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  • Lassila, Arne (Helsingfors universitet, 2012)
    Tutkimuksen tavoitteena oli selvittää Meilahden sairaalan endoskopiayksikössä vuonna 2010 tehtyjen paksusuolen tähystysten indikaatioita, löydöksiä, komplikaatioita, onnistumisastetta, tähystysten yhteydessä tehtyjä toimenpiteitä ja esilääkityksen käyttöä. Tutkimus tehtiin käymällä läpi kymmenen prosentin poiminta kaikista vuoden 2010 tähystyksistä sekä kaikki kyseisen vuoden anestesiassa tehdyt tähystystutkimukset. Tähystysten lausunnoista kerättiin tietoa edellä mainituista muuttujista. Tutkimuksessa keskeisimmiksi tähystysindikaatioiksi osoittautuivat tulehduksellisten suolistosairauksien ja leikatun syövän seuranta sekä adenoomapolyyppiseuranta. Erilaisten vatsaoireiden, kuten ripulin ja veriulosteen, osuus indikaationa oli pienempi. Esilääkityksen käyttö oli tutkimuksen mukaan varsin vähäistä, noin kahdessa kolmasosassa tähystyksistä ei käytetty mitään esilääkitystä. Yleisimpiä löydöksiä olivat tulehdukselliset suolistosairaudet, polyypit sekä normaalilöydökset. Kymmenen prosentin poiminnan tähystyksistä noin kolmeen prosenttiin liittyi jokin komplikaatio.
  • Koski, Katja (Helsingin yliopisto, 2014)
    Staff members' communication strategies determine how individuals with profound and multiple learning disabilities (PMLD) can more fully participate in their community. Such individuals often possess limited interaction skills and may never be able to use symbolic communication strategies. Since staff members are often the main communication partners for individuals with PMLD, achieving successful interaction situations requires that the staff members modify their interaction strategies to meet the different needs of the individuals. However, staff members often fail to do so. Thus, both observational studies and staff members themselves have concluded that communication skills are a professional competence requiring special training. Speech and language therapists (SLTs) working with individuals who have PMLD often provide their service via indirect therapy, which includes giving advice to staff members on how to improve the communication between them and their clients with PMLD. Yet despite such efforts, the staff members seldom change their communication habits. Thus, the aim of this thesis is to understand the process of indirect speech therapy. Specifically, which issues are important for staff members to learn during indirect therapy and which factors support staff members in maintaining the targeted skills. The theoretical background of this study is based on Bronfenbrenner's Ecological Systems Theory. This theory states that the entire surrounding ecological system affects human development. The interaction between staff members and individuals with PMLD is therefore defined at the level of different sub-systems of Bronfenbrenner's theory. In the microsystem, the communicative abilities of staff members and individuals with PMLD affects how the interaction succeeds. In the exosystem, the interaction is regarded at the organisational level; the values and practices of the organisations have an effect on the interactions between the individuals and staff members. Finally, in the macrosystem, the social values and practices surrounding organisations (eg. laws, structures, philosophy) influence how the organisations provide care to their clients with PMLD and thus shape the interaction between the staff members and their clients. This study tries to target both the microsystem and the exosystem. Therefore, the research interests are in the interactions between staff members and clients with PMLD and in the organisation which provides the framework of these interactions. The materials of this thesis were collected from a communication partner training programme OIVA, developed by the Communication and Technology Centre of the Finnish Association on Intellectual and Developmental Disabilities. OIVA training was aimed at staff members working with individuals who have PMLD. The data were drawn from a group situation where SLTs analysed the participating staff members' interaction skills and from semi-structured interviews directed at the participating staff members. The SLTs' analyses of the staff members interaction patterns were analysed both quantitatively and qualitatively. The staff members' interviews were analysed using qualitative methods. This study discovered that SLTs have contrasting views about which strategies staff members should use to achieve successful interactions with their clients. Even though there might not be one single way of being a successful interaction partner, this variable can be confusing to staff members if they work with several SLTs who offer different professional advice. The participating staff members stated that they had pondered several ethical questions relating to the individuals' sense of belonging in the community and concerning their right to be understood and to understand the communications presented to them. This resulted in staff members starting to ask individuals with PMLD for their opinions about daily life and to act according to the individuals wishes. Furthermore, the staff members in this study reported a need for more supervisory support to maintain the results of the training and to disseminate the new practices to non-trained staff. It seems that permanent change in staff members' behaviours comes depends on whether the organisation is willing to focus on the selected issues over a long period of time, perhaps for years, and whether the organisation has developed support systems to maintain the benefits of the training. This study emphasises that indirect speech and language therapy is a complex professional task. The SLTs providing this therapy need more knowledge about the interaction strategies and the thinking habits affecting the interaction between staff members and individuals with PMLD. They also require understanding of the organisational factors which promote the staff members opportunities to participate in indirect therapy and to use and maintain the newly learnt communication skills.
  • Heikel-Virkkunen, Sofia (2012)
    Få ämnen är lika laddade som regleringen av elproduktionen och -distributionen idag. Kyoto-avtal och allmän insikt i att våra naturresurser är begränsade har lett till en ökad reglering av produktion och distribution av el. Elmarknaden har i och med EU formellt öppnats för öppen konkurrens. Ändå råder i praktiken monopol på distribution och därigenom även strikt reglering av produktionen. Nya målsättningar om att allt större delar el skall produceras genom utnyttjande av förnybara energikällor indikerar att vi lever i en förändringens tid på elmarknaden. De finns stora vinster att göra om regeiverket är gynnsamt. I uppsatsen granskas den finländska elmarknaden och dess aktörer. En av aktörernas, den enskilda individens, rationella överväganden gällande elkonsumtion och -produktion anaiyseras mera ingående med hjälp av resuitat från en survey undersökning. För undersökningen används en för ändamålet utformad internetenkät med hjälp av vilken ett av Finlands befolkning representativt sampel samlats in. Resultaten indikerar att individen som aktör på elmarknaden i första hand strävar till ekonomisk rationalitet medan miljön endast av en relativt liten andel uppmärksammas vid de egna el anskaffningsbesiuten. Kunskapsnivån samt individens förestäliningar om elmarknaden och elproduktion är som oberoende variabler signifikanta för hur ofta ett hushålls el anskaffning konkurrensutsätts. Ur den för finländska befolkningen representativa survey undersökningsdata framgår att 73,8 % av Finlands fastighetsägare skulle ställa sig positivt till vindkraftsproduktion på eller i närheten av egen fastighet om de skulle få en del av vinsten. Dä ingen vinst utiovas är motsvarande andel 60,8%. Endast 6,3 % anger verkningar på miljö eller omgivning som en orsak till att de inte övervägt egen elproduktion. Som potentiell elproducent kan den finländska individen därför i relativt hög grad ses som ekonomiskt rationell.
  • Pemovska, Tea (Helsingin yliopisto, 2015)
    Adult acute myeloid leukemia (AML) effectively illustrates the challenges of contemporary cancer drug discovery and development, as molecularly targeted therapies have not yet been translated in clinical practice. In fact the standard therapy (cytarabine and an anthracycline) for AML has not been changed in over 40 years. As a consequence, outcome remains poor with overall survival of 30-40%. The genetic alterations that are associated with AML have been mapped, but the underlying disease mechanism is poorly defined due to large inter-patient heterogeneity. In contrast, chronic myeloid leukemia (CML) is strictly driven by BCR-ABL1 and drugs targeting the ABL1 kinase activity have paved the way for oncoprotein targeting drugs in the treatment of cancer. In CML the main clinical challenge is instead the emergence of resistance to ABL1-directed therapy. This resistance typically occurs through point mutations in the kinase domain of ABL1 such as the clinically challenging T315I mutation. Hence, in both leukemia types there is an unmet need for novel therapeutic strategies. This study focused on development and implementation of an Individualized Systems Medicine (ISM) platform to identify novel therapeutic strategies for leukemia patients. The ISM strategy incorporated functional ex vivo drug sensitivity and resistance testing (DSRT), deep molecular profiling and clinical information to facilitate identification of personalized therapy approaches. A large number of approved and investigational anti-cancer compounds were tested and individualized selective responses were quantified with drug sensitivity scores (DSS). RNA and exome sequencing data was used to identify genetic alterations that enabled associating drug sensitivities with genetic alterations and biomarkers. The DSRT approach enabled functional taxonomy of AML patient samples based on drug responses, provided insights into disease biology, and identified effective drugs and drug combinations for individual patients and thus facilitated drug repurposing. In addition, integration of DSRT and molecular data identified phenotype to genotype links that has a potential for rapid translation of results. Clinical implementation of ISM data was plausible in approximately 80% of relapsed and refractory AML patient cases, and meaningful and evaluable responses were achieved in approximately 40% of cases. Notably, emergence of in vivo resistance to targeted therapy was mirrored in the DSRT profile of the relapsed samples, highlighting a solid correlation between ex vivo and in vivo drug responses. Finally, this study identified a number of kinase inhibitors that can be repositioned for specific subtypes of AML and CML, such as dasatinib in combination with a FLT3 inhibitor for AML patients with FLT3-ITD mutations and axitinib for patients with BCR-ABL1(T315I)-driven leukemia. The results of this thesis demonstrate how unbiased drug sensitivity profiling of patient-derived cancer cells is a powerful way to discern unforeseen drug-disease and drug-target links with clinical implications and provides a workable concept that can be implemented in routine clinical care of cancer patients in the future.
  • Seikku, Paula (Helsingin yliopisto, 2008)
    Pediatric renal transplantation (TX) has evolved greatly during the past few decades, and today TX is considered the standard care for children with end-stage renal disease. In Finland, 191 children had received renal transplants by October 2007, and 42% of them have already reached adulthood. Improvements in treatment of end-stage renal disease, surgical techniques, intensive care medicine, and in immunosuppressive therapy have paved the way to the current highly successful outcomes of pediatric transplantation. In children, the transplanted graft should last for decades, and normal growth and development should be guaranteed. These objectives set considerable requirements in optimizing and fine-tuning the post-operative therapy. Careful optimization of immunosuppressive therapy is crucial in protecting the graft against rejection, but also in protecting the patient against adverse effects of the medication. In the present study, the results of a retrospective investigation into individualized dosing of immunosuppresive medication, based on pharmacokinetic profiles, therapeutic drug monitoring, graft function and histology studies, and glucocorticoid biological activity determinations, are reported. Subgroups of a total of 178 patients, who received renal transplants in 1988 2006 were included in the study. The mean age at TX was 6.5 years, and approximately 26% of the patients were <2 years of age. The most common diagnosis leading to renal TX was congenital nephrosis of the Finnish type (NPHS1). Pediatric patients in Finland receive standard triple immunosuppression consisting of cyclosporine A (CsA), methylprednisolone (MP) and azathioprine (AZA) after renal TX. Optimal dosing of these agents is important to prevent rejections and preserve graft function in one hand, and to avoid the potentially serious adverse effects on the other hand. CsA has a narrow therapeutic window and individually variable pharmacokinetics. Therapeutic monitoring of CsA is, therefore, mandatory. Traditionally, CsA monitoring has been based on pre-dose trough levels (C0), but recent pharmacokinetic and clinical studies have revealed that the immunosuppressive effect may be related to diurnal CsA exposure and blood CsA concentration 0-4 hours after dosing. The two-hour post-dose concentration (C2) has proved a reliable surrogate marker of CsA exposure. Individual starting doses of CsA were analyzed in 65 patients. A recommended dose based on a pre-TX pharmacokinetic study was calculated for each patient by the pre-TX protocol. The predicted dose was clearly higher in the youngest children than in the older ones (22.9±10.4 and 10.5±5.1 mg/kg/d in patients <2 and >8 years of age, respectively). The actually administered oral doses of CsA were collected for three weeks after TX and compared to the pharmacokinetically predicted dose. After the TX, dosing of CsA was adjusted according to clinical parameters and blood CsA trough concentration. The pharmacokinetically predicted dose and patient age were the two significant parameters explaining post-TX doses of CsA. Accordingly, young children received significantly higher oral doses of CsA than the older ones. The correlation to the actually administered doses after TX was best in those patients, who had a predicted dose clearly higher or lower (> ±25%) than the average in their age-group. Due to the great individual variation in pharmacokinetics standardized dosing of CsA (based on body mass or surface area) may not be adequate. Pre-Tx profiles are helpful in determining suitable initial CsA doses. CsA monitoring based on trough and C2 concentrations was analyzed in 47 patients, who received renal transplants in 2001 2006. C0, C2 and experienced acute rejections were collected during the post-TX hospitalization, and also three months after TX when the first protocol core biopsy was obtained. The patients who remained rejection free had slightly higher C2 concentrations, especially very early after TX. However, after the first two weeks also the trough level was higher in the rejection-free patients than in those with acute rejections. Three months after TX the trough level was higher in patients with normal histology than in those with rejection changes in the routine biopsy. Monitoring of both the trough level and C2 may thus be warranted to guarantee sufficient peak concentration and baseline immunosuppression on one hand and to avoid over-exposure on the other hand. Controlling of rejection in the early months after transplantation is crucial as it may contribute to the development of long-term allograft nephropathy. Recently, it has become evident that immunoactivation fulfilling the histological criteria of acute rejection is possible in a well functioning graft with no clinical sings or laboratory perturbations. The influence of treatment of subclinical rejection, diagnosed in 3-month protocol biopsy, to graft function and histology 18 months after TX was analyzed in 22 patients and compared to 35 historical control patients. The incidence of subclinical rejection at three months was 43%, and the patients received a standard rejection treatment (a course of increased MP) and/or increased baseline immunosuppression, depending on the severity of rejection and graft function. Glomerular filtration rate (GFR) at 18 months was significantly better in the patients who were screened and treated for subclinical rejection in comparison to the historical patients (86.7±22.5 vs. 67.9±31.9 ml/min/1.73m2, respectively). The improvement was most remarkable in the youngest (<2 years) age group (94.1±11.0 vs. 67.9±26.8 ml/min/1.73m2). Histological findings of chronic allograft nephropathy were also more common in the historical patients in the 18-month protocol biopsy. All pediatric renal TX patients receive MP as a part of the baseline immunosuppression. Although the maintenance dose of MP is very low in the majority of the patients, the well-known steroid-related adverse affects are not uncommon. It has been shown in a previous study in Finnish pediatric TX patients that steroid exposure, measured as area under concentration-time curve (AUC), rather than the dose correlates with the adverse effects. In the present study, MP AUC was measured in sixteen stable maintenance patients, and a correlation with excess weight gain during 12 months after TX as well as with height deficit was found. A novel bioassay measuring the activation of glucocorticoid receptor dependent transcription cascade was also employed to assess the biological effect of MP. Glucocorticoid bioactivity was found to be related to the adverse effects, although the relationship was not as apparent as that with serum MP concentration. The findings in this study support individualized monitoring and adjustment of immunosuppression based on pharmacokinetics, graft function and histology. Pharmacokinetic profiles are helpful in estimating drug exposure and thus identifying the patients who might be at risk for excessive or insufficient immunosuppression. Individualized doses and monitoring of blood concentrations should definitely be employed with CsA, but possibly also with steroids. As an alternative to complete steroid withdrawal, individualized dosing based on drug exposure monitoring might help in avoiding the adverse effects. Early screening and treatment of subclinical immunoactivation is beneficial as it improves the prospects of good long-term graft function.
  • Utz, Margarete (Helsingin yliopisto, 2010)
    Individual movement is very versatile and inevitable in ecology. In this thesis, I investigate two kinds of movement body condition dependent dispersal and small-range foraging movements resulting in quasi-local competition and their causes and consequences on the individual, population and metapopulation level. Body condition dependent dispersal is a widely evident but barely understood phenomenon. In nature, diverse relationships between body condition and dispersal are observed. I develop the first models that study the evolution of dispersal strategies that depend on individual body condition. In a patchy environment where patches differ in environmental conditions, individuals born in rich (e.g. nutritious) patches are on average stronger than their conspecifics that are born in poorer patches. Body condition (strength) determines competitive ability such that stronger individuals win competition with higher probability than weak individuals. Individuals compete for patches such that kin competition selects for dispersal. I determine the evolutionarily stable strategy (ESS) for different ecological scenarios. My models offer explanations for both dispersal of strong individuals and dispersal of weak individuals. Moreover, I find that within-family dispersal behaviour is not always reflected on the population level. This supports the fact that no consistent pattern is detected in data on body condition dependent dispersal. It also encourages the refining of empirical investigations. Quasi-local competition defines interactions between adjacent populations where one population negatively affects the growth of the other population. I model a metapopulation in a homogeneous environment where adults of different subpopulations compete for resources by spending part of their foraging time in the neighbouring patches, while their juveniles only feed on the resource in their natal patch. I show that spatial patterns (different population densities in the patches) are stable only if one age class depletes the resource very much but mainly the other age group depends on it.
  • Hormio, Säde (2009)
    Kongon demokraattinen tasavalta on köyhä maa, jossa kaivosteollisuuden tuottamat rahat päätyvät usein ruokkimaan vuosia kestänyttä veristä konfliktia. Onko ylikansallisilla elektroniikkayrityksillä ja heidän tyontekijöillään vastuu käyttämiensä raaka-aineiden alkuperästä? Tutkielmani käsittelee työntekijän moraalista vastuuta työroolin sisällä (roolivastuu), sekä sen ulkopuolella (vastuu ihmisenä). Keskityn yksittäisen työntekijän henkilökohtaisen vastuun osuuteen kollektiivisesta vastuusta. Koska työtä tehdään usein virallisissa rooleissa, pohdin aluksi roolien syntyprosesseja ja rajoja. Käyn läpi työntekijän moraalisen vastuun peruskysymykset ja havainnollistan niitä esimerkkien avulla. Kirjoitan roolien syntymisestä, tarpeellisuudesta ja ominaisuuksista yleisesti mutta keskityn erityisesti työntekijän rooliin ja työpaikkojen luonteeseen. Selvennän myös eri tapoja, miten yksilö voi olla vastuussa asioista (vastuun ja moraalisen toimijuuden ehdot). Esittelen teorioita kollektiivisen vastuun jakautumisesta, sekä pohdin niiden ongelmia, keskustellen myös siitä, minkälaiset organisaatiot ja yhteisöt voivat olla kollektiivisesti vastuussa jostakin. Keskityn yksittäisen työntekijän moraalisen vastuun muodostumiseen ja siihen, millaisissa olosuhteissa työntekijä on vastuussa työnsä laajemmista seurauksista. Byrokraattiset rakenteet ja roolit saavat ihmiset usein ajattelemaan eri tavalla sekä teoistaan että niiden seurauksista. Roolien ja isojen organisaatioiden avulla ihmiset voivat tehdä tekoja, joihin eivät yksin pystyisi. Moraalinen vastuu työn seurauksista kuuluu siten sekä yksittäisille työntekijöille että organisaatiolle. Monet yritykset on kuitenkin rakennettu tarkoituksella sellaisella tavalla, että on vaikea osoittaa, kenellä on vastuu. Byrokratian luoma moraalisen vastuun haihtuminen on harha, vaikka vastuuta isoissa organisaatioissa on usein ongelmallista osoittaa tai joissain tapauksissa edes tiedostaa. Yritysten suunnittelussa onkin moraalikysymykset tuotava enemmän esille, ja organisaatioiden rakenteita on tarpeen vaatiessa pystyttävä muokkaamaan moraalinen vastuu huomioon ottaen. Yksilö on aina vastuun keskipisteessä ja vastuu ei katoa niin helposti kuin joskus väitetään.
  • Hormio, Säde (Helsingin yliopisto, 2009)
    I discuss role responsibly, individual responsibility and collective responsibility in corporate multinational setting. My case study is about minerals used in electronics that come from the Democratic Republic of Congo. What I try to show throughout the thesis is how many things need to be taken into consideration when we discuss the responsibility of individuals in corporations. No easy and simple answers are available. Instead, we must keep in mind the complexity of the situation at all times, judging cases on individual basis, emphasizing the importance of individual judgement and virtue, as well as the responsibility we all share as members of groups and the wider society. I begin by discussing the demands that are placed on us as employees. There is always a potential for a conflict between our different roles and also the wider demands placed on us. Role demands are usually much more specific than the wider question of how we should act as human beings. The terminology of roles can also be misleading as it can create illusions about our work selves being somehow radically separated from our everyday, true selves. The nature of collective decision-making and its implications for responsibility is important too. When discussing the moral responsibility of an employee in a corporate setting, one must take into account arguments from individual and collective responsibility, as well as role ethics. Individual responsibility is not a separate or competing notion from that of collective responsibility. Rather, the two are interlinked. Individuals' responsibilities in collective settings combine both individual responsibility and collective responsibility (which is different from aggregate individual responsibility). In the majority of cases, both will apply in various degrees. Some members might have individual responsibility in addition to the collective responsibility, while others just the collective responsibility. There are also times when no-one bears individual moral responsibility but the members are still responsible for the collective part. My intuition is that collective moral responsibility is strongly linked to the way the collective setting affects individual judgements and moulds the decisions, and how the individuals use the collective setting to further their own ends. Individuals remain the moral agents but responsibility is collective if the actions in question are collective in character. I also explore the impacts of bureaucratic ethic and its influence on the individual. Bureaucracies can compartmentalize work to such a degree that individual human action is reduced to mere behaviour. Responsibility is diffused and the people working in the bureaucracy can come to view their actions to be outside the normal human realm where they would be responsible for what they do. Language games and rules, anonymity, internal power struggles, and the fragmentation of information are just some of the reasons responsibility and morality can get blurry in big institutional settings. Throughout the thesis I defend the following theses: ● People act differently depending on their roles. This is necessary for our society to function, but the more specific role demands should always be kept in check by the wider requirements of being a good human being. ● Acts in corporations (and other large collectives) are not reducible to individual actions, and cannot be explained fully by the behaviour of individual employees. ● Individuals are responsible for the actions that they undertake in the collective as role occupiers and are very rarely off the hook. Hiding behind role demands is usually only an excuse and shows a lack of virtue. ● Individuals in roles can be responsible even when the collective is not. This depends on if the act they performed was corporate in nature or not. ● Bureaucratic structure affects individual thinking and is not always a healthy environment to work in. ● Individual members can share responsibility with the collective and our share of the collective responsibility is strongly linked to our relations. ● Corporations and other collectives can be responsible for harm even when no individual is at fault. The structure and the policies of the collective are crucial. ● Socialization plays an important role in our morality at both work and outside it. We are all responsible for the kind of moral context we create. ● When accepting a role or a position in a collective, we are attaching ourselves with the values of that collective. ● Ethical theories should put more emphasis on good judgement and decision-making instead of vague generalisations. My conclusion is that the individual person is always in the centre when it comes to responsibility, and not so easily off the hook as we sometimes think. What we do, and especially who we choose to associate ourselves with, does matter and we should be more careful when we choose who we work for. Individuals within corporations are responsible for choosing that the corporation they associate with is one that they can ascribe to morally, if not fully, then at least for the most part. Individuals are also inclusively responsible to a varying degree for the collective activities they contribute to, even in overdetermined contexts. We all are responsible for the kind of corporations we choose to support through our actions as consumers, investors and citizens.
  • Koskela, Jukka (Helsingin yliopisto, 2015)
    Managing chronic respiratory conditions such as asthma and Chronic Obstructive Pulmonary Disease (COPD) forms a notable burden on the healthcare system while the burden on an individual is equally notable as patients might suffer from a symptomatic disease for decades. However, not all asthma and COPD patients develop a disabling disease with frequent disease exacerbations and highest cost (in Quality Adjusted Life Years lost or healthcare spending). This variation in disease trajectories enables the analytical identification of distinct phenotypes over time. Retrospective data collected from a large number of patients could be used efficiently as the electronic health records are increasingly made available to researchers around the world. The aim of this project is to develop disease models based on longitudinal data to better capture the essential characteristics of obstructive lung disease, mainly focusing on COPD. Projects I III in this thesis are based on 2398 asthma and COPD patients retrospectively followed through electronic health records from year 2000 onwards. We aimed to analyse this real-world hospital based data using Hierarchical Models to assess the variation of development between individual patients over time. Unpublished Project IV is based on Health 2000 to 2011 follow-up study consisting of 1113 subjects from random Finnish population. The aim was to estimate Single Nucleotide Polymorphism (SNP) based heritability of Forced Expiratory Volume in 1 s (FEV1) level and development and to perform a Genome-Wide Association Study (GWAS) to identify possible genetic markers associated with FEV1 development over time. Our results suggest that the major determinants of Health Related Quality of Life (HRQoL) in mild or moderate COPD are the common comorbidities associated with COPD while in severe diseases the accentuated lung function has a major role. Over time, observable individual trajectories of HRQoL are presented in Asthma and COPD. Significant decline of HRQoL in Asthma was found to associate with obesity related diseases and states while the main determinants in COPD were poor lung function and increasing age. Psychiatric conditions were found associated in both Asthma and COPD. Using an unbalanced data (varying number of measurements and length of follow-up time) of lung function measurements, we were able to observe significant individual trajectories of FEV1 based on the past development. Significant and rapid decline was seen in 30% of the COPD cohort in the study while significant improvement was extremely rare. Rapid decline was associated with numerous exacerbation related markers. Our unpublished results suggest that development of FEV1 is significantly affected by common variants in DNA as genetic effects were estimated to explain 1/3 of the phenotypic variance in random Finnish population. One locus previously associated with the level of FEV1 was found associated with the development of FEV1. Suggestive evidence for two novel loci associated with FEV1 development was also identified. The findings underline the varying trajectories of HRQoL and lung function seen in a homogenous cohort of Asthma and COPD patients. This thesis aims to provide approaches and aspects to better understand the trajectories of a chosen parameter in asthma and COPD. The variation of e.g. lung function development is abundant, and we should not consider this variation as an obstacle but as a useful source of information as there might be genetic or environmental determinants causing this variation.
  • Korpela, Ilkka (Helsingin yliopisto, 2004)
  • Lepäntalo, Aino (Helsingin yliopisto, 2007)
    Antiplatelet medication is known to decrease adverse effects in patients with atherothrombotic disease. However, despite ongoing antiplatelet medication considerable number of patients suffer from atherothrombotic events. The aims of the study were 1) to evaluate the individual variability in platelet functions and compare the usability of different methods in detecting it, 2) to assess variability in efficacy of antiplatelet medication with aspirin (acetylsalicylic acid) or the combination of aspirin and clopidogrel and 3) to investigate the main genetic and clinical variables as well as potential underlying mechanisms of variability in efficacy of antiplatelet medication. In comparisons of different platelet function tests in 19 healthy individuals PFA-100® correlated with traditional methods of measuring platelet function and was thus considered appropriate for testing individual variability in platelet activity. Efficacy of ongoing 100mg aspirin daily was studied in 101 patients with coronary artery disease (CAD). Aspirin response was measured with arachidonic acid (AA)-induced platelet aggregation, which reflects cyclo-oxygenase (COX)-1 dependent thromboxane (Tx) A2 formation, and PFA-100®, which evaluates platelet activation under high shear stress in the presence of collagen and epinephrine. Five percent of patients failed to show inhibition of AA-aggregation and 21% of patients had normal PFA-100® results despite aspirin and were thus considered non-responders to aspirin. Interestingly, the two methods of assessing aspirin efficacy, platelet aggregation and PFA-100®, detected different populations as being aspirin non-responders. It could be postulated that PFA-100® actually measures enhanced platelet function, which is not directly associated with TxA2 inhibition exerted by aspirin. Clopidogrel efficacy was assessed in 50 patients who received a 300mg loading dose of clopidogrel 2.5 h prior to percutaneous coronary intervention (PCI) and in 51 patients who were given a loading dose of 300mg combined with a five day treatment of 75mg clopidogrel daily mimicking ongoing treatment. Clopidogrel response was assessed with ADP-induced aggregations, due to its mechanism of action as an inhibitor of ADP-induced activation. When patients received only a loading dose of clopidogrel prior to PCI, 40% did not gain measurable inhibition of their ADP-induced platelet activity (inhibition of 10% or less). Prolongation of treatment so that all patients had reached a plateau of inhibition exerted by clopidogrel, decreased the incidence of non-responders to 20%. Polymorphisms of COX-1 and GP VI, as well as diabetes and female gender, were associated with decreased in vitro aspirin efficacy. Diabetes also impaired the in vitro efficacy of short-term clopidogrel. Decreased response to clopidogrel was associated with limited inhibition by ARMX, an antagonist of P2Y12-receptor, suggesting the reason for clopidogrel resistance to be receptor-dependent. Conclusions: Considerable numbers of CAD patients were non-responders either to aspirin, clopidogrel or both. In the future, platelet function tests may be helpful to individually select effective and safe antiplatelet medication for these patients.
  • Shawesh, Amna Mohammed (Helsingin yliopisto, 2015)
    Indomethacin (IND) is a potent non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis, acute gout and other disorders. IND is available worldwide mostly in the form of capsules and suppositories, however, these formulations usually create side effects. Consequently, an alternate route of administration to avoid or minimize side effects may be found in the form of semisolid dermatological formulations, now available in few countries. The specific goals of this study were: (I) to determine the solubility of IND using different co-solvents: hexylene glycol (HG), propylene glycol (PG), polyethylene glycol 300 (PEG), butylene glycols (1,2 BG; 1,3 BG and 1,4 BG) and ethanol (ETOH). 1% (w/w) Tween® 80 or polyvinyl pyrrolidone (PVP-25) were used as enhancers; (II) to develop suitable topical gel preparations using 20% (w/w) Pluronic® (PF-127) or 1% (w/w) Carbopol ETD® 2001 (C2001) as gelling agents and HG or PEG 300 as solvents (1% (w/w) Tween® 80 and PVP-25 were added as excipients); (III) To evaluate the effect of composition of prepared gel formulations on the following parameters: appearance, crystallization, pH and rheological behaviour and (IV) to investigate the influence of storage time and storage conditions on the characteristics of the gels. These results indicate that all the solvents tested increased the solubility of IND to varying degrees. Tween® 80 and PVP-25 only slightly enhanced the solubility of IND. 1% (w/w) IND was able to form a structural gel with both PF-127 and C2001. Storing the INDPF-127 gels at 6°C resulted in the precipitation of IND. All gels stored at room temperature exhibited good stability. The gels stored at 45°C developed a dark yellow colour. Gels with C2001 and PF-127/PEG had slightly decreased viscosities with increasing storage time, while the gels with PF-127/HG showed increase in viscosities with time. In conclusion, the water solubility of IND was increased by the addition of co-solvents. 1% (w/w) IND gel can be suitable for using as a gel formulation and it is stable at room temperature. The search for suitable gels for IND topical formulation needs to be continued with more stability studies. Moreover, in-vitro and in-vivo experiments will be necessary for providing data on bioavailability.
  • Rönkkö, Anitra Sofia (2002)
    Tutkimus käsittelee Indonesiaa konfliktiteoreettisesta näkökulmasta. Tutkimuksen tavoitteena on selvittää, mikä on Indonesian oletettu konfliktirakenne ja miten se vaikuttaa tapaustutkimuksen kohteena olevaan Acehin alueeseen, joka vaatii itsenäisyyttä Indonesiasta muun muassa historiallisin ja taloudellisin perustein. Tavoitteena on myös analysoida konfliktirakenteen purkamisyrityksiä ja esitellä vaihtoehtoisia strategioita. Teoreettisena viitekehyksenä on käytetty Edward E. Azarin pitkittyneen sosiaalisen konfliktin teoriaa sekä täydentävänä teoriana Indonesian olosuhteista erikoistutkija Timo Kivimäen näkemyksiä Indonesian konfliktialttiudesta. Tutkimuksessa aineistoa käsitellään Azarin teorian pohjalta aina siirtomaa-ajasta nykyaikaan konfliktirakenteen syvällisemmän ymmärtämyksen saavuttamiseksi. Azarin mukaan konfliktirakenteeseen vaikuttavat moniyhteisöllisyys, jossa yhteisöjen vastakkaisuus nousee ongelmatekijäksi sekä tarpeiden tyydyttämättömyys, jotka jaetaan hyväksynnän, pääsyn ja turvallisuuden tarpeisiin. Azar tarkoittaa tällä implisiittisesti demokratian puutetta, joka Kivimäen mukaan ilmenee Itä- ja Kaakkois-Aasian alueella sijaitsevissa valtioissa siten, että ne ovat olleet silmiinpistävän vahvoja ja väkivaltaisia kansalaisiaan kohtaan. Tämä puolestaan patoaa konfliktin impulsseja. Azarin teoriassa käsitellään myös valtion roolia, joka pitkittyneen sosiaalisen konfliktin maissa on usein heikko ja legitimiteetin puutteesta kärsivä. Konfliktin kansainvälinen ulottuvuus on Azarin teoriassa joko sotilaallis-poliittisiin suhteisiin perustuva tai taloudellinen. Tutkimuksessa havaitaan Indonesian konfliktirakenteen rakentuvan pala palalta siirtomaakaudesta lähtien. Erityisen tärkeä konfliktirakenteen kannalta on Indonesian itsenäistymisen kausi, jolloin käytiin perustuslaillista keskustelua Indonesian valtiomuodosta ja päädyttin epädemokraattiseen perustuslakiin olosuhteiden vuoksi. Toinen tärkeä konfliktirakenteen tekijä on presidentti Suharton kausi, jolloin vahvistettiin keskitettyä hallintoa. Suharton kaudessa havaitaan myös eliittitason vaikutus konfliktiin. Keskitetty hallinto yhdessä korruptoituneen hallinnon kanssa on tehnyt Indonesian demokraattisen murroksen hyvin vaikeaksi. Nykyajassa Indonesian suurin ongelma Acehin kohdalla on asevoimien ihmisoikeusrikkomukset Acehissa sekä hallituksen sitoutumattomuus konfliktin ratkaisuyrityksiin. Indonesian ja Acehin välille on syntynyt konfliktin kierre jota on vaikea katkaista, kun hallitus pitäytyy vanhoihin strategioihin, joka puolestaan vaikuttaa negatiivisesti konfliktirakenteen purkuyrityksiin. Tutkimuksen aineisto on kvalitatiivista ja se sisältää akateemisia julkaisuja, aikakausilehtien artikkeleita, raportteja ja uutisia koskien Indonesiaa. Konfliktiteoreettinen aineisto perustuu em. Edward E. Azarin teokseen “The Management of Protracted Social Conflict. Theory and Cases.” sekä Timo Kivimäen teokseen ”Saarivaltio viidakkoveitsen terällä. Analyysi Indonesian konflikteista.” Indonesiaa koskevassa osiossa on käytetty Indonesian tutkijoiden ja asiantuntijoiden teoksia, joista tärkeimpänä Adam Schwartzin ”A nation in waiting. Indonesia´s Search for Stability.”
  • Malinen, Anna (2005)
    Demokraattisten valtioiden lukumäärä maailmassa on moninkertaistunut demokratian kolmannen aallon myötä. Demokratisoituminen on globaali ilmiö, jota voidaan selittää erilaisista tekijöistä käsin. Tässä tutkielmassa demokratisoitumista tutkitaan Laurence Whiteheadin teoksessa (2002) "Democratization. Theory and Experience." nimeämien tekijöiden kautta, joita ovat: demokraattinen transitio eli vallanvaihto, kansalaisyhteiskunta, poliittisten instituutioiden suunnittelu, poliittinen korruptio, rahapoliittinen toimivalta (monetary authority) ja kansalaisten turvallisuus. Tutkimuksen tarkoituksena on selvittää, miksi Indonesian on ollut vaikea demokratisoitua ja ylläpitää demokratiaa. Tarkoituksena on myös selvittää, miten Laurence Whiteheadin lähestymistapa demokratisoitumiseen toimii tarkasteltaessa Indonesian demokratisoitumisprosesia. Whiteheadin mukaan demokratisoitumisprosessit ovat kompleksisia, pitkäkestoisia, avoimia ja dynaamisia prosesseja, joihin on vaikea soveltaa mitään määrättyä kaavaa. Varsinkin nykyajan demokratisoitumisprosessit eroavat toisistaan niin monella tavalla, että niitä on mahdotonta luokitella mihinkään kategorioihin. Esimerkkinä tällaisesta nykyaikaisesta demokratisoitumisprosessista on Indonesian demokratisoituminen,joka lähti käyntiin vuonna 1998 Presidentti Suharton luovuttua vallasta. Indonesian demokratisoitumisprosessin kulkua seurataan vuoteen 2004 asti. Whiteheadin lähestymistapa on tulkinnallinen, ja se korostaa valtion historiallisten ja kulttuuristen piirteiden huomioimista demokratisoitumistutkimuksessa. Whiteheadin lähestymistapa sopii hyvin kuvaamaan Indonesian demokratisoitumisprosessia, sillä Indonesian poliittisessa järjestelmässä on monia erityispiirteitä, jotka juontavat juurensa maan historiaan tai kulttuuriin, ja jotka vaikuttavat sen demokratisoitumiseen ainutlaatuisella tavalla, kuten:1) Indonesian armeijalla on ollut omalaatuinen poliittinen roolinsa maan itsenäistymisestä lähtien, ja Indonesian poliittinen eliitti on vieläkin suurelta osin armeijataustaista. 2) Kansalaisyhteiskunnan toiminta on hajanaista ja sitä vaivaa ammattimaisten johtajien puute. Kansalaisyhteiskunnan toiminta ei myöskään ole täysin turvattua. 3) Poliittista toimintaa leimaa korruptoituneisuus, tehottomuus ja vanhan hallinnon perinteet. Myös lakien toimeenpano ontuu. 4) Korruption levinneisyys yhteiskunnan joka sektorille estää Indonesian hallintokoneiston tehokkaan toiminnan. Indonesian demokratisoitumisprosessi on päässyt hyvään alkuun, mutta paljon on vielä saavuttamatta. Whitehead korostaakin, että on tärkeämpää tutkia demokratisoitumisprosessia itsessään kuin ruveta arvailemaan sen lopputulosta, sillä prosessi voi kestää vuosikymmeniä, ja lopputulos voi jäädä avoimeksi.