Proton magnetic resonance spectroscopy of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex

Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a 10B-carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction that generates heavy particles to damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the 10B-carrier. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. Proton magnetic resonance spectroscopy (1H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectrum region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of 1H MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel 1H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T using single voxel 1H MRS, and at 1.5 T using MRSI. In phantom conditions, BPA quantification accuracy of ± 5% and ± 15% were achieved with single voxel MRS using external or internal (internal water signal) concentration references, respectively. For MRSI, a quantification accuracy of <5% was obtained using an internal concentration reference (creatine). The detection limits of BPA in phantom conditions for the PRESS sequence were 0.7 (3.0 T) and 1.4 mM (1.5 T) mM with 20 × 20 × 20 mm3 single voxel MRS, and 1.0 mM with acquisition-weighted MRSI (nominal voxel volume 10(RL) × 10(AP) × 7.5(SI) mm3), respectively. In the in vivo study, an MRSI or single voxel MRS or both was performed for ten patients (patients 1-10) on the day of BNCT. Three patients had glioblastoma multiforme (GBM), and five patients had a recurrent or progressing GBM or anaplastic astrocytoma gradus III, and two patients had head and neck cancer. For nine patients (patients 1-9), MRS/MRSI was performed 70-140 min after the second irradiation field, and for one patient (patient 10), the MRSI study began 11 min before the end of the BPA-F infusion and ended 6 min after the end of the infusion. In comparison, single voxel MRS was performed before BNCT, for two patients (patients 3 and 9), and for one patient (patient 9), MRSI was performed one month after treatment. For one patient (patient 10), MRSI was performed four days before infusion. Signals from the tumour spectrum aromatic region were detected on the day of BNCT in three patients, indicating that in favourable cases, it is possible to detect BPA in vivo in the patient’s brain after BNCT treatment or at the end of BPA-F infusion. However, because the shape and position of the detected signals did not exactly match the BPA spectrum detected in the in vitro conditions, assignment of BPA is difficult. The opportunity to perform MRS immediately after the end of BPA-F infusion for more patients is necessary to evaluate the suitability of 1H MRS for BPA detection or quantification for treatment planning purposes. However, it could be possible to use MRSI as criteria in selecting patients for BNCT.

Nuorten mäntyjen ulkoisen laadun kehitykseen vaikuttavat tekijät

Männyn laatuun vaikuttavista tekijöistä tässä tutkimuksessa selvitettiin, mitkä tekijät aiheuttavat nuorissa männyissä oksikkuutta, mutkaisuutta käsittäen myös lenkouden ja haaraisuutta. Jokaiselle laatuvialle laadittiin kolme eritasoista mallia. Eniten keskityttiin tutkimaan oksikkuutta aiheuttavia tekijöitä, koska oksikkuus vaikuttaa männyn sisäiseen oksaisuuteen, joka on yleisin sahatavarakappaleen laatuluokan määräävä ominaisuus. Lisäksi mutkaisuus ja erityisesti haaraisuus osoittautuivat melko sattumanvaraisesti esiintyviksi laatuvioiksi, minkä takia niiden kehittymiseen vaikuttavia tekijöitä on vaikea määritellä. Tutkimuksessa käytettiin Metsäntutkimuslaitoksen taimikoiden inventointikokeiden (TINKA-kokeet) aineiston ensimmäisen ja kolmannen mittauskerran tuloksia. Näiden mittauskertojen väli oli 15 vuotta. Tutkimuksen perustuminen useampaan kuin yhteen mittauskertaan erottaa tämän tutkimuksen monista muista mäntyjen laatua käsittelevistä tutkimuksista, jotka ovat perustuneet yhden mittauskerran poikkileikkausaineistoon. Laadittujen kolmen eritasoisen mallin perusteella voidaan todeta, että oksikkuuden ja mutkaisuuden kehittymistä mäntyihin pystytään arvioimaan kohtalaisesti jo metsikön perustietojen (syntytapa, kasvupaikka, lämpösumma) avulla, jotka metsänomistajalla on tiedossaan jo taimikkoa perustaessaan. Puutason mittauksilla pystytään selvästi tarkentamaan arviota siitä, tuleeko männystä oksikas vai ei. Sitä vastoin puutason mittaukset parantavat vain vähän arviota mutkaisuuden kehittymisestä. Haaraisuuden esiintymistä luotettavasti ennustavaa mallia ei pystytty tekemään. Oksikkuutta lisääviä tekijöitä mallien mukaan olivat mm. männyn suuri läpimitan kasvu, suuri suhteellinen pituus saman metsikön muihin puihin verrattuna, alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa ja taimikonhoidon tekemättä jättäminen. Mutkaisuutta lisääviä tekijöitä olivat mm. suuri lämpösumma eli männikön sijainti Etelä-Suomessa, männyn suuri läpimitan kasvu, pieni suhteellinen pituus, alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa ja taimikonhoidon tekemättä jättäminen. Eri uudistamistavoista kylvö osoittautui parhaimmaksi laadun kannalta sekä oksikkuutta että mutkaisuutta tarkasteltaessa. Haaraisuutta lisääviä tekijöitä olivat mm. pieni lämpösumma eli männikön sijainti Pohjois-Suomessa, männyn suuri läpimitan kasvu ja alhainen kasvatustiheys männyntaimikon alkukehitysvaiheessa.

Metsämaan vesitaseen muutokset Suomessa ilmaston muuttuessa

Muuttuva ilmasto, erityisesti kohoava lämpötila ja hiilidioksidipitoisuus, ei voi olla vaikuttamatta metsien kasvuun Suomessa. Metsätalouden sopeutumistoimilla voidaan pyrkiä lisääntyvän tuotospotentiaalin hyödyntämiseen ja metsätuhoriskien pienentämiseen. Sopeutumistoimien suunnittelemiseksi tarvitaan kuitenkin ensin tietoa siitä, miten ilmasto muuttuu ja mitä vaikutuksia ilmastonmuutoksella on. Työni oli osa vuonna 2005 käynnistettyä Ilmastonmuutoksen sopeutumistutkimusohjelmaa (ISTO). ISTO, ja näin myös oma tutkimukseni, tuottaa siis tietoa, jonka avulla voidaan mukauttaa metsänhoitoa vastaamaan muuttuvia ilmastooloja. Työssä tarkasteltiin maan vesipitoisuutta menneessä, nykyisessä ja muuttuvassa ilmastossa. Tavoitteena oli ennustaa, miten kuivuuden esiintyminen muuttuu Suomessa. Lisäksi menneiden kuivien vuosien kasvuvaikutuksia tutkittiin lustomittausten avulla. Vesitasemuutoksia lähdettiin tutkimaan mallilaskelmilla. Laskelmat perustuivat yksinkertaiseen open bucket – tyyppiseen vesimalliin. Mallissa maaperä ajatellaan tilana, johon sadanta ja lumen sulaminen tuovat vettä. Haihdunta ja valunta päinvastaisesti vähentävät sitä. Mallia sovellettiin Metlan yhdeksällä provenienssikoealueella, joihin lukeutui sekä kuusikoita että männiköitä eri kasvupaikoilta. Mallin yksinkertaisuuden takia koealueilta tarvittiin ainaostaan päivittäiset tiedot lämpötilasta, sadannasta, säteilystä ja VPD:stä. Lisäksi tuli selvittää kasvupaikkojen savi- ja hiekkapitoisuudet maaperäparametrien laskemiseksi. Vesimallilla tehtiin kahdet laskelmat. Ensimmäisissä laskettiin päivittäistä vesitasetta vuosina 1961-2008 mitattua sääaineistoa käyttäen. Toisissa laskelmissa käytettiin mitatusta säädatasta modifioitua sääennustetta. Lämpötilaa ja sadantaa oli kasvatettu vastaamaan vuosisadan lopulle tehtyä ennustetta. Näiden kahden laskelman tuloksia vertailtiin keskenään kuivuuspäivien lukumäärän osalta. Malliin oli siis ohjelmoitu kuivuuspäiväindeksi. Indeksin perusteella kuivuutta katsottiin olleen päivänä, jolloin kasveille käyttökelpoisen veden määrä laski alle 4 prosentin ja haihdunta leikkaantui 90 prosentilla normaalitasoon nähden. Kuivuuspäivät lisääntyivät kaikilla provenienssikoealueilla. Suurin muutos olisi tulosten perusteella odotettavissa etelärannikolla ja männyn kasvupaikoilla, jotka jo entuudestaan olivat alueista kuivimpia. Vähäisin muutos olisi taas odotettavissa kuusen kasvupaikoilla, etenkin jos sijainti ei ole aivan eteläisimmässä Suomessa. Kasvuvaikutuksia koskevien tulosten perusteella maan vesipitoisuus ei ole ollut merkittävä lustojen kasvua rajoittava tekijä provenienssikoealueilla menneinä vuosikymmeninä. Kuivuuspäivien määriin ei tule suhtautua absoluuttisina totuuksina, sillä ne ovat määritelmänsä mukaisesti vain suuntaa antavia. Niiden avulla voidaan tehdä ainoastaan päätelmiä metsiköiden ja vuosien välisistä suhteellisista eroista ja kehityssuunnista. Suoria johtopäätöksiä puuston kasvusta tai elinvoimaisuudesta ei pystytä tekemään. Eikä myöskään pystytä arvioimaan, reagoivatko mänty ja kuusi ennustettuihin muutoksiin eri tavoin. Voidaan kuitenkin päätellä, että keskimääräisten vuotuisten kuivuuspäivien lukumäärän kasvu johtaa brutto- ja nettoprimäärituotoksen vähenemiseen. Tätä kautta kuivuuden lisääntyminen alentaa myös kasvua verrattuna tilanteeseen, jossa kuivuuspäivien määrä pysyisi muuttumattomana.

Helsingin metropolialueen maisemaekologiset muutokset vuosina 1955-2009

Landscape is shaped by natural environment and increasingly by human activity. In landscape ecology, the concept of landscape can be defined as a kilometre-scale mosaic formed by different land-use types. In Helsinki Metropolitan Region, the landscape change caused by urbanization has accelerated after the 1950s. Prior to that, the landscape of the region was mainly only shaped by agriculture. The goal of this study was in addition to describing the landscape change to discuss the factors impacting the landscape change and evaluate thelandscape ecological impacts of the change. Three study areas at different distances from Helsinki city centre were chosen in order to look at the landscape change. Study areas were Malmi, Espoo and Mäntsälä regions representing different parts of the urban-to-rural gradient in 1955, 1975, 1990 and 2009. Land-use of the maps was then digitized into five classes: agricultural lands, semi-natural grasslands, built areas, waters and others using GIS methods. First, landscape change was studied using landscape ecological indices. Indices used were PLAND i.e. the proportions of the different land-use types in the landscape; MPS, SHEI and SHDI which describe fragmentation and heterogeneity of the landscape; and MSI and ED which are measures of patch shape. Second, landscape change was studied statistically in relation to topography, soil and urban structure of the study areas. Indicators used concerning urban structure were number of residents, car ownership and travel-related zones of urban form which indicate the degree of urban sprawl within the study areas. For the statistical analyses, each of the 9.25 x 9.25 km sized study areas was further divided into grids with resolution of 0.25 x 0.25 kilometres. Third, the changes in the green structure of the study areas were evaluated. The landscape change reflected by the proportions of the land-use types was the most notable in Malmi area where a large amount of agricultural land was developed from 1955 to 2009. The proportion of semi-natural grasslands also showed an interesting pattern in relation to urbanization. When urbanization started, a great number of agricultural lands were abandoned and turned into semi-natural grasslands but as the urbanization accelerated, the number of semi-natural grasslands started to decline because of urban densification. Landscape fragmentation and heterogeneity were the most widespread in Espoo study area which is not only because of the great differences in relative heights within the region but also its location in the rural-urban fringe. According to the results, urbanization induced agricultural lands to be more regular in shape both spatially and temporally whereas for built areas and semi-natural grasslands the impact of urbanization was reverse. Changes in landscape were the most insignificant in the most rural study area Mäntsälä. In Mäntsälä, built area per resident showed the greatest values indicating a widespread urban sprawl. The values were the smallest in highly urbanized Malmi study area. Unlike other study areas, in Mäntsälä the proportion of developing land in the ecologically disadvantageous cardependent zone was on the increase. On the other hand, the green structure of the Mäntsälä study area was the most advantageous whereas Malmi study area showed the most ecologically disadvantageous structure. Considering all the landscape ecological criteria used, the landscape structure of Espoo study area proved to be the best not least because of the great heterogeneity of its landscape. Thus the study confirmed the previous results according to which landscape heterogeneity is the most significant in areas exposed to a moderate human impact.

Viljakylvösiemensektorin toimintaedellytykset

Viljakylvösiemensektorin toimintaympäristön muutoksiin on hyvä valmistautua ennalta ja pohtia toimintatapoja, joiden turvin toimia muuttuvassa toimintaympäristössä. Suomen kylvösiemenmarkkinat ovat pienentyneet voimakkaasti 1980-luvun lopulta lähtien. 2000-luvulla sertifioidun siemenen käyttöaste on ollut keskimäärin vain 30 % ja viljojen kohdalla käyttöaste on ollut tätäkin alhaisempi. Tulevaisuudessa yhteisen maatalouspolitiikan uudistukset, kiristyvä kilpailu, ilmastonmuutos, teknologian kehitys, kulutustottumusten muutokset sekä lähivuosina uudistava EU:n siemenlainsäädäntö tulevat muokkaamaan alan toimintaympäristöä. Jotta tulevaisuuden haasteisiin voidaan vastata, kartoitettiin tutkimuksessa asiantuntijoiden näkemyksiä siitä, mitkä ovat tuotantoketjun ongelmakohdat sekä alan toiminnan edistämismahdollisuudet. Työn teoreettisena viitekehyksenä oli toimialan taloustiede. Teorian rakennetta käytettiin siemenalan ongelmakohtien jäsentämiseen ja toimenpide-ehdotusten kartoittamiseen. Asiantuntijat näkivät sertifioidun siemenen heikkoon kysyntään vaikuttavan korvaavien tuotteiden, eli tilan oman kylvösiemen ja sertifioimattomana markkinoidun kylvösiemenen ns. harmaan siemenen, yleisyys. Tilan oman siemenen kohdalla suurin epäkohta on sen arvottamisessa. Harmaan siemenen käytön suosioon vaikuttavat sen edullisuuden lisäksi myös kaupan asiakaslähtöisyys. Sertifioidun siemenen kysyntää heikentävät myös puutteelliset markkinointitavat, kausivaihtelu sekä siemenmyyjien tietämättömyys viljelijöiden ostokäyttäytymisestä. Tarjonnan epäkohdiksi nousivat siemenestä saatava hinta, tuotantotekijäsidonnaisuus sekä hukkakauran leviäminen. Siemenestä saatu hinta ei aina riitä kattamaan paljon tuotantotekijöitä vaativan siementuotannon kustannuksia. Myös hukkakauran leviäminen vaikeuttaa ja rajoittaa tuotannon lisäämistä. Lisäksi siemenketjun kannalta ongelmia aiheuttivat teknologian ja tuotantoprosessien myönteinen mutta hidas kehitys. Markkinan rakenteen ongelmakohtina olivat markkinoiden oligopolisuisuus sekä tuotteiden tehoton erilaistaminen asiakkaiden tarpeiden mukaisesti. Alan yritysrakenteen todettiin olevan pienyritysvaltainen ja osin tehoton, vaikka rakennekehitystä onkin viime vuosina tapahtunut. Alalle tulon esteet liittyvät siemenviljelijöiden ja -pakkaajien kohdalla läheisesti tuotantotekijäsidonnaisuuteen sekä hukkakauran leviämiseen ja hukkakauralainsäädäntöön. Vastaavasti Suomen syrjäinen sijainti ja ilmasto- olosuhteet ovat pitäneet ulkomaisen kilpailun vähäisenä. Toimialan kustannusten todettiin jakaantuneen epätasaisesti siemenketjun toimijoiden välillä. Kustannusrakenteen todettiin olevan nykyisellään kestämätön ja tilanteen todettiin korjaantuvan ainoastaan tuntuvalla volyymin kasvulla. Lisäksi toimijoiden välinen vertikaalinen integraatio nähtiin vähäiseksi, vaikka sillä olisi merkittävä vaikutus tuotannon kannattavuuteen. Asiantuntijat näkivät maatalouspolitiikan sekä markkinoiden ja talouden muutosten etenevän eri suuntiin. Suurimpina epäkohtina nousivat siementuotannon tuen loppuminen sekä lainsäädännön asettamat rajoitukset. Lisäksi isona ongelmana pidettiin ulkoisen tiedottamisen tehottomuutta. Tutkimuksen perusteella viljakylvösiemensektorin toimintaedellytykset liittyvät pääasiallisesti markkinointiosaamisen ja informoinnin kehittämiseen sekä verkostoitumisen lisäämiseen. Tärkeänä osana toimintaedellytysten turvaamisessa on myös vaikuttaminen tulevaan EU:n siemenlainsäädäntöön siten, että kansalliset poikkeukset olisivat mahdollisia myös tulevaisuudessa.

Onnellisten kylät : Vertaileva tapaustutkimus Kumpulan ja Sundsbergin asukkaiden subjektiivisesta hyvinvoinnista sekä onnellisuuden rakentumisesta

The aim of this masters thesis was to examine subjective wellbeing and personal happiness. Empirical study of happiness is part of broader wellbeing reseach and is based on an idea that the best experts of personal wellbeing are the individuals themselves. In addition to perceptions of personal happiness, the aim was also to acquire knowledge about personal values and components personal happiness is based on. In this study, moving into certain community and the charesteristics of neigbourhood contributing happiness, were defined to represent these values. The object was, through comparative casestudy, to obtain knowledge about subjective wellbeing of the inviduals in two different residental areas inside metropolitan area of Helsinki. In comparative case study the intention usually is that the examined units represent spesific "cases" from something broader and therefore the results can be somehow generalized. Consequently the chosen cases in this study were selected due to their image of "urban village" and thus the juxtapositioning was constructed between secluded post-suburban village and more heterogeneous urban village better attached to excisting urban structure. The researh questins were formed as follows: Are there any differencies between the areas regarding the components personal happines is based on? Are there any differencies between the areas regarding the level of residents subjective wellbeing? Based on the residents assesments, what are the most important charesteristics of neigbourhood contributing personal happiness? The data used in order to gain aswers to these questions was obtained from internet-based survey questionnaire. Based on the data residents of post-suburban village Sundsberg seem to share highly family oriented set of values and actualizing these values is ensured with high income, wealth and secure work situation. Insteadt in Kumpula the components of happiness seem place more towards learning and personal developement, interesting leisure and hobbies and specially having an influence regarding communal decisions. Conserning subjective wellbeing of residents there can be seen some differencies as well. Personal life is experienced a bit more happier in Sundsberg than in Kumpula. People are more satified with their personal health and job satisfaction in Sundsberg and additionally feelings of loneliness, inadequancy and frustration are bit more common in Kumpula. Regarding the charesteristics of neigbourhood contributing happiness data suggests that key charesteristics of area are peacefulness and safely, good location and connections and proximity of parks and recreational areas. These charesteristics were concidered highly significant in both areas but they were experienced to actualize better in Kumpula. In addition to these components the residents in Kumpula were overall more satisfied with various charecteristics contiburing happiness in their residental area. Besides these attributes mentioned above residents in Kumpula emphasize also some "softer" elements connecting into social, functional and communal side of area. From Sundsberg point of view residental area best contributing happiness is child friendly and safe community based on likeminded people who share the same sosioeconomical situation. The results of this study can be linked back into the society and metropolitan area, which they were chosen from as a cases to be studied. The results can thereby be seen as an example of differentation of conditions of personal happiness between certain population segments. It is possible to detect an spatial dimetion to this process as well and thereby the results suggests that regional segmentation affects between high-ranking residental areas as well. Thereby the results of this reseach contributes to the debate on innovative, diverse and dynamic urban area and as well cohesion of metropolitan area and the society in whole.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

Optimal Use of Treatment Modalities and Treatment Results of Osteosarcoma and Soft Tissue Sarcomas

Soft tissue sarcomas are malignant tumours of mesenchymal origin. Because of infiltrative growth pattern, simple enucleation of the tumour causes a high rate of local recurrence. Instead, these tumours should be resected with a rim of normal tissue around the tumour. Data on the adequate margin width are scarce. At Helsinki University Central Hospital (HUCH) a multidisciplinary treatment group started in 1987. Surgical resection with a wide margin (2.5 cm) is the primary aim. In case of narrower margin radiation therapy is necessary. The role of adjuvant chemotherapy remains unclear. Our aims were to study local control by the surgical margin and to develop a new prognostic tool to aid decision-making on which patients should receive adjuvant chemotherapy. Patients with soft tissue sarcoma of the extremity or the trunk wall referred to HUCH during 1987-2002 form material in Studies I and II. External validation material comes from the Lund university sarcoma registry. The smallest surgical margin of at least 2.5 centimetres yielded local control of 89 per cent at five years. Amputation rate was 9 per cent. The proposed prognostic model with necrosis, vascular invasion, size on a continuous scale, depth, location and grade worked well both in Helsinki material and in the validation material, and it also showed good calibration. Based on the present study, we recommend the smallest surgical margin of 2-3 centimetres in soft tissue sarcoma irrespective of grade. Improvement in local control was present but modest in margins wider than 1 centimetre. In cases where gaining a wider margin would lead to a considerable loss of function, smaller margin is to be considered combined to radiation therapy. Patients treated with inadequate margins should be offered radiation therapy irrespective of tumour grade. Our new prognostic model to estimate 10-year survival probability in patients with soft tissue sarcoma of the extremities or trunk wall showed good dicscrimination and calibration. For time being the prognostic model is available for scientific use and further validations. In the future, the model may aid in clinical decision-making. For operable osteosarcoma, neoadjuvant multidrug chemotherapy followed by delayed surgery and multidrug adjuvant chemotherapy is the treatment of choice. Overall survival rates at five years are approximately 75 per cent in modern trials with classical osteosarcoma. All patients diagnosed and reported to the Finnish Cancer Registry with osteosarcoma in Finland during 1971-2005 form the material in Studies III and IV. Limb-salvage rate increased from 23 per cent to 78 per cent during 1971-2005. The 10-year sarcoma-specific survival for the whole study population improved from 32 per cent to 62 per cent. It was 75 per cent for patients with a local high-grade osteosarcoma of the extremity diagnosed during 1991-2005. This study outlines the improved prognosis of osteosarcoma patients in Finland with modern chemotherapy. The 10-year survival rates are good also in an international scale. Nonetheless, their limb-salvage rate remains inferior to those seen for highly selected patient series. Overall, the centralisation of osteosarcoma treatment would most likely improve both survival and limb-salvage rates even further.

Functional regulation of the Neurofibromatosis 2 tumor suppressor merlin

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.

Asuntopolitiikka ja vieraskielisen väestön alueellinen keskittyminen Helsingissä vuosina 1992-2005

The aim of the thesis was to study the extent of spatial concentration of immigrant population in Helsinki and to analyse the impact of housing policy on ethnic residential segregation in 1992-2005. For the purpose of the study, immigrant population was defined based on the language spoken at home. The theory of residential segregation by Andersson and Molina formed the main theoretical framework for the study. According to Andersson and Molina ethnic residential segregation results from different dynamic intra-urban migration processes. Institutionally generated migration, i.e. migration patterns generated by various housing and immigrant policies and procedures, is one of the central factors in the development of ethnic segregation. The data of the study consisted of population and housing statistics and housing and immigrant policy documents of Helsinki municipality. Spatial concentration of immigrant population was studied both at district and building levels using GIS-methods and statistical methods. The housing policy of Helsinki municipality was analysed using a method created by Musterd et al. Musterd et al. categorise two types of policy approaches to residential segregation: spatial dispersion policy and compensating policy. The housing policy of Helsinki has a strong focus on social mixing and spatial dispersion of housing stock. Ethnic segregation is regarded as a threat. The importance of ethnic communities and networks is, however, acknowledged and small-scale concentration is therefore not considered harmful. Despite the spatial dispersion policy, the immigrant population is concentrated in the eastern, north-eastern and north-western suburbs of Helsinki. The spatial pattern of concentration was formed already at the beginning of the 1990's when immigration to Finland suddenly peaked. New immigrant groups were housed in the neighbourhoods where public housing was available at the time. Housing policy, namely the location of new residential areas and public housing blocks and the policies of public housing allocation were key factors influencing the residential patterns of immigrant population in the 1990's. The immigration and refugee policies of the state have also had an impact on the development. The concentration of immigrant population has continued in the same areas in the beginning of the 2000's. Dispersion to new areas has mainly taken place within the eastern and north-eastern parts of the city or in the adjacent areas. The migration patterns of native population and the reasonably rapid changes in the housing market have emerged as new factors generating and influencing the ethnic residential segregation in Helsinki in the 2000's. Due to social mixing and spatial dispersion policies, ethnic segregation in Helsinki has so far been fairly small-scale, concentrated in particular housing blocks. The number of residential buildings with a high share of immigrant population is very modest. However, the number of such buildings has doubled between 1996-2002. The concentration of immigrant population concerns mainly the public housing sector. The difference in the level of concentration between the public housing sector and privately owned housing companies is remarkable.

Community-based Ecotourism as a Sustainable Development Option in the Taita Hills, Kenya

This study aims at identifying the existing and potential resources, as well as recognizing the hinderances, for community-based ecotourism development in the Taita Hills in south-eastern Kenya. The indigenous mountain rain forests on the hills are rich in biodiversity, but severely degraded because of encroachment caused by the dynamics of increased population, socio-politics and economics. The research problems are based on the hypothesis that there is no tourism in the Taita Hills generating income for the local economy and high population density combined with poverty creates a need for alternative employment opportunities as well as for sustainable ways of forest resource management. The data for this study was gathered during two field trips in Kenya, in January-February 2004 and 2005, as a part of the Taita Project within the Department of Geography at the University of Helsinki. The qualitative methods used consist of RRA and PRA techniques, in-depth interviews, a structured questionnaire and literature analysis as well as attendance on excursions and a workshop with conservation experts and officials. Four case areas in the Taita Hills are studied. The study concludes that alternative livelihoods are needed among the Taita Hills´ rural population and community-based ecotourism is seen as a way of bringing financial benefits for households as well as reviving the fading cultural traditions and indigenous knowledge about forest use. The governmental policies, district level development plans and some NGOs support ecotourism development. The Forest Act 2005 forms base for local participation in forest management. The unique natural features, the welcoming Taita-culture and the location in the coastal tourism circle favour Taita Hills. However, this kind of development has its risks, such as too rapid change of sorest usage level and the exposure of communities to an ecotourism treadmill process. The costbenefit ration of marketing for hard ecotourists is generally low and the tourism infrastructure needs upgrading in the Taita Hills. More tight collaboration is important between the different level stakeholders working for conservation and development. Community-based ecotourism in Taita Hills, when carefully planned and managed, could be one opportunity for Kenya to diversify its tourism product supply and for forestadjacent communities to gain tangible benefits on a sustainable basis from forests.

Asemakaavoitus Helsingin seudun kasvun hallinnassa

Many Finnish municipalities need to control their growth. In this research growth is understood as developments of land utilisation and also as a wide range of other changes that have mainly ap-peared as a result of a long term growth in population. The development growth control contains four areas: 1. adequate productivity of town planning, 2. stationing the growth to needs led and for sustainable developments, 3. quality of the developing environment, and 4. producing growth with communicative and transparent process. The aim of the research is to represent connection between town planning and development growth control. Research defines the role of town planning in the municipalities development growth control. In addition research focuses on links between town planning and development growth control in history, present and in the development work for the future. According to the hypothesis the extensive examination of town planning enables better growth control and promotes appropriate response to municipal changes regarding housing delivery. As an example there are five outskirt municipalities in the Helsinki region. They are called Kirkkonummi, Vihti, Nurmijärvi, Tuusula and Sipoo. The decision was to use examples based on a contingence theory. According to the theory there is no one correct way to operate. Therefore development should be based on individual municipal needs. In the research, municipality s needs were collected by 20 semi- structured interviews from municipal officials. In addition there were group interviews in Uusimaa Regional Council and in Uusimaa Regional Environmental Centre. There was also secondary material collected from official papers and statistics. Operationalisation was the analysis tool between empiric and literature reviews. The role of town planning has evolved during the 20th century from a more simple town plan level to operative stage in town planning hierarchy. Outskirt municipalities town planning was established during the 1960s. Since then one of the most important aims in the town planning has been to produce growth and building possibilities. Currently the challenge is to reach the satisfying rate of productivity and to meet increased housing demand. Other challenges include locating the appropriate geographical areas for growth; and the balance between required developments and planning permission decisions. Findings concluded that town planning should be more viable and it should have better ability to co-operate and operate in the changing operational environment. Municipality s ability to receive growth can increase and growth control can advance by planned and workable town planning. It is essential to take wide perspective of the each municipality's unique needs to improve productivity rather than to focus simply on productivity.

Plan af Ekenäs stad utgifven 1843 af C. W. Gyldén

Tammisaaren kartta. - 1 kartta : vär. ; 40 x 53,7 cm, lehti 45 x 60 cm. - Mittakaava [1:4000]. - Sisältää luettelot kortteleista ja julkisista rakennuksista.

Plan af Nyslott utgifven 1843 af C. W. Gyldé

Claes Wilhelm Gyldén (1802-1872) oli maanmittauksen ja metsänhoidon ylihallituksen ylitirehtööri vuosina 1854-72. Ylitirehtööri omisti paljon aikaansa metsänhoidon ja maanjakotoiminnan lisäksi myös maamme kartastotoiminnalle. Hän julkaisi vuonna 1853 Suomenmaan korko-kartan, joka on maailman ensimmäisiä korkeusvyöhykekarttoja. Myös Suomen yleiskartan 1:400 000 (Karta över Finland) ensimmäisen painoksen karttalehdet painettiin vuosina 1864-1872 hänen johtajakaudellaan. Vuosina 1837-1843 toimiessaan maanmittausinsinöörinä maanmittaushallituksessa C. W. Gyldén julkaisi Suomen kaikkien silloisten kaupunkien kaupunkikartat, yhteensä 31 karttalehteä. Nämä asemakaavakartat painettiin kaikki samassa koossa 50,8 x 65,9 cm. Tästä johtuen karttojen mittakaavat vaihtelivat asteikkojen 1:3200 – 1:10000 välillä. Kaupungin asemakaavan lisäksi jokaisessa kartassa on yleissilmäyskartta, julkisten rakennusten luettelo sekä niiden sijainti. Lisäksi hän julkaisi vuonna 1844 näiden kaupunkien historiaa ja tilastotietoja kuvaavan selityskirjan.

Plan af Borgå utgifven 1843 af C. W. Gyldén

Porvoon kartta. - 1 kartta : vär. ; 40 x 53,7 cm, lehti 45 x 60 cm. - Mittakaava [1:4000]. - Sisältää luettelot kortteleista ja julkisista rakennuksista.