Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand 11C-PIB

Early Detection of Alzheimer's Disease Beta-amyloid Pathology -Applicability of Positron Emission Tomography with the Amyloid Radioligand ¹¹C-PIB Accumulation of beta amyloid (Abeta) in the brain is characteristic for Alzheimer’s disease (AD). Carbon-11 labeled 2-(4’-methylaminophenyl)-6-hydroxybenzothiazole (¹¹C-PIB) is a novel positron emission tomography (PET) amyloid imaging agent that appears to be applicable for in vivo Abeta plaque detection and quantitation. The biodistribution and radiation dosimetry of ¹¹C-PIB were investigated in 16 healthy subjects. The reproducibility of a simplified ¹¹C-PIB quantitation method was evaluated with a test-retest study on 6 AD patients and 4 healthy control subjects. Brain ¹¹C-PIB uptake and its possible association with brain atrophy rates were studied over a two-year follow-up in 14 AD patients and 13 healthy controls. Nine monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment and 9 unrelated controls were examined to determine whether brain Abeta accumulation could be detected with ¹¹C-PIB PET in cognitively intact persons who are at increased genetic risk for AD. The highest absorbed radiation dose was received by the gallbladder wall (41.5 mjuGy/MBq). About 20 % of the injected radioactivity was excreted into urine, and the effective whole-body radiation dose was 4.7 mjuSv/MBq. Such a dose allows repeated scans of individual subjects. The reproducibility of the simplified ¹¹C-PIB quantitation was good or excellent both at the regional level (VAR 0.9-5.5 %) and at the voxel level (VAR 4.2-6.4 %). ¹¹C-PIB uptake did not increase during 24 months’ follow-up of subjects with mild or moderate AD, even though brain atrophy and cognitive decline progressed. Baseline neocortical ¹¹C-PIB uptake predicted subsequent volumetric brain changes in healthy control subjects (r = 0.725, p = 0.005). Cognitively intact monozygotic co-twins – but not dizygotic co-twins – of memory-impaired subjects exhibited increased ¹¹C-PIB uptake (117-121 % of control mean) in their temporal and parietal cortices and the posterior cingulate (p<0.05), when compared with unrelated controls. This increased uptake may be representative of an early AD process, and genetic factors seem to play an important role in the development of AD-like Abeta plaque pathology. ¹¹C-PIB PET may be a useful method for patient selection and follow-up for early-phase intervention trials of novel therapeutic agents. AD might be detectable in high-risk individuals in its presymptomatic stage with ¹¹C-PIB PET, which would have important consequences both for future diagnostics and for research on disease-modifying treatments.

Idea- ja innovaatioporfolion hallinta

Tässä kandidaatintyössä tarkastellaan idea- ja innovaatioportfolion hallintaa, portfoliojohtamista sekä näihin soveltuvia erilaisia menetelmiä yrityksen näkökulmasta. Tavoitteena on luoda yleiskatsaus yleisimpiin käytettyihin menetelmiin ja viitekehyksiin. Lähteinä työssä on käytetty sähköisiä tietokantoja ja alan kirjallisuutta. Käytetyimmät portfolion hallintamenetelmät voidaan jakaa neljään ryhmään: taloudelliset ja rahamääräiset mittarit, liiketoimintastrategiat, portfoliokartat tai kupla-diagrammit, scorecard:it eli pisteytystaulukot sekä tarkistuslistat. Idea- ja innovaatioportfolion hallinnan tavoitteena on luoda yrityksen kannalta mahdollisimman tehokas ja tuottava portfolio, joka on kuitenkin linjassa yrityksen strategian kanssa. Portfolion projekteille jaettavissa olevat resurssit ovat niukat, joten resurssien jakoon ja tehokkaaseen hyödyntämiseen tulee kiinnittää huomiota. Portfolion tasapainottamiseksi on hyvä tarkastella kehitys- ja tutkimusprojektien määrää, kokoa ja riskiä. Teknologiatiekartta on yrityksen strateginen työkalu, jolla se voi suunnata toimintaansa kohti sen visiota. Teknologiatiekartta koostuu yrityksen valitsemista markkinoista, niille suunnatuista tuotteista tai palveluista, sekä näiden vaatimista tuotekehitysprojekteista ja teknologioista. Projektien etenemistä voidaan tarkastella stage-gate -mallin avulla. Stage-gate jakaa projektin porteilla eri vaiheisiin. Jokaisen portin läpäistäkseen projektin tulee täyttää sille asetetut vaatimukset. Menetelmät eivät takaa menestystä, vaan yrityksen on valittava itselleen sopivat menetelmät siten, että ne tukevat portfoliojohtamista ja sopivat yhteen yrityskulttuurin kanssa. Pelkkä mittareihin tuijottaminen ei riitä, vaan niiden taakse on myös osattava katsoa ja huomioida yrityksen strategia.

Survival and Quality of Life among Patients with Severe Lower Extremity Peripheral Arterial Disease

Lower extremity peripheral arterial disease (PAD) is associated with decreased functional status, diminished quality of life (QoL), amputation, myocardial infarction, stroke, and death. Nevertheless, public awareness of PAD as a morbid and mortal disease is low. The aim of this study was to assess the incidence of major lower extremity amputation due to PAD, the extent of reamputations, and survival after major lower extremity amputation (LEA) in a population based PAD patient cohort. Furthermore, the aim was to assess the functional capacity in patients with LEA, and the QoL after lower extremity revascularization and major amputation. All 210 amputees due to PAD in 1998–2002 and all 519 revascularized patients in 1998–2003 were explored. 59 amputees alive in 2004 were interviewed using a structured questionnaire of QoL. Two of each amputee age-, gender- and domicile-matched controls filled in and returned postal self-administered QoL questionnaire as well as 231 revascularized PAD patients (the amount of these patients who engaged themselves to the study), and one control person for each patient completed postal self-administered QoL questionnaire. The incidence rate of major LEA was 24.1/100 000 person-years and it was considerably high during the years studied. The one-month mortality rate was 21%, 52% at one-year, and the overall mortality rate was 80%. When comparing the one-year mortality risk of amputees, LEAs were associated with a 7.4-fold annual mortality risk compared with the reference population in Turku. Twenty-two patients (10%) had ipsilateral transversions from BK to AK amputation. Fifty patients (24%) ended up with a contralateral major LEA within two to four amputation operations. Three bilateral amputations were performed at the first major LEA operation. Of the 51 survivors returning home after their first major LEA, 36 (71%) received a prosthesis; (16/36, 44%) and were able to walk both in- and outdoors. Of the 68 patients who were discharged to institutional care, three (4%) had a prosthesis one year after LEA. Both amputees and revascularized patients had poor physical functioning and significantly more depressive symptoms than their controls. Depressive symptoms were more common in the institutionalized amputees than the home-dwelling amputees. The surviving amputees and their controls had similar life satisfaction. The amputees felt themselves satisfied and contented, whether or not they lived in long-term care or at home. PAD patients who had undergone revascularizations had poorer QoL than their controls. The revascularized patients’ responses on their perceived physical functioning gave an impression that these patients are in a declining life cycle and that revascularizations, even when successful, may not be sufficient to improve the overall function. It is possible that addressing rehabilitation issues earlier in the care may produce a more positive functional outcome. Depressive symptoms should be recognized and thoroughly considered at the same time the patients are recovering from their revascularization operation. Also primary care should develop proper follow-up, and community organizations should have exercise groups for those who are able to return home, since they very often live alone. In rehabilitation programs we should consider not only physical disability assessment but also QoL.

Työterveys- ja työturvallisuusriskienhallinnan kehittäminen

Työturvallisuuslaki (738/2002) asettaa vaatimuksia yrityksen suorittamalle työterveys- ja työturvallisuusriskienhallinalle ja TTT-toiminnan kehittämiselle. Organisaation tulee tunnistaa järjestelmällisesti työympäristön vaarat ja hallita niiden aiheuttamia riskejä. Taatakseen TTT-toiminnan jatkuvan kehittämisen ja lakisääteisten vaatimuksien täyttymisen organisaatiot laativat turvallisuusjohtamisjärjestelmä spesifikaatio OHSAS 18001 mukaisen TTT-järjestelmän ohjaamaan toimintaa. Työssä selvitetään, miten eräs suomalainen suuryritys on suoriutunut OHSAS 18001:fi mukaisen TTT-riskienhallintatoiminnan implementoinnista ja, mitkä ovat toiminnan suurimmat haasteet ja ongelmat. Työ pyrkii luomaan tietoa yrityksen TTT-toiminnan kehittämisen tueksi ja esittämään kehitysehdotukset toiminnassa ilmenneiden ongelmien korjaamiseksi. Teoreettisena lähtökohtana on käytetty yrityksen TTT-riskinarvioinnin ohjeistamiseksi laadittua kirjallisuutta sekä pohdittu riskienhallinnan ja turvallisuuskulttuurin vuorovaikutusta. Riskinarviointi edistää organisaation avointa raportointikulttuuria, joka on edellytys hyvän turvallisuuskulttuurin muodostumiselle. Selvityksessä havaittiin, että vastuiden ja valtuuksien epäselvyys organisaatioyksiköiden välillä ja sisällä vaikuttaa merkittävästi riskienhallinnan tehokkuuteen. Lisäksi riskinarviointitoiminta on edelleen irrallinen kokonaisuus organisaation jokapäiväisistä toiminnoista, mikä heikentää riskinarvioinnin tuloksien siirtymistä kenttätasolle.

Heikot signaalit osana yrityksen strategista päätöksentekoa

Yritykset toimivat monimuotoisessa ympäristössä, joka muuttuu yhä nopeammin. Yritysjohdon on pystyttävä ennakoimaan tulevaisuuden muutoksia ja johtamaan yritystä kohti haluttua tulevaisuutta. Tämän tutkimuksen tavoitteena on selvittää, miten yritys voi hyödyntää heikkoja signaaleja tulevaisuutta koskevassa strategisessa päätöksenteossa. Työssä perehdytään ensin kirjallisuuden perusteella heikkojen signaalien luonteeseen ja signaalien havainnointiin. Lisäksi selvitetään, miten signaalien sisältämä informaatio saadaan reititettyä yrityksen business intelligence –prosessiin ja sitä kautta hyödynnettyä strategisessa päätöksenteossa. Kirjallisuustutkimuksen perusteella luodaan viitekehys, jossa heikkojen signaalien prosessi ja strategiaprosessi asetetaan rinnakkain vuorovaikutukseen toistensa kanssa. Viitekehyksen ohjaamana tehdään tapaustutkimus heikkojen signaalien hyödyntämisestä Hansaprint Oy:n New Ventures –yksikössä. Heikkojen signaalien havainnointi aktivoi yritystä pohtimaan tulevaisuuttaan uudenlaisista näkökulmista hyvissä ajoin ja antaa organisaatiolle aikaa varautua tulevaan joko valmistautumalla kohtaamaan markkinoilla olevan uhkan tai hyödyntämään siellä piilevän mahdollisuuden. Heikkojen signaalien hyödyntäminen on keino luoda yrityksen tulevaisuutta ja näin olennainen osa yrityksen strategista suunnittelua. Tämän vuoksi heikkojen signaalien prosessi ei missään olosuhteissa voi olla täysin irrallinen strategiaprosessista.

Operation and Maintenance Security Service for OSS-RC networks

Security issues in telecommunication networks have become more important due to the development of the industry. The number of network elements and services has increased in the radio network as in the core network side, which has increased the number of security related issues. Ericsson has developed an OSS-RC product for operation and maintenance porpoises into the telecommunication networks. OSS-RC is used in a number of telecommunications operators, which have Ericsson's products used in their telecommunication networks. Ericsson provides product installation and maintenance support and guidance, but despite this, the product may have security related issues, either due to lack of following the instructions, human error or defect in the product itself or in a third party products attached. Ericsson’s Operation and Maintenance Security Service for OSS-RC networks aims to provide tools for checking the security level of the O&M product so that it meets all requirements and Ericsson’s own security related rules. Each customer has a unique telecommunications network structure and services, and so the security service has to be to create individually depending on the customer. The purpose of this thesis is to define the basic instructions for creating the security service for different customers.

Service Description Creation Empowerment to Mobile End Users

Increasing usage of Web Services has been result of efforts to automate Web Services discovery and interoperability. The Semantic Web Service descriptions create basis for automatic Web Service information management tasks such as discovery and interoperability. The discussion of opportunities enabled by service descriptions have arisen in recent years. The end user has been considered only as a consumer of services and information sharing occurred from one service provider to public in service distribution. The social networking has changed the nature of services. The end user cannot be seen anymore only as service consumer, because by enabling semantically rich environment and right tools, the end user will be in the future the producer of services. This study investigates the ways to provide for end users the empowerment to create service descriptions on mobile device. Special focus is given to the changed role of the end user in service creation. In addition, the Web Services technologies are presented as well as different Semantic Web Service description approaches are compared. The main focus in the study is to investigate tools and techniques to enable service description creation and semantic information management on mobile device.

Junan audiovahvistimen laitesuunnittelu

Joukkoliikenteen merkitys suurten ihmismäärien liikuttamisessa on kasvanut. Kaupunkikeskustat ovat monin paikoin ruuhkautuneet ja joukkoliikenteestä pyritään tekemään mahdollisimman houkuttelevaa ruuhkien helpottamiseksi. Yksi keino houkutella ihmisiä joukkoliikennevälineiden käyttäjiksi on parantaa matkustajille tarjottavan informaation määrää ja laatua. Matkustajainformaatiojärjestelmä on monipuolinen kokonaisuus, jolla joukkoliikenteen käyttäjälle tarjotaan muun muassa opastusta, aikataulutietoa ja häiriötietoa. Informaatio voi olla staattista kuten painetut aikataulut ja kiinteät opasteet tai dynaamista kuten reaaliaikaiset näytöt ja kuulutukset. Informaatiota voidaan tarjota matkustajan käyttöön niin kotona ja liikenneasemilla kuin liikkuvassa kalustossakin. Matkustajainformaatiojärjestelmiä on käytössä erilaisissa joukkoliikennevälineissä, joista tässä diplomityössä syvennytään raideliikenteeseen. Työssä suunnitellaan ja toteutetaan raideliikenteen vaatimukset täyttävä IP-pohjainen audiovahvistin. Valmis vahvistin liittyy Ethernet-verkon välityksellä raideliikenteen matkustajainformaatio-järjestelmään. Laite toimii kuulutus- ja puhelinjärjestelmän keskusyksikkönä. Työn tuloksena saatiin toimiva ja sarjatuotantokelpoinen audiovahvistin. Laitteen tyyppitestit ovat tätä työtä palautettaessa vielä kesken, mutta tähän mennessä testit ovat menneet hyvin ja laite on toiminut hyvin myös osana järjestelmää.

Lattiajäähdytyksen mitoitus ja säätö

Mitoitukseen on olemassa standardoitu laskentamenetelmä, mutta se ei yksistään ole riittävä jäähdytettävän lattiarakenteen suunnitteluun. Rakenteen lämpötilajakaumaa jäähdytystilanteessa tutkittiin lisäksi FDM-ohjelmistolla tehdyillä simuloinneilla. Lattiajäähdytyksessä kosteuden tiivistymisen riski ja mukavuustekijät rajoittavat käytettävissä olevaa lämpötilaa. Saavutettavissa olevan teho on puolestaan suoraan riippuvainen jäähdytettävän tilan ja jäähdyttävän pinnan välisestä lämpötilaerosta. Kirjallisuudesta, standardeista ja aiemmasta tutkimuksesta etsittiin tietoa jäähdytetyn lattian vaikutuksesta asumismukavuuteen sekä kosteusteknisessä mielessä käytettävissä oleva lämpötila-alue. Asuintiloissa lattiapinnan minimilämpötila on 19 °C, millä lattiarakenteesta ja materiaaleista riippuen päästään 20 - 30 W/m2 jäähdytystehoihin. Järjestelmän säätömahdollisuuksia selvitettiin kirjallisuudesta ja vaihtoehtoisia toteutustapoja, sekä niihin tarvittavia komponentteja on esitelty työn loppuosassa.  

Uusperheen voimavarat ja lasten hyvinvointi

The resources of the step family and the children’s well-being The present study investigates children's well-being in stepfamilies and fac¬tors, both external and internal, that are related to the children's well-being. Of the external factors, the study focuses on factors related to the structure of the stepfamily, parents' education, socio-economic status and factors related to work, livelihood and living conditions. The internal resources include the general functioning of the family, parenthood and parenting, family support networks and issues that the stepfamilies themselves consider important. Another important resource in a stepfamily is a functioning network of human relationships, which in the present study is approached from the maternal viewpoint. Changing family relations are considered a potential threat to the children's well-being. Therefore, in addition to looking into the stepfamily's resources, the other important goal of the study is to explore other factors potentially related to the well-being of children living in stepfamilies. In view of the stepfamily's resources, it is important to explore how the functioning of the relationships network is linked with the child's well-being. The study employs survey and interview data. The survey data (n=2236) are part of national survey data on the well-being of families and children and factors impacting them which were gathered as part of ”Origins of Exclusion in Early Childhood”, a research project carried out in 2002. The data consists of 667 stepfamilies. The interview data consists of interviews with 24 parents in stepfamilies. In the study, the analyses of survey and interview data are combined. Both descriptive statistical analyses and multivariate methods are employed. Content analysis is employed in the analysis of the interview data. The results indicate that the stepfamilies’ resources in general but their external resources in particular differed from those of the nuclear and single-parent families. The level of education and the socio-economic status of the stepfamily parents were somewhat lower than those of the nuclear family parents. The differences in relation to single-parent families were primarily related to the better economic status of the stepfamilies. The analysis of internal resources showed relatively minor differences: the stepfamilies assessed themselves a somewhat better general functioning of the family than did the nuclear families. Parenting issues caused more disagreement in stepfamilies than in nuclear families. The analysis of the functioning of the human relations in stepfamilies showed that the stepfamily mothers experienced the external relationships of the family (e.g., between the child and the absent father) as significantly more problematic than the relationships within the stepfamily. Living in a stepfamily thus challenges the functioning of the relationship between the child and the absent father. As a result of the analysis of the relationships networks in the stepfamilies, three groups were formed. One group had the nuclear family as an ideal goal, another valued an extended family composed of a variety of relationships, and the third one appreciated a strong intimate relationship between the parents. In the present study, the most common group was the multi-relationship, extended type of stepfamily. In conclusion, living in a stepfamily does not seem to pose a risk to the child’s well-being, but it may influence the family’s resources and thus have an indirect effect on the child’s well-being. In view of the resources of the stepfamily, the child’s well-being was best supported by a functioning network of human relationships in the stepfamily: there was a distinct connection with the children’s problems and the non-functioning of the relationships network. According to the mothers, the internal relationships in the stepfamily seemed to be more important than the external relationships of the family. A child’s functioning relationship with the absent father can be viewed as a positive resource, supporting the child’s well-being in the stepfamily.

The Vulnerable Brain and Very Preterm Infants - Findings from the PIPARI-Study

Preterm birth is a risk for normal brain development. Brain maturation that normally happens in the uterus is in very preterm infants a developmental challenge during their stay in a neonatal intensive care unit (NICU). Typical brain injuries of preterm infants include ischemic injuries, brain haemorrhages, ventricular dilatation (VD), and reduced brain volumes. Brain injury is a serious complication of prematurity leading to possible long term consequences for the neurodevelopment of the very low birth weight (VLBW) infant, such as cerebral palsy (CP), hearing impairments, vision problems, and delay in cognitive development.There is a need for further studies to ascertain the potential risk factors and their causal relationships to brain vulnerability, growth and development in the increasing number of surviving VLBW infants. This thesis consists of four studies evaluating the definitions, causes and consequences of brain lesions in VLBW(<1500g) or very low gestationalage (VLGA) (gestational age <32 gestational weeks) infants. We showed that the redistribution of fetal blood flow is a risk factor for smaller brain volumes at term. In addition,we showed that brain lesions related to prematurity are not associated with increased spontaneous crying behaviour or circadian rhythm development in infancy. However, the preterm infants began to fuss more often and were held more than term infants at five months of age. Furthermore, we showed that VD is associated with brain lesions and smaller brain volumes. Therefore, brain magneticresonance imaging can be recommended for infants with VD. VD together with other brain pathology is a risk factor for the onset of developmental impairments in VLBW/VLGA infants at two years of age.

Accounting Beta Measuring Systematic Risk: Empirical Evidence from the Finnish Markets

The main purpose of this study is to examine whether accounting-based variables can be used to measure systematic risk of a company using Finnish data. When the fundamental sources of systematic risk are known, companies are able to manage these risks and increase company value. Accounting beta was formed based on OLS regression models. Theoretical background for the study was based on the findings of studies according to which business risk, financial risk, operating risk and growth risk can be theoretically regarded as determinants of the systematic risk. The results reveal that accounting variables describe systematic risk of a company. The accounting beta is found to be particularly sensitive to the changes in the risk components. The investigation is confidential until 15.10.2012.

Investment risks in Russia: A Finnish perspective

Purpose of this study is to analyze the effect of Russia's economic environment changes in the total return indexes of Finnish companies. The research data consisted of Finnish publicly listed companies, which have made physical investments to Russia, and operating in the area. The study used six different variables to model the Russian operating environment. The data consists of total return indexes of Finnish companies. From those we calculated the monthly mean interval between timeline of 1 January 2000 to 31 December 2009. Sample period is divided into two different parts. Variables impact on companies' total return indices is tested by regression analysis. By F-test we tested significance of model and squared coefficient correlation told us how much model explains from changes. Goodness of the β-coefficient is tested in the model by t-test. The research results shows that the Russian operating environment, or changes in which the active Finnish companies in total return indices. On partial sample periods results were not so significant.

Varallisuudenhoito indeksiosuusrahastoilla

Tässä tutkielmassa käsiteltiin varallisuuden hoitoa indeksiosuusrahastoilla (excange-traded fund). Tavoitteena oli selvittää yleisesti indeksiosuusrahastojen ominaisuuksia sekä rakentaa excelissä indeksiosuusrahastoista sijoitussalkku. Kuukausituottoainestona oli iSharesin 31 indeksiosuusrahastoa vuosilta 2006 - 2009. Havaintoja oli yhteensä 1468. Tutkimuksessa havaittiin, että aikavälillä 2006 - 20009 indeksiosuusrahastot seuraavat hyvin vertailuindeksiään, sisältävät keskimäärin markkinoihin nähden vähäisesti riskiä sekä tarjoavat tasaista tuottoa.

Characteristics of credit risk assessment methods of major Nordic banks in allocating capital when extending credits to large corporations

Credit risk assessment is an integral part of banking. Credit risk means that the return will not materialise in case the customer fails to fulfil its obligations. Thus a key component of banking is setting acceptance criteria for granting loans. Theoretical part of the study focuses on key components of credit assessment methods of Banks in the literature when extending credits to large corporations. Main component is Basel II Accord, which sets regulatory requirement for credit risk assessment methods of banks. Empirical part comprises, as primary source, analysis of major Nordic banks’ annual reports and risk management reports. As secondary source complimentary interviews were carried out with senior credit risk assessment personnel. The findings indicate that all major Nordic banks are using combination of quantitative and qualitative information in credit risk assessment model when extending credits to large corporations. The relative input of qualitative information depends on the selected approach to the credit rating, i.e. point-in-time or through-the-cycle.