Peritoneal dialysis and neurological outcome in infants and small children

Although improved outcomes for children on peritoneal dialysis (PD) have been seen in recent years, the youngest patients continue to demonstrate inferior growth, more frequent infections, more neurological sequelae, and higher mortality compared to older children. Also, maintain-ing normal intravascular volume status, especially in anuric patients, has proven difficult. This study was designed to treat and monitor these youngest PD patients, which are relatively many due to the high prevalence of congenital nephrotic syndrome of the Finnish type (CNF, NPHS1) in Finland, with a strict protocol, to evaluate the results and to improve metabolic balance, growth, and development. A retrospective analysis of 23 children under two years of age at onset of PD, treated between 1995 and 2000, was performed to obtain a control population for our prospective PD study. Respectively, 21 patients less than two years of age at the beginning of PD were enrolled in prospective studies between 2001 and 2005. Medication for uremia and nutrition were care-fully adjusted during PD. Laboratory parameters and intravascular volume status were regu-larly analyzed. Growth was analyzed and compared with midparental height. In a prospective neurological study, the risk factors for development and the neurological development was determined. Brain images were surveyed. Hearing was tested. In a retrospective neurological study, the data of six NPHS1 patients with a congruent neurological syndrome was analyzed. All these patients had a serious dyskinetic cerebral palsy-like syndrome with muscular dysto-nia and athetosis (MDA). They also had a hearing defect. Metabolic control was mainly good in both PD patient groups. Hospitalization time shortened clearly. The peritonitis rate diminished. Hypertension was a common problem. Left ventricular hypertrophy decreased during the prospective study period. None of the patients in either PD group had pulmonary edema or dialysis-related seizures. Growth was good and catch-up growth was documented in most patients in both patient groups during PD. Mortality was low (5% in prospective and 9% in retrospective PD patients). In the prospective PD patient group 11 patients (52%) had some risk factor for their neuro-development originating from the predialysis period. The neurological problems, detected be-fore PD, did not worsen during PD and none of the patients developed new neurological com-plications during PD. Brain infarcts were detected in four (19%) and other ischemic lesions in three patients (14%). At the end of this study, 29% of the prospectively followed patients had a major impairment of their neurodevelopment and 43% only minor impairment. In the NPHS1+MDA patients, no clear explanation for the neurological syndrome was found. The brain MRI showed increased signal intensity in the globus pallidus area. Kernic-terus was contemplated to be causative in the hypoproteinemic newborns but it could not be proven. Mortality was as high as 67%. Our results for young PD patients were promising. Metabolic control was acceptable and growth was good. However, the children were significantly smaller when compared to their midparental height. Although many patients were found to have neurological impairment at the end of our follow-up period, PD was a safe treatment whereby the neurodevelopment did not worsen during PD.

Constructing Fair Tourism in Ecuador: The Case of Asoguabo

Tämän pro gradu-tutkielman tarkoitus on tutkia, miten reilun kaupan banaania tuottavan El Guabon pienten banaaninviljelijöiden järjestön Asoguabon reilun turismin projekti on rakennettu. Projektin muotoutumista tutkitaan tässä työssä kahdesta eri näkökulmasta: siitä, miksi ja miten Asoguabo on monipuolistanut viljelystä turismiin, sekä siitä, millainen kuva projektista on rakennettu markkinoinnin kautta ja miten reilun kaupan mainonnasta tuttuja ilmiöitä on hyödynnetty reilun turismin rakentamisessa. Tutkielman teoreettisena taustana on maaseudun muutoksia tarkasteleva uuden ruraliteetin käsite. Turismi on viime vuosikymmenten aikana muuttunut, ja matkailijat etsivät yhä enemmän aitoja ja autenttisia matkailukokemuksia. Samanaikaisesti turismia on tuotteistettu korostamalla sen tiettyjä, kestävän kehityksen mukaisia piirteitä, ja erityisesti kehittyvissä maissa turismia markkinoidaan usein vaihtoehtoisena, yhteisöpohjaisena tai ekoturismina. Reilu turismi on uutena käsitteenä tullut mukaan tähän laajaan kirjoon, ja tämä tutkielma käsitteleekin Asoguabon projektia nimenomaan reilun turismin näkökulmasta. Tämä tutkielma on tapaustutkimus Asoguabon turismiprojektista, ja pohjautuu kuukauden pituiseen kenttätyöhön Ecuadorissa tammikussa 2010 sekä kirjoittajan aiempiin kokemuksiin Asoguabosta. Aineisto koostuu 21 puoli-strukturoidusta laadullisesta haastattelusta kuudentoista informantin kanssa, joista suurin osa oli hyvin läheisesti tekemisissä projektin kanssa. Tämän lisäksi aineistonkeruussa on käytetty havainnointia sekä projektin markkinointimateriaalien sisällönanalyysia. Tutkielma osoittaa reilun turismin projektin sisältävän monia haasteita ennen kuin se voi saavuttaa tavoitteensa tuottaa lisätuloja Asoguabon toimintaan. Tutkimushetkellä projekti hyödytti suoraan pääasiassa muutamia järjestön viljelijöitä, lähinnä niitä, jotka toimivat projektissa oppaina. Nämä oppaat hyötyvät projektista saamalla pieniä lisätuloja, kasvattamalla sosiaalista pääomaansa, sekä saamalla mahdollisuuden oppia muun muassa osallistumalla kursseille. Tutkimuksen keskeiset tulokset osoittavat myös, kuinka vuorovaikutus-ongelmat projektin eri toimijoiden välillä vaikeuttavat tiedonkulkua ja täten reilun turismin toimintaa. Nämä ongelmat myös lisäävät epätietoisuutta Asoguabon muiden viljelijöiden parissa. Lisäksi tutkimus osoittaa, kuinka reilun turismin projektin mainonnassa käytetään osittain samoja keinoja kuin reilun kaupan tuotteiden mainonnassa, joskin tuottajia on kuvattu mainosmateriaaleissa yllättävän vähän ja pääosassa ovat usein eurooppalaiset turistit.

Silva Fennica Vol. 21, 1987.

Julkaistu Silva Fennica Vol. 21(4) -numeron liitteenä.

Genomic alterations in Myeloproliferative Neoplasms and Myelodysplastic Syndromes

Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders whose etiology and molecular pathogenesis are poorly understood. During the past decade, enormous developments in microarray technology and bioinformatics methods have made it possible to mine novel molecular alterations in a large number of malignancies, including MPN and MDS, which has facilitated the detection of new prognostic, predictive and therapeutic biomarkers for disease stratification. By applying novel microarray techniques, we profiled copy number alterations and microRNA (miRNA) expression changes in bone marrow aspirate and blood samples. In addition, we set up and validated an miRNA expression test for bone marrow core biopsies in order to utilize the large archive material available in many laboratories. We also tested JAK2 mutation status and compare it with the in vitro growth pattern of hematologic progenitors cells. In the study focusing on 100 MPN cases, we detected a Janus kinase 2 (JAK2) mutation in 71 cases. We observed spontaneous erythroid colony growth in all mutation-positive cases in addition to nine mutation negative cases. Interestingly, seven JAK2V167F negative ET cases showed spontaneous megakaryocyte colony formation, one case of which also harbored a myeloproliferative leukemia virus oncogene (MPL) mutation. We studied copy number alterations in 35 MPN and 37 MDS cases by using oligonucleotide-based array comparative hybridization (array CGH). Only one essential thrombocythemia (ET) case presented copy number alterations in chromosomes 1q and 13q. In contrast, MDS cases were characterized by numerous novel cryptic chromosomal aberrations with the most common copy number losses at 5q21.3q33.1 and 7q22.1q33, while the most common copy number gain was trisomy 8. As for the study of the bone marrow core biopsy samples, we showed that even though these samples were embedded in paraffin and underwent decalcification, they were reliable sources of miRNA and suitable for array expression analysis. Further, when studying the miRNA expression profiles of the 19 MDS cases, we found that, compared to controls, two miRNAs (one human Epstein-Barr virus (miR-BART13) miRNA and one human (has-miR-671-5p) miRNA) were downregulated, whereas two other miRNAs (hsa-miR-720 and hsa-miR-21) were upregulated. However, we could find no correlation between copy number alterations and microRNA expression when integrating these two data. This thesis brings to light new information about genomic changes implicated in the development of MPN and MDS, and also underlines the power of applying genome-wide array screening techniques in neoplasias. Rapid advances in molecular techniques and the integration of different genomic data will enable the discovery of the biological contexts of many complex disorders, including myeloid neoplasias.

Change detection and controlling forest information using multi-temporal Landsat TM imagery.

A method was developed for relative radiometric calibration of single multitemporal Landsat TM image, several multitemporal images covering each others, and several multitemporal images covering different geographic locations. The radiometricly calibrated difference images were used for detecting rapid changes on forest stands. The nonparametric Kernel method was applied for change detection. The accuracy of the change detection was estimated by inspecting the image analysis results in field. The change classification was applied for controlling the quality of the continuously updated forest stand information. The aim was to ensure that all the manmade changes and any forest damages were correctly updated including the attribute and stand delineation information. The image analysis results were compared with the registered treatments and the stand information base. The stands with discrepancies between these two information sources were recommended to be field inspected.

Autoimmune Regulator (AIRE) in the Maintenance of Immunological Tolerance

Autoimmune regulator (AIRE) is the gene mutated in the human polyglandular autoimmune disease called Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) that belongs to the Finnish disease heritage. Murine Aire has been shown to be important in the generation of the T cell central tolerance in the thymus by promoting the expression of ectopic tissue-specific antigens in the thymic medulla. Aire is also involved in the thymus tissue organization during organogenesis. In addition to the thymus, AIRE/Aire is expressed in the secondary lymphoid organs. Accordingly, a role for AIRE/Aire in the maintenance of peripheral tolerance has been suggested. Peripheral tolerance involves mechanisms that suppress immune responses in secondary lymphoid organs. Regulatory T cells (Tregs) are an important suppressive T cell population mediating the peripheral tolerance. Tregs are generated in the thymus but also in the peripheral immune system T cells can acquire the Treg-phenotype. The aim of this study was to characterize Tregs in APECED patients and in the APECED mouse model (Aire-deficient mice). In the mouse model, it was possible to separate Aire expression in the thymus and in the secondary lymphoid organs. The relative importance of thymic and peripheral Aire expression in the maintenance of immunological tolerance was studied in an experimental model that was strongly biased towards autoimmunity, i.e. lymphopenia-induced proliferation (LIP) of lymphocytes. This experimental model was also utilised to study the behaviour of T cells with dual-specific T cell receptors (TCR) during the proliferation. The Treg phenotype was studied by flow cytometry and relative gene expression with real-time polymerase chain reaction. TCR repertoires of the Tregs isolated from APECED patients and healthy controls were also compared. The dual-specific TCRs were studied with the TCR repertoire analysis that was followed with sequencing of the chosen TCR genes in order to estimate changes in the dual-specific TCR diversity. The Treg function was tested with an in vitro suppression assay. The APECED patients had normal numbers of Tregs but the phenotype and suppressive functions of the Tregs were impaired. In order to separate Aire functions in the thymus from its yet unknown role in the secondary lymphoid organs, the phenomenon of LIP was utilised. In this setting, the lymphocytes that are adoptively transferred to a lymphopenic recipient proliferate to stimuli from self-originating antigens. This proliferation can result in autoimmunity if peripheral tolerance is not fully functional. When lymphocytes that had matured without Aire in the thymus were transferred to lymphopenic Aire-sufficient recipients, no clinical autoimmunity followed. The Aire-deficient donor-originating lymphocytes hyperproliferated, and other signs of immune dysregulation were also found in the recipients. Overt autoimmunity, however, was prevented by the Aire-deficient donor-originating Tregs that hyperproliferated in the recipients. Aire-deficient lymphopenic mice were used to study whether peripheral loss of Aire had an impact on the maintenance of peripheral tolerance. When normal lymphocytes were transferred to these Aire-deficient lymphopenic recipients, the majority of recipients developed a clinically symptomatic colitis. The colitis was confirmed also by histological analysis of the colon tissue sections. In the Aire-deficient lymphopenic recipients Tregs were proliferating significantly less than in the control group s recipients that had normal Aire expression in their secondary lymphoid organs. This study shows that Aire is not only important in the central tolerance but is also has a significant role in the maintenance of the peripheral tolerance both in mice and men. Aire expressed in the secondary lymphoid organs is involved in the functions of Tregs during an immune response. This peripheral expression appears to be relatively more important in some situations since only those lymphopenic recipients that had lost peripheral expression of Aire developed a symptomatic autoimmune disease. This AIRE-related Treg defect could be clinically important in understanding the pathogenesis of APECED.

Factors affecting perceptions of corporate social responsibility implementation: an emphasis on values

This dissertation is a broad study of factors affecting perceptions of CSR issues in multiple stakeholder realms, the main purpose being to determine the effects of the values of individuals on their perceptions regarding CSR. It examines perceptions of CSR both at the emic (observing individuals and stakeholders) and etic levels (conducting cross-cultural comparison) through a descriptive-empirical research strategy. The dissertation is based on quantitative interview data among Chinese, Finnish and US stakeholder groups of industry companies (with an emphasis on the forest industries) and consists of four published articles and two submitted manuscripts. Theoretically, this dissertation provides a valuable and unique philosophical and intellectual perspective on the contemporary study of CSR `The Harmony Approach to CSR'. Empirically, this dissertation does values assessment and CSR evaluation of a wide variety of business activities covering CSR reporting, business ethics, and three dimensions of CSR performance. From the multi-stakeholder perspective, this dissertation use survey methods to examine the perceptions and stakeholder salience in the context of CSR by describing, comparing the differences between demographic factors as well as hypothetical drivers behind perceptions. The results of study suggest that the CSR objective of a corporation's top management should be to manage the divergent and conflicting interests of multiple stakeholders, taking others than key stakeholders into account as well. The importance of values as a driver of ethical behaviour and decision-making has been generally recognized. This dissertation provides more empirical proof of this theory by highlighting the effects of values on CSR perceptions. It suggests that since the way to encourage responsible behaviour and develop CSR is to develop individual values and cultivate their virtues, it is time to invoke the critical role of moral (ethics) education. The specific studies of China and comparison between Finland and the US contribute to a common understanding of the emerging CSR issues, problems and opportunities for the future of sustainability. The similarities among these countries can enhance international cooperation, while the differences will open up opportunities and diversified solutions for CSR in local conditions.

Basic and translational studies on species B adenoviruses

Human adenoviruses (Ads) have been classified into six species (A to F) currently containing 55 serotypes. For almost 2 decades vectors derived from group C serotype Ad5 have been extensively used for gene transfer studies. These Ad5 based vectors are able to efficiently infect many mammalian cell types (including both mitotic and post-mitotic cells) through interaction with a primary attachment receptor, the coxsackie and adenovirus receptor (CAR). Despite the many advantages of Ad5 based vectors a number of limitations have affected their therapeutic application to many diseases. Although they can transduce many tissue types, Ad5 based vectors are unable to efficiently transduce several potential disease target cell types, including hematopoietic stem cells and malignant tumor cells. Therefore, newer vectors have been developed based on Ad serotypes other than Ad5. This thesis focuses on species B Ads. Species B Ads are comprised of three groups based on their receptor usage. Group 1 of species B Ads (Ad16, 21, 35, 50) nearly exclusively utilize CD46 as a receptor; Group 2 (Ad3, Ad7, 14) share a common, unidentified receptor/s, which is not CD46 and which was tentatively named receptor X; Group 3 (Ad11) preferentially interacts with CD46, but also utilizes receptor X if CD46 is blocked. Species B group Ads are important human pathogens. Species B group 2 serotypes are isolated from patients with respiratory tract infections, whereas the Group 1 viruses are described as causing kidney and urinary tract infections. B-group Ad infections often occur in immunocompromised patients, including AIDS patients, recipients of bone marrow transplants, or chemotherapy patients. Recent studies performed in U.S. military training facilities indicate an emergence of diverse species B serotypes at the majority of sites. This included the group 1 serotype 21 and the group 2 serotypes 3, 7, and 14. CD46-targeting vectors derived from Ad35 and Ad11 are important tools for in vitro gene transfer into human stem cells, including hematopoietic stem cells and induced pluripotent stem cells. Ad35 and Ad11 have been used as tools for cancer therapy, because CD46 appears to be uniformely overexpressed on many cancers. Furthermore, receptor X-targeting vectors, i.e vectors derived from Ad3 or vectors containing Ad3 fibers have shown superior in the transduction of tumor cells both in vitro and in vivo and are currently being used clinically in cancer patients. While extensive basic virology studies have been done on Ad5, the information of species B group 1 interaction with CD46 is limited. Furthermore, the receptor for a major subgroup of species B Ads (receptor X) is unknown. The goal of this thesis was it therefore to better understand virological and translational aspects of species B Ads. The specific findings described in this thesis include i) the identification of CD46 binding sites within the Ad35 fiber knob, ii) the study of the in vitro and in vivo properties of Ad vectors with increased affinity to CD46. iii) the study of the receptor usage of a newly emergent Ad14a, iv) the identification of desmoglein 2 as the receptor for Ad3, Ad7, Ad11, and Ad14, v) the delineation of structural details of Ad3 virus interaction with DSG2, and vi) the analysis of functional consequences of Ad3-DSG2 interaction. As a result of these basic virology studies two Ad-derived recombinant proteins have been generated that can be used to enhance cancer therapy by monoclonal antibodies.

Näkemyksiä käsityöopetuksen kehitystarpeista yhtenäisessä perusopetuksessa

The objective of this study was to find out what development targets craft teachers could identify in the comprehensive school classes 1 through 9 after the curriculum of the year 2004 had declared craft education uniform in textile and technical craft. Earlier research had shown that after this curricular reform craft education had been carried out in dissimilar ways in different municipalities and schools. This causes differences in the contents of teaching and thus in learning outcomes on national level. The most problematic situations occur on the 7th grade when the classes contain pupils with very heterogeneous skill levels. My intention is to find general themes in craft education that are significant when considering developmental objectives. The problem was explored by four research questions as follows: What kind of problems have craft teachers confronted during the application of the curriculum 2004, what are the most important objectives and contents in craft for the comprehensive school, how craft education should be arranged in the future and what prerequisites should be considered to generate high quality craft education? The study was carried out by a qualitative research approach. The informants consisted of 21 persons, out of which 15 were textile or technical teachers and six were textile or technical teacher students. The research data was collected in the form of short open narratives, based on a partially structured inquiry. Respectively content analysis was applied for analysis of the narratives. Research results revealed that craft teachers were mainly satisfied in uniform craft and hoped that both textile and technical craft could be compulsory school subjects for both genders. Textile and technical craft should be defined as separate independent school subjects, both of which should be developed with broader and high quality contents. Craft subjects should be allocated more teaching time. Teachers asked for a more logically proceeding curriculum, initiating from the beginning to the end of the compulsory school. It was suggested that this could be done by a qualified subject teacher. A uniform curriculum solution must be found for the whole country.

Literature Review: Investigating Drug Transport at the Blood-Brain Barrier and the Effects of P-glycoprotein on the Brain Distribution of Drugs.

The blood-brain barrier (BBB) is a unique barrier that strictly regulates the entry of endogenous substrates and xenobiotics into the brain. This is due to its tight junctions and the array of transporters and metabolic enzymes that are expressed. The determination of brain concentrations in vivo is difficult, laborious and expensive which means that there is interest in developing predictive tools of brain distribution. Predicting brain concentrations is important even in early drug development to ensure efficacy of central nervous system (CNS) targeted drugs and safety of non-CNS drugs. The literature review covers the most common current in vitro, in vivo and in silico methods of studying transport into the brain, concentrating on transporter effects. The consequences of efflux mediated by p-glycoprotein, the most widely characterized transporter expressed at the BBB, is also discussed. The aim of the experimental study was to build a pharmacokinetic (PK) model to describe p-glycoprotein substrate drug concentrations in the brain using commonly measured in vivo parameters of brain distribution. The possibility of replacing in vivo parameter values with their in vitro counterparts was also studied. All data for the study was taken from the literature. A simple 2-compartment PK model was built using the Stella™ software. Brain concentrations of morphine, loperamide and quinidine were simulated and compared with published studies. Correlation of in vitro measured efflux ratio (ER) from different studies was evaluated in addition to studying correlation between in vitro and in vivo measured ER. A Stella™ model was also constructed to simulate an in vitro transcellular monolayer experiment, to study the sensitivity of measured ER to changes in passive permeability and Michaelis-Menten kinetic parameter values. Interspecies differences in rats and mice were investigated with regards to brain permeability and drug binding in brain tissue. Although the PK brain model was able to capture the concentration-time profiles for all 3 compounds in both brain and plasma and performed fairly well for morphine, for quinidine it underestimated and for loperamide it overestimated brain concentrations. Because the ratio of concentrations in brain and blood is dependent on the ER, it is suggested that the variable values cited for this parameter and its inaccuracy could be one explanation for the failure of predictions. Validation of the model with more compounds is needed to draw further conclusions. In vitro ER showed variable correlation between studies, indicating variability due to experimental factors such as test concentration, but overall differences were small. Good correlation between in vitro and in vivo ER at low concentrations supports the possibility of using of in vitro ER in the PK model. The in vitro simulation illustrated that in the simulation setting, efflux is significant only with low passive permeability, which highlights the fact that the cell model used to measure ER must have low enough paracellular permeability to correctly mimic the in vivo situation.

Sydämen hypertrofian ja kroonisen vajaatoiminnan farmakologinen hoito

Sydämen krooninen vajaatoiminta on merkittävä maailmanlaajuinen ongelma. Se on erilaisten sydän- ja verisuonisairauksien aiheuttama monimuotoinen oireyhtymä. Sydämen vasemman kammion hypertrofia eli sydämen seinämien paksuuntuminen on yksi keskeinen tekijä, joka voi olla sydämen vajaatoiminnan taustalla. Kohonnut verenpaine on yleisin syy, joka johtaa sydänlihaksen paksuuntumiseen. Tämä johtaa sydämen pumppaustoiminnan häiriintymiseen, erilaisten neurohormonaalisten mekanismien aktivaatioon ja edelleen sydämen vajaatoimintaan. Sydämen vajaatoiminnan neurohormonaalisista mekanismeista tärkeimmät ovat reniini-angiotensiini-aldosteroni-järjestelmän ja sympaattisen hermoston aktivaatio, sydämen rakenteiden uudelleenmuovautuminen, sydänlihassolujen apoptoosi ja systeeminen tulehdustila. Sydämen hypertrofiaa ja sen syntymistä pyritään estämään kohonneen verenpaineen lääkehoidolla. Reniini-angiotensiini-aldosteronijärjestelmällä on keskeinen merkitys sydämen vajaatoiminnassa. Sydämen vajaatoiminnan ennusteeseen vaikuttavista lääkeaineista angiotensiinikonvertasin estäjät (ACEestäjät) ovat säilyttäneet johtoasemansa jo vuosikymmenten ajan. Angiotensiinireseptoreiden salpaajien (AT1-salpaajien) odotettiin syrjäyttävän ACE-estäjät sydämen vajaatoiminnan hoidossa, mutta toistaiseksi niitä pidetään vain vaihtoehtoisina lääkkeinä. Sympaattisen hermoston aktivaatiota vähentävät β-salpaajat ovat vakiinnuttaneet asemansa toiseksi tärkeimpänä lääkeryhmänä. Diureetit ovat paljon käytetty lääkeaineryhmä sydämen vajaatoiminnan hoidossa, mutta niistä ainoastaan aldosteroniantagonisteilla on tutkitusti ennustetta parantavaa vaikutusta. Kroonisen vajaatoiminnan hoidossa käytetään edelleen myös digoksiinia. Tulevaisuudessa sydämen vajaatoiminnan ennusteeseen vaikuttavia lääkeaineita voivat olla reniinin estäjät, neutraaliendopeptidaasin estäjät, vasopressiinin antagonistit tai inflammatroisiin sytokiineihin vaikuttavat molekyylit. Erikoistyön kokeellisessa osiossa tarkoituksena oli tutkia sydämen hypertrofian kehittymistä vatsa-aortta kuristetuilla rotilla ja kalsiumherkistäjä levosimendaanin sekä AT1-salpaaja valsartaanin vaikutuksia hypertrofian kehittymiseen. Kokeellisessa osiossa arvioitiin myös sydämen hypertrofian ja vajaatoiminnan jyrsijämallina käytetyn vatsa-aortan kuristuksen (koarktaation) toimivuutta ja vaikutuksia ultraäänen avulla määritettyihin kardiovaskulaarisiin parametreihin. Vatsa-aortta kuristettiin munuaisvaltimoiden yläpuolelta. Kuristus saa aikaan verenpaineen kohoamisen ja sydämen työtaakan lisääntymisen. Pitkittyessään tila johtaa sydänlihaksen hypertrofiaan ja vajaatoimintaan. 64 eläintä jaettiin ryhmiin, siten että jokaiseen ryhmään tuli kahdeksan eläintä. Ryhmistä kolmelle annettiin lääkeaineena levosimendaania kolmella eri päiväannoksella (0,01 mg/kg; 0,10 mg/kg; 1,00 mg/kg) ja kolmelle valsartaania kolmella eri päiväannoksella (0,10 mg/kg; 1,00 mg/kg; 10,00 mg/kg) juomaveden mukana. Lääkitys aloitettiin leikkauksen jälkeen ja jatkettiin kahdeksan viikon ajan. Kardiovaskulaariset parametrit, kuten isovolumetrinen relaksaatioaika (IVRT), vasemman kammion läpimitta systolessa ja diastolessa sekä seinämäpaksuudet, ejektiofraktio (EF), supistuvuusosuus (FS), minuuttitilavuus (CO) ja iskutilavuus (SV) määritettiin kahdeksan viikon kuluttua leikkauksesta ultraäänitutkimuksen avulla. Lisäksi määritettiin eläinten sydämen paino suhteessa ruumiin painoon. Tuloksia verrattiin ilman lääkehoitoa olleeseen koarktaatioryhmään. Eläinmallin toimivuutta arvioitiin vertaamalla koarktaatioryhmän tuloksia sham-operoidun ryhmän tuloksiin. Levosimendaanilla havaittiin työssä sydämen systolista toimintaa parantava vaikutus. Tämä näkyi tendenssinä parantaa ejektiofraktioita ja vasemman kammion supistuvuusosuuksia. Sydämen diastoliseen toimintaan ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Diastolista toimintaa arvioitiin isovolumetrisen relaksaatioajan muutoksilla. Sydämen hypertrofian kehittymiseen ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Eläinmallin todettiin mallintavan hyvin sydämen hypetrofiaa ihmisellä, mutta ei niinkään sydämen vajaatoimintaa.

Ale jaskkot eatnigiella : Alkuperäiskansaliikkeen ja saamen kielen merkitys saamelaisten identiteetille

This study examines the Sámi people and the construction of the Sámi identity and the role of language in the cross-border Sámi movement within the context of the international indigenous movement and discourse between 1962 and 2008. The Sámi movement began as a reaction to state assimilation policies. This led to the birth of indigenous processes strengthening the Sámi cultures and languages. Activities across borders and the ethnopolitical processes in each of the Nordic countries in question also formed the basis of the internationalization of the Sámi people. The discourse on indigenous peoples has grown into a question of human rights, which is examined in different national and international contexts. The study is based on ethnographic data that has been collected via interviews, questionnaires and participant observation with the researched people in different meetings and events. Archive and newsprint material are also used. The approach of the study is auto-ethnographic. The post-colonial theories used in the study strive to destabilize power relations and the distinctions of otherness produced by colonialism, and to reclaim both one's own culture and language in the context of the indigenous movement. A standard model for this type of approach was created by Edward W. Said in his 1978 work Orientalism. The central concepts of the analysis are decolonization, otherness, ethnicity and identity. The dissertation consists of four published articles and an introduction. The subject matter is analyzed on three levels: global, European and Nordic. On the global level, the results demonstrate that the indigenous movement has constructed a new understanding of indigenousness with new rights. International treaties have facilitated the unification of new concepts and rights, such as the right to self-determination and language, also helping in transforming them into rights of the Sámi people on a national level. On the Nordic level, aligning the Sámi culture with indigenous discourse became significant for the process of developing the Sámi identity in the Sámi movement. In this process, the Sámi movement made use of Sámi languages in order to mobilize groups of people and to construct relatedness between different Sámi groups. The realization that one s own language is significant to one's culture has resulted in recreating the vitality, visibility and the legitimation of language in society more generally. The migration of the Sámi people from their traditional territories to increasingly multi-ethnic urban areas alters one's relationship to one's own community as the relationship to cultural traditions changes. Among the urban Sámi, who form a group of ‘new Sáminess’, linguistic discrimination and assimilation continue because of the lack of legislative and other effective language policy measures to promote the learning and use of the Sámi language.