Alikasvoksen mittaus ja kartoitus laserkeilauksella

Tasaikäisen metsän alle muodostuvilla alikasvoksilla on merkitystä puunkorjuun, metsänuudistamisen, näkemä-ja maisema-analyysien sekä biodiversiteetin ja hiilitaseen arvioinnin kannalta. Ilma-aluksista tehtävä laserkeilaus on osoittautunut tehokkaaksi kaukokartoitusmenetelmäksi varttuneiden puustojen mittauksessa. Laserkeilauksen käyttöönotto operatiivisessa metsäsuunnittelussa mahdollistaa aiempaa tarkemman tiedon tuottamisen alikasvoksista, mikäli alikasvoksen ominaisuuksia voidaan tulkita laseraineistoista. Tässä työssä käytettiin tarkasti mitattuja maastokoealoja ja kaikulaserkeilausaineistoja (discrete return LiDAR) usealta vuodelta (1–2 km lentokorkeus, 0,9–9,7 pulssia m-2). Laserkeilausaineistot oli hankittu Optech ALTM3100 ja Leica ALS50-II sensoreilla. Koealat edustavat suomalaisia tasaikäisiä männiköitä eri kehitysvaiheissa. Tutkimuskysymykset olivat: 1) Minkälainen on alikasvoksesta saatu lasersignaali yksittäisen pulssin tasolla ja mitkä tekijät signaaliin vaikuttavat? 2) Mikä on käytännön sovelluksissa hyödynnettävien aluepohjaisten laserpiirteiden selitysvoima alikasvospuuston ominaisuuksien ennustamisessa? Erityisesti haluttiin selvittää, miten laserpulssin energiahäviöt ylempiin latvuskerroksiin vaikuttavat saatuun signaaliin, ja voidaanko laserkaikujen intensiteetille tehdä energiahäviöiden korjaus. Puulajien väliset erot laserkaiun intensiteetissä olivat pieniä ja vaihtelivat keilauksesta toiseen. Intensiteetin käyttömahdollisuudet alikasvoksen puulajin tulkinnassa ovat siten hyvin rajoittuneet. Energiahäviöt ylempiin latvuskerroksiin aiheuttivat alikasvoksesta saatuun lasersignaaliin kohinaa. Energiahäviöiden korjaus tehtiin alikasvoksesta saaduille laserpulssin 2. ja 3. kaiuille. Korjauksen avulla pystyttiin pienentämään kohteen sisäistä intensiteetin hajontaa ja parantamaan kohteiden luokittelutarkkuutta alikasvoskerroksessa. Käytettäessä 2. kaikuja oikeinluokitusprosentti luokituksessa maan ja yleisimmän puulajin välillä oli ennen korjausta 49,2–54,9 % ja korjauksen jälkeen 57,3–62,0 %. Vastaavat kappa-arvot olivat 0,03–0,13 ja 0,10–0,22. Tärkein energiahäviöitä selittävä tekijä oli pulssista saatujen aikaisempien kaikujen intensiteetti, mutta hieman merkitystä oli myös pulssin leikkausgeometrialla ylemmän latvuskerroksen puiden kanssa. Myös 3. kaiuilla luokitustarkkuus parani. Puulajien välillä havaittiin eroja siinä, kuinka herkästi ne tuottavat kaiun laserpulssin osuessa puuhun. Kuusi tuotti kaiun suuremmalla todennäköisyydellä kuin lehtipuut. Erityisen selvä tämä ero oli pulsseilla, joissa oli energiahäviöitä. Laserkaikujen korkeusjakaumapiirteet voivat siten olla riippuvaisia puulajista. Sensorien välillä havaittiin selviä eroja intensiteettijakaumissa, mikä vaikeuttaa eri sensoreilla hankittujen aineistojen yhdistämistä. Myös kaiun todennäköisyydet erosivat jonkin verran sensorien välillä, mikä aiheutti pieniä eroavaisuuksia kaikujen korkeusjakaumiin. Aluepohjaisista laserpiirteistä löydettiin alikasvoksen runkolukua ja keskipituutta hyvin selittäviä piirteitä, kun rajoitettiin tarkastelu yli 1 m pituisiin puihin. Piirteiden selitysvoima oli parempi runkoluvulle kuin keskipituudelle. Selitysvoima ei merkittävästi alentunut pulssitiheyden pienentyessä, mikä on hyvä asia käytännön sovelluksia ajatellen. Lehtipuun osuutta ei pystytty selittämään. Tulosten perusteella kaikulaserkeilausta voi olla mahdollista hyödyntää esimerkiksi ennakkoraivaustarpeen arvioinnissa. Sen sijaan alikasvoksen tarkempi luokittelu (esim. puulajitulkinta) voi olla vaikeaa. Kaikkein pienimpiä alikasvospuita ei pystytä havaitsemaan. Lisää tutkimuksia tarvitaan tulosten yleistämiseksi erilaisiin metsiköihin.

Otoksen edustavuuden mittaus R-indikaattorin avulla Suomen uhritutkimuspilotissa

Tutkielmassa sovelletaan aineiston edustavuutta mittaavaa laatuindikaattoria Suomen uhritutkimuspilottiin tilanteessa, jossa ilmenee vastauskatoa. Vastauskato on kasvava ongelma tilastotutkimuksissa: jos tutkimukseen osallistuneet eivät edusta otosjoukkoa tutkittavan asian suhteen, voi vastauskadosta aiheutuva harha olla estimoiduissa tunnusluvuissa hyvinkin suuri. Tutkimuksissa näkee usein julkaistavan vastausasteen ikään kuin se kertoisi aukottomasti tutkimuksen laadusta. Pelkkä korkea vastausaste ei kuitenkaan välttämättä takaa estimaattien harhattomuutta, sillä se ei kerro mitään vastanneiden ja vastaamattomien eroista tutkittavan asian suhteen. Tarvitaan siis muita mittareita, joilla vastanneiden laatua voitaisiin paremmin arvioida, ja R-indikaattori tarjoaa yhden vaihtoehdon. R-indikaattori mittaa otosalkioiden vastausalttiuksien välistä vaihtelua. R-indikaattorin estimoiminen edellyttää siis vastausalttiuksien estimointia, mikä puolestaan edellyttää apumuuttujien olemassaoloa kaikille otosalkioille. Vastausalttiuksien estimoimiseen käytettiin linkkifunktiona sekä logistista mallia että ja Särndalin ja Lundströmin (2008) vastausvaikutusten mallia. Vastauskäyttäytymiseen vaikuttavan apumuuttujajoukon valinta tehtiin alan kirjallisuuteen perustuen (Groves & Couper 1998). Koska R-indikaattorin estimaattori on satunnaismuuttuja, täytyi sille estimoida varianssi ja mahdollinen harha (Shlomo ym. 2009). Estimoinnissa käytettiin Bootstrap-pseudotoistomenetelmää, jossa alkuperäisestä aineistosta poimitaan niin kutsuttuja pseudo-otoksia, joiden avulla R-indikaattorin estimaattorille voidaan laskea keskivirhe. Suomen uhritutkimuspilotti koostui kolmesta eri tiedonkeruumenetelmällä poimitusta otoksesta: CAPI-, CATI- CAVVIotoksesta. Vastausasteet vaihtelivat aineistoissa paljon, mutta R-indikaattorin estimaatit olivat kaikille aineistoille liki samat. Suurempi vastausaste ei siis merkinnyt parempaa edustavuutta. Lisäksi CAVVI-aineistossa muistutusviestein ja -kirjein suoritettu vastausasteen kasvattaminen huononsi edustavuutta R-indikaattorin näkökulmasta. Mielivaltainen vastausasteen kasvattaminen ei siis ole välttämättä perusteltua. R-indikaattorin estimaattorin ominaisuuksien osalta empiiriset tulokset vahvistivat RISQ-projektin aiempia tutkimustuloksia. Estimaattorin arvo oli sitä pienempi mitä enemmän vastausalttiuden mallissa oli selittäjiä, koska tällöin vastausalttiuksien varianssi kasvoi (Schouten ym. 2009). Otoskoko vaikutti merkittävästi varianssin suuruuteen: mitä pienempi otoskoko oli, sitä leveämmät olivat luottamusvälit ja sitä vaikeampi oli tehdä johtopäätöksiä edustavuudesta.

Strateginen suorituskyvyn mittaus osana johdon ohjausjärjestelmiä: Case-tutkimus johdon ohjausjärjestelmistä pakettina

Tämän tutkielman tavoitteena on kuvata ja analysoida johdon ohjausjärjestelmien toimintaa pakettina ja hahmottaa strategisen suorituskyvyn mittauksen merkitystä sekä roolia johdon ohjausjärjestelmäpaketissa. Paketti-näkökulman ottaminen johdon ohjausjärjestelmiin edustaa laajempaa näkemystä ohjauksesta, jossa johdon laskentatoimen järjestelmien lisäksi ohjausjärjestelmiksi katsotaan kaikki ne formaalit ja epäformaalit järjestelmät, joilla organisaatiota ohjataan kohti sen tavoitteita. Tutkielman teoreettinen viitekehys pohjautuu laajaan, mutta rakenteelliseen ohjausjärjestelmäpakettimalliin, johon strateginen suorituskyvyn mittaus luetaan osakokonaisuudeksi määritellen sen ominaispiirteet ohjauksen näkökulmasta. Tutkielman tutkimusote on luonteeltaan toiminta-analyyttinen ja empiirinen tutkimus toteutettiin case-tutkimuksena varsinaissuomalaisessa rakennusteollisuuden yrityksessä. Empiirinen aineisto koostuu case-yrityksen johdon sekä muun henkilöstön haastatteluista yhdessä case-yrityksessä suoritetun havainnoinnin sekä saadun sisäisen ja ulkoisen arkistomateriaalin kanssa. Tutkimuksen aineisto kerättiin vuoden 2010 syksyn ja 2011 kevään välisenä aikana. Suoritetun empiirisen tutkimuksen tulokset vahvistavat aikaisempia tuloksia siitä, miten johdon ohjausjärjestelmäpaketti toimii. Tutkimustulokset korostavat toiminnallisten vaatimusten ja johdonmukaisuuden merkitystä johdon ohjausjärjestelmäpakettia analysoitaessa. Kulttuuri havaittiin merkittäväksi ohjausjärjestelmäksi ja se osaltaan vaikutti siihen, millaiseksi paketin muiden ohjausjärjestelmien rooli muodostuu. Case-yrityksessä strategisella suorituskyvyn mittauksella tavoitellaan organisaation huomion kiinnittämistä strategian kannalta olennaisiin seikkoihin, jotka tässä tutkimuksessa tunnistettiin toiminnan tehostamiseksi ja kasvuksi. Strateginen suorituskyvyn mittaus nivoutuu yhteen erinäisten hallinnollisten ohjausjärjestelmien kanssa juuri sen interaktiivisen käytön kautta, ja siten se tukee asetettuihin toiminnallisiin vaatimuksiin vastaamista yhdessä kulttuurin kanssa. Näitä pääasiallisia ohjausjärjestelmiä tukevat muut johdon implementoimat ohjausjärjestelmät yhdessä päätöksien kanssa olla käyttämättä tiettyjä järjestelmiä ohjaukseen. Siten ohjausjärjestelmäpaketin sisäinen vuorovaikutus ilmenee eri ohjausjärjestelmien keskinäisen johdonmukaisuuden kautta, eivätkä ne ole erotettavissa toisistaan kuin analyyttisessä mielessä

Towards real-time understanding of processes in pharmaceutical powder technology

There is a need for better understanding of the processes and new ideas to develop traditional pharmaceutical powder manufacturing procedures. Process analytical technology (PAT) has been developed to improve understanding of the processes and establish methods to monitor and control processes. The interest is in maintaining and even improving the whole manufacturing process and the final products at real-time. Process understanding can be a foundation for innovation and continuous improvement in pharmaceutical development and manufacturing. New methods are craved for to increase the quality and safety of the final products faster and more efficiently than ever before. The real-time process monitoring demands tools, which enable fast and noninvasive measurements with sufficient accuracy. Traditional quality control methods have been laborious and time consuming and they are performed off line i.e. the analysis has been removed from process area. Vibrational spectroscopic methods are responding this challenge and their utilisation have increased a lot during the past few years. In addition, other methods such as colour analysis can be utilised in noninvasive real-time process monitoring. In this study three pharmaceutical processes were investigated: drying, mixing and tabletting. In addition tablet properties were evaluated. Real-time monitoring was performed with NIR and Raman spectroscopies, colour analysis, particle size analysis and compression data during tabletting was evaluated using mathematical modelling. These methods were suitable for real-time monitoring of pharmaceutical unit operations and increase the knowledge of the critical parameters in the processes and the phenomena occurring during operations. They can improve our process understanding and therefore, finally, enhance the quality of final products.

3 - 5-vuotiaiden lukemaan oppiminen : montessorivälineet kielellisen tietoisuuden ja varhaisen lukitaidon edistäjinä

Aims. The beginning point of this research was confusion between studies claiming, that children mature Metalinguistic to read at 6-7 of age, and the fact, that in Montessori playschools children easily start writing and reading at age 3 to 5. Aim was also find out how conception of slow Metalinguistic development has started, and if there is some evidence of phoneme awareness of reading of young children in the field of research of reading. Aim was also seek evidence of the sensitive period of reading as Montessori described it. The research also wanted to turn up, if phoneme awareness only develops in children, who work with graphemes and with reading, or could it be found in children, who do not. The mean was to research how the Montessori reading material supports child’s Metalinguistic development, when child begins learning to read. The research plans to represent knowledge about how young children learn to write and read. Methods. Research performed in ordinary kindergarten and in Montessori playschool in Espoo. In kindergarten observed six children, age 3-4, at eight grapheme-rhyme sessions from January to April 2007, and conducting a test based on Chaney’s (1992) study of phoneme awareness of young children. In Montessori kindergarten were observed 17 children about their phoneme awareness and reading competition from January 2007 to March 2008. Their developments in reading were also measured three times from 1.9.07 to 20.3.08 with classification constructed for this study, loosely based on Chall’s (1983) reading stages. The Montessori reading material was analyzed about the influence they have to a child’s Metalinguistic development. This was done based to theory and its concepts from the field of research of reading; phoneme awareness, morphological, syntactical and semantic consciousness. Results and conclusions. Research proved that children 3-5 have naturally developed phoneme awareness. In kindergarten and in Montessori playschool children between 2 and 4 could do phoneme synthesis, and in the latter they also could do phoneme segmentation of words. Montessori reading material guided children gradually, except to read, also to observe and absorb Metalinguistic knowledge. Children learned to write and read. At the last evaluating day almost 50 % of children write and read clauses or stories, and 82 % could read at least words. Children can develop Metalinguistic awareness, while using the Montessori materials for learning to write and read. To reach literacy is easy for children because of their phoneme awareness.

Langattoman peltotiedustelijan maanalainen toimintaympäristö ja laitesuunnittelu

Tässä väitöskirjassa esitellään langattomien maanalaisten peltotiedustelijoiden järjestelmän tavoitteet ja rajoitukset. Tarkoitus oli kehittää käytännön viljelyyn sovellettava pellon seurantajärjestelmä, sillä reaaliaikaisen kosteus- ja lämpötilatiedon keruulaitteiden puuttuminen haittaa viljelytoimenpiteiden suunnittelua. Mittaus-aineistosta voi tehdä sekä havaintoja pellon ominaisuuksista että muutoksista niissä. Tulevaisuudessa tiedustelijalla saatetaan voida mitata ravinteita tai kemikaaleja. Kun peltotiedustelijan 869 MHz:n radioaalto saavuttaa vastaanottoantennin, on 1) maa-aines vaimentanut sitä; 2) osa aallosta heijastunut rajapinnoilta; 3) pellosta ulos taittuva aalto hajaantunut ja; 4) aallon intensiteetti alentunut etäisyyden kasvaessa. Maan sähkökenttäkäyttäytymistä kuvaava permittiivisyys on kompleksinen suure, jonka reaaliosa kuvaa varautumiskykyä (polarisoitumista) ja imaginaariosa häviöllisyyttä (sähkönjohtavuutta). Pellon pinnassa aalto on pallomainen, joten heijastumisen lisäksi hajaannuttaa taittuminen suurilla taitekulmilla sen tehoa. Tiedustelijan prototyyppiä varten kehitettiin maa-aineksessa toimivat antennit, joiden taajuuskaistat kattoivat ne aallonpituudet, jotka 869 MHz:n radioaalto saa kuivassa ja märässä mullassa, sillä aallon etenemisnopeus ja pituus muuttuvat maan kosteudesta riippuen. Vaimennusmallin testausmittauksiin tehtiin discone-antenni, ja tiedustelijaa varten piirilevytekniikalla pienikokoinen elliptinen monopoliantenni, jonka piirikortille ladottiin myös tiedustelijan elektroniikka. Multalaatikkoon upotettujen antennien säteilyominaisuudet määritettiin piirianalysaattorilla heijastusvaimennusmittauksin. Elektroniikkasuunnittelun tavoitteita oli pieni koko ja pitkä toimintaikä. Näihin päästiin komponenttivalinnoilla sekä ohjelmoinnin keinoin. Tiedustelija teki mittaukset ja lähetti tulokset 10 min välein ja sen keskivirrankulutus oli 4,2 uA käytettäessä 3 V:n paristoa, jonka 1800 mAh kapasiteetti riittäisi huonollakin hyötysuhteella yli 10 vuodeksi. Vuoden mittaisen 12 prototyypin käytön perusteella voidaan kantamaa parantaa yli nykyisen 200 m:n ilman käyttöiän lyhentymistä 1) nostamalla laitteen lähetystehoa ja pariston käyttöastetta lisäkomponenteilla; 2) parantamalla vastaanottoantennin vahvistusta; 3) pidentämällä lähetysten jaksoa; 4) ohjelmoimalla tiedustelija suodattamaan mittaustietoja ja; 5) koodaamalla useita tuloksia samaan lähetteeseen. Järjestelmän ja mittaustulosten käytettävyyttä voidaan parantaa paikantamalla tiedustelijoiden syvyydet aaltoilevan lämpötilan vaihe-erojen perusteella ja ohjelmoimalla tiedustelijaan opastava asennustoiminto. Lisäksi maahan asennetun tiedustelijan toimintaparametrit tai jopa koko ohjelmisto voidaan vaihtaa langattomasti. Vastaanottoasemat matkapuhelinmastoissa voisivat vastaanottaa viestejä parin kilometrin säteeltä. Koostettu aineisto maaperäsimulaattoreihin yhdistettynä antaisi kuvan alueellisesta tilanteesta ja viljelijän omille lohkoille sijoitetut tiedustelijat korjauspisteitä keskiarvosta.

Construction of a global map of human gene expression : the process, tools and analysis

This thesis studies human gene expression space using high throughput gene expression data from DNA microarrays. In molecular biology, high throughput techniques allow numerical measurements of expression of tens of thousands of genes simultaneously. In a single study, this data is traditionally obtained from a limited number of sample types with a small number of replicates. For organism-wide analysis, this data has been largely unavailable and the global structure of human transcriptome has remained unknown. This thesis introduces a human transcriptome map of different biological entities and analysis of its general structure. The map is constructed from gene expression data from the two largest public microarray data repositories, GEO and ArrayExpress. The creation of this map contributed to the development of ArrayExpress by identifying and retrofitting the previously unusable and missing data and by improving the access to its data. It also contributed to creation of several new tools for microarray data manipulation and establishment of data exchange between GEO and ArrayExpress. The data integration for the global map required creation of a new large ontology of human cell types, disease states, organism parts and cell lines. The ontology was used in a new text mining and decision tree based method for automatic conversion of human readable free text microarray data annotations into categorised format. The data comparability and minimisation of the systematic measurement errors that are characteristic to each lab- oratory in this large cross-laboratories integrated dataset, was ensured by computation of a range of microarray data quality metrics and exclusion of incomparable data. The structure of a global map of human gene expression was then explored by principal component analysis and hierarchical clustering using heuristics and help from another purpose built sample ontology. A preface and motivation to the construction and analysis of a global map of human gene expression is given by analysis of two microarray datasets of human malignant melanoma. The analysis of these sets incorporate indirect comparison of statistical methods for finding differentially expressed genes and point to the need to study gene expression on a global level.

Prevalence and determinants of respiratory symptoms, asthma, chronic bronchitis and allergic sensitization in Helsinki : A comparison between Finland, Sweden and Estonia. The FinEsS studies - Helsinki I

Objectives: To assess the prevalence and risk factor profiles of respiratory symptoms, asthma and chronic bronchitis in Helsinki, and to compare these results with those for Sweden and Estonia. Other important aims were to evaluate the prevalence and determinants of type 1 sensitization in Helsinki. Materials and methods: This presentation is a part of a large epidemiological study in Finland, Estonia and Sweden (FinEsS). The first part of the study consisted of a postal questionnaire in 1995-1996 distributed to subjects in eight study centres. The study population in each centre was a population-based random sample designed to be representative of the general population. The original study sample in Helsinki consisted of 8000 subjects aged 20-69 years, 6062 (76%) of whom participated. Comparisons between countries were based on a narrower age group, 20-64 years, since 64 years was the upper age limit used in the original study in Estonia. Thus, altogether 58 661 subjects aged 20-64 years were invited to participate in Finland, Sweden and Estonia, and 44 483 (76%) did so. The second part of the study was a clinical study with a structured interview, lung function measurements and skin-prick tests with 15 common allergens. This thesis reports only the results of the prick tests in Helsinki. Of the 1200 subjects invited to participate in Helsinki, 643 (54%) consented. Skin-prick tests were performed on subjects ≤ 60 years of age; thus, a total of 498 tests were done. Results: In Helsinki, the prevalence of physician-diagnosed asthma was 6.6% and of physician-diagnosed chronic bronchitis 3.7% among subjects aged 20-69 years. Comparison of the results between Finland, Sweden and Estonia in subjects 20-64 years of age revealed the highest prevalence of physician-diagnosed asthma in Sweden, 7.8%, while the prevalence in Finland was 5.9% and in Estonia 2.0% (p<0.001). The prevalence of physician-diagnosed asthma among those aged 20-29 years was 7.9% in Stockholm, 6.3% in Helsinki and 2.8% in Tallinn. Asthma-related symptoms were most common in Estonia, and among those with typical asthma symptoms the diagnosis of asthma was least likely in Estonia. Physician-diagnosed chronic bronchitis was reported to be 10.7% in Estonia, 3.1% in Sweden and 2.9% in Finland among subjects aged 20-64 years (p<0.001). Among those aged 20-29 years, 7.6% in Tallinn reported physician-diagnosed chronic bronchitis, while the prevalence estimates were 1.4% in Stockholm and 1.3% in Helsinki. The prevalence of smoking was similar for women in all three countries, around 30%, but large differences in smoking habits were present among men; 60% of Estonian, 39% of Finnish and 28% of Swedish men smoked. Skin-prick tests in Helsinki revealed a high prevalence of sensitization, 46.9%. For subjects aged 26-39 years, the prevalence was highest, 56.8%, and 23.7% were sensitized to at least four allergens. The most common sensitizing allergen was the dog. Sensitization to multiple allergens was associated with a high prevalence of asthma and allergic rhinitis. Conclusions: Compared with earlier Finnish studies, a higher prevalence of asthma and a lower prevalence of chronic bronchitis were found in Helsinki. The prevalence of physician-diagnosed chronic bronchitis was low in Helsinki, with only one-fifth of subjects fulfilling the symptom criteria for chronic bronchitis reporting having a diagnosis of chronic bronchitis. The prevalences of asthma and chronic bronchitis were similar in Finland and Sweden, but in Estonia physician-diagnosed asthma was less common and physician-diagnosed chronic bronchitis more common, particularly among young subjects. Further analyses revealed that the diagnosis of asthma was favoured in Finland and Sweden, while the diagnosis of chronic bronchitis was more likely in Estonia for subjects with the same symptoms. Allergic sensitization was common in Helsinki. Our findings of multiple sensitization also speak in favour of evaluating the degree of sensitization when assessing allergies.

Preoperative visual acuity of cataract patients. Repeatability of visual acuity and refractive error measurements in clinical settings

Visual acuities at the time of referral and on the day before surgery were compared in 124 patients operated on for cataract in Vaasa Central Hospital, Finland. Preoperative visual acuity and the occurrence of ocular and general disease were compared in samples of consecutive cataract extractions performed in 1982, 1985, 1990, 1995 and 2000 in two hospitals in the Vaasa region in Finland. The repeatability and standard deviation of random measurement error in visual acuity and refractive error determination in a clinical environment in cataractous, pseudophakic and healthy eyes were estimated by re-examining visual acuity and refractive error of patients referred to cataract surgery or consultation by ophthalmic professionals. Altogether 99 eyes of 99 persons (41 cataractous, 36 pseudophakic and 22 healthy eyes) with a visual acuity range of Snellen 0.3 to 1.3 (0.52 to -0.11 logMAR) were examined. During an average waiting time of 13 months, visual acuity in the study eye decreased from 0.68 logMAR to 0.96 logMAR (from 0.2 to 0.1 in Snellen decimal values). The average decrease in vision was 0.27 logMAR per year. In the fastest quartile, visual acuity change per year was 0.75 logMAR, and in the second fastest 0.29 logMAR, the third and fourth quartiles were virtually unaffected. From 1982 to 2000, the incidence of cataract surgery increased from 1.0 to 7.2 operations per 1000 inhabitants per year in the Vaasa region. The average preoperative visual acuity in the operated eye increased by 0.85 logMAR (in decimal values from 0.03to 0.2) and in the better eye 0.27 logMAR (in decimal values from 0.23 to 0.43) over this period. The proportion of patients profoundly visually handicapped (VA in the better eye <0.1) before the operation fell from 15% to 4%, and that of patients less profoundly visually handicapped (VA in the better eye 0.1 to <0.3) from 47% to 15%. The repeatability visual acuity measurement estimated as a coefficient of repeatability for all 99 eyes was ±0.18 logMAR, and the standard deviation of measurement error was 0.06 logMAR. Eyes with the lowest visual acuity (0.3-0.45) had the largest variability, the coefficient of repeatability values being ±0.24 logMAR and eyes with a visual acuity of 0.7 or better had the smallest, ±0.12 logMAR. The repeatability of refractive error measurement was studied in the same patient material as the repeatability of visual acuity. Differences between measurements 1 and 2 were calculated as three-dimensional vector values and spherical equivalents and expressed by coefficients of repeatability. Coefficients of repeatability for all eyes for vertical, torsional and horisontal vectors were ±0.74D, ±0.34D and ±0.93D, respectively, and for spherical equivalent for all eyes ±0.74D. Eyes with lower visual acuity (0.3-0.45) had larger variability in vector and spherical equivalent values (±1.14), but the difference between visual acuity groups was not statistically significant. The difference in the mean defocus equivalent between measurements 1 and 2 was, however, significantly greater in the lower visual acuity group. If a change of ±0.5D (measured in defocus equivalents) is accepted as a basis for change of spectacles for eyes with good vision, the basis for eyes in the visual acuity range of 0.3 - 0.65 would be ±1D. Differences in repeated visual acuity measurements are partly explained by errors in refractive error measurements.

Development of Novel Assays for Measuring Different Molecular Forms of Prostate Specific Antigen

Prostate cancer (PCa) is the most commonly diagnosed non-skin cancer and second leading cause of cancer-related death of men in developed countries. Measurement of prostate specific antigen (PSA) is a very sensitive method for diagnosing and monitoring of prostate cancer (PCa), but the specificity needs improvement. Measurements of different molecular forms of PSA have been shown to improve differentiation between PCa and benign prostatic diseases. However, accurate measurement of some isoforms has not been achieved in previous assays. The aim of the present study was to develop new assays that reliably measure enzymatically active PSA, PSA-α1-chymotryposin (PSA-ACT) and PSA-α1-protease inhibitor (PSA-API), and to evaluate their diagnostic value. Double-label immunofluorometric assays using a novel monoclonal antibody (MAb) and another antibody to either free PSA (fPSA) or total PSA (tPSA) were developed and used to measure PSA-ACT and fPSA or tPSA at the same time. These assays provide enough sensitivity for measurement of PSA-ACT in sera with low PSA levels. The results obtained confirmed that proportion of PSA-ACT to tPSA (%PSA-ACT) was as useful as proportion of fPSA to tPSA (%fPSA) for discrimination between PCa and benign prostatic hyperplasia (BPH). We developed an immunoassay for detection of PSA-API based on proximity ligation, which improved assay sensitivity 10-fold compared with conventional assays. Our results confirmed previous findings that the PSA-API level is somewhat lower in men with than without PCa, and the combination of %fPSA and proportion of PSA-API to tPSA (%PSA-API) provides diagnostic improvement compared with either method alone. Assays based on this principle should be applicable to other immunoassays in which the nonspecific background is a problem. An immunopeptidometric sandwich assay (IPMA) was developed to measure the enzymatically active PSA. This assay showed high specificity, but sensitivity was not good enough for measurement of PSA concentrations in the gray zone, 2-10 µg/L, in which tPSA does not efficiently differentiate between PCa and BPH. We further developed a solid-phase proximity ligation immunoassay, which provided a 10-fold improvement in sensitivity. This proof of concept study shows that peptides reacting with proteins are potentially useful for sensitive and specific measurement of protein variants for which specific MAbs cannot be obtained.

Opioid dependence: Brain structure and function : a magnetic resonance imaging, neuropsychological, and electromagnetic study

Background: Opiod dependence is a chronic severe brain disorder associated with enormous health and social problems. The relapse back to opioid abuse is very high especially in early abstinence, but neuropsychological and neurophysiological deficits during opioid abuse or soon after cessation of opioids are scarcely investigated. Also the structural brain changes and their correlations with the length of opioid abuse or abuse onset age are not known. In this study the cognitive functions, neural basis of cognitive dysfunction, and brain structural changes was studied in opioid-dependent patients and in age and sex matched healthy controls. Materials and methods: All subjects participating in the study, 23 opioid dependents of whom, 15 were also benzodiazepine and five cannabis co-dependent and 18 healthy age and sex matched controls went through Structured Clinical Interviews (SCID) to obtain DSM-IV axis I and II diagnosis and to exclude psychiatric illness not related to opioid dependence or personality disorders. Simultaneous magnetoencephalography (MEG) and electroencephalography (EEG) measurements were done on 21 opioid-dependent individuals on the day of hospitalization for withdrawal therapy. The neural basis of auditory processing was studied and pre-attentive attention and sensory memory were investigated. During the withdrawal 15 opioid-dependent patients participated in neuropsychological tests, measuring fluid intelligence, attention and working memory, verbal and visual memory, and executive functions. Fifteen healthy subjects served as controls for the MEG-EEG measurements and neuropsychological assessment. The brain magnetic resonance imaging (MRI) was obtained from 17 patients after approximately two weeks abstinence, and from 17 controls. The areas of different brain structures and the absolute and relative volumes of cerebrum, cerebral white and gray matter, and cerebrospinal fluid (CSF) spaces were measured and the Sylvian fissure ratio (SFR) and bifrontal ratio were calculated. Also correlation between the cerebral measures and neuropsychological performance was done. Results: MEG-EEG measurements showed that compared to controls the opioid-dependent patients had delayed mismatch negativity (MMN) response to novel sounds in the EEG and P3am on the contralateral hemisphere to the stimulated ear in MEG. The equivalent current dipole (ECD) of N1m response was stronger in patients with benzodiazepine co-dependence than those without benzodiazepine co-dependence or controls. In early abstinence the opioid dependents performed poorer than the controls in tests measuring attention and working memory, executive function and fluid intelligence. Test results of the Culture Fair Intelligence Test (CFIT), testing fluid intelligence, and Paced Auditory Serial Addition Test (PASAT), measuring attention and working memory correlated positively with the days of abstinence. MRI measurements showed that the relative volume of CSF was significantly larger in opioid dependents, which could also be seen in visual analysis. Also Sylvian fissures, expressed by SFR were wider in patients, which correlated negatively with the age of opioid abuse onset. In controls the relative gray matter volume had a positive correlation with composite cognitive performance, but this correlation was not found in opioid dependents in early abstinence. Conclusions: Opioid dependents had wide Sylvian fissures and CSF spaces indicating frontotemporal atrophy. Dilatation of Sylvian fissures correlated with the abuse onset age. During early withdrawal cognitive performance of opioid dependents was impaired. While intoxicated the pre-attentive attention to novel stimulus was delayed and benzodiazepine co-dependence impaired sound detection. All these changes point to disturbances on frontotemporal areas.

Preterm delivery and selected biomarkers : phosphorylated insulin-like growth factor-binding protein-1 and matrix metalloproteinase-8 – in cervical fluid

Premature delivery is a major cause of neonatal morbidity and mortality. The incidence of premature deliveries has increased around the world. In Finland 5.3%, or about 3,000 children per year are born prematurely, before 37 weeks of gestation. The corresponding figure in the United States is about 13%. The morbidity and mortality are highest among infants delivered before 32 weeks of gestation - about 600 children each year in Finland. Approximately 70% of premature deliveries are unexplained. Preterm delivery can be caused by an asympto-matic infection between uterus and the fetal membranes, such can begin already in early pregnancy. It is difficult to predict preterm delivery, and many patients are therefore unnecessarily admitted to hospital for observation and exposed to medical treatments. On the other hand, the high risk women should be identified early for the best treatment of the mother and preterm infant. --- In the prospective study conducted at the Department of Obstetric and Gynecology, Helsinki University Central Hospital two biochemical inflammation related markers were measured in the lower genital tract fluids of asymp-tomatic women in early and mid pregnancy in an order to see whether these markers could identify women with an increased risk of preterm delivery. These biomarkers were phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) and matrix metalloproteinase-8 (MMP-8). The study involved 5180 asymptomatic pregnant women, examined during the first and second ultrasound screening visits. The study samples were taken from the vagina and cervicix. In addition, 246 symptomatic women were studied (pregnancy weeks 22 – 34). The study showed that increased phIGFBP-1 concentration in cervical canal fluid in early pregnancy increased the risk for preterm delivery. The risk for very premature birth (before 32 weeks of gestation) was nearly four-fold. Low MMP-8 concentration in mid pregnancy increased the risk of subsequent premature preterm rupture of fetal membranes (PPROM). Significantly high MMP-8 concentrations in the cervical fluid increased the risk for prema-ture delivery initiated by preterm labour with intact membranes. Among women with preterm contractions the shortened cervical length measured by ultrasound and elevated cervical fluid phIGFBP-1 both predicted premature delivery. In summary, because of the relatively low sensitivity of cervical fluid phIGFBP-1 this biomarker is not suitable for routine screening, but provides an additional tool in assessing the risk of preterm delivery. Cervical fluid MMP-8 is not useful in early or mid pregnancy in predicting premature delivery because of its dual role. Further studies on the role of MMP-8 are therefore needed. Our study confirms that phIGFBP-1 testing is useful in predicting pre-term delivery.

Serial Changes in Markers Measuring Coagulation, Fibrinolysis, and Vasoactivity in Patients with Ischemic Stroke

Ischemic stroke (IS) is a heterogeneous disease in which outcome is influenced by many factors. The hemostatic system is activated in association with cerebral ischemia, and thus, markers measuring coagulation, fibrinolysis, and vasoactivity could be useful tools in clinical practice. We investigated whether repeated measurements of these markers reveal patterns that might help in evaluating IS patients, including the early diagnosis of stroke subtypes, in estimating prognosis and risk of recurrence, and in selecting a treatment for secondary prevention of stroke. Vasoconstrictor peptide endothelin-1 (ET-1), homocysteine (Hcy), indicators of thrombin formation and activation (prothrombin fragment 1+2/F1+2, thrombin-antithrombin complex/TAT), indicators of plasmin formation and fibrinolysis (tissue plasminogen activator/t-PA, plasminogen activator inhibitor-1/PAI-1, and D-dimer), and natural anticoagulants (antithrombin/AT, protein C/PC, and protein S/PS) were measured in 102 consecutive mild to moderate IS patients on four occasions: on admission and at 1 week, 1 month, and 3 months after stroke, and once in controls. All patients underwent neurological examination and blood sampling in the same session. Furthermore, 42 IS patients with heterozygous factor V Leiden mutation (FVLm) were selected from 740 IS patients without an obvious etiology, and evaluated in detail for specific clinical, laboratory, and radiological features. Measurements of ET-1 and Hcy levels did not disclose information that could aid in the diagnostic evaluation of IS patients. F1+2 level at 3 months after IS had a positive correlation with recurrence of thromboembolic events, and thus, may be used as a predictive marker of subsequent cerebral events. The D-dimer and AT levels on admission and 1 week after IS were strongly associated with stroke severity, outcome, and disability. The specific analysis of IS patients with FVLm more often revealed a positive family history of thrombosis, a higher prevalence of peripheral vascular disease, and multiple infarctions in brain images, most of which were `silent infarcts´. Results of this study support the view that IS patients with sustained activation of both the fibrinolytic and the coagulation systems and increased thrombin generation may have an unfavorable prognosis. The level of activation may reflect the ongoing thrombotic process and the extent of thrombosis. Changes in these markers could be useful in predicting prognosis of IS patients. A clear need exists for a randomized prospective study to determine whether a subgroup of IS patients with markers indicating activation of fibrinolytic and coagulation systems might benefit from more aggressive secondary prevention of IS.

Detection and progression of chronic allograft nephropathy : A study based on protocol biopsies

Background. Kidney transplantation (KTX) is considered to be the best treatment of terminal uremia. Despite improvements in short-term graft survival, a considerable number of kidney allografts are lost due to the premature death of patients with a functional kidney and to chronic allograft nephropathy (CAN). Aim. To investigate the risk factors involved in the progression of CAN and to analyze diagnostic methods for this entity. Materials and methods. Altogether, 153 implant and 364 protocol biopsies obtained between June 1996 and April 2008 were analyzed. The biopsies were classified according to Banff ’97 and chronic allograft damage index (CADI). Immunohistochemistry for TGF-β1 was performed in 49 biopsies. Kidney function was evaluated by creatinine and/or cystatin C measurement and by various estimates of glomerular filtration rate (GFR). Demographic data of the donors and recipients were recorded after 2 years’ follow-up. Results. Most of the 3-month biopsies (73%) were nearly normal. The mean CADI score in the 6-month biopsies decreased significantly after 2001. Diastolic hypertension correlated with ΔCADI. Serum creatinine concentration at hospital discharge and glomerulosclerosis were risk factors for ΔCADI. High total and LDL cholesterol, low HDL and hypertension correlated with chronic histological changes. The mean age of the donors increased from 41 -52 years. Older donors were more often women who had died from an underlying disease. The prevalence of delayed graft function increased over the years, while acute rejections (AR) decreased significantly over the years. Sub-clinical AR was observed in 4% and it did not affect long-term allograft function or CADI. Recipients´ drug treatment was modified along the Studies, being mycophenolate mophetil, tacrolimus, statins and blockers of the renine-angiotensin-system more frequently prescribed after 2001. Patients with a higher ΔCADI had lower GFR during follow-up. CADI over 2 was best predicted by creatinine, although with modest sensitivity and specificity. Neither cystatin C nor other estimates of GFR were superior to creatinine for CADI prediction. Cyclosporine A toxicity was seldom seen. Low cyclosporin A concentration after 2 h correlated with TGF- β1 expression in interstitial inflammatory cells, and this predicted worse graft function. Conclusions. The progression of CAN has been affected by two major factors: the donors’ characteristics and the recipients’ hypertension. The increased prevalence of DGF might be a consequence of the acceptance of older donors who had died from an underlying disease. Implant biopsies proved to be of prognostic value, and they are essential for comparison with subsequent biopsies. The progression of histological damage was associated with hypertension and dyslipidemia. The augmented expression of TGF-β1 in inflammatory cells is unclear, but it may be related to low immunosuppression. Serum creatinine is the most suitable tool for monitoring kidney allograft function on every-day basis. However, protocol biopsies at 6 and 12 months predicted late kidney allograft dysfunction and affected the clinical management of the patients. Protocol biopsies are thus a suitable surrogate to be used in clinical trials and for monitoring kidney allografts.