Detection of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of Novel PET Imaging Probes With Experimental Models

Atherosclerosis is a life-long vascular inflammatory disease and the leading cause of death in Finland and in other western societies. The development of atherosclerotic plaques is progressive and they form when lipids begin to accumulate in the vessel wall. This accumulation triggers the migration of inflammatory cells that is a hallmark of vascular inflammation. Often, this plaque will become unstable and form vulnerable plaque which may rupture causing thrombosis and in the worst case, causing myocardial infarction or stroke. Identification of these vulnerable plaques before they rupture could save lives. At present, in the clinic, there exists no appropriated, non-invasive method for their identification. The aim of this thesis was to evaluate novel positron emission tomography (PET) probes for the detection of vulnerable atherosclerotic plaques and to characterize, two mouse models of atherosclerosis. These studies were performed by using ex vivo and in vivo imaging modalities. The vulnerability of atherosclerotic plaques was evaluated as expression of active inflammatory cells, namely macrophages. Age and the duration of high-fat diet had a drastic impact on the development of atherosclerotic plaques in mice. In imaging of atherosclerosis, 6-month-old mice, kept on high-fat diet for 4 months, showed matured, metabolically active, atherosclerotic plaques. [18F]FDG and 68Ga were accumulated in the areas representative of vulnerable plaques. However, the slow clearance of 68Ga limits its use for the plaque imaging. The novel synthesized [68Ga]DOTA-RGD and [18F]EF5 tracers demonstrated efficient uptake in plaques as compared to the healthy vessel wall, but the pharmacokinetic properties of these tracers were not optimal in used models. In conclusion, these studies resulted in the identification of new strategies for the assessment of plaque stability and mouse models of atherosclerosis which could be used for plaque imaging. In the used probe panel, [18F]FDG was the best tracer for plaque imaging. However, further studies are warranted to clarify the applicability of [18F]EF5 and [68Ga]DOTA-RGD for imaging of atherosclerosis with other experimental models.

Non-Markovian dynamics and quantum information probes

This Thesis discusses the phenomenology of the dynamics of open quantum systems marked by non-Markovian memory effects. Non-Markovian open quantum systems are the focal point of a flurry of recent research aiming to answer, e.g., the following questions: What is the characteristic trait of non-Markovian dynamical processes that discriminates it from forgetful Markovian dynamics? What is the microscopic origin of memory in quantum dynamics, and how can it be controlled? Does the existence of memory effects open new avenues and enable accomplishments that cannot be achieved with Markovian processes? These questions are addressed in the publications forming the core of this Thesis with case studies of both prototypical and more exotic models of open quantum systems. In the first part of the Thesis several ways of characterizing and quantifying non-Markovian phenomena are introduced. Their differences are then explored using a driven, dissipative qubit model. The second part of the Thesis focuses on the dynamics of a purely dephasing qubit model, which is used to unveil the origin of non-Markovianity for a wide class of dynamical models. The emergence of memory is shown to be strongly intertwined with the structure of the spectral density function, as further demonstrated in a physical realization of the dephasing model using ultracold quantum gases. Finally, as an application of memory effects, it is shown that non- Markovian dynamical processes facilitate a novel phenomenon of timeinvariant discord, where the total quantum correlations of a system are frozen to their initial value. Non-Markovianity can also be exploited in the detection of phase transitions using quantum information probes, as shown using the physically interesting models of the Ising chain in a transverse field and a Coulomb chain undergoing a structural phase transition.

Switchable lanthanide fluorescence probes in homogenous molecular diagnostics

The number of molecular diagnostic assays has increased tremendously in recent years.Nucleic acid diagnostic assays have been developed, especially for the detection of human pathogenic microbes and genetic markers predisposing to certain diseases. Closed-tube methods are preferred because they are usually faster and easier to perform than heterogenous methods and in addition, target nucleic acids are commonly amplified leading to risk of contamination of the following reactions by the amplification product if the reactions are opened. The present study introduces a new closed-tube switchable complementation probes based PCR assay concept where two non-fluorescent probes form a fluorescent lanthanide chelate complex in the presence of the target DNA. In this dual-probe PCR assay method one oligonucleotide probe carries a non-fluorescent lanthanide chelate and another probe a light absorbing antenna ligand. The fluorescent lanthanide chelate complex is formed only when the non-fluorescent probes are hybridized to adjacent positions into the target DNA bringing the reporter moieties in close proximity. The complex is formed by self-assembled lanthanide chelate complementation where the antenna ligand is coordinated to the lanthanide ion captured in the chelate. The complementation probes based assays with time-resolved fluorescence measurement showed low background signal level and hence, relatively high nucleic acid detection sensitivity (low picomolar target concentration). Different lanthanide chelate structures were explored and a new cyclic seven dentate lanthanide chelate was found suitable for complementation probe method. It was also found to resist relatively high PCR reaction temperatures, which was essential for the PCR assay applications. A seven-dentate chelate with two unoccupied coordination sites must be used instead of a more stable eight- or nine-dentate chelate because the antenna ligand needs to be coordinated to the free coordination sites of the lanthanide ion. The previously used linear seven-dentate lanthanide chelate was found to be unstable in PCR conditions and hence, the new cyclic chelate was needed. The complementation probe PCR assay method showed high signal-to-background ratio up to 300 due to a low background fluorescence level and the results (threshold cycles) in real-time PCR were reached approximately 6 amplification cycles earlier compared to the commonly used FRET-based closed-tube PCR method. The suitability of the complementation probe method for different nucleic acid assay applications was studied. 1) A duplex complementation probe C. trachomatis PCR assay with a simple 10-minute urine sample preparation was developed to study suitability of the method for clinical diagnostics. The performance of the C. trachomatis assay was equal to the commercial C. trachomatis nucleic acid amplification assay containing more complex sample preparation based on DNA extraction. 2) A PCR assay for the detection of HLA-DQA1*05 allele, that is used to predict the risk of type 1 diabetes, was developed to study the performance of the method in genotyping. A simple blood sample preparation was used where the nucleic acids were released from dried blood sample punches using high temperature and alkaline reaction conditions. The complementation probe HLA-DQA1*05 PCR assay showed good genotyping performance correlating 100% with the routinely used heterogenous reference assay. 3) To study the suitability of the complementation probe method for direct measurement of the target organism, e.g., in the culture media, the complementation probes were applied to amplificationfree closed-tube bacteriophage quantification by measuring M13 bacteriophage ssDNA. A low picomolar bacteriophage concentration was detected in a rapid 20- minute assay. The assay provides a quick and reliable alternative to the commonly used and relatively unreliable UV-photometry and time-consuming culture based bacteriophage detection methods and indicates that the method could also be used for direct measurement of other micro-organisms. The complementation probe PCR method has a low background signal level leading to a high signal-to-background ratio and relatively sensitive nucleic acid detection. The method is compatible with simple sample preparation and it was shown to tolerate residues of urine, blood, bacteria and bacterial culture media. The common trend in nucleic acid diagnostics is to create easy-to-use assays suitable for rapid near patient analysis. The complementation probe PCR assays with a brief sample preparation should be relatively easy to automate and hence, would allow the development of highperformance nucleic acid amplification assays with a short overall assay time.

Novel Cellular Luminescence Probes for Immunological and Toxicological Assessments

Escherichia coli K-12 (pEGFPluxABCDEAmp) (E. coli-lux), constitutively emitting bioluminescence (BL), was constructed and its BL emitting properties tested in different growth and killing conditions. The BL emission directly correlated with the number of viable E. coli-lux cells, and when subjected to the antimicrobial agent, the diminishment of the BL signal was linked directly to the number of killed bacterial cells. The method provided a very convenient application, especially when compared to conventional plate counting assays. This novel real-time based method was utilized in both immunological and toxicological assessments. The parameters such as the activation phase, the lytic phase and the capacity of the killing of the serum complement system were specified not only in humans but also in other species. E. coli-lux was also successfully used to study the antimicrobial activities of insect haemolymph. The mechanisms of neutrophil activity, like that of a myeloperoxidase (MPO)-H2O2-halide system, were studied using the E. coli-lux approach. The fundamental role of MPO was challenged, since during the actual killing in described circumstances in phagolysosome the MPO system was inactivated and chlorination halted. The toxicological test system, assessing indoor air total toxicity, particularly suitable for suspected mold damages, was designed based on the E. coli-lux method. Susceptibility to the vast number of various toxins, both pure chemicals and dust samples from the buildings and extracts from molds, were investigated. The E. coli-lux application was found to possess high sensitivity and specificity attributes. Alongside the analysis system, the sampling kit for indoor dust was engineered based on the swipe stick and the container. The combination of practical specimen collector and convenient analysis system provided accurate toxic data from the dust sample within hours. Neutrophils are good indicators of the pathophysiological state of the individual, and they can be utilized as a toxicological probe due to their ability to emit chemiluminescence (CL). Neutrophils can either be used as probe cells, directly exposed to the agent studied, or they can act as indicators of the whole biological system exposed to the agent. Human neutrophils were exposed to the same toxins as tested with the E. coli-lux system and measured as luminol amplified CL emission. The influence of the toxins on the individuals was investigated by exposing rats with moniliniformin, the mycotoxin commonly present in Finnish grains. The activity of the rat neutrophils was found to decrease significantly during the 28 days of exposure.

Metal-Ion-Binding Oligonucleotides: High-Affinity Probes for Nucleic Acid Sequences

Small non-coding RNAs have numerous biological functions in cell and are divided into different classes such as: microRNA, snoRNA, snRNA and siRNA. MicroRNA (miRNA) is the most studied non-coding RNA to date and is found in plants, animals and some viruses. miRNA with short sequences is involved in suppressing translation of target genes by binding to their mRNA post-transcriptionally and silencing it. Their function besides silencing of the viral gene, can be oncogenic and therefore the cause of cancer. Hence, their roles are highlighted in human diseases, which increases the interest in using them as biomarkers and drug targets. One of the major problems to overcome is recognition of miRNA. Owing to a stable hairpin structure, chain invasion by conventional Watson-Crick base-pairing is difficult. One way to enhance the hybridization is exploitation of metal-ion mediated base-pairing, i. e. oligonucleotide probes that tightly bind a metal ions and are able to form a coordinative bonds between modified and natural nucleobases. This kind of metallo basepairs containing short modified oligonucleotides can also be useful for recognition of other RNA sequences containing hairpin-like structural motives, such as the TAR sequence of HIV. In addition, metal-ion-binding oligonucleotides will undoubtedly find applications in DNA-based nanotechnology. In this study, the 3,5-dimethylpyrazol-1-yl substituted purine derivatives were successfully incorporated within oligonucleotides, into either a terminal or non-terminal position. Among all of the modified oligonucleotides studied, a 2-(3,5-dimethylpyrazol-1-yl)-6-oxopurine base containing oligonucleotide was observed to bind most efficiently to their unmodified complementary sequences in the presence of both Cu2+ or Zn2+. The oligonucleotide incorporating 2,6-bis(3,5-dimethylpyrazol-1-yl)purine base also markedly increased the stability of duplexes in the presence of Cu2+ without losing the selectivity.

Computational and Experimental Analysis of Flow Field in the Diffusers of Centrifugal Compressors

Centrifugal compressors are widely used for example in process industry, oil and gas industry, in small gas turbines and turbochargers. In order to achieve lower consumption of energy and operation costs the efficiency of the compressor needs to be improve. In the present work different pinches and low solidity vaned diffusers were utilized in order to improve the efficiency of a medium size centrifugal compressor. In this study, pinch means the decrement of the diffuser flow passage height. First different geometries were analyzed using computational fluid dynamics. The flow solver Finflo was used to solve the flow field. Finflo is a Navier-Stokes solver. The solver is capable to solve compressible, incompressible, steady and unsteady flow fields. Chien's k-e turbulence model was used. One of the numerically investigated pinched diffuser and one low solidity vaned diffuser were studied experimentally. The overall performance of the compressor and the static pressure distribution before and after the diffuser were measured. The flow entering and leaving the diffuser was measured using a three-hole Cobra-probe and Kiel-probes. The pinch and the low solidity vaned diffuser increased the efficiency of the compressor. Highest isentropic efficiency increment obtained was 3\% of the design isentropic efficiency of the original geometry. It was noticed in the numerical results that the pinch made to the hub and the shroud wall was most beneficial to the operation of the compressor. Also the pinch made to the hub was better than the pinchmade to the shroud. The pinch did not affect the operation range of the compressor, but the low solidity vaned diffuser slightly decreased the operation range.The unsteady phenomena in the vaneless diffuser were studied experimentally andnumerically. The unsteady static pressure was measured at the diffuser inlet and outlet, and time-accurate numerical simulation was conducted. The unsteady static pressure showed that most of the pressure variations lay at the passing frequency of every second blade. The pressure variations did not vanish in the diffuser and were visible at the diffuser outlet. However, the amplitude of the pressure variations decreased in the diffuser. The time-accurate calculations showed quite a good agreement with the measured data. Agreement was very good at the design operation point, even though the computational grid was not dense enough inthe volute and in the exit cone. The time-accurate calculation over-predicted the amplitude of the pressure variations at high flow.

Artificially Intelligent and Adaptive Methods for Prediction and Analysis of Superheater Fireside Corrosion in Fluidized Bed Boilers

Superheater corrosion causes vast annual losses for the power companies. With a reliable corrosion prediction method, the plants can be designed accordingly, and knowledge of fuel selection and determination of process conditions may be utilized to minimize superheater corrosion. Growing interest to use recycled fuels creates additional demands for the prediction of corrosion potential. Models depending on corrosion theories will fail, if relations between the inputs and the output are poorly known. A prediction model based on fuzzy logic and an artificial neural network is able to improve its performance as the amount of data increases. The corrosion rate of a superheater material can most reliably be detected with a test done in a test combustor or in a commercial boiler. The steel samples can be located in a special, temperature-controlled probe, and exposed to the corrosive environment for a desired time. These tests give information about the average corrosion potential in that environment. Samples may also be cut from superheaters during shutdowns. The analysis ofsamples taken from probes or superheaters after exposure to corrosive environment is a demanding task: if the corrosive contaminants can be reliably analyzed, the corrosion chemistry can be determined, and an estimate of the material lifetime can be given. In cases where the reason for corrosion is not clear, the determination of the corrosion chemistry and the lifetime estimation is more demanding. In order to provide a laboratory tool for the analysis and prediction, a newapproach was chosen. During this study, the following tools were generated: · Amodel for the prediction of superheater fireside corrosion, based on fuzzy logic and an artificial neural network, build upon a corrosion database developed offuel and bed material analyses, and measured corrosion data. The developed model predicts superheater corrosion with high accuracy at the early stages of a project. · An adaptive corrosion analysis tool based on image analysis, constructedas an expert system. This system utilizes implementation of user-defined algorithms, which allows the development of an artificially intelligent system for thetask. According to the results of the analyses, several new rules were developed for the determination of the degree and type of corrosion. By combining these two tools, a user-friendly expert system for the prediction and analyses of superheater fireside corrosion was developed. This tool may also be used for the minimization of corrosion risks by the design of fluidized bed boilers.

On the Reversed Brayton Cycle with High Speed Machinery

This work was carried out in the laboratory of Fluid Dynamics, at Lappeenranta University of Technology during the years 1991-1996. The research was a part of larger high speed technology development research. First, there was the idea of making high speed machinery applications with the Brayton cycle. There was a clear need to deepen theknowledge of the cycle itself and to make a new approach in the field of the research. Also, the removal of water from the humid air seemed very interesting. The goal of this work was to study methods of designing high speed machinery to the reversed Brayton cycle, from theoretical principles to practical applications. The reversed Brayton cycle can be employed as an air dryer, a heat pump or a refrigerating machine. In this research the use of humid air as a working fluid has an environmental advantage, as well. A new calculation method for the Braytoncycle is developed. In this method especially the expansion process in the turbine is important because of the condensation of the water vapour in the humid air. This physical phenomena can have significant effects on the level of performance of the application. Also, the influence of calculating the process with actual, achievable process equipment efficiencies is essential for the development of the future machinery. The above theoretical calculations are confirmed with two different laboratory prototypes. The high speed machinery concept allows one to build an application with only one rotating shaft including all the major parts: the high speed motor, the compressor and the turbine wheel. The use of oil free bearings and high rotational speed outlines give several advantages compared to conventional machineries: light weight, compact structure, safe operation andhigher efficiency at a large operational region. There are always problems whentheory is applied to practice. The calibrations of pressure, temperature and humidity probes were made with care but still measurable errors were not negligible. Several different separators were examined and in all cases the content of the separated water was not exact. Due to the compact sizes and structures of the prototypes, the process measurement was slightly difficult. The experimental results agree well with the theoretical calculations. These experiments prove the operation of the process and lay a ground for the further development. The results of this work give very promising possibilities for the design of new, commercially competitive applications that use high speed machinery and the reversed Brayton cycle.

Kuumalanka-anemometri virtausmittauksissa

Tässä työssä selostetaan kuumalanka-anemometrin käyttö virtausmittauksissa. Kuumalanka-anemometrilla saadaan mitattua virtausnopeuden ja -suunnan lisäksi nopeusheilahteluja. Mittaustaajuus on tyypillisesti useita kymmeniä tuhansia mittauksia sekunnissa ja signaali on jatkuva. Nykytekniikalla pystytään helposti tallentamaan mittauslaitteistolta saatu viesti tietokoneelle ja muuntamaan se nopeudeksi. Hetkellisten nopeuksien avulla voidaan laskea turbulenttisen virtauksen ominaisuuksia, kuten turbulenssin intensiteetti ja spektri. Kuumalanka-anemometrissa lämmitetään sähköisesti ohutta lankaa, joka on mitattavassa virtauksessa. Langan sähköteho on suunnilleen yhtäsuuri kuin langasta konvektiolla siirtyvä lämpöteho. Tällöin on teoreettisesti mahdollista laskea virtausnopeus lämpötehosta lämmönsiirtokorrelaatioilla. Käytännössä laitteisto joudutaan kuitenkin erikseen kalibroimaan, mutta sähkötehon teoreettista riippuvuutta konvektiosta käytetään hyväksi. Kuumalangan lämmitettävä osuus on tyypillisesti halkaisijaltaan 5 µm ja pituudeltaan noin 1 mm. Sitä käytetään pääasiassa kaasuvirtausten mittaamiseen ja valtaosassa mittauksissa virtausaineena on ilma. Kuumalanka voi olla toteutettu kuumakalvotekniikalla, jossa halkaisijaltaan noin 50 - 70 µm paksuinen kuitu on päällystetty ohuella sähköä johtavalla kalvolla. Kuumakalvoanturin ei tarvitse olla muodoltaan sylinterimäinen, se voi olla mm. kartiomainen tai kiilamainen. Erikoispäällystetyllä kuumakalvoanturilla on mahdollista mitata myös nestevirtauksia. Mitattaessa kaasuvirtauksia kuumakalvon etuna on selvästi parempi kestävyys verrattuna kuumalankaan. Nimitystä kuumalanka-anemometri käytetään yleisesti molemmista anturityypeistä Tämän työn alussa käsitellään sylinterin yli tapahtuvaan virtaukseen liittyvää virtausmekaniikkaa ja lämmönsiirtoa. Anemometrin sähköinen osa, laitteisto ja sen kalibrointi käydään läpi. Langan suuntariippuvuuden laskentaan esitetään tarvittavat yhtälöt. Työssä esitellään kolme laitteistolla tehtyä perusmittausta: anturin kohtauskulman muuttaminen, pyörähdyssymmerisen suihkun nopeuskenttä ja tuulitunnelin rajakerros. Lisäksi esitellään yksi käytännöllinen ja vaativampi mittaus, jossa on mitattu nopeusprofiili radiaalikompressorin diffuusorin loppuosassa.

A Large-Sized Multiwire Proportional Counter for Radiological Survey of Large Areas and Surfaces

Työn tavoitteena oli selvittää, miten eri parametrit vaikuttavat monilankaisen verrannollisuuslaskurin laskennallisiin ominaisuuksiin sekä voidaanko suurikokoista monilankaverrannollisuuslaskuria käyttää tehokkaasti suurien pintojen ? - ja ?- kontaminaation mittaamiseen. Ensin selvitettiin EU:n nykyistä clearing-käytäntöä sekä hahmoteltiin tulevia materiaalivirtoja, esiteltiin verrannollisuuslaskurin ja sen monilankamallin toimintaperiaate sekä käytettävien materiaalien ominaisuudet. Kootun teorian pohjalta selvitettiin tärkeimpien parametrien vaikutus ilmaisimen laskennallisiin ominaisuuksiin. Lopuksi suoritettiin rakenteilla olevan monilankaverrannollisuuslaskurin alustava testaus. Tulevien vuosien aikana eri puolilla maailmaa suljettavat erityyppiset ydinlaitokset luovat suuren tarpeen tehokkaiden kontaminaatiomittauslaitteistojen kehittämiselle. Tällä hetkellä mittaukset suoritetaan lähinnä noin 1 dm2 käsi-instrumentein, joten suurikokoinen, automatisoitu mittauslaitteisto sekä tehostaisi mittausprosessia suuresti sekä säästäisi runsaasti miestyötunteja. Jatkotoimenpiteiksi ehdotetaan laitteiston jatkotestausta, liikkeen ja nopeuden testausta sekä lopulta paikkaherkkyystoiminnon toteuttamisperiaatteen valintaa ja testausta.

Polttoaineseoksen ja prosessiolosuhteiden vaikutus kerrosleijukattilan tulistinalueen likaantumiseen

Työn tavoitteena oli löytää yhteys kerrosleijukattilaan syötetyn polttoaineseoksen sekä kattilan likaantumisen välille. Tulistinalueen likaantumista tutkittiin kahden kerrostumasondin avulla 28 päivää kestäneellä mittausjaksolla. Mittausten aikana otettiin näytteitä polttoaineseoksesta, lentotuhkasta sekä nuohouksen aikaisesta tuhkavirrasta. Mittausjakson jälkeen myös sondien tuhkakerrostumien pitoisuudet määritettiin. Mittausjakson aikana sondien jättöpinnoille muodostui tuhkakerrostumaa, joka voitiin poistaa nuohouksella, kun taas tulopinnalle syntyi pysyvää kerrostumaa. Nuohouksella irtoavan tuhkakerrostuman havaittiin sisältävän suuremmat pitoisuudet piitä, alumiinia, natriumia ja kaliumia kuin kattilan läpi jatkuvasti kulkevan lentotuhkan. Tuhkakerrostuma, jota ei nuohouksella saatu poistettua, sisälsi enemmän natriumia, rikkiä, kaliumia ja lyijyä kuin muut tuhkanäytteet. Polttoaineista turpeella oli merkittävin vaikutus likaantumiseen. Turpeen osuuden ollessa suurimmillaan jäivät jättöpinnan tuhkakerrostuman lämpövastukset pienemmiksi kuin muulloin eli lyhytaikaista kerrostumaa syntyi tällöin vähemmän. Pysyvän kerrostuman kasvu hidastui, kun turpeen osuus oli suuri, ja jopa pysähtyi, kun turpeen osuus oli 42-51 %. Prosessiolosuhteista tutkittiin kattilan kuorman vaikutusta likaantumiseen. Havaittiin, että ajettaessa kattilaa isommilla kuormilla, syntyi lyhytaikaista kerrostumaa vähemmän kuin muulloin.

A study of electromagnetic shielding properties of Ni79Fe16Mo5/copper films

The plane wave electromagnetic interference (EMI) shielding properties of DC sputtered Ni79Fe16Mo5 and copper layers were studied according to ASTM D 4935-89 on frequency range of 50 MHz – 2.5 GHz and RF magnetic shielding effectiveness by shielded magnetic loop probes. Results show that Ni79Fe16Mo5 provides better RF magnetic shielding above the layer thickness of approximately 120 nm. Copper provides better plane wave shielding effectiveness. The effect of shield internal interfaces was studied by depositing thin multilayer structures with and without a dielectric spacer layer.

Periodontal Diseases in Tanzania

Tutkimuksen tavoitteena oli kuvata hampaiden kiinnityskudossairauksien esiintyvyyttä ja suuhygieniatottumuksia Tansaniassa. Viiden eri tutkimuksen avulla kartoitettiin suuhygieniatottumuksia, kiinnityskudosten tilaa, kiinnityskudossairauksien riskitekijöitä ja hoidon tarvetta (CPITN) sekä ienvetäymiä. Tutkimukset toteutettiin eri paikkakunnilla vuosien 1987 ja 2003 välillä. Tutkittavat valittiin satunnaisesti tai harkitusti; tutkittavien määrä vaihteli 201:stä 1764:ään. Aineistot kerättiin kysymyslomakkeilla ja kliinisten tutkimusten avulla. Kliinisesti mitattiin plakin, hammaskiven ja ienten verenvuodon määrä, ientaskujen syvyys, ienvetäymien laajuus ja puuttuvien hampaiden lukumäärä. Tutkimusvälineinä käytettiin peiliä, Williamsin ja WHO:n ientaskumittareita. Muoviharjaksista hammasharjaa ilmoitti käyttävänsä 51,5-97,8% tutkituista. Ns. harjaustikun käyttö vaihteli paljon: 0,9-32,0 %. Plakkia löydettiin 65-100 %:lla tutkituista. Hammaskiveä oli suurimmalla osalla tutkituista. Myös ienverenvuotoa löytyi valtaosalta (79-100%). Ienverenvuotoa oli enemmän miehillä kuin naisilla sekä alhaisemman koulutustason omaavilla. Neljäkymmentä vuotta täyttäneiltä löydettiin 4–5 mm:n syvyisiä ientaskuja 82,1 %:lta ja ≥ 6 mm:n taskuja 43,8 %:lta. Suun terveystottumusten ohjaamiseen oli tarvetta yli 90 %:lla, hammaskiven poistoon ja juurten pinnan tasoitukseen yli 80%:lla. Yleisimmät riskitekijät kiinnityskudossairauksille olivat ikä (≥ 35 vuotta), miessukupuoli, alhainen koulutustaso, plakin, hammaskiven ja ientulehduksen määrä sekä asuminen maaseudulla. Ienvetäymiä (≥ 4 mm) löytyi noin 54%:lla tutkituista. Ienvetäymiä oli useammin miehillä kuin naisilla ja ne olivat yhteydessä ikään sekä hammaskiven ja ienverenvuodon esiintymiseen. Suuhygieniataso tutkituilla henkilöillä oli huono ja ienvetäymien esiintyvyys korkea. Syviä ientaskuja löytyi kuitenkin harvoilta tutkituilta. Riskitekijät kiinnityskudossairauksille olivat ikä, miessukupuoli, alhainen koulutustaso, plakin, hammaskiven ja ientulehduksen määrä sekä asuminen maaseudulla. Ienvetäymien riskit olivat ikä, miessukupuoli, hammaskivi ja ienverenvuoto

Autologous Stem Cell Transplantation In Multiple Myeloma

Background. Multiple myeloma (MM) is the second most common hematologic malignancy after lymphomas In Finland: the annual incidence of MM is approximately 200. For three decades the median survival remained at 3 to 4 years from diagnosis until high-dose melphalan treatment supported by autologous stem cell transplantation (ASCT) became the standard of care for newly diagnosed MM since the mid 1990’s and the median survival increased to 5 – 6 years. This study focuses on three important aspects of ASCT, namely 1) stem cell mobilization, 2) single vs. double ASCT as initial treatment, and 3) the role of minimal residual disease (MRD) for longterm outcome. Aim. The aim of this series of studies was to evaluate the outcomes of MM patients and the ASCT procedure at the Turku University Central Hospital, Finland. First, we tried to identify which factors predict unsuccessful mobilization of autologous stem cells. Second, we compared the use of short-acting granulocyte-colony stimulating factor (GCSF) with long-acting G-CSF as mobilization agents. Third, one and two successive ASCTs were compared in 100 patients with MM. Fourth, for patients in complete response (CR) after stem cell transplantation (SCT), patient-specific probes for quantitative allele-specific oligonucleotide polymerase-chain reaction (qASO-PCR) measurements were designed to evaluate MRD and its importance for long-term outcome. Results. The quantity of previous chemotherapy and previous interferon use were significant pre-mobilization factors that predicted mobilization failure, together with some factors related to mobilization therapy itself, such as duration and degree of cytopenias and occurrence of sepsis. Short-acting and long-acting G-CSF combined with chemotherapy were comparable as stem cells mobilizers. The progression free (PFS) and overall survival (OS) tended to be longer after double ASCT than after single ASCT with a median follow-up time of 4 years, but this difference disappeared as the follow-up time increased. qASO-PCR was a good and sensitive divider of the CR patients into two prognostic groups: MRD low/negative (≤ 0.01%) and MRD high (>0.01%) groups with a significant difference in PFS and suggestively also in OS. Conclusions. When the factors prediciting a poor outcome of stem cell mobilization prevail, it is possible to identify those patients who need specific efforts to maximize the mobilization efficacy. Long-acting pegfilgrastim is a practical and effective alternative to short-acting filgrastim for mobilization therapy. There is no need to perform double ASCT on all eligible patients. MRD assessment with qASO-PCR is a sensitive method for evaluation of the depth of the CR response and can be used to predict long-term outcome after ACST.

Liquid transportation and distribution during (re)wetting : impact on coated papers in printing

In many industrial applications, such as the printing and coatings industry, wetting of porous materials by liquids includes not only imbibition and permeation into the bulk but also surface spreading and evaporation. By understanding these phenomena, valuable information can be obtained for improved process control, runnability and printability, in which liquid penetration and subsequent drying play important quality and economic roles. Knowledge of the position of the wetting front and the distribution/degree of pore filling within the structure is crucial in describing the transport phenomena involved. Although exemplifying paper as a porous medium in this work, the generalisation to dynamic liquid transfer onto a surface, including permeation and imbibition into porous media, is of importance to many industrial and naturally occurring environmental processes. This thesis explains the phenomena in the field of heatset web offset printing but the content and the analyses are applicable in many other printing methods and also other technologies where water/moisture monitoring is crucial in order to have a stable process and achieve high quality end products. The use of near-infrared technology to study the water and moisture response of porous pigmented structures is presented. The use of sensitive surface chemical and structural analysis, as well as the internal structure investigation of a porous structure, to inspect liquid wetting and distribution, complements the information obtained by spectroscopic techniques. Strong emphasis has been put on the scale of measurement, to filter irrelevant information and to understand the relationship between interactions involved. The near-infrared spectroscopic technique, presented here, samples directly the changes in signal absorbance and its variation in the process at multiple locations in a print production line. The in-line non-contact measurements are facilitated by using several diffuse reflectance probes, giving the absolute water/moisture content from a defined position in the dynamic process in real-time. The nearinfrared measurement data illustrate the changes in moisture content as the paper is passing through the printing nips and dryer, respectively, and the analysis of the mechanisms involved highlight the roles of the contacting surfaces and the relative liquid carrier properties of both non-image and printed image areas. The thesis includes laboratory studies on wetting of porous media in the form of coated paper and compressed pigment tablets by mono-, dual-, and multi-component liquids, and paper water/moisture content analysis in both offline and online conditions, thus also enabling direct sampling of temporal water/moisture profiles from multiple locations. One main focus in this thesis was to establish a measurement system which is able to monitor rapid changes in moisture content of paper. The study suggests that near-infrared diffuse reflectance spectroscopy can be used as a moisture sensitive system and to provide accurate online qualitative indicators, but, also, when accurately calibrated, can provide quantification of water/moisture levels, its distribution and dynamic liquid transfer. Due to the high sensitivity, samples can be measured with excellent reproducibility and good signal to noise ratio. Another focus of this thesis was on the evolution of the moisture content, i.e. changes in moisture content referred to (re)wetting, and liquid distribution during printing of coated paper. The study confirmed different wetting phases together with the factors affecting each phase both for a single droplet and a liquid film applied on a porous substrate. For a single droplet, initial capillary driven imbibition is followed by equilibrium pore filling and liquid retreat by evaporation. In the case of a liquid film applied on paper, the controlling factors defining the transportation were concluded to be the applied liquid volume in relation to surface roughness, capillarity and permeability of the coating giving the liquid uptake capacity. The printing trials confirmed moisture gradients in the printed sheet depending on process parameters such as speed, fountain solution dosage and drying conditions as well as the printed layout itself. Uneven moisture distribution in the printed sheet was identified to be one of the sources for waving appearance and the magnitude of waving was influenced by the drying conditions.