35 resultados para TARGETED DELIVERY


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This thesis was made for a large forest industry company’s business segment. The purpose of the study was to improve the performance of the order-to-delivery process of the business segment. The study proceeded in three phases. The first phase was to define customer expectations in the market. The second phase was to analyse the performance and the operations of the order-to-delivery process, and to define any challenges or problems in serving the customers. The third and final phase was improving the performance of the order-to-delivery process, within the scope defined by the first two phases. The analysis showed that the delivery reliability is an essential but a challenging issue in the case company’s markets. On delivery reliability standpoint, the most challenging factors were the detected information flow distortions within the company as well as in the whole supply chain, and the lack of horizontal control over the multi-stage process.

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The goal of the study was to analyse orthodontic care in Finnish health centres with special reference to the delivery, outcome and costs of treatment. Public orthodontic care was studied by two questionnaires sent to the chief dental officers of all health centres (n = 276) and to all specialist orthodontists in Finland (n = 146). The large regional variation was mentioned by the orthodontists as the most important factor requiring improvement. Orthodontic practices and outcome were studied in eight Finnish municipal health centres representing early and late timing of treatment. A random sample of 16- and 18-year-olds (n = 1109) living in these municipalities was examined for acceptability of occlusion with the Occlusal Morphology and Function Index (OMFI). In acceptability of occlusion, only minor differences were found between the two timing groups. The percentage of subjects with acceptable morphology was higher among untreated than among treated adolescents. The costs of orthodontic care were estimated among the adolescents with a treatment history. The mean appliance costs were higher in the late, and the mean visit costs higher in the early timing group. The cost-effectiveness of orthodontic services differed among the health centres, but was almost equal in the two timing groups. National guidelines and delegation of orthodontic tasks were suggested as the tools for reducing the variation among the health centres. In the eight health centres, considerable variation was found in acceptability of occlusion and in cost-effectiveness of services. The cost-effectiveness was not directly connected with the timing of treatment.

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Photosynthetic reactions are divided in two parts: light-driven electron transfer reactions and carbon fixation reactions. Electron transfer reactions capture solar energy and split water molecules to form reducing energy (NADPH) and energy-carrying molecules (ATP). These end-products are used for fixation of inorganic carbon dioxide into organic sugar molecules. Ferredoxin-NADP+ oxidoreductase (FNR) is an enzyme that acts at the branch point between the electron transfer reactions and reductive metabolism by catalyzing reduction of NADP+ at the last step of the electron transfer chain. In this thesis, two isoforms of FNR from A rabidopsis thaliana, FNR1 and FNR2, were characterized using the reverse genetics approach. The fnr1 and fnr2 mutant plants resembled each other in many respects. Downregulation of photosynthesis protected the single fnr mutant plants from excess formation of reactive oxygen species (ROS), even without significant upregulation of antioxidative mechanisms. Adverse growth conditions, however, resulted in phenotypic differences between fnr1 and fnr2. While fnr2 plants showed downregulation of photosynthetic complexes and upregulation of antioxidative mechanisms under low-temperature growth conditions, fnr1 plants had the wild-type phenotype, indicating that FNR2 may have a specific role in redistribution of electrons under unfavorable conditions. The heterozygotic double mutant (fnr1xfnr2) was severely devoid of chloroplastic FNR, which clearly restricted photosynthesis. The fnr1xfnr2 plants used several photoprotective mechanisms to avoid oxidative stress. In wild-type chloroplasts, both FNR isoforms were found from the stroma, the thylakoid membrane, and the inner envelope membrane. In the absence of the FNR1 isoform, FNR2 was found only in the stroma, suggesting that FNR1 and FNR2 form a dimer, by which FNR1 anchors FNR2 to the thylakoid membrane. Structural modeling predicted formation of an FNR dimer in complex with ferredoxin. In this thesis work, Tic62 was found to be the main protein that binds FNR to the thylakoid membrane, where Tic62 and FNR formed high molecular weight complexes. The formation of such complexes was shown to be regulated by the redox state of the chloroplast. The accumulation of Tic62-FNR complexes in darkness and dissociation of complexes from the membranes in light provide evidence that the complexes may have roles unrelated to photosynthesis. This and the high viability of fnr1 mutant plants lacking thylakoid-bound FNR indicate that the stromal pool of FNR is photosynthetically active.

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The purpose of this thesis is to study organizational core values and their application in practice. With the help of literature, the thesis discusses the implementation of core values and the benefits that companies can gain by doing it successfully. Also, ways in which companies can improve their values’ application to their everyday work are presented. The case company’s value implementation is evaluated through a survey research conducted on their employees. The true power of values lies in their application, and therefore, core values should be the basis for all organizational behavior, integrated into everything a company does. Applying values in practice is an ongoing process and companies should continuously work towards creating a more value-based organizational culture. If a company does this effectively, they will most likely become more successful with stakeholders as well as financially. Companies looking to turn their values into actions should start with a self-assessment. Employee surveys are effective in assessing the current level of value implementation, since employees have valuable, first-hand information regarding the situations and behaviors they face in their everyday work. After the self-assessment, things like management commitment, communication, training, and support are key success factors in value implementation.

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The use of intensity-modulated radiotherapy (IMRT) has increased extensively in the modern radiotherapy (RT) treatments over the past two decades. Radiation dose distributions can be delivered with higher conformality with IMRT when compared to the conventional 3D-conformal radiotherapy (3D-CRT). Higher conformality and target coverage increases the probability of tumour control and decreases the normal tissue complications. The primary goal of this work is to improve and evaluate the accuracy, efficiency and delivery techniques of RT treatments by using IMRT. This study evaluated the dosimetric limitations and possibilities of IMRT in small (treatments of head-and-neck, prostate and lung cancer) and large volumes (primitive neuroectodermal tumours). The dose coverage of target volumes and the sparing of critical organs were increased with IMRT when compared to 3D-CRT. The developed split field IMRT technique was found to be safe and accurate method in craniospinal irradiations. By using IMRT in simultaneous integrated boosting of biologically defined target volumes of localized prostate cancer high doses were achievable with only small increase in the treatment complexity. Biological plan optimization increased the probability of uncomplicated control on average by 28% when compared to standard IMRT delivery. Unfortunately IMRT carries also some drawbacks. In IMRT the beam modulation is realized by splitting a large radiation field to small apertures. The smaller the beam apertures are the larger the rebuild-up and rebuild-down effects are at the tissue interfaces. The limitations to use IMRT with small apertures in the treatments of small lung tumours were investigated with dosimetric film measurements. The results confirmed that the peripheral doses of the small lung tumours were decreased as the effective field size was decreased. The studied calculation algorithms were not able to model the dose deficiency of the tumours accurately. The use of small sliding window apertures of 2 mm and 4 mm decreased the tumour peripheral dose by 6% when compared to 3D-CRT treatment plan. A direct aperture based optimization (DABO) technique was examined as a solution to decrease the treatment complexity. The DABO IMRT technique was able to achieve treatment plans equivalent with the conventional IMRT fluence based optimization techniques in the concave head-and-neck target volumes. With DABO the effective field sizes were increased and the number of MUs was reduced with a factor of two. The optimality of a treatment plan and the therapeutic ratio can be further enhanced by using dose painting based on regional radiosensitivities imaged with functional imaging methods.

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The focus of this thesis is the issues related to the operational purchasing level supply chain process. Due to this limitation, the physical product quality issues do not belong to the primary concerns of this thesis, whereas the bilateral processes between the supplier and the purchasing organizations are of interest. Also, the issues related to the delivery timing are excluded from the study. Because the perspective is on the issues involved in the supply chain operations, the bilateral communication issues between supplier representative and purchaser are also considered.

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Cesarean section (CS) is the most common major surgery performed on women worldwide. CS can save the life of the mother or the fetus, but is associated with the typical complications of any major surgery: hemorrhage, infection, venous thromboembolism and complications of anesthesia, sometimes leading to maternal death. Recently there have been several reports from well resourced countries on increased severe maternal morbidity and even mortality. Increased rates of CS, obesity and older mothers may explain this rise. The aim of this thesis is to study the rates and risk factors of short term maternal complications associated with CS. Also, we compared maternal morbidity by mode of delivery and over time. The complication rates were assessed in a prospective study involving 2496 CS performed in the 12 largest delivery units in Finland in 2005. The rates of severe complications were studied by mode of delivery in a register-based study comparing national cohorts in 1997 and 2002. The impact of several risk factors on severe maternal morbidity by mode of delivery was studied in a register-based study of all singleton deliveries in 2007-2011. In the prospective study, 27% of the women who underwent CS had one or more intraoperative or postoperative complications during their hospital stay, and 10% had a severe complication. In the register-based study the incidence of life-threatening maternal complications was 7.6 in 1000 deliveries. The incidence was lowest for vaginal delivery (VD), followed by instrumental VD and elective CS, and highest in emergency CS. An attempt of VD, including the risks associated with emergency CS, seems to be the safest mode of delivery, even for most high-risk women.

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Biokuvainformatiikan kehittäminen – mikroskopiasta ohjelmistoratkaisuihin – sovellusesimerkkinä α2β1-integriini Kun ihmisen genomi saatiin sekvensoitua vuonna 2003, biotieteiden päätehtäväksi tuli selvittää eri geenien tehtävät, ja erilaisista biokuvantamistekniikoista tuli keskeisiä tutkimusmenetelmiä. Teknologiset kehitysaskeleet johtivat erityisesti fluoresenssipohjaisten valomikroskopiatekniikoiden suosion räjähdysmäiseen kasvuun, mutta mikroskopian tuli muuntua kvalitatiivisesta tieteestä kvantitatiiviseksi. Tämä muutos synnytti uuden tieteenalan, biokuvainformatiikan, jonka on sanottu mahdollisesti mullistavan biotieteet. Tämä väitöskirja esittelee laajan, poikkitieteellisen työkokonaisuuden biokuvainformatiikan alalta. Väitöskirjan ensimmäinen tavoite oli kehittää protokollia elävien solujen neliulotteiseen konfokaalimikroskopiaan, joka oli yksi nopeimmin kasvavista biokuvantamismenetelmistä. Ihmisen kollageenireseptori α2β1-integriini, joka on tärkeä molekyyli monissa fysiologisissa ja patologisissa prosesseissa, oli sovellusesimerkkinä. Työssä saavutettiin selkeitä visualisointeja integriinien liikkeistä, yhteenkeräytymisestä ja solun sisään siirtymisestä, mutta työkaluja kuvainformaation kvantitatiiviseen analysointiin ei ollut. Väitöskirjan toiseksi tavoitteeksi tulikin tällaiseen analysointiin soveltuvan tietokoneohjelmiston kehittäminen. Samaan aikaan syntyi biokuvainformatiikka, ja kipeimmin uudella alalla kaivattiin erikoistuneita tietokoneohjelmistoja. Tämän väitöskirjatyön tärkeimmäksi tulokseksi muodostui näin ollen BioImageXD, uudenlainen avoimen lähdekoodin ohjelmisto moniulotteisten biokuvien visualisointiin, prosessointiin ja analysointiin. BioImageXD kasvoi yhdeksi alansa suurimmista ja monipuolisimmista. Se julkaistiin Nature Methods -lehden biokuvainformatiikkaa käsittelevässä erikoisnumerossa, ja siitä tuli tunnettu ja laajalti käytetty. Väitöskirjan kolmas tavoite oli soveltaa kehitettyjä menetelmiä johonkin käytännönläheisempään. Tehtiin keinotekoisia piidioksidinanopartikkeleita, joissa oli "osoitelappuina" α2β1-integriinin tunnistavia vasta-aineita. BioImageXD:n avulla osoitettiin, että nanopartikkeleilla on potentiaalia lääkkeiden täsmäohjaussovelluksissa. Tämän väitöskirjatyön yksi perimmäinen tavoite oli edistää uutta ja tuntematonta biokuvainformatiikan tieteenalaa, ja tämä tavoite saavutettiin erityisesti BioImageXD:n ja sen lukuisten julkaistujen sovellusten kautta. Väitöskirjatyöllä on merkittävää potentiaalia tulevaisuudessa, mutta biokuvainformatiikalla on vakavia haasteita. Ala on liian monimutkainen keskimääräisen biolääketieteen tutkijan hallittavaksi, ja alan keskeisin elementti, avoimen lähdekoodin ohjelmistokehitystyö, on aliarvostettu. Näihin seikkoihin tarvitaan useita parannuksia,

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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Personalized nanomedicine has been shown to provide advantages over traditional clinical imaging, diagnosis, and conventional medical treatment. Using nanoparticles can enhance and clarify the clinical targeting and imaging, and lead them exactly to the place in the body that is the goal of treatment. At the same time, one can reduce the side effects that usually occur in the parts of the body that are not targets for treatment. Nanoparticles are of a size that can penetrate into cells. Their surface functionalization offers a way to increase their sensitivity when detecting target molecules. In addition, it increases the potential for flexibility in particle design, their therapeutic function, and variation possibilities in diagnostics. Mesoporous nanoparticles of amorphous silica have attractive physical and chemical characteristics such as particle morphology, controllable pore size, and high surface area and pore volume. Additionally, the surface functionalization of silica nanoparticles is relatively straightforward, which enables optimization of the interaction between the particles and the biological system. The main goal of this study was to prepare traceable and targetable silica nanoparticles for medical applications with a special focus on particle dispersion stability, biocompatibility, and targeting capabilities. Nanoparticle properties are highly particle-size dependent and a good dispersion stability is a prerequisite for active therapeutic and diagnostic agents. In the study it was shown that traceable streptavidin-conjugated silica nanoparticles which exhibit a good dispersibility could be obtained by the suitable choice of a proper surface functionalization route. Theranostic nanoparticles should exhibit sufficient hydrolytic stability to effectively carry the medicine to the target cells after which they should disintegrate and dissolve. Furthermore, the surface groups should stay at the particle surface until the particle has been internalized by the cell in order to optimize cell specificity. Model particles with fluorescently-labeled regions were tested in vitro using light microscopy and image processing technology, which allowed a detailed study of the disintegration and dissolution process. The study showed that nanoparticles degrade more slowly outside, as compared to inside the cell. The main advantage of theranostic agents is their successful targeting in vitro and in vivo. Non-porous nanoparticles using monoclonal antibodies as guiding ligands were tested in vitro in order to follow their targeting ability and internalization. In addition to the targeting that was found successful, a specific internalization route for the particles could be detected. In the last part of the study, the objective was to clarify the feasibility of traceable mesoporous silica nanoparticles, loaded with a hydrophobic cancer drug, being applied for targeted drug delivery in vitro and in vivo. Particles were provided with a small molecular targeting ligand. In the study a significantly higher therapeutic effect could be achieved with nanoparticles compared to free drug. The nanoparticles were biocompatible and stayed in the tumor for a longer time than a free medicine did, before being eliminated by renal excretion. Overall, the results showed that mesoporous silica nanoparticles are biocompatible, biodegradable drug carriers and that cell specificity can be achieved both in vitro and in vivo.

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Targeted measures bring the greatest benefits for environmental protection in agriculture final report of the TEHO Plus project (2011–2014). Particular priority areas of the project activities included creating a training package for agri-environment advisers and testing it, farm-specific advisory services and exploitation of experiences of advice provision, putting together an information package of agri-environment issues, farm-level experiments, and development of water quality monitoring. The recommendations issued by advisers on targeting environmental measures were based on utilising geographical information material and nutrient balances. The project was implemented in cooperation by Southwest Finland Centre for Economic Development, Transport and the Environment, MTK-Satakunta and MTK-Varsinais-Suomi. The project received funding from the Ministry of Agriculture and Forestry and the Ministry of the Environment. Participating farmers, with whom environmental advice was developed and experiments were carried out, were important partners for the project. The operating area of the project was Satakunta and Varsinais-Suomi in Southwest Finland, but its outcomes can be exploited nationally. A national perspective was ensured by close cooperation with actors in different provinces. This final report describes project experiences and outcomes including environmental advisory services, training of agri-environmental advisers, farm visits and the feedback received from farmers on agri-environmental advice, development of water quality monitoring, experiments and project work.

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Customer satisfaction should be the main focus for all of the parts of the business. Usually supply chain behind the business is in a key role when this focus is pursued especially in repair service business. When focusing on the materials that are needed to make repairs to equipment under service contracts, the time aspect of quality is critical. Do late deliveries from supplier have an effect on the service performance of repairs when distribution center of a centralized purchasing unit is acting as a buffer between suppliers and repair service business? And if so, how should the improvement efforts be prioritized? These are the two main questions that this thesis focuses on. Correlation and linear regression was tested between service levels of supplier and distribution center. Percentage of on-time deliveries were compared to outbound delivery service level. It was found that there is statistically significant correlation between inbound and outbound operations success. The other main question of the thesis, improvement prioritization, was answered by creating material availability based supplier classification and additional to that, by developing the decision process for the analysis of most critical suppliers. This was built on a basis of previous supplier and material classification methods.

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The target of this thesis is to evaluate a bid, project and resource management IT tool for service delivery process via proof-of-concept (POC) project to assess, if the tested software is an appropriate tool for the Case Company’s business requirements. Literature suggests that IT projects implementation is still a grey area in scientific research. Also, IT projects have a notably high rate of failure, one significant reason for this being insufficient planning. To tackle this risk, the Case Company decided to perform a POC project, which involved a hands-on testing period of the assessed system. End users from the business side feel that current, highly tailored project management tool is inflexible, difficult to use, and sets unnecessary limitations for the business. Semi-structured interviews and a survey form are used to collect information about current business practices and business requirements related to the IT tool. For the POC project, a project group involving members from each of the Case Company’s four business divisions was established to perform the hands-on testing. Based on data acquired during the interviews and the hands-on testing period, a target state was defined and a gap analysis was carried out by comparing the features provided by the current tool and the tested tool to the target state, which are, together with the current state description, the most important result of the thesis.