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  • Lohman, Martina (Helsingin yliopisto, 2001)
  • Soljanlahti, Sami (Helsingin yliopisto, 2008)
    Cardiovascular diseases (CVD) are, in developed countries, the leading cause of mortality. The majority of premature deaths and disability caused by CVD are due to atherosclerosis, a degenerating inflammatory disease affecting arterial walls. Early identification of lesions and initiation of treatment is crucial because the first manifestations quite often are major disabling cardiovascular events. Methods of finding individuals at high risk for these events are under development. Because magnetic resonance imaging (MRI) is an excellent non-invasive tool to study the structure and function of vascular system, we sought to discover whether existing MRI methods are able to show any difference in aortic and intracranial atherosclerotic lesions between patients at high risk for atherosclerosis and healthy controls. Our younger group (age 6-48) comprised 39 symptomless familial hypercholesterolemia (FH) patients and 25 healthy controls. Our older group (age 48-64) comprised 19 FH patients and 18 type 2 diabetes mellitus (DM) patients with coronary heart disease (CHD) and 29 healthy controls. Intracranial and aortic MRI was compared with carotid and femoral ultrasound (US). In neither age-group did MRI reveal any difference in the number of ischemic brain lesions or white matter hyperintensities (WMHIs) - possible signs of intracranial atherosclerosis - between patients and controls. Furthermore, MRI showed no difference in the structure or function of the aorta between FH patients and controls in either group. DM patients had lower compliance of the aorta than did controls, while no difference appeared between DM and FH patients. However, ultrasound showed greater plaque burden and increased thickness of carotid arterial walls in FH and DM patients in both age-groups, suggesting a more advanced atherosclerosis. The mortality of FH patients has decreased substantially after the late 1980´s when statin treatment became available. With statins, the progression of atherosclerotic lesions slows. We think that this, in concert with improvements in treatment of other risk factors, is one reason for the lack of differences between FH patients and controls in MRI measurements of the aorta and brain despite the more advanced disease of the carotid arteries assessed with US. Furthermore, whereas atherosclerotic lesions between different vascular territories correlate, differences might still exist in the extent and location of these lesions among different diseases. Small (<5 mm in diameter) WMHIs are more likely a phenomenon related to aging, but the larger ones may be the ones related to CVD and may be intermediate surrogates of stroke. The image quality in aortic imaging, although constantly improving, is not yet optimal and thus is a source of bias.
  • Kiuru, Martti (Helsingin yliopisto, 2002)
  • Korhonen, Petri (Helsingin yliopisto, 2002)
  • Pomoell, Jens (Helsingin yliopisto, 2012)
    Solar eruptions are a consequence of the complex dynamics occurring in the tenuous, hot magnetized plasma that characterizes the solar corona. From a socio-economic viewpoint, solar eruptions can be argued to be the most important manifestation of the magnetic activity of the Sun due to their role as the main drivers of space weather, i.e., conditions in space that can have an adverse impact on space- as well as ground-based technologies such as telecommunication, electric power systems and satellite navigation. The launch of new space-based solar observatories during the past two decades has resulted in a dramatic improvement of the instrumentation monitoring the inner heliosphere. In spite of the advances in the observational capabilities, the physics of the solar eruptions as well as the nature of the various transient large-scale coronal phenomena observationally associated with the eruptions remain elusive. Constructing models capable of simulating the coronal and heliospheric dynamics is a viable path for gaining a more complete understanding of these phenomena. This thesis is concerned with developing a simulation tool based on the magnetohydrodynamic (MHD) description of plasmas and employing it for studying the characteristics of large-scale waves and shocks launched into the solar corona by the lift-off of a solar eruption such as a coronal mass ejection (CME). A particular focus is on discussing the role of large-amplitude waves in producing transient phenomena such as EIT waves and solar energetic particle (SEP) events that are known to appear in conjunction with CMEs. A suite of MHD models of the solar corona are constructed that allow the study of the coronal dynamics in varying environments at several stages of the eruption. For this purpose, novel robust numerical methods for solving the equations of magnetohydrodynamics in orthogonal curvilinear geometries in multiple dimensions are derived, forming the basis of the numerical simulation tool developed for the thesis. The results show that a dynamically intricate global shock front degenerating to a fast-mode MHD wave towards the surface of the Sun is an essential and natural part of the eruption complex that plays a key role in the generation of eruption-related transient phenomena. For instance, the close resemblance between the on-disk signatures produced by the fast-mode wave and EIT waves suggest a wave interpretation of the latter. The simulations also reveal that a highly non-trivial evolution of the shock properties on coronal field lines occurs even for simple coronal conditions, highlighting the need for more sophisticated models of particle acceleration than generally used so far. The results of the thesis are of particular importance for the continuing efforts to construct reliable physics-based models of the inner heliosphere for use in space weather applications.
  • Pykälä, Juha (Helsingin yliopisto, 2007)
    Semi-natural grasslands are the most important agricultural areas for biodiversity. The present study investigates the effects of traditional livestock grazing and mowing on plant species richness, the main emphasis being on cattle grazing in mesic semi-natural grasslands. The two reviews provide a thorough assessment of the multifaceted impacts and importance of grazing and mowing management to plant species richness. It is emphasized that livestock grazing and mowing have partially compensated the suppression of major natural disturbances by humans and mitigated the negative effects of eutrophication. This hypothesis has important consequences for nature conservation: A large proportion of European species originally adapted to natural disturbances may be at present dependent on livestock grazing and / or mowing. Furthermore, grazing and mowing are key management methods to mitigate effects of nutrient-enrichment. The species composition and richness in old (continuously grazed), new (grazing restarting 3-8 years ago) and abandoned (over 10 years) pastures differed consistently across a range of spatial scales, and was intermediate in new pastures compared to old and abandoned pastures. In mesic grasslands most plant species were shown to benefit from cattle grazing. Indicator species of biologically valuable grasslands and rare species were more abundant in grazed than in abandoned grasslands. Steep S-SW-facing slopes are the most suitable sites for many grassland plants and should be prioritized in grassland restoration. The proportion of species trait groups benefiting from grazing was higher in mesic semi-natural grasslands than in dry and wet grasslands. Consequently, species trait responses to grazing and the effectiveness of the natural factors limiting plant growth may be intimately linked High plant species richness of traditionally mowed and grazed areas is explained by numerous factors which operate on different spatial scales. Particularly important for maintaining large scale plant species richness are evolutionary and mitigation factors. Grazing and mowing cause a shift towards the conditions that have occurred during the evolutionary history of European plant species by modifying key ecological factors (nutrients, pH and light). The results of this Dissertation suggest that restoration of semi-natural grasslands by private farmers is potentially a useful method to manage biodiversity in the agricultural landscape. However, the quality of management is commonly improper, particularly due to financial constraints. For enhanced success of restoration, management regulations in the agri-environment scheme need to be defined more explicitly and the scheme should be revised to encourage management of biodiversity.
  • Palikhe, Anil (Helsingin yliopisto, 2008)
    Most of the genes in the MHC region are involveed in adaptive and innate immunity, with essential function in inflammatory reactions and in protection against infections. These genes might serve as a candidate region for infection and inflammation associated diseases. CAD is an inflammatory disease. The present set of studies was performed to assess whether the MHC region harbors genetic markers for CAD, and whether these genetic markers explain the CAD risk factors: e.g., C. pneumoniae, periodontitis, and periodontal pathogens. Study I was performed using two separate patient materials and age- and sex-matched healthy controls, categorizing them into two independent studies: the HTx and ACS studies. Both studies consistently showed the HLA-A3– B35– DR1 (35 ancestral haplotype) haplotype as a susceptible MHC genetic marker for CAD. HLA-DR1 alone was associated not only with CAD, but also with CAD risk factor diseases, e.g., diabetes mellitus, and hyperlipidemia. The ACS study further showed the HLA-B*07 and -DRB1*15 -related haplotype as a protective MHC haplotype for CAD. Study II showed that patients with CAD showed signs of chronic C. pneumoniae infection when compared to age- and sex-matched healthy controls. HLA-B*35 or -related haplotypes associated with the C. pneumoniae infection markers. Among these haplotype carriers, males and smokers associated with elevated C. pneumoniae infection markers. Study III showed that CAD patients with periodontitis had elevated serum markers of P. gingivalis and occurrence of the pathogen in saliva. LTA+496C strongly associated with periodontitis, while HLA-DRB1*01 with periodontitis and with the elevated serum antibodies of P. gingivalis. Study IV showed that the increased level of C3/C4 ratio was a new risk factor and was associated with recurrent cardiovascular end-points. The increased C3 and decreased C4 concentrations in serum explained the increased level of the C3/C4 ratio. Both the higher than cut-off value (4.53) and the highest quartile of the C3/C4 ratio were also associated with worst survival, increased end-points, and C4 null alleles. The presence of C4 null alleles associated with decreased serum C4 concentration, and increased C3/C4 ratio. In conclusion, the present studies show that the CAD susceptibility haplotype (HLA-A3− B35− DR1 -related haplotypes, Study I) partially explains the development of CAD in patients possessing several recognized and novel risk factors: diabetes mellitus, increased LDL, smoking, C4B*Q0, C. pneumnoiae, periodontitis, P. gingivalis, and complement C3/C4 ratio (Study II, III, and IV).
  • Paakkanen, Riitta (Helsingin yliopisto, 2013)
    Atherosclerosis is a chronic, inflammatory, lifestyle-disease that is also influenced by genetic factors. Coronary atherosclerosis manifests as silent, chronic and acute forms. The acute forms, acute coronary syndromes (ACS) are an important cause of death due to coronary atherosclerosis. The major histocompatibility complex (MHC) region is a collection of genes on chromosome 6 that are associated with immune response. The genes in this region are usually inherited as a strongly linked genetic combination, a haplotype. Certain alleles and haplotypes of the MHC region have been linked with different forms of coronary atherosclerosis. The Thesis was set to study the role of selected MHC genes/alleles in ACS. First aim of the Thesis was to develop a novel quantitative polymerase chain reaction (qPCR) method for complement component C4 analyses. A qPCR method with a novel concentration range approach and SYBR® Green dye was developed (I). It was validated by applying it to over 1600 patient samples with available C4 protein data and by analysing 129 samples that were also assessed with other methods for C4 gene analysis. The results indicated that the developed method can be used to reliably assess C4 copy number variation. The second aim was to confirm the role of selected MHC genes and haplotypes in different clinical forms of ACS. Based on previous studies, four MHC markers that had been reported to be associated with coronary atherosclerosis were selected (HLA-DRB1*01, HLA-B*35, deficiency of complement component C4A or C4B). A haplotype with DRB1*01, with neither C4 deficiencies nor B*35 was more frequently detected in patients suffering from ACS than in healthy controls (11 vs. 5%; III). None of the markers alone was associated with a significantly increased risk of ACS (II-IV). However, the power was too low to exclude a weak association of C4 deficiency and ACS (II, IV). If only men were studied, both DRB1*01 alone and the DRB1*01-haplotype were significantly associated with ACS. The third aim was to evaluate the possible inflammatory mechanisms through which the association of MHC genes/haplotypes and ACS could be mediated. The DRB1*01-haplotype was associated with higher hsCRP levels (III). C4 deficiency segregated patients that benefitted from macrolide treatment in secondary prevention of recurrent ACS (II). C4 deficiency was also associated with elevated heat shock protein 60 IgA autoantibody levels, which, in turn, was shown to be associated with ACS and recurrent cardiovascular end points (IV). C4 deficiency was also increased in patients suffering from recurrent infections (I). The genetic polymorphism in MHC may be linked with ACS by affecting the inflammatory responses. These data are observational and thus do not indicate causality. However, these data might help to elucidate the complex interplay of inflammatory reactions in ACS and in directing patient care.
  • Karttunen, Marie-Louise (Helsingin yliopisto, 2005)
  • Helenius, Katja (Helsingin yliopisto, 2011)
    All protein-encoding genes in eukaryotes are transcribed into messenger RNA (mRNA) by RNA Polymerase II (RNAP II), whose activity therefore needs to be tightly controlled. An important and only partially understood level of regulation is the multiple phosphorylations of RNAP II large subunit C-terminal domain (CTD). Sequential phosphorylations regulate transcription initiation and elongation, and recruit factors involved in co-transcriptional processing of mRNA. Based largely on studies in yeast models and in vitro, the kinase activity responsible for the phosphorylation of the serine-5 (Ser5) residues of RNAP II CTD has been attributed to the Mat1/Cdk7/CycH trimer as part of Transcription Factor IIH. However, due to the lack of good mammalian genetic models, the roles of both RNAP II Ser5 phosphorylation as well as TFIIH kinase in transcription have provided ambiguous results and the in vivo kinase of Ser5 has remained elusive. The primary objective of this study was to elucidate the role of mammalian TFIIH, and specifically the Mat1 subunit in CTD phosphorylation and general RNAP II-mediated transcription. The approach utilized the Cre-LoxP system to conditionally delete murine Mat1 in cardiomyocytes and hepatocytes in vivo and and in cell culture models. The results identify the TFIIH kinase as the major mammalian Ser5 kinase and demonstrate its requirement for general transcription, noted by the use of nascent mRNA labeling. Also a role for Mat1 in regulating general mRNA turnover was identified, providing a possible rationale for earlier negative findings. A secondary objective was to identify potential gene- and tissue-specific roles of Mat1 and the TFIIH kinase through the use of tissue-specific Mat1 deletion. Mat1 was found to be required for the transcriptional function of PGC-1 in cardiomyocytes. Transriptional activation of lipogenic SREBP1 target genes following Mat1 deletion in hepatocytes revealed a repressive role for Mat1apparently mediated via co-repressor DMAP1 and the DNA methyltransferase Dnmt1. Finally, Mat1 and Cdk7 were also identified as a negative regulators of adipocyte differentiation through the inhibitory phosphorylation of Peroxisome proliferator-activated receptor (PPAR) γ. Together, these results demonstrate gene- and tissue-specific roles for the Mat1 subunit of TFIIH and open up new therapeutic possibilities in the treatment of diseases such as type II diabetes, hepatosteatosis and obesity.
  • Seppänen, Johanna (Helsingin yliopisto, 2008)
    A population-based early detection program for breast cancer has been in progress in Finland since 1987. According to regulations during the study period 1987-2001, free of charge mammography screening was offered every second year to women aged 50-59 years. Recently, the screening service was decided to be extended to age group 50-69. However, the scope of the program is still frequently discussed in public and information about potential impacts of mass-screening practice changes on future breast cancer burden is required. The aim of this doctoral thesis is to present methodologies for taking into account the mass-screening invitation information in breast cancer burden predictions, and to present alternative breast cancer incidence and mortality predictions up to 2012 based on scenarios of the future screening policy. The focus of this work is not on assessing the absolute efficacy but the effectiveness of mass-screening, and, by utilizing the data on invitations, on showing the estimated impacts of changes in an existing screening program on the short-term predictions. The breast cancer mortality predictions are calculated using a model that combines incidence, cause-specific and other cause survival on individual level. The screening invitation data are incorporated into modeling of breast cancer incidence and survival by dividing the program into separate components (first and subsequent rounds and years within them, breaks, and post screening period) and defining a variable that gives the component of the screening program. The incidence is modeled using a Poisson regression approach and the breast cancer survival by applying a parametric mixture cure model, where the patient population is allowed to be a combination of cured and uncured patients. The patients risk to die from other causes than breast cancer is allowed to differ from that of a corresponding general population group and to depend on age and follow-up time. As a result, the effects of separate components of the screening program on incidence, proportion of cured and the survival of the uncured are quantified. According to the predictions, the impacts of policy changes, like extending the program from age group 50-59 to 50-69, are clearly visible on incidence while the effects on mortality in age group 40-74 are minor. Extending the screening service would increase the incidence of localized breast cancers but decrease the rates of non-localized breast cancer. There were no major differences between mortality predictions yielded by alternative future scenarios of the screening policy: Any policy change would have at the most a 3.0% reduction on overall breast cancer mortality compared to continuing the current practice in the near future.
  • Alestalo, Paula Kaarina (Helsingin yliopisto, 2015)
    ABSTRACT The general objective of this thesis was to study management and leadership in the Public Dental Service (PDS) in Finland during the major Dental Care Reform in 2003–2011. The specific aims were to study 1) how dentists became leaders in the PDS and 2) what characterised their leadership, 3) distribution of leadership positions between women and men, 4) chief dentists’ position in the municipal hierarchy, as seen from their own superiors’ and subordinates’ points of view and 5) chief dentists’ attitudes to the Dental Care Reform and the changes it caused in the work environment. Four questionnaire surveys based on four data sets were carried out in 2003. The target groups were the chief dentists of the municipal PDS units (health centres) (n=265), the chief physicians (n=233), the line managers (superiors) of the chief dentists, PDS dentists who were subordinates to the chief dentists (n=365), and the chairpersons of Municipal Boards of Social Affairs and Health (MBSH) (n=233). In 2011, the target group was the chief dentists alone (n=161). Factor analysis, linear regression analysis, parametric and non-parametric tests were used in the analysis of the materials. The results showed that only fewer than a fifth (17%) of chief dentists were full-time leaders in 2011 and they worked in the largest health centres. The rest also provided patient care, to varying degrees. In 2003 and 2011, nearly two thirds (62%) of the chief dentists identified themselves as leaders instead of seeing themselves only as dentists among other dentists in the PDS, though fewer than a third (31%) of them had applied for their posts. More precisely, just 21% of female and 43% of male chief dentists (p<0.001) had applied for the chief dentist posts they held. Chief dentists felt they were better people-oriented leaders than goal-oriented managers (p<0.001). Nevertheless, 49% p<0.001) of their job satisfaction was explained by the fact that they were motivated to lead, their position as superiors to their subordinates was good, they had enough (3-4 on a scale 1-4) decision making power, they were good goal-oriented managers (good in sum variables ≥3 on a scale 1-4 from very bad to very good), and had received enough (3 on a scale 1-3) leadership education. In addition, if they had a good position as subordinates to their superiors, chief physicians and MBSH chairpersons (p<0.001), and when they had applied for their posts, they felt contented (p<0.001). In 2003, their subordinates, the PDS dentists, appreciated their people-oriented female superiors highest. Chief dentists themselves as subordinates felt they received little feedback and support from their superiors (chief physicians), and their own subordinates, the PDS dentists, felt the same (p<0.001). Chief dentists’ superiors (chief physicians and MBSH chairpersons) evaluated the chief dentists as good managers and leaders, whereas the chief dentists’ subordinates evaluated their superiors in less positive terms. In 2003, more than half (59%) of the chief dentists were very positive (4 on a scale 1-4) towards the recently introduced reforms of the Health Insurance Act (HIA) promoting adults’ treatment in the private sector by increasing reimbursement for dental care. Fewer than half (43%) were very positive towards the reform of the Primary Health Care Act (PHCA) improving adults’ access to care in the public sector (p<0.001). In 2011, only 20% totally agreed (4 on a scale 1-4) that the implementation of the Dental Care Reform had succeeded. The respondents’ general opinion was that the timetable for the Reform was too tight and not enough resources were allocated. In general, the chief dentists considered their position as isolated and rather weak in the municipal hierarchy. Effective and rewarding leadership in the PDS needs more attention in the future.
  • Heikinheimo, Outi (Helsingin yliopisto, 2000)
  • Rasinmäki, Jussi (2007)
    During the last decades there has been a global shift in forest management from a focus solely on timber management to ecosystem management that endorses all aspects of forest functions: ecological, economic and social. This has resulted in a shift in paradigm from sustained yield to sustained diversity of values, goods and benefits obtained at the same time, introducing new temporal and spatial scales into forest resource management. The purpose of the present dissertation was to develop methods that would enable spatial and temporal scales to be introduced into the storage, processing, access and utilization of forest resource data. The methods developed are based on a conceptual view of a forest as a hierarchically nested collection of objects that can have a dynamically changing set of attributes. The temporal aspect of the methods consists of lifetime management for the objects and their attributes and of a temporal succession linking the objects together. Development of the forest resource data processing method concentrated on the extensibility and configurability of the data content and model calculations, allowing for a diverse set of processing operations to be executed using the same framework. The contribution of this dissertation to the utilisation of multi-scale forest resource data lies in the development of a reference data generation method to support forest inventory methods in approaching single-tree resolution.
  • Pöyry, Juha (Helsingin yliopisto, 2007)
    This work focuses on the factors affecting species richness, abundance and species composition of butterflies and moths in Finnish semi-natural grasslands, with a special interest in the effects of grazing management. In addition, an aim was set at evaluating the effectiveness of the support for livestock grazing in semi-natural grasslands, which is included in the Finnish agri-environment scheme. In the first field study, butterfly and moth communities in resumed semi-natural pastures were com-pared to old, annually grazed and abandoned previous pastures. Butterfly and moth species compo-sition in restored pastures resembled the compositions observed in old pastures after circa five years of resumed cattle grazing, but diversity of butterflies and moths in resumed pastures remained at a lower level compared with old pastures. None of the butterfly and moth species typical of old pas-tures had become more abundant in restored pastures compared with abandoned pastures. There-fore, it appears that restoration of butterfly and moth communities inhabiting semi-natural grass-lands requires a longer time that was available for monitoring in this study. In the second study, it was shown that local habitat quality has the largest impact on the occurrence and abundance of butterflies and moths compared to the effects of grassland patch area and connec-tivity of the regional grassland network. This emphasizes the importance of current and historical management of semi-natural grasslands on butterfly and moth communities. A positive effect of habitat connectivity was observed on total abundance of the declining butterflies and moths, sug-gesting that these species have strongest populations in well-connected habitat networks. Highest species richness and peak abundance of most individual species of butterflies and moths were generally observed in taller grassland vegetation compared with vascular plants, suggesting a preference towards less intensive management in insects. These differences between plants and their insect herbivores may be understood in the light of both (1) the higher structural diversity of tall vegetation and (2) weaker tolerance of disturbances by herbivorous insects due to their higher trophic level compared to plants. The ecological requirements of all species and species groups inhabiting semi-natural grasslands are probably never met at single restricted sites. Therefore, regional implementation of management to create differently managed areas is imperative for the conservation of different species and species groups dependent on semi-natural grasslands. With limited resources it might be reasonable to focus much of the management efforts in the densest networks of suitable habitat to minimise the risk of extinction of the declining species.