroke recurrence : the cerebral small-vessel disease perspective

The aim of the present study was to investigate the influence of different manifestations of cerebral SVD on poststroke survival and ischemic stroke recurrence in long-term follow-up. The core imaging features of small-vessel disease (SVD) are confluent and extensive white matter changes (WMC) and lacunar infarcts. These are associated with minor motor deficits but a major negative influence on cognition, mood, and functioning in daily life, resulting from small-vessel lesions in the fronto-subcortical brain network. These sub-studies were conducted as part of the Helsinki Stroke Aging Memory (SAM) study. The SAM cohort consisted of 486 consecutive patients aged 55 to 85 years who were admitted to Helsinki University Central Hospital with acute ischemic stroke. The study included comprehensive clinical, neuropsychological, psychiatric and radiological assessment three months poststroke. The patients were followed up up for 12 years using extensive national registers. The effect of different manifestations of cerebral SVD on poststroke survival and stroke recurrence was analyzed controlling for factors such as age, education, and cardiovascular risk factors. Poststroke dementia and cognitive impairment relate to poor long-term survival. In particular, deficits in executive functions as well as visuospatial and constructional abilities predict poor outcome. The predictive value of cognitive deficits is further underlined by the finding that depression-executive dysfunction syndrome (DES), but not depression in itself, is associated with poor poststroke survival. Delirium is not independently associated with increased risk for long-term poststroke mortality, although it is associated with poststroke dementia. Furthermore, acute index stroke attributable to SVD is associated with poorer long-term survival and a higher risk for cardiac death than other stroke subtypes. Severe WMC, a surrogate of SVD, is independently related to an increased risk of stroke recurrence at five years. In summary, cognitive poststroke outcomes reflecting changes in the executive network brain, and the presence of cerebral SVD are important determinants of poststroke mortality and ischemic stroke recurrence, regardless of whether SVD is the cause of the index stroke or a condition concurrent to some other etiology.