Scrum-prosessimallin käyttöliittymäriskien minimointi simulointipohjaisella GDD-käyttöliittymäsuunnittelumenetelmällä

Scrum-prosessimalli jättää menettelyt ohjelmiston käyttöliittymän tuottamiseen auki ja käyttöliittymä syntyy pahimmillaan toimintolistan pohjalta ohjelmoinnin sivutuotteena. Näin syntynyt järjestelmä soveltuu suurella riskillä huonosti käyttötarkoitukseensa. Tässä tutkielmassa analysoitiin Scrum-prosessimallin käyttöliittymäriskikohtia, joita löytyi kolme: asiakkaan toivomat ominaisuudet päätyvät sellaisinaan ohjelmiston vaatimuksiksi, toimintolistan pohjalta syntyy käytettävyydeltään heikkoja käyttöliittymäratkaisuja ja käyttöliittymän arviointi sprintin katselmoinnissa tuottaa epäluotettavia tuloksia. Tutkielmassa käsitellään Scrum-prosessimallin käyttöliittymäriskien minimointia simulointipohjaisella GDD-käyttöliittymäsuunnittelulla. Riskien minimointia tarkastellaan esimerkkitapauksen avulla, jossa ohjelmistoyritys Reaktor toteutti ammattikorkeakoulun toiminnansuunnittelujärjestelmän vuosisuunnitteluosion. Esimerkkitapauksessa Scrumin käyttöliittymäriskit saatiin minimoitua selvittämällä loppukäyttäjien käyttötilanteet kontekstuaalisilla haastatteluilla, suunnittelemalla käyttöliittymä GDD-menetelmällä ja arvioimalla käyttöliittymää hyödyllisyysläpikäynneillä. Alkuperäisessä Scrumissa liiketoiminnallisesta kannattavuudesta vastaava tuotteen omistaja ja toteutustiimi ottavat vastuulleen myös käyttöliittymän toimintalogiikan. GDD:n myötä vastuu toimintalogiikasta siirretään käyttöliittymäsuunnittelijalle, jolloin Scrumin roolit muuttuvat. Tässä työssä käsitellään GDD-käyttöliittymäsuunnittelun tuomat muutokset Scrumin rooleihin ja käytäntöihin. Scrumin käyttöliittymäriskien minimoinnin jälkeen toteutusvaiheeseen jää vielä Scrumista riippumattomia käyttöliittymäriskejä. Tämän työn esimerkkitapauksessa keskeisin näistä oli käyttöliittymätoteutukseen päätyneet puutteelliset interaktiot. Riski eliminoitiin hyväksymismenettelyllä, jossa ohjelmoija antaa toteutetun ominaisuuden käyttöliittymäsuunnittelijalle tarkistettavaksi. Hyväksymismenettelyn avulla projektin työnjako selkiytyi, toteutustyön laatu parani ja toteutustiimin ja käyttöliittymäsuunnittelijoiden välinen kommunikaatio tehostui.

Korkean käytettävyyden klusterointiteknologioiden vertailu

Tutkielma käsittelee korkean käytettävyyden klustereita. Tavoitteena on vertailla eri klusteriteknologioiden eroja ja arvioida tulosten perusteella sopivia käyttökohteita eri klusterituotteille. Samoja funktioita tarjoavat eri klusterituotteet asetetaan paremmuusjärjestykseen. Arviointi perustuu erilaisiin määrällisiin arvoihin, kuten solmulaitteiden maksimilukumäärä, sekä laadullisiin arvoihin, kuten käyttöönoton ja hallinnoinnin helppous. Erityisesti tavoitteena on tuoda esille eri tuotteiden vahvuuksia ja heikkouksia. Vertailtavia tuotteita ovat Microsoft Cluster Service (MSCS), TruCluster Server for Tru64 UNIX, Steeleye Lifekeeper for Windows ja Sun Cluster. ACM Computing Classification System (CSS): D.4 OPERATING SYSTEMS (C) D.4.5 Reliability

Turvetuotannon luvallistaminen muuttuvassa ympäristössä

Työssä tutkitaan turvetuotannon luvallistamiskysymyksiä luonnonsuojelullisten ja luonnonvarojen käyttöä korostavien tavoitteiden kohtauspinnassa. Tutkielman metodiksi on valikoitunut avoin, keskustelukeskeinen lähestymistapa, joka osoittautui sopivan hyvin tieteellisen tutkimuksen välineeksi. Erityisiä oikeuslähdeopillisia kysymyksiä tarkastellaan tutkimuksessa vain niiltä osin kuin työn muut osat sitä vaativat. Siksi yksittäisiä oikeuslähdeopillisia kysymyksiä ei oteta esille tutkimuksessa kattavasti. Ensimmäisessä varsinaisessa tutkimusjaksossa keskistytään lainsäädäntöhistoriaan. Lainsäädäntöhistoriasta oli löydettävissä sekä luonnonsuojelua että luonnonvarojen käyttämistä tukevia argumentteja, joiden sisältö voidaan melkein suoraan siirtää nykyiseen keskusteluun. Ennen kuin työssä siirrytään varsinaiseen tuotannon luvallistamisen käsittelyyn, siinä luodaan lyhyt katsaus ympäristövaikutusten arviointimenettelyn asemaan. Menettelyllä ei ole laajaa käyttöä turveteollisuudessa. Turveteollisuuden luvallistamiskysymyksiä käsitellään tutkimuksessa kolmessa eri kokonaisuudessa. Ensimmäisessä näistä hahmotetaan luvallistamista alueellisena ja ajallisena kokonaisuutena. Hahmotustapa osoittautui käyttökelpoiseksi ja hyvin turveteollisuuden todellisia oikeudellisia ongelmakohtia vastaavaksi. Keskimmäisessä luvallistamiskysymyksiä tarkastelevista jaksoista keskitytään ajankohtaiseen ongelmaan ilmaston lämpenemisestä. Jaksossa tarkastellaan teoreettista mahdollisuutta huomioida lupamenettelyssä toiminnan vaikutukset ilmastonmuutokselle. Erityisesti tässä jaksossa painottuu tutkimuksen metodin soveltaminen, jonka avulla voidaan ratkaista suhtautuminen tuotannosta esitettyihin, jopa vastakohtaisiin luonnontieteellisiin väitteisiin. Tarkastelussa päädytään siihen, että yksi mahdollinen tulkinta voimassaolevan oikeuden sisällöstä on toiminnan ilmastovaikutusten huomioiminen ympäristölupaharkinnassa. Viimeisimmässä tuotannon luvallistamista käsittelevässä jaksossa tutkimuskohteena on joitain toiminnan osia, joille edellytetään vesilain mukaista lupaa. Tässä jaksossa tutkimuskohteen rajaaminen osoittautui erityisen tärkeäksi, koska vaihtoehtoja tutkimuskohteiksi oli tarjolla runsaasti. Tutkimusalueeseen kuuluvat luvallistamiskysymykset, jotka tulivat vahvimmin esille työn aluksi tehdyissä haastatteluissa. Rajaamalla tutkimuskohde tällä perusteella pysytellään mahdollisimman tiiviisti alkuperäisessä tutkimusasetelmassa. Työn lopuksi käsitellään luvallistamisen suhdetta kaavoitukseen, nimenomaan maakuntakaavoihin ja valtakunnallisiin alueidenkäyttötavoitteisiin, joilla pyritään sääntelemään tuotantoa. Lyhyen katsauksen perusteella päätelmänä on instrumenttien vähäinen tosiasiallinen merkitys.

How terrorist campaigns end : The Rode Jeugd in the Netherlands and the Symbionese Liberation Army in the United States

This study explores the decline of terrorism by conducting source-based case studies on two left-wing terrorist campaigns in the 1970s, those of the Rode Jeugd in the Netherlands and the Symbionese Liberation Army in the United States. The purpose of the case studies is to bring more light into the interplay of different external and internal factors in the development of terrorist campaigns. This is done by presenting the history of the two chosen campaigns as narratives from the participants’ points of view, based on interviews with participants and extensive archival material. Organizational resources and dynamics clearly influenced the course of the two campaigns, but in different ways. This divergence derives at least partly from dissimilarities in organizational design and the incentive structure. Comparison of even these two cases shows that organizations using terrorism as a strategy can differ significantly, even when they share ideological orientation, are of the same size and operate in the same time period. Theories on the dynamics of terrorist campaigns would benefit from being more sensitive to this. The study also highlights that the demise of a terrorist organization does not necessarily lead to the decline of the terrorist campaign. Therefore, research should look at the development of terrorist activity beyond the lifespan of a single organization. The collective ideological beliefs and goals functioned primarily as a sustaining force, a lens through which the participants interpreted all developments. On the other hand, it appears that the role of ideology should not be overstated. Namely, not all participants in the campaigns under study fully internalized the radical ideology. Rather, their participation was mainly based on their friendship with other participants. Instead of ideology per se, it is more instructive to look at how those involved described their organization, themselves and their role in the revolutionary struggle. In both cases under study, the choice of the terrorist strategy was not merely a result of a cost-benefit calculation, but an important part of the participants’ self-image. Indeed, the way the groups portrayed themselves corresponded closely with the forms of action that they got involved in. Countermeasures and the lack of support were major reasons for the decline of the campaigns. However, what is noteworthy is that the countermeasures would not have had the same kind of impact had it not been for certain weaknesses of the groups themselves. Moreover, besides the direct impact the countermeasures had on the campaign, equally important was how they affected the attitudes of the larger left-wing community and the public in general. In this context, both the attitudes towards the terrorist campaign and the authorities were relevant to the outcome of the campaigns.

Environmental effects of thermal and radioactive discharges from nuclear power plants in the boreal brackish-water conditions of the northern Baltic Sea

During recent decades, thermal and radioactive discharges from nuclear power plants into the aquatic environment have become the subject of lively debate as an ecological concern. The target of this thesis was to summarize the large quantity of results obtained in extensive monitoring programmes and studies carried out in recipient sea areas off the Finnish nuclear power plants at Loviisa and Olkiluoto during more than four decades. The Loviisa NPP is located on the coast of the Gulf of Finland and Olkiluoto NPP on that of the Bothnian Sea. The state of the Gulf of Finland is clearly more eutrophic; the nutrient concentrations in the surface water are about 1½ 2 times higher at Loviisa than at Olkiluoto, and the total phosphorus concentrations still increased in both areas (even doubled at Loviisa) between the early 1970s and 2000. Thus, it is a challenge to distinguish the local effects of thermal discharges from the general eutrophication process of the Gulf of Finland. The salinity is generally low in the brackish-water conditions of the northern Baltic Sea, being however about 1 higher at Olkiluoto than at Loviisa (the salinity of surface water varying at the latter from near to 0 in early spring to 4 6 in late autumn). Thus, many marine and fresh-water organisms live in the Loviisa area close to their limit of existence, which makes the biota sensitive to any additional stress. The characteristics of the discharge areas of the two sites differ from each other in many respects: the discharge area at Loviisa is a semi-enclosed bay in the inner archipelago, where the exchange of water is limited, while the discharge area at Olkiluoto is more open, and the exchange of water with the open Bothnian Sea is more effective. The effects of the cooling water discharged from the power plants on the temperatures in the sea were most obvious in winter. The formation of a permanent ice cover in the discharge areas has been delayed in early winter, and the break-up of the ice occurs earlier in spring. The prolonging of the growing season and the disturbance of the overwintering time, in conditions where the biota has adjusted to a distinct rest period in winter, have been the most significant biological effects of the thermal pollution. The soft-bottom macrofauna at Loviisa has deteriorated to the point of almost total extinction at many sampling stations during the past 40 years. A similar decline has been reported for the whole eastern Gulf of Finland. However, the local eutrophication process seems to have contributed into the decline of the zoobenthos in the discharge area at Loviisa. Thermal discharges have increased the production of organic matter, which again has led to more organic bottom deposits. These have in turn increased the tendency of the isolated deeps to a depletion of oxygen, and this has further caused strong remobilization of phosphorus from the bottom sediments. Phytoplankton primary production and primary production capacity doubled in the whole area between the late 1960s and the late 1990s, but started to decrease a little at the beginning of this century. The focus of the production shifted from spring to mid- and late summer. The general rise in the level of primary production was mainly due to the increase in nutrient concentrations over the whole Gulf of Finland, but the thermal discharge contributed to a stronger increase of production in the discharge area compared to that in the intake area. The eutrophication of littoral vegetation in the discharge area has been the most obvious, unambiguous and significant biological effect of the heated water. Myriophyllum spicatum, Potamogeton perfoliatus and Potamogeton pectinatus, and vigorous growths of numerous filamentous algae as their epiphytes have strongly increased in the vicinity of the cooling water outlet, where they have formed dense populations in the littoral zone in late summer. However, the strongest increase of phytobenthos has extended only to a distance of about 1 km from the outlet, i.e., the changes in vegetation have been largest in those areas that remain ice-free in winter. Similar trends were also discernible at Olkiluoto, but to a clearly smaller extent, which was due to the definitely weaker level of background eutrophy and nutrient concentrations in the Bothnian Sea, and the differing local hydrographical and biological factors prevailing in the Olkiluoto area. The level of primary production has also increased at Olkiluoto, but has remained at a clearly lower level than at Loviisa. In spite of the analogous changes observed in the macrozoobenthos, the benthic fauna has remained strong and diversified in the Olkiluoto area. Small amounts of local discharge nuclides were regularly detected in environmental samples taken from the discharge areas: tritium in seawater samples, and activation products, such as 60Co, 58Co, 54Mn, 110mAg, 51Cr, in suspended particulate matter, bottom sediments and in several indicator organisms (e.g., periphyton and Fucus vesiculosus) that effectively accumulate radioactive substances from the medium. The tritium discharges and the consequent detection frequency and concentrations of tritium in seawater were higher at Loviisa, but the concentrations of the activation products were higher at Olkiluoto, where traces of local discharge nuclides were also observed over a clearly wider area, due to the better exchange of water than at Loviisa, where local discharge nuclides were only detected outside Hästholmsfjärden Bay quite rarely and in smaller amounts. At the farthest, an insignificant trace amount (0.2 Bq kg-1 d.w.) of 60Co originating from Olkiluoto was detected in Fucus at a distance of 137 km from the power plant. Discharge nuclides from the local nuclear power plants were almost exclusively detected at the lower trophic levels of the ecosystems. Traces of local discharge nuclides were very seldom detected in fish, and even then only in very low quantities. As a consequence of the reduced discharges, the concentrations of local discharge nuclides in the environment have decreased noticeably in recent years at both Loviisa and Olkiluoto. Although the concentrations in environmental samples, and above all, the discharge data, are presented as seemingly large numbers, the radiation doses caused by them to the population and to the biota are very low, practically insignificant. The effects of the thermal discharges have been more significant, at least to the wildlife in the discharge areas of the cooling water, although the area of impact has been relatively small. The results show that the nutrient level and the exchange of water in the discharge area of a nuclear power plant are of crucial importance.

Study of sleep and evaluation of sumatriptan and rizatriptan in the acute treatment of migraine in children and adolescents

Migraine is a common disease in children and adolescents, affecting roughly 10% of school-aged children. Recent studies have revealed an increasing incidence of childhood migraine, but migraine remains an underrecognized and undertreated condition in the pediatric population. Migraine attacks are painful and disabling and can affect a child´s life in many ways. Effective drug treatment is usually needed. The new migraine drugs, triptans, were introduced at the beginning of the 1990s and have since been shown to be very effective in the treatment of migraine attacks in adults. Although they are widely used in adults, the acute treatment of migraine in children and adolescents is still based on paracetamol and nonsteroidal anti-inflammatory drugs. Some children can control their attacks satisfactorily with simple analgesics, but at least one-third need more powerful treatments. When this thesis work commenced, hardly any information existed on the efficacy and safety of triptans in children. The study aim of the thesis was to identify more efficient treatments of migraine for children and adolescents by investigating the efficacy of sumatriptan nasal spray and oral rizatriptan compared with placebo in them. Sleep has an impact on migraine in many aspects. Despite the clinical relevance and common manifestation of sleep in the context of migraine in children, very little research data on the true frequency of sleep exist. As sleeping is so often related to childhood migraine, it can be a confounding factor in clinical drug trials of migraine treatments in children and adolescents. How the results of a sleeping child should be analyzed is under continual debate. The aim of the thesis was also to clarify this as well as to evaluate the frequency of sleeping during migraine attacks in children and factors affecting frequency. Both nasal sumatriptan and oral rizatriptan were effective (superior to placebo), and well tolerated in treatment of migraine attacks in children and adolescents aged 8-17 and 6-17 years, respectively. No serous adverse effects were observed. The results of this work suggest that nasal sumatriptan 20 mg and rizatriptan 10 mg can be effectively and safely used to treat migraine attacks in adolescents aged over 12 years if more effective drugs than NSAIDs are needed. No difference was observed in efficacy or safety of nasal sumatriptan and rizatriptan between children aged younger than 12 years and older children, but because the treated number of patients under 12 years is still small, more studies are needed before sumatriptan or rizatriptan can be recommended for use in this population. Sleeping during migraine attacks was very common, and most children at least occasionally slept during an attack. Falling asleep was especially common in children under eight years of age and during the first hour after the onset of attack. Children who were able to sleep soon after attack onset were more likely pain-free at two hours. Sleeping probably both improves recovery from a migraine attack and is a sign of headache relief. Falling asleep should be classified as a sign of headache relief in clinical drug trials when studying migraine treatments in children and adolescents.

Novel surgical and imaging methods of the middle ear and temporal bone

Välikorvaleikkauksiin usein liittyvän välikorvan ja kuuloluuketjun kirurgisen rekonstruktion tavoitteena on luoda olosuhteet, jotka mahdollistavat hyvän kuulon sekä välikorvan säilymisen tulehduksettomana ja ilmapitoisena. Välikorvan rekonstruktiossa on käytetty implanttimateriaaleina perinteisesti potilaan omia kudoksia sekä tarvittaessa erilaisia hajoamattomia biomateriaaleja, mm. titaania ja silikonia. Ongelmana biomateriaalien käytössä voi olla bakteerien adherenssi eli tarttuminen vieraan materiaalin pintaan, mikä saattaa johtaa biofilmin muodostumiseen. Tämä voi aiheuttaa kroonisen, huonosti antibiootteihin reagoivan infektion kudoksessa, mikä usein käytännössä johtaa uusintaleikkaukseen ja implantin poistoon. Maitohappo- ja glykolihappopohjaiset biologisesti hajoavat polymeerit ovat olleet kliinisessä käytössä jo vuosikymmeniä. Niitä on käytetty erityisesti tukimateriaaleina mm. ortopediassa sekä kasvo- ja leukakirurgiassa. Niitä ei ole toistaiseksi käytetty välikorvakirurgiassa. Korvan kuvantamiseen käytetään ensisijaisesti tietokonetomografiaa (TT). TT-tutkimuksen ongelmana on potilaan altistuminen suhteellisen korkealle sädeannokselle, joka kasvaa kumulatiivisesti, jos kuvaus joudutaan toistamaan. Väitöskirjatyö selvittää uuden, aiemmin kliinisessä työssä rutiinisti lähinnä hampaiston ja kasvojen alueen kuvantamiseen käytetyn rajoitetun kartiokeila-TT:n soveltuvuutta korvan alueen kuvantamiseen. Väitöskirjan kahdessa ensimmäisessä osatyössä tutkittiin ja verrattiin kahden kroonisia ja postoperatiivisia korvainfektioita aiheuttavan bakteerin, Staphylococcus aureuksen ja Pseudomonas aeruginosan, in vitro adherenssia titaanin, silikonin ja kahden eri biohajoavan polymeerin (PLGA) pintaan. Lisäksi tutkittiin materiaalien albumiinipinnoituksen vaikutusta adherenssiin. Kolmannessa osatyössä tutkittiin eläinmallissa PLGA:n biokompatibiliteettia eli kudosyhteensopivuutta kokeellisessa välikorvakirurgiassa. Chinchillojen välikorviin istutettiin PLGA-materiaalia, eläimiä seurattiin, ja ne lopetettiin 6 kk:n kuluttua operaatiosta. Biokompatibiliteetin arviointi perustui kliinisiin havaintoihin sekä kudosnäytteisiin. Neljännessä osatyössä tutkittiin kartiokeila-TT:n soveltuvuutta korvan alueen kuvantamiseen vertaamalla sen tarkkuutta perinteisen spiraali-TT:n tarkkuuteen. Molemmilla laitteilla kuvattiin ohimo- eli temporaaliluita korvan alueen kliinisesti ja kirurgisesti tärkeiden rakenteiden kuvantumisen tarkkuuden arvioimiseksi. Viidennessä osatyössä arvioitiin myös operoitujen temporaaliluiden kuvantumista kartiokeila-TT:ssa. Bakteeritutkimuksissa PLGA-materiaalin pintaan tarttui keskimäärin korkeintaan saman verran tai vähemmän bakteereita kuin silikonin tai titaanin. Albumiinipinnoitus vähensi bakteeriadherenssia merkitsevästi kaikilla materiaaleilla. Eläinkokeiden perusteella PLGA todettiin hyvin siedetyksi välikorvassa. Korvakäytävissä tai välikorvissa ei todettu infektioita, tärykalvon perforaatioita tai materiaalin esiin työntymistä. Kudosnäytteissä näkyi lievää tulehdusreaktiota ja fibroosia implantin ympärillä. Temporaaliluutöissä rajoitettu kartiokeila-TT todettiin vähintään yhtä tarkaksi menetelmäksi kuin spiraali-TT välikorvan ja sisäkorvan rakenteiden kuvantamisessa, ja sen aiheuttama kertasäderasitus todettiin spiraali-TT:n vastaavaa huomattavasti vähäisemmäksi. Kartiokeila-TT soveltui hyvin välikorvaimplanttien ja postoperatiivisen korvan kuvantamiseen. Tulokset osoittavat, että PLGA on välikorvakirurgiaan soveltuva, turvallinen ja kudosyhteensopiva biomateriaali. Biomateriaalien pinnoittaminen albumiinilla vähentää merkittävästi bakteeriadherenssia niihin, mikä puoltaa pinnoituksen soveltamista implanttikirurgiassa. Kartiokeila-TT soveltuu korvan alueen kuvantamiseen. Sen tarkkuus kliinisesti tärkeiden rakenteiden osoittamisessa on vähintään yhtä hyvä ja sen potilaalle aiheuttama sädeannos pienempi kuin nykyisen korva-spiraali-TT:n. Tämä tekee menetelmästä spiraali-TT:aa potilasturvallisemman vaihtoehdon erityisesti, jos potilaan tilanne vaatii seurantaa ja useampia kuvauksia, ja jos halutaan kuvata rajoitettuja alueita uni- tai bilateraalisesti.

Determinants of outcome in critically ill patients

Assessment of the outcome of critical illness is complex. Severity scoring systems and organ dysfunction scores are traditional tools in mortality and morbidity prediction in intensive care. Their ability to explain risk of death is impressive for large cohorts of patients, but insufficient for an individual patient. Although events before intensive care unit (ICU) admission are prognostically important, the prediction models utilize data collected at and just after ICU admission. In addition, several biomarkers have been evaluated to predict mortality, but none has proven entirely useful in clinical practice. Therefore, new prognostic markers of critical illness are vital when evaluating the intensive care outcome. The aim of this dissertation was to investigate new measures and biological markers of critical illness and to evaluate their predictive value and association with mortality and disease severity. The impact of delay in emergency department (ED) on intensive care outcome, measured as hospital mortality and health-related quality of life (HRQoL) at 6 months, was assessed in 1537 consecutive patients admitted to medical ICU. Two new biological markers were investigated in two separate patient populations: in 231 ICU patients and 255 patients with severe sepsis or septic shock. Cell-free plasma DNA is a surrogate marker of apoptosis. Its association with disease severity and mortality rate was evaluated in ICU patients. Next, the predictive value of plasma DNA regarding mortality and its association with the degree of organ dysfunction and disease severity was evaluated in severe sepsis or septic shock. Heme oxygenase-1 (HO-1) is a potential regulator of apoptosis. Finally, HO-1 plasma concentrations and HO-1 gene polymorphisms and their association with outcome were evaluated in ICU patients. The length of ED stay was not associated with outcome of intensive care. The hospital mortality rate was significantly lower in patients admitted to the medical ICU from the ED than from the non-ED, and the HRQoL in the critically ill at 6 months was significantly lower than in the age- and sex-matched general population. In the ICU patient population, the maximum plasma DNA concentration measured during the first 96 hours in intensive care correlated significantly with disease severity and degree of organ failure and was independently associated with hospital mortality. In patients with severe sepsis or septic shock, the cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA was an independent predictor for ICU mortality, but not for hospital mortality. The degree of organ dysfunction correlated independently with plasma DNA concentration in severe sepsis and plasma HO-1 concentration in ICU patients. The HO-1 -413T/GT(L)/+99C haplotype was associated with HO-1 plasma levels and frequency of multiple organ dysfunction. Plasma DNA and HO-1 concentrations may support the assessment of outcome or organ failure development in critically ill patients, although their value is limited and requires further evaluation.

Randomised Evaluation of New Technologies within the Population‐Based Cervical Cancer Screening Programme in Finland: Cross‐Sectional Performance and Validity

A randomised and population-based screening design with new technologies has been applied to the organised cervical cancer screening programme in Finland. In this experiment the women invited to routine five-yearly screening are individually randomised to be screened with automation-assisted cytology, human papillomavirus (HPV) test or conventional cytology. By using the randomised design, the ultimate aim is to assess and compare the long-term outcomes of the different screening regimens. The primary aim of the current study was to evaluate, based on the material collected during the implementation phase of the Finnish randomised screening experiment, the cross-sectional performance and validity of automation-assisted cytology (Papnet system) and primary HPV DNA testing (Hybrid Capture II assay for 13 oncogenic HPV types) within service screening, in comparison to conventional cytology. The parameters of interest were test positivity rate, histological detection rate, relative sensitivity, relative specificity and positive predictive value. Also, the effect of variation in performance by screening laboratory on age-adjusted cervical cancer incidence was assessed. Based on the cross-sectional results, almost no differences were observed in the performance of conventional and automation-assisted screening. Instead, primary HPV screening found 58% (95% confidence interval 19-109%) more cervical lesions than conventional screening. However, this was mainly due to overrepresentation of mild- and moderate-grade lesions and, thus, is likely to result in overtreatment since a great deal of these lesions would never progress to invasive cancer. Primary screening with an HPV DNA test alone caused substantial loss in specificity in comparison to cytological screening. With the use of cytology triage test, the specificity of HPV screening improved close to the level of conventional cytology. The specificity of primary HPV screening was also increased by increasing the test positivity cutoff from the level recommended for clinical use, but the increase was more modest than the one gained with the use of cytology triage. The performance of the cervical cancer screening programme varied widely between the screening laboratories, but the variation in overall programme effectiveness between respective populations was more marginal from the very beginning of the organised screening activity. Thus, conclusive interpretations on the quality or success of screening should not be based on performance parameters only. In the evaluation of cervical cancer screening the outcome should be selected as closely as possible to the true measure of programme effectiveness, which is the number of invasive cervical cancers and subsequent deaths prevented in the target population. The evaluation of benefits and adverse effects of each new suggested screening technology should be performed before the technology becomes an accepted routine in the existing screening programme. At best, the evaluation is performed randomised, within the population and screening programme in question, which makes the results directly applicable to routine use.

Predictors of violent reconvictions and mortality among impulsive alcoholic violent offenders: A prospective study

Acts of violence lays a great burden on humankind. The negative effects of violence could be relieved by accurate prediction of violent recidivism. However, prediction of violence has been considered an inexact science hampered by scare knowledge of its causes. The study at hand examines risk factors of violent reconvictions and mortality among 242 Finnish male violent offenders exhibiting severe alcoholism and severe externalizing personality disorders. The violent offenders were recruited during a court-ordered 2-month inpatient mental status examination between 1990—1998. Controls were 1210 individuals matched by sex-, age-, and place of birth. After a 9-year non-incarcerated follow-up criminal register and mortality data were obtained from national registers. Risk analyses were applied to estimate odds and relative risk for recidivism and mortality. Risk variables that were included in the analyses were antisocial personality disorder (ASPD), borderline personality disorder (BPD), a comorbidity of ASPD and BPD, childhood adversities, alcohol consumption, age, and monoamine oxidase A (MAOA) genotype. In addition to risk analyses, temperament dimensions (Tridimensional Personality Questionnaire [TPQ]) were assessed. The prevalence of recidivistic acts of violence (32%) and mortality (16%) was high among the offenders. Severe personality disorders and childhood adversities increased the risk for recidivism and mortality both among offenders (OR 2.0–10.4) and in comparison between offenders and controls (RR 4.3–53.0). Offenders having BPD and a history of childhood maltreatment emerged as a group with a particularly poor prognosis. MAOA altered the effects of alcohol consumption and ageing. Alcohol consumption (+2.3%) and age (–7.3%) showed significant effects on the risk for violent reconvictions among the high activity MAOA (MAOA-H) offenders, but not among the low activity MAOA (MAOA-L) offenders. The offenders featured temperament dimensions of high novelty seeking, high harm avoidance, and low reward dependence matching Cloninger’s definition of explosive personality. The fact that the risk for recidivistic acts of violence and mortality accumulated into clearly defined subgroups supports future efforts to provide for evidence based violence prevention and risk assessments among violent offenders.

Acute renal failure in critically ill patients : With special reference to prediction of outcome

Acute renal failure (ARF) is a clinical syndrome characterized by rapidly decreasing glomerular filtration rate, which results in disturbances in electrolyte- and acid-base homeostasis, derangement of extracellular fluid volume, and retention of nitrogenous waste products, and is often associated with decreased urine output. ARF affects about 5-25% of patients admitted to intensive care units (ICUs), and is linked to high mortality and morbidity rates. In this thesis outcome of critically ill patients with ARF and factors related to outcome were evaluated. A total of 1662 patients from two ICUs and one acute dialysis unit in Helsinki University Hospital were included. In study I the prevalence of ARF was calculated and classified according to two ARF-specific scoring methods, the RIFLE classification and the classification created by Bellomo et al. (2001). Study II evaluated monocyte human histocompatibility leukocyte antigen-DR (HLA-DR) expression and plasma levels of one proinflammatory (interleukin (IL) 6) and two anti-inflammatory (IL-8 and IL-10) cytokines in predicting survival of critically ill ARF patients. Study III investigated serum cystatin C as a marker of renal function in ARF and its power in predicting survival of critically ill ARF patients. Study IV evaluated the effect of intermittent hemodiafiltration (HDF) on myoglobin elimination from plasma in severe rhabdomyolysis. Study V assessed long-term survival and health-related quality of life (HRQoL) in ARF patients. Neither of the ARF-specific scoring methods presented good discriminative power regarding hospital mortality. The maximum RIFLE score for the first three days in the ICU was an independent predictor of hospital mortality. As a marker of renal dysfunction, serum cystatin C failed to show benefit compared with plasma creatinine in detecting ARF or predicting patient survival. Neither cystatin C nor plasma concentrations of IL-6, IL-8, and IL-10, nor monocyte HLA-DR expression were clinically useful in predicting mortality in ARF patients. HDF may be used to clear myoglobin from plasma in rhabdomyolysis, especially if the alkalization of diuresis does not succeed. The long-term survival of patients with ARF was found to be poor. The HRQoL of those who survive is lower than that of the age- and gender-matched general population.

Detection of renal dysfunction during and after anaesthesia and surgery - evaluation of the influence of inorganic fluoride, ketorolac and clonidine

Drugs and surgical techniques may have harmful renal effects during the perioperative period. Traditional biomarkers are often insensitive to minor renal changes, but novel biomarkers may more accurately detect disturbances in glomerular and tubular function and integrity. The purpose of this study was first, to evaluate the renal effects of ketorolac and clonidine during inhalation anesthesia with sevoflurane and isoflurane, and secondly, to evaluate the effect of tobacco smoking on the production of inorganic fluoride (F-) following enflurane and sevoflurane anesthesia as well as to determine the effect of F- on renal function and cellular integrity in surgical patients. A total of 143 patients undergoing either conventional (n = 75) or endoscopic (n = 68) inpatient surgery were enrolled in four studies. The ketorolac and clonidine studies were prospective, randomized, placebo controlled and double-blinded, while the cigarette smoking studies were prospective cohort studies with two parallel groups. As a sign of proximal tubular deterioration, a similar transient increase in urine N-acetyl-beta-D-glucosaminidase/creatinine (U-NAG/crea) was noted in both the ketorolac group and in the controls (baseline vs. at two hours of anesthesia, p = 0.015) with a 3.3 minimum alveolar concentration hour sevoflurane anesthesia. Uncorrelated U-NAG increased above the maximum concentration measured from healthy volunteers (6.1 units/l) in 5/15 patients with ketorolac and in none of the controls (p = 0.042). As a sign of proximal tubular deterioration, U-glutathione transferase-alpha/crea (U-GST-alpha/crea) increased in both groups at two hours after anesthesia but a more significant increase was noted in the patients with ketorolac. U-GST-alpha/crea increased above the maximum ratio measured from healthy volunteers in 7/15 patients with ketorolac and in 3/15 controls. Clonidine diminished the activation of the renin-angiotensin aldosterone system during pneumoperitoneum; urine output was better preserved in the patients treated with clonidine (1/15 patients developed oliguria) than in the controls (8/15 developed oliguria (p=0.005)). Most patients with pneumoperitoneum and isoflurane anesthesia developed a transient proximal tubular deterioration, as U-NAG increased above 6.1 units/L in 11/15 patients with clonidine and in 7/15 controls. In the patients receiving clonidine treatment, the median of U-NAG/crea was higher than in the controls at 60 minutes of pneumoperitoneum (p = 0.01), suggesting that clonidine seems to worsen proximal tubular deterioration. Smoking induced the metabolism of enflurane, but the renal function remained intact in both the smokers and the non-smokers with enflurane anesthesia. On the contrary, smoking did not induce sevoflurane metabolism, but glomerular function decreased in 4/25 non-smokers and in 7/25 smokers with sevoflurane anesthesia. All five patients with S-F- ≥ 40 micromol/L, but only 6/45 with S-F- less than 40 micromol/L (p = 0.001), developed a S-tumor associated trypsin inhibitor concentration above 3 nmol/L as a sign of glomerular dysfunction. As a sign of proximal tubulus deterioration, U-beta 2-microglobulin increased in 2/5 patients with S-F- over 40 micromol/L compared to 2/45 patients with the highest S-F- less than 40 micromol/L (p = 0.005). To conclude, sevoflurane anesthesia may cause a transient proximal tubular deterioration which may be worsened by a co-administration of ketorolac. Clonidine premedication prevents the activation of the renin-angiotensin aldosterone system and preserves normal urine output, but may be harmful for proximal tubules during pneumoperitoneum. Smoking induces the metabolism of enflurane but not that of sevoflurane. Serum F- of 40 micromol/L or higher may induce glomerular dysfunction and proximal tubulus deterioration in patients with sevoflurane anesthesia. The novel renal biomarkers warrant further studies in order to establish reference values for surgical patients having inhalation anesthesia.

Development of biogenic VOC emission inventories for the boreal forest

Luonnosta haihtuvat orgaaniset yhdisteet, joita pääsee ilmaan etenkin metsistä, voivat vaikuttaa paikalliseen ja alueelliseen ilmanlaatuun, koska ne reagoivat ilmakehässä. Niiden reaktiotuotteet voivat myös osallistua uusien hiukkasten muodostumiseen ja kasvuun, millä voi olla vaikutusta ilmakehän säteilytaseeseen ja tätä kautta myös ilmastoon. Hiukkaset absorboivat ja sirottavat auringon säteilyä ja maapallon lämpösäteilyä minkä lisäksi ne vaikuttavat pilvien säteilyominaisuuksiin, määrään ja elinikään. Koko maapallon mittakaavassa luonnosta tulevat hiilivetypäästöt ylittävät ihmistoiminnan aiheuttamat päästöt moninkertaisesti. Tämän vuoksi luonnon päästöjen arviointi on tärkeää kun halutaan kehittää tehokkaita ilmanlaatu- ja ilmastostrategioita. Tämä tutkimus käsittelee boreaalisen metsän hiilivetypäästöjä. Boreaalinen metsä eli pohjoinen havumetsä on suurin maanpäällinen ekosysteemi, ja se ulottuu lähes yhtenäisenä nauhana koko pohjoisen pallonpuoliskon ympäri. Sille on tyypillistä puulajien suhteellisen pieni kirjo sekä olosuhteiden ja kasvun voimakkaat vuodenaikaisvaihtelut. Työssä on tutkittu Suomen yleisimmän boreaalisen puun eli männyn hiilivetypäästöjen vuodenaikaisvaihtelua sekä päästöjen riippuvuutta lämpötilasta ja valosta. Saatuja tuloksia on käytetty yhdessä muiden boreaalisilla puilla tehtyjen päästömittaustulosten kanssa Suomen metsiä varten kehitetyssä päästömallissa. Malli perustuu lisäksi maankäyttötietoihin, suomen metsille kehitettyyn luokitukseen ja meteorologisiin tietoihin, joiden avulla se laskee metsien hiilivetypäästöt kasvukauden aikana. Suomen metsien päästöt koostuvat koko kasvukauden ajan suurelta osin alfa- ja beta-pineenistä sekä delta-kareenista. Kesällä ja syksyllä päästöissä on myös paljon sabineenia, jota tulee etenkin lehtipuista. Päästöt seuraavat lämpötilan keskimääräistä vaihtelua, ovat suurimmillaan maan eteläosissa ja laskevat tasaisesti pohjoiseen siirryttäessä. Metsän isopreenipäästö on suhteellisen pieni – Suomessa tärkein isopreeniä päästävä puu on vähäpäästöinen kuusi, koska runsaspäästöisten pajun ja haavan osuus metsän lehtimassasta on hyvin pieni. Tässä työssä on myös laskettu ensimmäinen arvio metsän seskviterpeenipäästöistä. Seskviterpeenipäästöt alkavat Juhannuksen jälkeen ja ovat kasvukauden aikana samaa suuruusluokkaa kuin isopreenipäästöt. Vuositasolla Suomen metsien hiilivetypäästöt ovat noin kaksinkertaiset ihmistoiminnasta aiheutuviin päästöihin verrattuna.

Geant4 Hadronic Cascade Models and CMS Data Analysis : Computational Challenges in the LHC era

This work belongs to the field of computational high-energy physics (HEP). The key methods used in this thesis work to meet the challenges raised by the Large Hadron Collider (LHC) era experiments are object-orientation with software engineering, Monte Carlo simulation, the computer technology of clusters, and artificial neural networks. The first aspect discussed is the development of hadronic cascade models, used for the accurate simulation of medium-energy hadron-nucleus reactions, up to 10 GeV. These models are typically needed in hadronic calorimeter studies and in the estimation of radiation backgrounds. Various applications outside HEP include the medical field (such as hadron treatment simulations), space science (satellite shielding), and nuclear physics (spallation studies). Validation results are presented for several significant improvements released in Geant4 simulation tool, and the significance of the new models for computing in the Large Hadron Collider era is estimated. In particular, we estimate the ability of the Bertini cascade to simulate Compact Muon Solenoid (CMS) hadron calorimeter HCAL. LHC test beam activity has a tightly coupled cycle of simulation-to-data analysis. Typically, a Geant4 computer experiment is used to understand test beam measurements. Thus an another aspect of this thesis is a description of studies related to developing new CMS H2 test beam data analysis tools and performing data analysis on the basis of CMS Monte Carlo events. These events have been simulated in detail using Geant4 physics models, full CMS detector description, and event reconstruction. Using the ROOT data analysis framework we have developed an offline ANN-based approach to tag b-jets associated with heavy neutral Higgs particles, and we show that this kind of NN methodology can be successfully used to separate the Higgs signal from the background in the CMS experiment.

Evaluation and modelling of the spatial and temporal variability of particulate matter in urban areas

This thesis contains three subject areas concerning particulate matter in urban area air quality: 1) Analysis of the measured concentrations of particulate matter mass concentrations in the Helsinki Metropolitan Area (HMA) in different locations in relation to traffic sources, and at different times of year and day. 2) The evolution of traffic exhaust originated particulate matter number concentrations and sizes in local street scale are studied by a combination of a dispersion model and an aerosol process model. 3) Some situations of high particulate matter concentrations are analysed with regard to their meteorological origins, especially temperature inversion situations, in the HMA and three other European cities. The prediction of the occurrence of meteorological conditions conducive to elevated particulate matter concentrations in the studied cities is examined. The performance of current numerical weather forecasting models in the case of air pollution episode situations is considered. The study of the ambient measurements revealed clear diurnal variation of the PM10 concentrations in the HMA measurement sites, irrespective of the year and the season of the year. The diurnal variation of local vehicular traffic flows seemed to have no substantial correlation with the PM2.5 concentrations, indicating that the PM10 concentrations were originated mainly from local vehicular traffic (direct emissions and suspension), while the PM2.5 concentrations were mostly of regionally and long-range transported origin. The modelling study of traffic exhaust dispersion and transformation showed that the number concentrations of particles originating from street traffic exhaust undergo a substantial change during the first tens of seconds after being emitted from the vehicle tailpipe. The dilution process was shown to dominate total number concentrations. Minimal effect of both condensation and coagulation was seen in the Aitken mode number concentrations. The included air pollution episodes were chosen on the basis of occurrence in either winter or spring, and having at least partly local origin. In the HMA, air pollution episodes were shown to be linked to predominantly stable atmospheric conditions with high atmospheric pressure and low wind speeds in conjunction with relatively low ambient temperatures. For the other European cities studied, the best meteorological predictors for the elevated concentrations of PM10 were shown to be temporal (hourly) evolutions of temperature inversions, stable atmospheric stability and in some cases, wind speed. Concerning the weather prediction during particulate matter related air pollution episodes, the use of the studied models were found to overpredict pollutant dispersion, leading to underprediction of pollutant concentration levels.