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Many drugs are associated with the risk of QT prolongation and torsades de pointes (TdP). The risk increases with other risks factors for QT prolongation. Recognizing risk factors and QT prolonging drugs is critical in the management of this drug-related problem. The aim of this master’s thesis was to study the prevalence of use of QT prolonging drugs in older adults receiving home care. Additionally, the aim was to study concomitant use of QT prolonging drugs as well as clinically significant QT prolonging drug-drug interactions in the participants. The secondary objective was to study the most commonly used QT prolonging in the participants. The material used in this master’s thesis originated from a randomized controlled trial in City of Lohja, Finland, which enhanced a coordination in medication risk management for older home care clients. The analysis of the baseline data collected in fall 2015 was only deepened regarding QT prolonging drugs. The participants (n=188) were older adults (≥65 years) receiving regular home care from City of Lohja, randomized into an intervention group (n=101) and a control group (n=87). The majority of the participants were women (69%). The mean age of the participants was 83 years. Data on the participants’ drugs were collected from their medication lists. Clinically significant drug-drug interactions were identified using the SFINX database. The QTDrugs Lists of CredibleMeds were used for identifying drugs associated with QT prolongation and TdP. On average, the participants (n=188) used 2.3 drugs (SD 1.3, median 2.0) associated with QT prolongation and TdP. Of the participants, 36% (n=67) used drugs with known risk of TdP (QTDrugs List 1). The most commonly used drugs with known risk of TdP were donepezil and citalopram. The prevalence of QTDrugs List 2 drugs (possible risk of TdP) was 36% (n=67). Most of the participants (n=156, 83%) used drugs which under certain circumstances are associated with TdP (QTDrugs List 3). One fifth (21%) of the participants used concomitantly 2-3 drugs associated with QT prolongation and TdP. QT prolonging drugdrug interactions (SFINX-D interactions) were found in 3% of the participants. The drugs involved in the drug-drug interactions were donepezil, (es)citalopram and haloperidol. The prevalence of use of clinically relevant QT prolonging drugs (QTDrugs Lists 1-2) was higher in this study compared with the prevalence in outpatients in previous studies. Concomitant use of QT prolonging drugs is common in outpatients. Health care professionals need to be educated on the risks of QT prolongation, TdP and the risks of using QT prolonging drugs concomitantly. Risk assessment tools considering patient-specific risk factors could be more widely used, as they may reduce modifiable risk factors, and actual events of QT prolongation and TdP may be avoided. There is a need for systematic procedures for assessing and managing the risks of QT prolongation and TdP in the Finnish health care system.

This work is about the qualitative theory of autonomous ordinary differential equation (ODE) systems. The purpose of the work is threefold. First, it is intended to familiarize the reader with the essential theory of autonomous systems in dimension n. Second, it is hoped that the reader will learn the importance of planar autonomous systems, such the beautiful result of the Poincaré-Bendixson theorem. Third, since the theory is utilised in applied science, considerably space has been devoted to analytical methods that are used widely in applications. The fundamental theory of existence and uniqueness of solutions to ODE systems are presented in Chapter 2. Then, Chapter 3 treats with the essential theory of autonomous systems in dimension n, such as the orbits and the limit sets of solutions. In Chapter 4 we consider planar autonomous systems. What makes planar systems different from higher dimensions is the existence of Jordan Curve theorem, which has made it possible for the theory to go much further. In particular, the Poincaré-Bendixson theorem, which is a statement about the long-term behavior of solutions to an autonomous system in the plane. Note that the Jordan Curve theorem is stated without proof, since the proof is terribly difficult but the result is obvious. Lastly, in order not to lose sight of the applied side of the subject, Chapters 5 and 6 are devoted to analytical methods of autonomous systems. First, Chapter 5 treats with local stability analysis of an equilibrium. Then, in Chapter 6 we work with a relatively large study of an abnormal competing species model based on the science fiction movie The Terminator (1984), which should be taken with a pinch of salt. In its dystopian world there are two powerful forces of Men and the Terminator cyborgs trying to get completely rid of one another. Lack of space has, however, forced us to simplify some of the individual behaviour. These simplifications are partly justified by the fact that the purpose is to present how the theory can be applied even in a (hopefully) fictional situation and, of course, to answer the puzzling question whether the human race would stand a chance against the Terminators.

Pharmaceutical industry is supervised by several competent authorities. These authorities all over the world inspect manufacturers in order to make sure they comply with the Good Manufacturing Practice (GMP) guidelines and produce quality products. If non-compliance with the guidelines is detected, the authorities can revoke manufacturing licenses and deny access of the products. Recent trend in pharmaceutical industry is that the Active Pharmaceutical Ingredient (API) manufacturing is concentrated in few factories. If this kind of manufacturer is declared non-compliant and is therefore unable to supply an API, it can lead to drug shortages. This research aimed to find out what kind of quality problems occur in API manufacturing. Because of the concentration trend, it is important to understand what kind of problems the manufacturers do struggle with to prevent any risk for shortages. This research aimed also to determine how much the quality problems in API manufacturing can impact on drug shortages. Also, the number and location of these non-compliance cases were investigated. The chosen time frame was 2016-2018. Several databases were used as information sources in this research. These databases are maintained by the authorities in the U.S. and Europe and they contain information about the inspections and the GMP deficiencies they have found during these inspections. With the information collected from the databases, an inductive content analysis was conducted to determine the reasons for non-compliance with GMP in API manufacturing. Other information (e.g. locations, names of APIs) was also collected from the databases and analysed to answer the rest of the research questions. Results show that the biggest problem areas in API manufacturing were data integrity and analytical testing. Other problems relating to documentation occurred also. The amount of these cases was quite stable, and the relative proportion declined during the time period. Comparison between the list of APIs and drug shortage databases showed that even over 30% of the non-compliant APIs were later in shortage. The effect was greater in Finland than in the U.S. Therefore, it was concluded that the most significant GMP deficiencies in API manufacturing were poor data integrity and inappropriate analytical testing procedures. Secondly, the number of non-compliance cases in API manufacturing has not increased during this time, but these problems may have had an impact on drug availability problems.

Semiconductor radiation detectors are devices used to detect electromagnetic and particle radiation. The signal formation is based on the transportation of charges between the valence band and conduction band. The interaction between the detector material and the radiation generates free electrons and holes that move in opposite directions in the electric field applied between the electrodes. The movement of charges induces a current in the external electrical circuit, which can be used for particle identification, measurement of energy or momentum, timing, or tracking. There are several different detector materials and designs and, new options are continuously developed. Diamond is a detector material that has received a great amount of interest in many fields. This is due to its many unique properties. Many of them arise from the diamond crystal structure and the strength of the bond between the carbon atoms. The tight and rigid structure makes diamond a strong and durable material, which allows operation of diamond detectors in harsh radiation environments. This, combined with the fast signal formation and short response time makes diamond detector an excellent choice for high energy physics applications. The diamond structure leads also to a wide band gap. Thanks to the wide band bap, diamond detectors have low leakage current and they can be operated even in high temperatures without protection from surrounding light. Especially electrical properties of semiconductors strongly depend on the concentration of impurities and crystal defects. Determination of electrical properties can therefore be used to study the crystal quality of the material. The electrical properties of the material determine the safe operational region of the device and knowledge of the leakage current and the charge carrier transportation mechanism are required for optimized operation of detectors. Characterization of electrical properties is therefore an important part of semiconductor device fabrication. Electrical characterization should be done at different stages of the fabrication in order to detect problems at an early stage and to get an idea of what could have caused them. This work describes the quality assurance process of single crystal CVD (chemical vapour deposition) diamond detectors for the PPS-detectors for the CMS-experiment. The quality assurance process includes visual inspection of the diamond surfaces and dimensions by optical and cross polarized light microscopy, and electrical characterization by measurement of leakage current and CCE (charge collection efficiency). The CCE measurement setup was improved with a stage controller, which allows automatic measurement of CCE in several positions on the diamond detector. The operation of the new setup and the reproducibility of the results were studied by repeated measurements of a reference diamond. The setup could successfully be used to measure CCE over the whole diamond surface. However, the measurement uncertainty is quite large. Further work is needed to reduce the measurement uncertainty and to determine the correlation between observed defects and the measured electrical properties.

Since the beginning of the 1990s the emphasis of participatory democracy has become stronger in Finnish policy- and decision-making. This development involves various stakeholders participating in negotiations, or more specifically deliberations, around current issues in order to reach consensus and enable a continuance in the policy process. According to research, the more consensual a democracy is the more favourable are the policy outcomes towards environmental issues. The three case studies investigated, ie. the Forest Biodiversity Programme for Southern Finland, the Working Group on Renewable Energy, and the Natura 2000 Network of European Union nature protection areas, support this notion. The case studies are focused on how the key players involved have conceived the decision-making process in terms of achieved goals and degree of agreement as well as on the specific issue context as a backdrop to the development of policy. The cases displayed significant differences of outcomes depending on the achieved level of consensus and deliberation. The outcomes are analysed within the theoretical frameworks of Arend Lijpharts consensus vs majoritarian model of democracy and Martin Jänickes consensual capacity for ecological modernisation. Further, applying Joshua Cohens theory of deliberative democracy and his suggestions for achieving ideal deliberation, the results suggest that the connection between consensus democracy and more effective environmental conservation policy is not that clear-cut. Nevertheless, consensus democracy provides a promising point of departure for overcoming the main disputes between the stakeholders, and common starting points and general goals to be agreed on, which is crucial in order for any progress in environmental conservation to take place.

Objective of this article was to analyze whether the reporting of the 3rd and 4th degree obstetric anal sphincter injuries differ between the patient data recording systems. The study was retrospective. The setting included all six delivery units in the Hospital District of Helsinki and Uusimaa (HUS) comprising one third of all deliveries in Finland. Population was all deliveries in HUS in 2012 (n=18099). The incidence of the sphincter injury was extracted from three electronic medical record (EMR) systems (Obstetrix, Opera and Oberon), using the national versions of International Classification of Diseases 10th revision (ICD10) and the Nordic Classification of Surgical Procedures (NOMESCO). All observed cases were studied carefully from the patient records and the reliability of different systems was analyzed and compared to the data reported to national registers (MBR Medical Birth Register and HDR Hospital Discharge Register). Main outcome measure was sphincter injury rate in delivery units. We found that the actual rate of sphincter injury in all the EMRs combined in HUS was higher (1.8%) than the rate delivered from any single reporting system (from 1.5% to 1.7%) and varied even more among single delivery units. The coverage in the MBR (88%) was much higher than in the HDR (3%). In conclusion the simultaneous use of several patient data recording systems is confusing and prone for systematic errors. One common database – preferably an EMR with a structured format - would clarify the registering and enable reliable quality reports creating a sustainable base for quality improvements.

Ranskankielinen maisterintutkielmani käsittelee Euroopan parlamentin täysistuntokeskusteluissa käytettyjä ranskan- ja saksankielisiä fraseologismeja sekä niiden suomenkielisiä tulkkeita. Fraseologiantutkimuksen painopiste on kauan ollut kaunokirjallisuudessa, minkä vuoksi politiikan kielen tutkimus on ajankohtaisten kriisien vuoksi osoittautunut mielekkääksi tutkimuskohteeksi fraseologiassa. Tutkimuksessani tarkastelen fraseologismien kielellisiä funktioita Roman Jakobsonin jaottelun pohjalta ja funktioiden välittymistä suomenkielisiin tulkkeisiin. Tutkimuskysymykseni ovat: Mitä ovat fraseologismit? Minkälaisia fraseologismeja Euroopan parlamentin täysistuntojen puheenvuoroissa esiintyy ja mitä kielellisiä funktioita niillä on? Miten fraseologismeja on tulkattu suomeen? Aineistoni käsittelee aiheeltaan voimakkaita mielipiteitä ja kannanottoja herättäviä keskusteluja 24. helmikuuta 2022 alkaneesta Venäjän ja Ukrainan välisestä sotilaallisesta konfliktista. Kielinä ranska ja saksa ovat EU:n tärkeimmät työkielet ja suomen lisäksi osa oman opintopolkuni ydintä. Aluksi käsittelen fraseologismien ominaispiirteitä ja luonnetta teoreettisesta näkökulmasta yleisellä tasolla. Fraseologismit ovat kiteytettynä useampisanaisia ilmauksia, joiden merkitys tai rakenne ei vastaa osiensa summaa vaan muodostavat oman kielellisen yksikkönsä. Aineistosta käy kuitenkin selvästi ilmi, että kiteytyneisyyden aste saattaa vaihdella paljonkin eri ilmaustyyppien välillä. Tutkimustulokseni osoittavat, että täysistuntokeskusteluissa, etenkin kriisitilanteissa, käytetään runsaasti kuvaannollista kieltä ja hyvin erityyppisiä fraseologismeja. Aineistoni suurimpina fraseologismityyppeinä ovat nominaaliset puhutteluilmaukset, metaforiset fraseologismit ja terminologiset fraseologismit. Eri ilmaustyyppejä käytetään moniin eri tarkoituksiin varsinkin tutkielmani kontekstissa, jossa sotilaallinen konflikti aiheuttaa puhujissa voimakkaita tunnetiloja. Ensimmäisen ilmaustyypin pääfunktiona on faattinen funktio, toisen emotiivinen ja poeettinen funktio ja kolmannen referentiaalinen funktio. Tulkit onnistuvat pääsääntöisesti säilyttämään lähdepuheenvuoron kielellisen funktion, vaikka eivät aina tulkkauksen rajoitteista johtuen löydäkään idiomaattista muotovastinetta. Etenkin metaforisten fraseologismien ymmärtäminen saattaa olla tulkeille vaikeaa, mikä johtaa epäselvyyksiin tulkkauksessa. Siksi sekä kääntäjien että tulkkien on syytä kehittää omien työkielten, etenkin vieraan B-työkielen, fraseologismien osaamista. Todettakoon lopuksi, että työtä fraseologian ja kuvaannollisen kielen tutkimiseksi laajemminkin kannattaa jatkaa idiomaattisen kielenkäytön juurruttamiseksi myös osaksi asiatekstikääntäjän ja tulkin ammattiosaamista ja valmistautumista toimeksiantoihin.

Introduction: A significant barrier to medical diagnostics in low-resource environments is the lack of medical care and equipment. Here we present a low-cost, cloud-connected digital microscope for applications at the point-of-care. We evaluate the performance of the device in the digital assessment of estrogen receptor-alpha (ER) expression in breast cancer samples. Studies suggest computer-assisted analysis of tumor samples digitized with whole slide-scanners may be comparable to manual scoring, here we study whether similar results can be obtained with the device presented. Materials and methods: A total of 170 samples of human breast carcinoma, immunostained for ER expression, were digitized with a high-end slide-scanner and the point-of-care microscope. Corresponding regions from the samples were extracted, and ER status was determined visually and digitally. Samples were classified as ER negative (<1% ER positivity) or positive, and further into weakly (1-10% positivity) and strongly positive. Interobserver agreement (Cohen's kappa) was measured and correlation coefficients (Pearson's product-momentum) were calculated for comparison of the methods. Results: Correlation and interobserver agreement (r = 0.98, p < 0.001, kappa = 0.84, CI95% = 0.75-0.94) were strong in the results from both devices. Concordance of the point-of-care microscope and the manual scoring was good (r = 0.94, p < 0.001, kappa = 0.71, CI95% = 0.61-0.80), and comparable to the concordance between the slide scanner and manual scoring (r = 0.93, p < 0.001, kappa = 0.69, CI95% = 0.60-0.78). Fourteen (8%) discrepant cases between manual and device-based scoring were present with the slide scanner, and 16 (9%) with the point-of-care microscope, all representing samples of low ER expression. Conclusions: Tumor ER status can be accurately quantified with a low-cost imaging device and digital image-analysis, with results comparable to conventional computer-assisted or manual scoring. This technology could potentially be expanded for other histopathological applications at the point-of-care.

The natural carbon cycle is affected by human activity. Terrestrial carbon stocks have been decreasing as at the same time carbon dioxide concentration in the atmosphere has increased causing climate change. The Paris Agreement sets the target to limit climate change to 1.5°C and to reach that goal, all possible mitigation practises should be included into global framework to avoid the most serious consequences of warming. Carbon sequestration into natural soil and biomass could be one mitigation practice. To enhance carbon sequestration activities and to include natural carbon stocks into to the EU climate policy, it would be necessary to quantify stock sizes and changes in those stocks. For developing carbon trading markets, the quantification methods should provide accurate results and at the same time be practical and financially achievable. Used research method in this thesis was comparatively literature survey and aim was to gather and compere information about currently used carbon stock quantification methods against developing carbon trading markets. Soil carbon stocks can be quantified with direct soil sampling, spectroscopic sensing methods or by mathematical models. Biomass carbon stocks can be quantified with inventory-based field measurements and modelling and by remote sensing. The full carbon budget on the ecosystem level can be achieved with carbon flux measurements. Quantification of different terrestrial carbon stocks and their changes is not a simple task. There is a lot of variation between different stocks and in some cases, the stock changes occur slow. Cost of carbon stock quantification depends on the accuracy, size of the area under focus and frequency of the measures. Methods for terrestrial carbon stock quantification are dependent on high quality data and there is demand for research considering carbon sequestration. For carbon offsetting purposes of developing carbon markets, the modelling approach is achievable, cost efficient, repeatable and transparent. There is no perfect model or one universal model that would fit to every situation and thus the differences must be known. At this stage, this approach could be one possibility to include small scale projects and enhance climate actions. Different quantification methods provide information which can be used to different method developments and to increase accuracies. It’s important to know, how all information can be effectively utilized.

Norway spruce (Picea abies (L.) Karst.) is one of the economically most important tree species in Finland. It is known to be drought-sensitive species and expected to suffer from the warming climate. In addition, warmer temperatures benefit pest insect Eurasian spruce bark beetle (Ips typographus L.) and pathogen Heterobasidion parviporum, which both use Norway spruce as their host and can make the future of Norway spuce in Finland even more difficult. In this thesis, adult Norway spruce mortality was studied from false colour aerial photographs taken in years between 2010 and 2021. Dead trees were detected from the photos by visual inspection, and mortality was calculated based on the difference in the number of dead trees in the photos from different years. The aim was to find out if Norway spruce mortality in Finland had increased over time, and what were the factors that had been driving tree mortality. The results indicate that tree mortality was the highest in the last third of the studied 10-year period, so it was concluded that tree mortality had increased over time. Various possible tree mortality drivers were analysed and found to be connected to tree mortality. Each driver was analysed individually by testing correlation with tree mortality. In addition, linear regression analysis and segmented linear regression with one breakpoint were used with the continuous variables. Increased tree mortality correlated with higher stand mean age, mean height, mean diamater, and mean volume, supporting the findings in earlier research. Mortality was connected to the proportion of different tree species in the stand: the higher the proportion of spruce, the higher the mortality, and the higher the proportion of deciduous trees, the lower the mortality. Of different fertility classes, tree mortality was the highest in the second most fertile class, herb-rich heat forest, and mortality decreased with decreasing fertility. Dead trees were also found to be located closer to stand edges than the stand centroid. Increased temperature resulted in increased mortality. Increased vapour pressure deficit (VPD) and drought, which was analysed with Standardized Precipitation Evapotranspiration Index (SPEI) of different time scales, were also connected with increased tree mortality. Further research is required for understanding and quantifying the joint effect of all the interacting mortality drivers. Nevertheless, it seems that for Norway spruce, the warmer future with increased mortality is already here, and it should be taken into consideration in forest management. Favouring mixed stands could be one of the solutions to help Norway spruce survive in the warming climate.