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  • Kulovesi, Pipsa (Helsingin yliopisto, 2015)
    The tear film covers the cornea and conjunctiva providing nutrients to the corneal cells and protecting it from the external environment. Tear film is composed of three intermixed layers. Mucous matrix covers the epithelial cells and is gradually mixed with the aqueous layer which is covered by a thin lipid layer. The lipid layer consists of both polar and nonpolar lipids. Lipids are thought to prevent the collapse of the tear film onto the ocular surface and to retard evaporation from the tears. In this study several in vitro methods were used to study the surface properties and organization of different lipid mixtures resembling those in the tear film lipid layer. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), and freefatty acids (FFA) were used as the polar lipids and cholesterol oleate (CO), triglycerides (TG), and wax esters(WE) were used as the nonpolar lipids. Langmuir film technique was used to examine the behavior of the lipid films during compressions and de-compression. Brewster angle microscopy (BAM) and atomic force microscopy (AFM) were utilized for visualizing the films. Grazing incidence X-ray difraction was used for surface structure studies. The results of experimental studies were compared with coarse-grained molecular dynamics simulations. Custom built system was used to evaluate the evaporation retarding effect of several lipid mixtures containing wax esters. Compression isotherms showed one to two kinks in the compression curve that account for the rearrangement of the lipids in the film for all mixtures studied. Hysteresis was small meaning that these films are very stable and little, if any, solubilization of lipids into the aqueous phase takes place. All lipid films studied were more or less inhomogeneous when viewed with BAM, especially in higher surface pressures. This is most likely caused by the nonpolar lipids aggregating on the lipid film surface. This was also seen in the simulation studies where CO and TG formed circular aggregates on top of the polar lipids. Nonpolar lipids stabilized the films under high compression by arranging so that the lipid film could have a lower surface pressure than would be expected for small surface areas. However, an excess of nonpolar lipids caused the films to be more inhomogenous and to have less stable structure. Lipid mixtures that contained wax esters did not retard evaporation, which suggests that lipids' function in the tear film may have more to do with maintaining a thin tear film and preventing its collapse rather than preventing evaporation. The task of TFLL is still under debate, although it has been regarded to be the evaporation barrier, hindering the movement of water molecules out from the tear fluid. This, however has been questioned in this thesis project. Although some WEs have been shown to retard the evaporation of water, this effect is lost when different lipid species are mixed, as was done in this study where several WE species were mixed with PC, CO, and TG. No evaporation retarding effect was detected for any mixtures studied. Evaporation retarding lipid films must be very tightly packed but this is not possible for TFLL-like films because the tear film lipids must also be suitable for the environment they are in where they must adapt to fast changes in surface pressure and must also be fluid. This cannot be achieved by the films that have been shown to retard evaporation as these films are rather stiff and cannot be compressed.
  • Venhoranta, Heli (Helsingin yliopisto, 2015)
    Dairy cattle breeding programs rely heavily on artificial insemination (AI). The AI enables intense selection for desired traits, but the use of few elite bulls carries a risk that inherited defects may proliferate in the population. The emergence of inherited defects is a recurrent issue in cattle breeding and rapid identification and management of genetic defects are crucial for preventing economic losses and maintaining good animal welfare. Modern molecular genetics techniques enable efficient detection of causative mutations, information which is needed for DNA testing. In this study, we investigated three inherited congenital bovine defects and located causative mutations for these diseases. 1. A microdeletion in PEG3 domain causes intrauterine growth restriction and stillbirths to almost half of the pregnancies sired by a single Ayrshire AI bull. The deletion, when inherited from the sire, is semi-lethal but the female mutation carriers can breed normally. The deletion truncates the 3 end of the non-coding maternally imprinted MIMT1 transcript and also causes expression changes in other genes of the domain. The expression changes of hundreds of genes in the foetal side of the placenta were also demonstrated. 2. Inherited gonadal hypoplasia with incomplete penetrance in Northern Finncattle and Swedish Mountain breed is associated with homozygosity for the Cs29 allele. This allele is an ectopic segment that is duplicated and translocated from chromosome 6 to 29 and encompasses the KIT gene. Cs29 allele is associated with colour sidedness in various cattle breeds, which coheres with the results that gonadal hypoplasia is connected with white coat colour. The KIT gene is known to regulate the migration of the germ cells and precursors of melanocytes. 3. A new recessive developmental disorder defined as PIRM (ptosis, intellectual disability, retarded growth and mortality) in Ayrshire breed was associated with single base substitution in the UBE3B gene. Mutation causes in-frame exon skipping, resulting in an altered protein lacking 40 amino acids, which likely comprises protein function. In humans, mutations in the UBE3B gene are associated with Kaufman oculocerebrofacial syndrome, with similar pathological effects as for PIRM syndrome. The UBE3B mutation may be connected with the AH1 haplotype, which is associated with reduced fertility and has a carrier frequency of 26.1% in the North American Ayrshire population. The mutations related to these three defects or syndromes can now be easily tested for. The results can be used to avoid risky matings, cull carriers and provide a veterinary diagnostic. The expression analyses proved that the mutations in Ayrshires also affected the RNA expression of the respective mutated gene or even hundreds of other genes. The described genotype-phenotype associations can be used as a basis for approaches to locate quantitative trait loci in cattle or provide new insights into developmental biology and inform translational research across species.
  • Mattila, Osmo (Helsingin yliopisto, 2015)
    Forests offer various, sometimes contradictory utilities to their owners and all other users on the global societal and ecological levels. In Finland, meeting the industrial requirements for a stable roundwood supply has defined the forestry service market, as it has been widely supported by the forest owners, the industrial buyers, and the national forest policy. Along with the changes among the owners themselves, demand for forestry services has fragmented. Recently, by introducing the new Forest Act, which gives more freedom for forest owners to choose between management practices, Finnish government has triggered a change that aims at the creation of more market-oriented distribution of forestry services. Based on the concepts of institutional transition at the market level, service-orientation as value-creation logic change, and business model thinking as the unit-level logic, the theoretical objective of the thesis is to define the ongoing renewal of the forestry service market. Using public and private owners as customers and the current forestry service organizations as service providers, the practical aim of this dissertation is to identify potential opportunities and barriers with respect to creating new services in the forestry service market. Methodologically both qualitative interview studies on forestry service organizations (n=22 and n=17) and quantitative multivariate analysis based on survey data with private (n=557) and public (n=139) forest owners are used. According to the results, there is a growing tension in the market environment accelerated by institutional transition: private forest owners are fragmented into multifaceted groups with various needs, while public owners (such as municipalities) are facing versatile user pressures on their publicly owned forests. Therefore, it seems that the traditional roundwood supply approach may no longer match the needs of versatile customer groups. From structural perspective, the established service market dominated by a small number of players is limiting the successful entry of new enterprises. The lack of dynamic middle-sized companies in the Finnish forest sector coupled with difficulties in adopting a more cooperative mind set is proving to be hindrance for renewal of the forestry service market despite the development of information technology, which can facilitate the use of participative methods in forest management and service marketing.
  • Laine, Merja (Helsingin yliopisto, 2015)
    Cardiometabolic health among male former elite athletes Regular physical activity is one of the cornerstones in the prevention of chronic diseases. The aim of this study was to assess whether a former career as a male elite athlete associates with various cardiometabolic disorders and whether it has any effect on leukocyte telomere length in later life. The original study population (N=4136) consists of 2424 male former elite athletes and 1712 matched controls. Of those, 599 (392 former athletes, 207 controls) participated in a clinical study in 2008. The athletes were divided into three groups based upon their previous career: endurance, mixed and power sports. The clinical study in 2008 included a physical examination, laboratory tests, and several questionnaires. Data on use of medication was obtained from the Finnish Social Insurance Institution. Among the participants, the former elite athletes tend to have lower age-adjusted prevalence of type 2 diabetes compared with the controls (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.45-1.01). The male former athletes also had lower age-adjusted risk for hypertension (OR 0.69, 95% CI 0.49-0.98), metabolic syndrome (OR 0.57, 95% CI 0.40-0.81), and non-alcoholic fatty liver disease (OR 0.61, 95% CI 0.42-0.88) compared to the controls. The former athletes had significantly lower age-adjusted body fat percentage compared to the controls (p=0.021) whereas no significant differences in mean age-adjusted leukocyte telomere lenght between the athlete and control groups (p = 0.845) were observed. Moreover, with aging the former athletes maintained their physically active lifestyle better than their controls. A male former elite athlete career seems to protect from type 2 diabetes, hypertension, metabolic syndrome, and non-alcoholic fatty liver disease at older age. It was also associated with a more favorable body composition. The volume of current leisure time physical activity was inversely associated with these cardiometabolic outcomes.
  • Sorsa, Essi (Helsingin yliopisto, 2015)
    Tutkimuksen kohteena ovat yhden suomalaisen kirjankustantajan, Kustannusosakeyhtiö Otavan, vuoden 2014 aikana myynnissä olleiden oppimateriaalien nimet. Tavoitteena on selvittää, mistä osista oppimateriaalien nimet muodostuvat, miten ja missä oppimateriaalien nimiä muodostetaan sekä miten oppimateriaalien nimiä hyödynnetään oppimateriaalisarjojen markkinoinnissa. Tutkimus on osa kaupallisen nimistön tutkimusta. Aineisto käsittää yhteensä 1 072 oppimateriaalin nimeä, jotka on kerätty painetuista tuotekatalogeista sekä kustantamon verkkosivuilta vuoden 2014 aikana. Nimiaineiston lisäksi tutkimuksen toisena aineistona toimivat viisi haastattelua. Haasteltavat ovat Kustannusosakeyhtiö Otavan oppimateriaaliosastojen työntekijöitä. Kolme haastatteluista on toteutettu kasvokkain ja äänitetty ja kaksi haastatteluista on toteutettu kirjallisina. Tarkastelun kohteena olevia nimiä kutsutaan oppimateriaalien nimiksi tai oppimateriaalinimiksi. Alussa tehdään lyhyesti selkoa Otavan oppimateriaalinimien historiasta ja esitellään nimiä kustantamon perustamisvuodesta (1891) nykypäivään saakka. Historiallinen katsaus paljastaa, että aiempina vuosikymmeninä oppimateriaalien nimet olivat yksiselitteisiä ja informatiivisia ja niitä muodostettiin melko vakiintuneella kaavalla (esim. Koulun biologia). Oppimateriaalinimien rakenteellisessa analyysissa nimet jaetaan kahtia sarjojen nimiin ja tuoteperheiden osien nimiin. Sarjojen nimet identifioivat kyseisen tuotteen ja toimivat sarjan päänimenä (esim. Tuhattaituri, Kipinä) kun taas tuoteperheiden osien nimet ovat moniosaisempia alanimiä, jotka tarkentavat sarjan nimeä ja kertovat tuotteen lajin (esim. Tuhattaituri 1a oppikirja, Kipinä 3 Tehtäviä). Aineistosta vain vajaa 10 % (102 nimeä) on sarjojen nimiä. Sarjojen nimet jaetaan Christoph Platenin luokittelumallin mukaan todellisiin kielen sanoihin, luoviin muodosteisiin sekä tekosanoihin. Tuoteperheiden osien nimistä tarkastellaan erilaisia nimenosia, kuten oppiainetta tai luokka-astetta ilmaisevia osia. Nimiä tutkitaan myös Paula Sjöblomin ja Yvonne Bertillsin funktioita soveltaen viidessä eri funktiossa: informatiivinen, käytännöllinen, houkutteleva, integroiva sekä narratiivinen ja tyylillinen. Tutkimuksen toisessa osassa selvitetään haastattelujen avulla oppimateriaalien nimeämisprosessia: nimeämistapoja ja nimeämisen lähtökohtia. Haastateltavat tuovat ilmi, että toimivan oppimateriaalin nimen on oltava käytännöllinen ja oppimateriaalinimelle on asetettu seuraavia periaatteita: selkeä, suomenkielinen, yhtenäinen, kohderyhmälle sopiva, monikäyttöinen, pitkäikäinen, ajankohtainen ja logoksi taipuva. Tutkimuksessa käydään läpi myös uusimpien oppimateriaalisarjojen nimiehdotuksia. Lopussa tarkastellaan esimerkkien kautta, miten oppimateriaalien nimiä hyödynnetään markkinoinnissa ja millaiset nimet toimivat hyvin markkinointiteksteissä (esim. Kipinää kirjoittamiseen!). Tutkimuksessa verrataan myös Otavan oppimateriaalien nimiä muiden kustantajien oppimateriaalien nimiin. Tarkastelu osoittaa, että tällä hetkellä oppimateriaalien nimet ovat rakenteeltaan yleensä lyhyitä, yksisanaisia, suomenkielisiä, monimerkityksisiä sanoja (esim. Särmä, Manner, Vire), joista voi muodostaa visuaalisia logoja. Yksi haastateltavista tiivistää ajatuksen nimien takana näin: ehkä nää [uudet lyhyet nimet] on niinku tavallaan sen nykypäivän niinku brändäys- tai sen tuotteistamisajattelun mukaisia. Vaikuttaa, että muotiin on kuitenkin tulossa myös pidempiä, kuvailevampia nimiä (esim. Tutkimusmatka). Tutkimus osoittaa, että nimeämistä ohjaa jonkinlainen, tiedostettu tai tiedostamaton, nimimalli. Varsinaista oppimateriaalinimen prototyyppiä ei silti voi esittää.
  • Lehtonen, Heini (Helsingin yliopisto, 2015)
    This thesis examines language use in interaction among adolescents in two junior high schools in Eastern Helsinki. The pupils represent several ethnic backgrounds, and some twenty different first languages are spoken in the schools. The thesis analyses the ways in which the adolescents position themselves and each other with regard to social categories related to ethnicity, gender, and style, focusing on the linguistic resources used in the positioning. The attitudes vis-a-vis linguistic diversity and asymmetry are explored as well. The research questions are as follows: 1) How does a linguistic feature become a social indexical? 2) How do (linguistic) styles get enregistered? 3) How are ownership and foreignness of language negotiated and construed? The thesis participates in the current discussions on ways of conceptualizing multilingualism in the globalization era. Questions of immigration and second language acquisition, learning and teaching are discussed from a sociolinguistic point of view. Theoretically and methodologically, the thesis encompasses the fields of linguistic ethnography, interactional sociolinguistics, and the sociolinguistics of globalization. The data consist of 1) field notes and a field diary, 2) recorded interviews with 37 adolescents, 3) several audio and video recordings of spontaneous interaction during both the lessons and the breaks, and 4) retrospective interviews. The analysis shows the adolescents orientating to the categories of Finns and foreigners , but the meaning of these categorizations is construed in local stylistic practices and does not necessarily resemble to the similar labels used in public discourses. Ethnicity, gender, and enregistered styles (such as hip hop) intertwine in such ways, that the participation in local stylistic practices may guarantee a stronger ownership of linguistic resources than one s ethnic background. All types of linguistic features (phonetic, prosodic, morphological, syntactic, lexical) were found to function as social indexicals. Frequent resources that stand out and establish social relationships between participants are especially likely to develop into social indexicals. As a part of local social practices and in the metapragmatic accounts commenting the practices, linguistic features get associated to specific social personae and their characteristics, and get enregistered to styles. Social indexicals are employed in stylized performances that bring another s voice into the interaction. The stylisations serve as a resource for stance-taking, but also as metapragmatic accounts of the features employed in them. The questions of who knows Finnish or does not know Finnish are negotiated both explicitly and implicitly. One of the implicit means of such negotiations are the stylized bad Finnish performances, where the adolescents carnevalize the stereotypical representations of immigrants or non-native Finns .
  • von Boehm, Jukka (2015)
    The study analyses the performance history and Wirkungsgeschichte of Richard Wagner s Lohengrin (premiered 1850) in Germany and Russia in the 20th century. In Wagner s opera the mysterious knight arrives in medieval Brabant, where the people receive him as their redeemer . Lohengrin became one of Adolf Hitler s favourite operas. Through analysis of Lohengrin s influence, the study casts light on a broad and complex theme: how did Wagner s ideas and art become intertwined with Nazi ideology? Or how were they received in the context of other radical societal experiments, namely Soviet and East German socialism? This examination of different interpretations of the same text (Lohengrin) on stage and through its reception will reveal prevailing societal attitudes, taboos, values and hopes. Case study I discusses the reception of a few nationalist themes in Lohengrin. Specifically, the focus is on ultra-nationalist projections onto Lohengrin, which emerged during the resurgence of late 19th-century German Hurrah-patriotism and Nazi ideology. The focus of Case study II is on Heinz Tietjen s direction of Lohengrin at the Bayreuth Festival during the Third Reich (1936). The study demonstrates how Tietjen embedded Nazi ideology in his reading. Case study III takes another look at Lohengrin s influence on Soviet and East German socialism. The study scrutinises the ambivalent role of Lohengrin in the context of a dogmatic communist cultural policy that valued (socialist) realism. Another theme discussed is the problematic relationship of Lohengrin to the German Democratic Republic and its anti-fascism. Case study IV analyses Peter Konwitschny s innovative direction of Lohengrin in 1998. Characteristic of the deconstructive style of German director s theatre , the opera was set in a school classroom before the outbreak of the First World War. Konwitschny s interpretation offers an excellent case for analysing strategies by which a modern direction can take up the challenge of ideologically ambivalent opera. The study challenges the commonly oversimplified narrative that presents Wagner as a forerunner of Hitler and Nazism. Although there was irrational potential in Lohengrin, which became topical in the Third Reich, the relationship between Wagner s opera and National Socialism is much more complex, including the fact that Wagner s utopian ideas in Lohengrin also inspired the left. The main primary sources consist of German archival material, newspapers and journals.
  • Selim, Shaimaa (Helsingin yliopisto, 2015)
    The objective of the research described in this thesis was to increase the understanding of the transcriptional adaptations of genes encoding proteins, which have key roles in lipid and glucose metabolism, insulin signalling and inflammation, in situations of overfeeding energy during the dry period in dairy cows and summer grazing season in mares. Emphasis was placed on the potential to decrease metabolic disorders and to improve animal nutritional management and health. In the experiment I, dairy cows were fed a grass silage based diet either on a controlled energy level (on average 99 MJ/d metabolizable energy (ME), n = 8) during the last six weeks of the dry period or high energy level (on average 141 MJ/d ME, n = 8) for the first three weeks and then gradually decreasing energy allowance during three weeks to 99 MJ/d ME by parturition. In experiment II, dairy cows were fed ad libitum either grass silage (144 MJ/d ME, n = 8) or a mixture of grass silage, wheat straw and rapeseed meal (TMR, 55%: 40%: 5%, 109 MJ/d ME, n = 8) during the 8-wk dry period. Liver and adipose tissue biopsies and blood samples were collected during the transition period in experiments I and II. In the experiment III, the impact of grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland pasture (NG) on fat deposition, insulin resistance status and adipose tissue gene expression of Finnhorse mares was studied. Body measurements, intravenous glucose tolerance tests (IVGTT), and sampling for the determination of neck and tailhead adipose tissue gene expressions were conducted in May and September. In experiments I and II, overfed cows had greater total dry matter and ME intakes and ME balance before parturition than control cows, but no differences were observed after calving. Increases in body weight and body condition score were greater in the overfed cows of the experiment II during the dry period. In the experiment I, there was greater plasma insulin and lower glucagon/insulin ratio in overfed cows than in control cows, while in the experiment II, there were no differences in blood parameters between overfed and TMR group during the transition period. Down-regulation of key genes linked to hepatic gluconeogenesis and fatty acid β-oxidation in the overfed group of cows in the experiment I was found, suggesting impaired liver function compared to a controlled energy diet. In the experiment II, ad libitum feeding of grass silage throughout the dry period may have attenuated the increase of hepatic gluconeogenic capacity from propionate compared to a controlled TMR diet. However, there was no difference in the expression of genes related to hepatic glucose release during the transition period (II). In adipose tissue, there was some evidence that the level of energy overfeeding may have exacerbated the inflammatory status postpartum and temporarily decreased lipogenesis very near parturition relative to control energy diet (I). In the experiment II, prepartal ad libitum feeding of grass silage decreased lipogenesis and insulin sensitivity early postpartum compared to the TMR control group. In the experiment III, CG mares had higher median body condition score and body weight, and larger waist circumference than NG mares at the end of grazing. In September, greater basal and peak insulin concentrations, and faster glucose clearance rate during IVGTT were observed in CG mares than in NG mares. In addition, a greater decrease in plasma non-esterified fatty acids during IVGTT was noticed in CG mares. There were no differences in the expression of genes related to insulin resistance, inflammation and lipogenesis between the two groups. Significant temporal differences in the expression profiles of genes related to insulin resistance and lipogenesis were observed during the grazing season. Grazing on CG had moderate effects on responses during IVGTT, but did not exacerbate insulin resistance. In conclusion, overfeeding energy with concomitant weight gain moderately altered the expression of genes related to insulin resistance, inflammation and lipogenesis in adipose tissue of dairy cows. Prepartal overfeeding energy affected the expression of genes related to hepatic gluconeogenesis and fatty acid oxidation in dairy cows, but the extent of these effects differed depending on the dietary composition during the close-up period (e.g. feeding of cereal grain). In mares, the diets with variable energy content did not affect the expression of insulin resistance- or inflammation-related genes, although mares were different in their body condition scores.
  • Marinkovic, Ivan (Helsingin yliopisto, 2015)
    Intracerebral hemorrhage (ICH) represents the subtype of stroke carrying the most detrimental outcome and highest mortality. It is clearly underinvestigated and lacks an effective treatment except supportive management measures. The dismal outcomes of ICH are clearly associated with the mass effect of hematoma accompanied with dynamic perihematomal edema (PHE) and potential intraventricular bleeding (IVH), which is often complicated by development of hydrocephalus. In this thesis, we aimed to develop novel therapy modalities, which apart from experimental conditions, might be found effective in clinical scenario, and successfully implemented in ICH treatment clinical protocols in the future. In study (I), we utilized autologous blood injection model and magnetic resonance imaging (MRI) follow-up. Following the induction of deep right hemispheric hematoma of 75uL of volume, we performed decompressive craniectomy (DC) at 1 h, 6 h, and 24 h time points, aiming at diminishing high intracranial pressure (ICP) after the bleeding event. Control group did not undergo DC procedure. Decompressive craniectomy was found effective in reducing mortality and improving overall neurobehavioral outcome and mortality in all the 3 treatment groups. Effect of DC was most pronounced in the early craniectomy group (1 h). In study (II), we aimed to examine how deleterious is the influence of tissue plasminogen activator (tPA) in experimental ICH scenario, and whether the adverse tPA effects could be antagonized by the clinically safe mast-cell stabilizer chromoglycate. Animals were divided in four groups. We utilized intrahemispheric collagenase injection rat ICH model and MRI follow-up imaging up to 72h. Group 1 received tPA only, whereas Group 2 and Group 3 besides tPA received chromoglycate in single or double dose. Group 4 was used as a control having ICH, but receiving saline only. TPA-treated animals did not have significantly larger hematomas or hemispheric expansion even though been characterized by worse overall outcome. Application of chromoglycate in high dose mitigated detrimental outcomes present in the group being treated with tPA only, and diminished the extent of hemispheric expansion. This encourages further research to potentially establish "blind" thrombolysis concept coupled with concomitant application of MC inhibitors, as we could show that injurious tPA effects were successfully abolished by concomitant MC stabilization in experimental ICH scenario. In the third study (III), we decided to develop a novel combined ICH + intraventricular hemorrhage (IVH) model in the rat as such a model does not exist besides the fact that approximately 40% of all ICHs in human patients are complicated by presence of intraventricular hemorrhage which is known to worsen prognosis. We utilized different blood volumes of 100-250uL in modified autologous blood injection model to induce deep intrahemispheric ICH to establish a fully novel experimental approach of ICH followed by IVH. We performed 1-week MRI follow-up and consistent neurobehavioral evaluation at 24 h, 48 h, 72 h, and 1 week after hemorrhage. Using MRI, we identified the presence of hydrocephalus in all experimental subjects, and its progressive tendency during entire follow-up. The most prominent hemispheric expansion and the most pronounced hydrocephalus were present in experimental groups with >200uL blood injection. This model was reliable and highly reproducible, demonstrating promising initial point for ICH+IVH experimental research. These two novel treatment strategies established in our studies give promise for further refinements and potential applications in human patients. The novel ICH+IVH model we established in rat models may serve as an improved model for future experimental studies as it mimics human disease scenarios better than the existing models.
  • Müller, Susann (Helsingin yliopisto, 2015)
    Biogeochemical processes in sea ice and the ice-water interface depend on abiotic processes and biological activity. Abiotic processes in sea ice are controlled by the crystallization process of freezing water and the associated formation of saline brine. Also the heat budget of sea ice and the resulting changes in abiotic properties such as porosity and salinity need to be taken into account. The dissolved fraction of sea ice brines contain ions and dissolved organic matter (DOM). Ions are rejected from the ice by diffusion and gravity drainage whereas dissolved organic matter with highly complex and diverse chemical composition can react in many ways with other molecules and surfaces. Hence, the present work compares the behavior of different fractions of DOM to the ones of salts during initial sea ice formation. Controlled tank studies were combined with natural sea ice sampling to exclude the disadvantages of both systems such as the effects of small-scale experiments, artificial additions in tank experiments and the unknown history of natural samples. The studies were conducted with brackish sea ice from the Baltic Sea with its high nutrient and DOM concentrations, but also with oceanic sea ice from the North Sea and the Arctic Ocean. This allows a general conclusion about the behavior of solutes during the formation of sea ice. The present studies indicate that the major seawater ions are significantly fractionated due to differential diffusion and coupled diffuse-convective salt transport through the brine channel network. Ions with a lower diffusivity than Cl¯, in this study SO42¯, Ca+ and Mg2+, remained longer in the brine channel network and got therefore enriched in sea ice relative to Cl¯. K+, on the other hand, diffused faster than Cl¯ and was depleted in sea ice in this study. The behavior of DOM in sea ice was more complex compared to ions because of the complex structure of DOM and the effect of secondary processes on DOM, such as biological production and degradation in sea ice. The quantification of DOM is challenging since only certain fractions such as chromophoric DOM can be measured instead of estimating the total concentration of DOM. Nevertheless, the present studies on DOM in sea ice from Baltic and North Sea water indicated enrichment of DOM compared to sea water ions. The magnitude of this enrichment was higher than expected from diffusion and convection following the transport of salts. The enrichment varied among DOM fractions with highest enrichment of amino-acid like DOM and lowest enrichment of humic-like substances. The results therefore suggest that additional processes, such as selective drainage that depends on the chemical properties of the DOM molecules, affect the enrichment of DOM in sea ice. The optical properties of sea ice were used to develop a bio-optical model. The model estimates the primary production in Baltic Sea ice based on the absorption by particles and chromophoric DOM and the quantum yield for C fixation calculated from photosynthesis-irradiance curves. The results were compared to in situ primary production measurements. The combination of modelled primary production estimates and the measurements of optical properties and primary production in different types of Baltic Sea ice gave a good overview over bio-optical properties in Baltic Sea ice and can be used as a tool to improve different parameters of ecosystem models.
  • Hänninen, Timo (Helsingin yliopisto, 2015)
    Controlling integral operators by dyadic model operators, and studying the boundedness of dyadic operators on Lebesgue spaces are central themes in dyadic harmonic analysis. This dissertation consists of an introductory part and five articles contributing to these themes. Many operators of harmonic analysis can be dominated by positive dyadic operators by using Lerner's median oscillation decomposition. In the first and fifth article, we extend this decomposition to Banach space valued functions and non-doubling measures. Dyadic shifts and paraproducts are dyadic model operators for Calderón-Zygmund operators. In the second article, we study the boundedness of these operators on unweighted Lebesgue spaces in an abstract operator-valued setting. We prove that operator-valued dyadic shifts are bounded, and we characterize the boundedness of operator-valued dyadic paraproducts. Furthermore, we extend Hytönen's dyadic representation theorem, which states that every Calderón-Zygmund operator can be represented by dyadic shifts and paraproducts, to the operator-valued setting. In the third article, we characterize the boundedness of linear and bilinear positive dyadic operators from a weighted Lebesgue space to another. We consider the case that the Lebesgue exponent of the range side is strictly less than the Lebesgue exponent of the domain side. We show that, in this range of the exponents, the Sawyer testing condition is insufficient for the boundedness. We introduce a sequential testing condition, of which the Sawyer testing condition can be viewed as an endpoint case, and prove that this testing condition is both sufficient and necessary for the boundedness. No characterization in the bilinear case was available until this article. Furthermore, we show that the sequential testing condition is necessary for the boundedness of any positive linear or bilinear operator, and hence it may be helpful in charactering the boundedness of other operators as well. In the fourth article, we characterize the boundedness of positive dyadic operators from a weighted Lebesgue space to another in an abstract operator-valued setting. The purpose is to understand which kind of testing condition is needed in this setting. We prove that an operator-valued positive dyadic operator is bounded if and only if the operator and its adjoint are each bounded on the class of all functions localized on dyadic cubes and taking values on a unit sphere. Furthermore, we show that the boundedness on unweighted Lebesgue spaces is characterized by an endpoint case of this condition. We work directly with Lebesgue spaces, without using interpolation between endpoint spaces. In the second article, we give new (in our opinion simple) proofs for the key tools that we use: decoupling inequality for martingale differences and a variant of Pythagoras' theorem for Lebesgue spaces.
  • Litmanen, Topi (Helsingin yliopisto, 2015)
    This dissertation explores how higher education students experience their studies. Experiences were studied at three interconnected levels: cognitive, motivational and emotional; they were defined respectively as the student s perceptions of the learning environment, study-related personal goals and emotional experiences in the learning situation. The general research questions were: 1) What are the components of successful and unsuccessful engagement with the learning environment? 2) How do students experience different kinds of learning environments, and what kinds of roles do experiences and emotions have in the learning process? 3) To what extent are experiences of the learning environment related to the features of the faculty and student qualities? Four empirical studies were conducted to address these questions. Studies I, II and IV were quantitative and applied self-report questionnaires, and Study I also had a follow-up setting. Study III was also a follow-up study, in which experience sampling conducted with mobile phones was accompanied with qualitative interview data. Study I explored what kinds of study-related goals students have at the beginning of their studies and how they relate to their study progress. The participants (N=133) were theology students, who at the beginning of their studies were asked to complete a questionnaire about their personal goals. Study success was followed for the first three years of their studies. The results showed that students whose study-related goals were important and stressful, and who reported progress in achieving them, advanced more rapidly in their studies. Study II focused on how students experiences of their learning environment are related to their well-being and academic self-concept. The participants were 610 medical students. Structural equation modelling was used to investigate the relationships between the variables under study. Experiences about the learning environment were related to how interested the students were in their studies or how exhausted they had become as a result of them. In turn, interest and exhaustion were related to higher levels of academic self-concept. A cross-sectional design was used to compare experiences between different medical schools. Novice PBL (Problem Based Learning) students experienced higher levels of exhaustion, no differences were found in the later phases of studies. Thus, the PBL environment appeared challenging, but only during the first years of study. Study III followed the experiences of nine student teachers for two 14-day follow-ups. The first follow-up consisted mostly of lectures and ordinary small-group work. The second period ran parallel to the completion of an intensive inquiry-based project that was the focus of the present study. A multivariate analysis of variance revealed that studying during the inquiry-based period produced stronger experiences of being challenged as well as more negative emotional experiences than the teacher-centred period. However, the interview data indicated that the participants enjoyed the inquiry-based period. In Study IV, the objective was to study the relations between approaches to learning and both the disciplines of the students and their perceptions of the learning environment. Altogether 2,509 students from different fields participated in the study. The results indicated that both approaches to learning and the discipline have an effect on students experiences of the learning environment. The dissertation showed that combining different cognitive, motivational and emotional perspectives and using a variety of methodologies helps to build a more comprehensive picture of how higher education students experience their studies. The most important findings of this thesis were: 1) Successful engagement with the learning environment is not merely about seeing the studies as important, being satisfied with the faculty or career choice, or seeing oneself as capable of achieving the tasks. Stress, worry about competence and to some extent exhaustion are important components of engagement in studies. 2) Negative affects, experiences of high levels of challenge and exhaustion may be essential parts of the process of gradually learning to take responsibility for both individual and collaborative learning processes. 3) Students experiences of their learning environment are not related to a single feature or set of features, but are connected to both their approaches to learning and the characteristics of the learning environment, such as the pedagogy used.
  • Sandboge, Samuel (Helsingin yliopisto, 2015)
    Background. A small birth size, an indicator of a suboptimal intrauterine environment, is a risk factor for several non-communicable diseases (NCDs), a risk that in many cases is modified by childhood growth patterns. Regional variation in NCD prevalence could partly have its origin in early development. Lifestyle factors further influence NCD prevalence. Aims. We aimed to explore the associations between early growth and adult resting metabolic rate (RMR), body composition, non-alcoholic fatty liver disease (NAFLD), and hypertension. We also studied the associations between fructose intake and NAFLD, and differences in birth size between Helsinki and the Åland Islands. Subjects and methods. The Helsinki Birth Cohort Study consists of 13345 individuals born in Helsinki in 1934‒44. Detailed records are available for all participants including information on maternal and birth characteristics and measurements of childhood body size. 2003 individuals participated in a clinical study in 2001‒04 and 1083 of these additionally participated in a follow-up study in 2006‒08. The Åland records include 1697 births for the years 1937‒44. Results. The association between birth weight and RMR was inverse among women and quadratic among men. A higher attained adult weight than expected, based on weight and height measurements before age 11 years and adult height, was associated with higher adult body fat content. The odds ratio (OR) for NAFLD was 18.5 (95% CI 10.1; 33.6) among those who belonged to the lowest BMI tertile at age 2 years and subsequently were obese as adults, compared to those who were still lean or normal weight as adults. NAFLD was most common among individuals with the lowest dietary fructose intake. Systolic blood pressure (SBP) and the presence of hypertension were inversely associated with linear (height) growth between ages 2 and 11 years. Relative weight gain after age 11 years was positively associated with SBP. Ålandic babies born 1937‒44 were 87 grams (95% CI 61; 111) heavier and 0.4 cm (95% CI 0.3; 0.5) longer than their Helsinki peers. Conclusions. A more pronounced increase in relative weight after age 11 years than would be expected from previous body size, was positively associated with body fat content, NAFLD, and hypertension. Conversely, several growth measurements before age 11 years were negatively associated with the outcomes studied. None of the studied individuals were obese in childhood. Instead, a larger relative childhood body size in this group most likely represents a more beneficial childhood environment. Contrary to previous findings, we found that individuals with the highest fructose intake were least likely to suffer from NAFLD. We found a small but significant difference in birth size between the Åland Islands and Helsinki for the years 1937‒44.
  • Niinimäki, Teppo (Helsingin yliopisto, 2015)
    Bayesian networks are probabilistic graphical models, which can compactly represent complex probabilistic dependencies between a set of variables. Once learned from data or constructed by some other means, they can both give insight into the modeled domain and be used for probabilistic reasoning tasks, such as prediction of future data points. Learning a Bayesian network consists of two tasks: discovering a graphical dependency structure on variables, and finding the numerical parameters of a conditional distribution for each variable. Structure discovery has attracted considerable interest in the recent decades. Attention has mostly been paid to finding a structure that best fits the data under certain criterion. The optimization approach can lead to noisy and partly arbitrary results due to the uncertainty caused by a small amount of data. The so-called full Bayesian approach addresses this shortcoming by learning the posterior distribution of structures. In practice, the posterior distribution is summarized by constructing a representative sample of structures, or by computing marginal posterior probabilities of individual arcs or other substructures. This thesis presents algorithms for the full Bayesian approach to structure learning in Bayesian networks. Because the existing exact algorithms only scale to small networks of up to about 25 variables, we investigate sampling based, Monte Carlo methods. The state-of-the-art sampling algorithms draw orderings of variables along a Markov chain. We propose several improvements to this algorithm. First, we show that sampling partial orders instead of linear orders can lead to radically improved mixing of the Markov chain and consequently better estimates. Second, we suggest replacing Markov chain Monte Carlo by annealed importance sampling. This can further improve the accuracy of estimates and has also other advantages such as independent samples and easy parallelization. Third, we propose a way to correct the bias that is caused by sampling orderings of variables instead of structures. Fourth, we present an algorithm that can significantly speed up per-sample computations via approximation. In addition, the thesis proposes a new algorithm for so-called local learning of the Bayesian network structure. In local learning the task is to discover the neighborhood of a given target variable. In contrast to previous algorithms that are based on conditional independence tests between variables, our algorithm gives scores to larger substructures. This approach often leads to more accurate results.
  • Kainulainen, Tuija (2015)
    Apteekkien lääkkeistä saatavien katteiden ja siten liikevaihdon alenemisen myötä on vapaan kaupan tuotteiden myynnin merkitys apteekeille noussut. Valmistavien yritysten on kiinnitettävä erityistä huomiota tuotelanseerauksiensa onnistumiseen varmistaakseen, että juuri heidän tuotteensa päätyvät apteekkien hyllyille mahdollisten kilpailijoiden sijaan. Tutkimuksella haluttiin selvittää pätevätkö menestyksekkään lanseerauksen avaintekijät myös apteekkimarkkinoille lanseerattaessa. Lisäksi tutkittiin nähdäänkö näistä yleisistä menestystekijöistä jokin apteekkilaisten näkökulmasta tärkeimpänä vaikuttajana valikoimaan otto päätöksissä ja onko mahdollisesti olemassa vain apteekkilanseerauksien kannalta tärkeitä tekijöitä. Tutkimus suoritettiin apteekkihenkilökunnalle suunnatulla kyselytutkimuksella, jossa esimerkkituotteena käytettiin juuri markkinoille tullutta Elivo Vahva+ D50-valmistetta. Tämän lisäksi haastateltiin myöhemmin sähköpostitse muutamia lomaketutkimukseen osallistuneita henkilöitä. Tutkimuksen perusteella todettiin, että apteekkeja kiinnostavat vapaan kaupan tuotteet, jotka sopivat niiden valikoimaan, eli ovat tutkitusti tehokkaita ja asiakkaille todistettavasti hyödyllisiä. Tuotteiden on tuotava jotain lisäarvoa jo olemassa olevaan valikoimaan, oltava visuaalisesti houkuttelevia sekä hinnoittelultaan kohtuullisia. Kohderyhmän on hyvä olla selkeä ja riittävän suuri. Apteekkien valikoimaan otto päätöksiin eniten vaikutusta on edustajan käynneillä, tuotteen näkyvyydellä mediassa sekä asiakkaiden kysynnällä. Lisäksi apteekkiketjuun kuuluminen tuo monesti mukanaan velvoitteen pitää tiettyjä tuotteita valikoimissa. Vähiten vaikutusta päätöksien tekoon oli selvästi sähköisellä uutiskirjeellä sekä apteekkitapahtumilla. Apteekkien kate sekä mahdolliset ostoalennukset ja vapaan kaupan tuotteiden hyvityskäytännöt huomioidaan myös tuotevalikoimapäätöksiä tehtäessä. Lanseeraavan yrityksen on myös tärkeää panostaa edustajiensa koulutukseen ja tarjota apteekkeihin luotettavaa tuotetietoutta sekä perusteltavia myyntiargumentteja tuotteestaan esimerkiksi henkilökuntakoulutuksilla tai esitteiden muodossa. Lanseerauksen ajoituksessa on otettava huomioon myyntisesonkien vaihtelut sekä kilpailijoiden markkinoille tulo. Jos markkinoille ei ehditä ensimmäisenä, on tuotteella oltava todellista lisäarvoa muihin verrattuna.
  • Kiuru, Karoliina (2015)
    Nykyään yhä useampi uusi lääkeaine liukenee veteen huonosti, mikä voi olla ongelma lääkevalmisteen kehityksessä. Kiinteän dispersion käyttö on formulaatiotekniikka, jolla voidaan parantaa lääkeaineen liukenemisnopeutta. Kiinteät dispersiot, joissa lääkeaine on amorfisessa muodossa, ovat kuitenkin usein epästabiileja. Tämän vuoksi on kehitetty myös kiteiseen lääkeaineeseen perustuvia kiinteitä dispersioita. Lääkeaineen kiteytymistä ja kiteytymiseen vaikuttavia asioita, kuten esimerkiksi polymeerimäärän vaikutusta, on tärkeä tutkia toimivien lääkevalmisteiden kehittämiseksi. Kiteytymisen kinetiikkaa mallintamaan on kehitetty myös erilaisia matemaattisia malleja, joiden avulla kiteytymistä on mahdollista ymmärtää kattavammin. Tässä työssä tutkittiin amorfisen lääkeaineen kiteytymistä ilman polymeeriä ja pienen polymeerimäärän kanssa. Kiteytymistä tarkasteltiin myös matemaattisen mallin avulla tarkoituksena selvittää, kuvaako se kiteytymisen kinetiikkaa tässä tutkimuksessa. Mallilääkeaineena käytössä oli felodipiini ja polymeereinä käytettiin HPMCAS-LF ja PVP K30 polymeerejä. Polymeerien konsentraatio kiinteissä dispersioissa oli 10 % tai 20 %. Tutkimuksessa havaittiin, että pienellä polymeerimäärällä on hyvin merkittävä vaikutus felodipiinin kiteytymisnopeuteen. PVP:n kohdalla matemaattisesti määritetty kiteytymisnopeusvakion k:n arvo kasvoi 13 kertaisesti laskettaessa polymeerimäärää kahdestakymmenestä kymmeneen prosenttiin. Lisäksi polymeerimäärällä havaittiin olevan vaikutusta kiteytymistä edeltävän ydintenmuodostumisvaiheen kestoon. Esimerkiksi 10 % PVP polymeerimäärä hidastaa kiteen kasvua edeltävää ydintenmuodostumisvaihetta viisinkertaisesti ja 20 % polymeerimäärä kymmenkertaisesti. Työssä kävi lisäksi ilmi, että HPMCAS stabiloi felodipiinin amorfista tilaa paremmin kuin PVP 40 °C/75 % RH olosuhteissa. Tämä havaittiin sekä MTDSC-mittauksin että polarisoivan valon mikroskopointia käytettäessä. Polymeerien välisen eron felodipiinin stabiloijana arveltiin johtuvan PVP:n ja felodipiinin välisten vuorovaikutusten heikkenemisestä kosteissa olosuhteissa veden vaikutuksesta. Dissoluutio-ominaisuuksiin eri formulaatioilla ja kiteytymisasteella ei tämän tutkimuksen perusteella kuitenkaan ollut vaikutusta. Lisäksi tässä työssä käytetty kiteytymisen kinetiikkaa kuvaava malli ei ollut sopiva kaikille käytetyille lääkeaine-polymeeri yhdistelmille, joten matemaattisen mallin käyttöön ja valintaan tulee suhtautua kriittisesti.
  • Joenperä, Jasmin (2015)
    Borrelia burgdorferi ja Anaplasma phagocytophilum ovat puutiaisvälitteisiä bakteereja. B. burgdorferi aiheuttaa ihmisille borrelioosia, mutta sen merkitystä hevosten taudinaiheuttajana ei täysin tunneta. A. phagocytophilum puolestaan aiheuttaa granulosyyttistä anaplasmoosia ihmisillä, koiralla ja hevosella sekä laidunkuumetta märehtijöillä. Tämän tutkimuksen tarkoituksena oli tutkia Borrelia- ja Anaplasma-vasta-aineiden yleisyyttä suomalaisilla hevosilla. Eri Euroopan maissa tehdyissä tutkimuksissa on todettu Borrelia-vasta-aineita noin 3-29 %:lla ja Anaplasma-vasta-aineita noin 9-73 %:lla hevosista. Suomessa aihetta ei ole aiemmin tutkittu tässä mittakaavassa. Hypoteesina oli, että hevosista löydetään vasta-aineita molempia taudinaiheuttajia vastaan erityisesti etelässä ja rannikkoalueilla sekä iäkkäillä ja Suomeen tuoduilla hevosilla. Tutkimuksessa kerättiin 281 varsojen ja 319 aikuisten hevosten verinäytettä Manner-Suomesta ja Ahvenanmaalta. Hevosenomistajilta pyydettiin lisäksi tietoja hevosesta kysymyslomakkeella. Näytteet tutkittiin koirien vektorivälitteisten tartuntojen diagnostiikkaan kehitettyä SNAP 4DX Plus –pikatestiä. Tulosten tilastollinen analyysi suoritettiin SPSS-ohjelmalla käyttäen yhden muuttujan logistista regressioanalyysiä ja ristiintaulukointia. Borrelia-vasta-aineita todettiin 60/319 (18,8 %) aikuisella ja 11/281 (3,9 %) varsalla ja Anaplasma-vasta-aineita 20/319 (6,3 %) aikuisella ja 4/281 varsalla (1,4 %). Seroprevalenssit olivat korkeimmat Ahvenanmaalla (aikuisilla Borrelia 89,5 % ja Anaplasma 47,4 %), Etelä-Suomessa (25,5 % ja 4.9 %) sekä Itä-Suomessa (17,0 % ja 4,9 %). Borrelia-seropositiivisuuden kannalta tilastollisesti merkitseviä tekijöitä olivat hevosessa havaitut puutiaiset, alue, hevosen alkuperämaa, ikä, käyttötarkoitus, roturyhmä sekä Anaplasma-seropositiivisuus yhden muuttujan mallissa. Anaplasma-seropositiivisuuden kannalta mahdollisesti merkitseviä tekijöitä olivat puutiaiset, alue, hevosen alkuperämaa, ikä sekä Borrelia-seropositiivisuus. Tulosten perusteella Borrelia burgdorferi- ja Anaplasma phagocytophilum -tartuntoja esiintyy yleisesti suomalaisilla hevosilla. Tartuntapaine oli korkein Ahvenanmaalla sekä Etelä- ja Itä-Suomessa. Käytännössä bakteeria kantavan puutiaisen purema on ainoa syy tartuntaan, mutta taustatekijät kuten asuminen puutiaisen levinneisyysalueella tai ulkoileminen maastossa tai laitumella ja voivat altistaa hevosen puutiaisille ja siten Borrelia- tai Anaplasma-tartunnalle. Riskitekijöiden selvittäminen vaatii laajempaa tilastollista analyysiä ja esimerkiksi Borrelia-tartunnan mahdollista yhteyttä kliinisiin oireisiin pitäisi selvittää lisätutkimuksin.
  • Karvinen, Irina (2015)
    Tutkielmassa kartoitettiin suomalaisten lemmikkikanien suolistoloistilannetta. Tällaista tutkimusta ei tiettävästi ole aiemmin tehty Suomessa. Tutkimuksen kirjallisuusosuudessa on esitelty kaneilla yleisimmin esiintyviä suolistoloisia erityisesti keskittyen lemmikkikaneihin. Lemmikkikaneilla tehtyjä tutkimuksia on kansainvälisestikin vielä vähän verrattuna villi-ja laboratoriokaneihin. Kirjallisuuskatsaukseen valittiin esiteltäviksi seuraavat kanien suolistoloiset: Eimeria spp, Crytospordium spp, Passalurus ambiguus, Trichuris leporis, Trichystrongyloides retotaeformis, Cittataenia spp, ja Taenia pisiformis. Tutkimusosuudessa tutkittiin ulostenäytteitä McMaster-tekniikalla 159 kappaletta, näistä useamman kanin yhteisnäytteitä oli 11 kpl. Näytteistä Eimeria spp. eli kokkidipositiivisia oli 22,5%:a ja kihomatopositiivisia (Passalurus ambiguus) 4,4%:a. Muita loisia (Trichuris leporis) löytyi vain yhdeltä kaneilta. Kokonaisloisprevalenssi tässä tutkimuksessa oli 24,5%. Riskitekijöiksi kokkidi-infektiolle tässä tutkimuksessa todettiin monikanitalous (eli yli 3 kania taloudessa), p-arvo = 0,002. Riskitekijät, jotka korreloivat monikanitalouden kanssa olivat kanin hankinta kasvattajalta, jalostuskäyttö, nuori ikä, talouden muut eläimet, ulkoilu sekä se, ettei kania oltu lääkitty, steriloitu/kastroitu, eikä hoidettu eläinlääkärissä. Ulkoa kerätyt luonnonkasvit toimivat tässä tutkimuksessa loisinfektiolta suojaavana tekijänä. Selkeää syytä tähän ei löydetty, mutta luonnonkasveja syövät kanit poikkevat ehkä hoidoltaan muiltakin osin niistä kaneista, joille ei luonnonokasveja annettu ravinnoksi. Rutiininomaiset loislääkitykset lemmikkikaneille eivät ole tämän tutkimuksen perusteella tarpeellisia, mutta erityisesti isoissa kaniloissa olisi hyvä säännöllisesti tarkkailla loistilannetta. Mikäli tarvetta loishäädölle ilmenee, on lääkityksen lisäksi huolehdittavat myös hygieniasta ja ympäristön puhdistuksesta, etteivät kanit uudelleen infektoidu.
  • Tokariev, Anton (Helsingin yliopisto, 2015)
    In humans the few months surrounding birth comprise a developmentally critical period characterised by the growth of major neuronal networks as well as their initial tuning towards more functionally mature large-scale constellations. Proper wiring in the neonatal brain, especially during the last trimester of pregnancy and the first weeks of postnatal life, relies on the brain’s endogenous activity and remains critical throughout one’s life. Structural or functional abnormalities at the stage of early network formation may result in a neurological disorder later during maturation. Functional connectivity measures based on an infant electroencephalographic (EEG) time series may be used to monitor these processes. A neonatal EEG is temporally discrete and consists of events (e.g., spontaneous activity transients (SATs)) and the intervals between them (inter-SATs). During early maturation, communication between areas of the brain may be transmitted through two distinct mechanisms: synchronisation between neuronal oscillations and event co-occurrences. In this study, we proposed a novel algorithm capable of assessing the coupling on both of these levels. Our analysis of real data from preterm neonates using the proposed algorithm demonstrated its ability to effectively detect functional connectivity disruptions caused by brain lesions. Our results also suggest that SAT synchronisation represents the dominant means through which inter-areal cooperation occurs in an immature brain. Structural disturbances of the neuronal pathways in the brain carry a frequency selective effect on the functional connectivity decreasing at the event level. Next, we used mathematical models and computational simulations combined with real EEG data to analyse the propagation of electrical neuronal activity within the neonatal head. Our results show that the conductivity of the neonatal skull is much higher than that found in adults. This leads to greater focal spread of cortical signals towards the scalp and requires high-density electrode meshes for quality monitoring of neonatal brain activity. Additionally, we show that the specific structure of the neonatal skull fontanel does not represent a special pathway for the spread of electrical activity because of the overall high conductivity of the skull. Finally, we demonstrated that the choice of EEG recording montage may strongly affect the fidelity of non-redundant neuronal information registration as well as the output of functional connectivity analysis. Our simulations suggest that high-density EEG electrode arrays combined with mathematical transformations, such as the global average or current source density (CSD), provide more spatially accurate details about the underlying cortical activity and may yield results more robust against volume conduction effects. Furthermore, we provide clear instruction regarding how to optimise recording montages for different numbers of sensors.
  • Hiltunen, Anna (2015)
    Periodontitis is a globally significant disease which destroys the attachment tissues and alveolar bone of teeth, eventually leading to tooth loss. Biofilms, the most intrinsic lifestyle of bacteria, play a pivotal role in the occurrence of this disease. Periodontal biofilms can be treated with topically administered chlorhexidine and strain-specific antibiotics. However, these antimicrobials do not offer solutions for periodontal attachment tissue and alveolar bone loss. Some therapeutical alternatives for these conventional treatments have been investigated. In numerous studies, periodontitis is treated successfully (increased attachment and/or alveolar bone levels) with topically and systemically administered bisphosphonates. Furthermore, a topically administered bone graft substitute (bioactive glass) has shown to improve periodontal parameters. In addition, bioactive glass has known antimicrobial and anti-biofilm effects. Moreover, a few bisphosphonates have shown antimicrobial activity against some bacterial strains. Hence, both bisphosphonates and bioactive glass are promising materials for dental applications, also raising interest in their combination. Indeed, it could be hypothesized that this combination product could simultaneously treat both the underlying cause (biofilms) and consequences (alveolar bone and attachment tissue loss) of periodontitis. Open research questions remain for the combination product. Is the anti-biofilm effect enhanced when bioactive glass is combined with bisphosphonates? Moreover, do bisphosphonates have intrinsic anti-biofilm properties? These questions are investigated in this thesis, which is a continuation of a recent doctoral dissertation. In this dissertation, a clodronate-bioactive glass combination product was studied by applying it into periodontal pockets. However, anti-biofilm effects were not assessed. In this thesis, a close examination is carried out on these effects, utilizing relevant biofilm models. The aims of this work were to investigate anti-biofilm effects of bisphosphonates (alendronate, clodronate, etidronate, risedronate and zoledronate) (i) alone, administered as solutions and (ii) combined with bioactive glass S53P4. Optimization of the used assay methods (96-well plate assay, Static Biofilm method) was performed. The anti-biofilm effects of bisphosphonate solutions were screened in the 96-well plate assay using a model organism Staphylococcus aureus Newman and a periodontopathogen Aggregatibacter actinomycetemcomitans ATCC 33384. After this, experiments were conducted with bisphosphonate-bioactive glass combinations. The experiments were performed with a single-specie (A. actinomycetemcomitans ATCC 33384) dental biofilm model based on the Static Biofilm method. The model mimics conditions encountered by periodontal bacteria in the oral cavity. In this part, bisphosphonate particle sizes were measured to determine a suitable control material. In addition to bacterial experiments, pH measurements were carried out to gain an insight to a possible anti-biofilm mechanism. Bisphosphonates administered as stand-alone compounds did not have an effect on either the Gram-positive model organism (S. aureus Newman) or the Gram-negative periodontopathogen (A. actinomycetemcomitans ATCC 33384). In contrast, most combinations of bisphosphonate-bioactive glass revealed a statistically significant increase in anti-biofilm effect on A. actinomycetemcomitans ATCC 33384. The combinations were compared to a control composed of inert glass and bioactive glass. In these assay conditions, the risedronate-bioactive glass-combination was the most effective (significant statistical difference, p < 0.05). Other combinations also reduced biofilms (significant statistical differences, p < 0.05), with the exception of clodronate-bioactive glass, where the change was not statistically significant. The most effective combinations (containing risedronate and etidronate) subjected the biofilms to a period of low pH. Conversely, the least effective combination (clodronate-bioactive glass) rapidly became alkaline, similarly to the control compounds (inert glass and bioactive glass). Thus, anti-biofilm efficacy could be connected to lowered pH. This observation is supported by recent literature where A. actinomycetemcomitans has been deemed highly sensitive to acidity. However, establishing the anti-biofilm rank order of bisphosphonate-bioactive glass combinations would benefit from experiments with equal bisphosphonate particle sizes.