859 resultados para limitations of therapy


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The main goal of the present Master’s Thesis project was to create a field-programmable gate array (FPGA) based system for the control of single-electron transistors or other cryoelectronic devices. The FPGA and similar technologies are studied in the present work. The fixed and programmable logic are compared with each other. The main features and limitations of the hardware used in the project are investigated. The hardware and software connections of the device to the computer are shown in detail. The software development techniques for FPGA-based design are described. The steps of design for programmable logic are considered. Furthermore, the results of filters implemented in the software are illustrated.

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The growing importance of global sustainability issues has been causing many changes to the financial services industry. Facts such as climate change, social development and the financial crisis in 2008 have been making banks reconsider the manner that they consider environmental, social and economic factors in their decision-making process. At the same time, information technology (IT) has been transforming the financial service industry and its fast development has casted doubts on the way it should be managed within an organization. This current changing environment brings a number of uncertainties to the future that cannot be addressed using traditional forecasting techniques. This research investigates how IT can bring value to sustainability in the financial service industry in 2020. Through the use of a scenario planning technique, we analyzed how trends in the current environment (considering the relation between sustainability, financial institutions an IT) can lead to four different future scenarios. Then, we discussed how IT can improve a bank’s sustainability performance, considering the limitations of each scenario.

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The human body eliminates foreign compounds primarily by metabolizing them to hydrophilic forms to facilitate effective excretion through the kidneys. Cytochrome P450 (CYP) enzymes in the liver and intestine contribute to the metabolism of many drugs. Pharmacokinetic drugdrug interactions occur if the activity of CYPs are inhibited or induced by another drug. Prescribing multiple drugs to the improve effectiveness of therapy or to treat coexisting diseases is a common practice in clinical medicine. Polypharmacy predisposes patients to adverse effects because of the profound unpredictability in CYP enzymatic-mediated drug metabolism. S-ketamine is a phencyclidine derivative which functions as an antagonist of the N-methyl-Daspartate (NMDA) receptor in the central nervous system. It is a unique anaesthetic producing “dissociative anaesthesia” in high doses and analgesia in low doses. Studies with human liver microsomes suggest that ketamine is metabolized primarily via CYP3A4 and CYP2B6 enzymes. In this thesis, in healthy volunteers, randomized and controlled cross-over studies were conducted to investigate the effects of different CYP inducers and inhibitors on the pharmacokinetics and pharmacodynamics of oral and intravenous S-ketamine. The plasma concentrations of ketamine and its metabolite, norketamine, were determined at different timepoints over a 24 hour period. Other pharmacodynamic variables were examined for 12 hours. Results of these studies showed that the inhibition of the CYP3A4 pathway by clarithromycin or grapefruit juice increased the exposure to oral S-ketamine by 2.6- and 3.0-fold. Unexpectedly, CYP3A4 inhibition by itraconazole caused no significant alterations in the plasma concentrations of oral S-ketamine. CYP3A4 induction by St. John´s wort or rifampicin decreased profoundly the concentrations of oral S-ketamine. However, after rifampicin, there were no significant differences in the plasma concentrations of S-ketamine when it was administered intravenously. This demonstrated that rifampicin inhibited the metabolism of Sketamine at the intestinal level. When CYP2B6 was inhibited by ticlopidine, there was a 2.4- fold increase in the exposure of S-ketamine. These studies demonstrated that low dose oral Sketamine is metabolized both via CYP3A4 and CYP2B6 pathways. The concomitant use of drugs that affect CYP3A4 or CYP2B6, during oral S-ketamine treatment, may cause clinically significant drug-drug interactions.

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This monograph dissertation looks into the field of ICT-mediated health and well-being services. Through six chapters that extend the work done in the reviewed and published articles, the dissertation focuses on new and emerging technologies, and to impact of their use on the beneficiary; the individual who eventually derives advantage from the services. As the field is currently going through major changes particularly in the OECD countries, the focus is on shortterm developments in the field and the analysis on the long term developments is cursory by nature. The dissertation includes theoretical and empirical elements. Most of the empirical elements are linked to product development and conceptualization performed in the national MyWellbeing project that ended in 2010. In the project, the emphasis was on conceptualization of a personal aid for the beneficiary that could be used for managing information and services in the field of health and well-being services. This work continued the theme of developing individual-centric solutions for the field; a work that started in the InnoElli Senior program in 2006. The nature of this thesis is foremost a conceptual elaboration based on a literature review, illustrated in empirical work performed in different projects. As a theoretical contribution, this dissertation elaborates the role of a mediator, i.e. an intermediary, and it is used as an overarching theme. The role acts as a ‘lens’ through which a number of technology-related phenomena are looked at, pinned down and addressed to a degree. This includes introduction of solutions, ranging from anthropomorphic artefacts to decision support systems that may change the way individuals experience clinical encounters in the near-future. Due to the complex and multiform nature of the field, it is impractical and effectively impossible to cover all aspects that are related to mediation in a single work. Issues such as legislation, financing and privacy are all of equal importance. Consideration of all these issues is beyond the scope of this dissertation and their investigation is left to other work. It follows from this that the investigation on the role is not intended as inclusive one. The role of the mediator is also used to highlight some of the ethical issues related to personal health information management, and to mediating health and well-being related issues on behalf of another individual, such as an elderly relative or a fellow member of a small unit in the armed forces. The dissertation concludes in a summary about the use and functions of the mediator, describing some potential avenues for implementing such support mechanisms to the changing field of ICT-mediated health and well-being services. The conclusions also describe some of the limitations of this dissertation, including remarks on methodology and content.

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Nowadays the Western companies are considered responsible for the social and environmental issues in their whole supply chains. To influence the practices of their suppliers the Western companies have created suppliers codes of conduct (SCCs) which express their requirements. Suppliers’ compliance with the SCCs is checked through audits. The purpose of this thesis is to analyze SCCs as a means for Western companies to ensure socially and environmentally responsible actions in their global supply chains, and the sub-objectives are to find out 1) how well do the SCCs and their auditing work at suppliers’ production sites and 2) how can possible problems related to SCCs and their auditing be solved. This is a qualitative research carried out in the form of a case study with two case companies. In this study both primary and secondary data is used. The primary data is collected in the form of interviews of the case company representatives and three external experts. Based on a theoretical framework of previous research in the fields of corporate social responsibility and supply chain management, a model with eleven factors, which influence the success of SCC implementation and the auditing of SCC –implementation, is drafted. Also several different best-practices to help to solve and avoid possible problems related to SCC -implementation and auditing have been identified from previous research. Based on the findings of this study the theoretical model has been updated adding two new influential factors. It seems that how well the SCC and its auditing work at suppliers’ production sites depends on the joint effect of thirteen influential factors: buyer’s purchasing policy, supplier’s motivation, buyer’s commitment, the solving of agency problems, the contents of the SCC, supplier’s role and the buyer-supplier –relationship, complexity of supply chain, the limitations of the smaller buyers, cooperation through a business association or multi-stakeholder system, the role of supplier’s employees, SCC –related communication and supplier’s understanding, cheating in audits and the auditors. The possible problems related to SCCs and their auditing can be solved by adopting best-practices. Nine of the theoretical best-practices stand out from the findings of this study: 1) two-way communication and collecting feedback from suppliers, 2) the philosophy of continuous improvement, 3) long-term business relationships with the supplier, 4) informing the supplier about the advantages of SCC –compliance, 5) rewarding code-compliant suppliers, 6) building collaborative, good buyer-supplier relationships, 7) supporting and advising the supplier, 8) joining a business association or multi-stakeholder system and 9) interviewing supplier’s employees as a part of the audits.

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The aim of this master’s thesis is to introduce what is experimental research and how the researcher is able to use this researching method in business-to-business context. This work has been done with analyzing articles of four academic marketing journals from years 1992-2012. In the literature part there is introduction of the nature of the experimental research, its terminology and design. There is also discussion about limitations of experimental research and comparison of experimental research to quasi-experimental design. In the results part there is a review how experimental research has been used in the business-to-business context in the past two decades. In the analysis there is introduction of themes, samplings, different kinds of variables and main findings. The work offers a good understanding to nature of experimental research and useful data for organizing a real experimental study.

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Retaining players and re-attracting switching players has long been a central topic for SNG providers with regard to the post-adoption stage of playing an online game. However, there has not been much research which has explored players’ post-adoption behavior by incorporating the continuance intention and the switching intention. In addition, traditional IS continuance theories were mainly developed to investigate users’ continued use of utilitarian IS, and thus they may fall short when trying to explain the continued use of hedonic IS. Furthermore, compared to the richer literature on IS continuance, far too little attention has been paid to IS switching, leading to a dearth of knowledge on the subject, despite the increased incidence of the switching phenomenon in the IS field. By addressing the limitations of prior literature, this study seeks to examine the determinants of SNG players’ two different post-adoption behaviors, including the continuance intention and the switching intention. This study takes a positivist approach and uses survey research method to test five proposed research models based on Unified Theory of Acceptance and Use of Technology 2; Use and Gratification Theory; Push-Pull-Mooring model; Cognitive Dissonance Theory; and a self-developed model respectively with empirical data collected from the SNG players of one of the biggest SNG providers in China. A total of 3919 valid responses and 541 valid responses were used to examine the continuance intention and the switching intention, respectively. SEM is utilized as the data analysis method. The proposed research models are supported by the empirical data. The continuance intention is determined by enjoyment, fantasy, escapism, social interaction, social presence, social influence, achievement and habit. The switching intention is determined by enjoyment, satisfaction, subjective norms, descriptive norms, alternative attractiveness, the need for variety, change experience, and adaptation cost. This study contributes to IS theories in three important ways. Firstly, it shows IS switching should be included in IS post-adoption research together with IS continuance. Secondly, a modern IS is usually multi-functional and SNG players have multiple reasons for using a SNG, thus a player’s beliefs about the hedonic, social and utilitarian perceptions of their continued use of the SNG exert significant effects on the continuance intention. Thirdly, the determinants of the switch ing intention mainly exert push, pull, and mooring effects. Players’ beliefs about their current SNG and the available alternatives, as well as their individual characteristics are all significant determinants of the switching intention. SNG players combine these effects in order to formulate the switching intention. Finally, this study presents limitations and suggestions for future research.

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This study was done for ABB Ltd. Motors and Generators business unit in Helsinki. In this study, global data movement in large businesses is examined from a product data management (PDM) and enterprise resource planning (ERP) point-of-view. The purpose of this study was to understand and map out how a large global business handles its data in a multiple site structure and how it can be applied in practice. This was done by doing an empirical interview study on five different global businesses with design locations in multiple countries. Their master data management (MDM) solutions were inspected and analyzed to understand which solution would best benefit a large global architecture with many design locations. One working solution is a transactional hub which negates the effects of multisite transfers and reduces lead times. Also, the requirements and limitations of the current MDM architecture were analyzed and possible reform ideas given.  

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Abnormal riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson's disease (PD), while the classical determinants of homocysteine levels (B6, folic acid, and B12) were usually within normal limits. In contrast, only 3 of 10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status. The data for 12 patients who did not complete 6 months of therapy or did not comply with the proposed treatment paradigm were excluded from analysis. Nineteen PD patients (8 males and 11 females, mean age ± SD = 66.2 ± 8.6 years; 3, 3, 2, 5, and 6 patients in Hoehn and Yahr stages I to V) received riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet. After 1 month the riboflavin status of the patients was normalized from 106.4 ± 34.9 to 179.2 ± 23 ng/ml (N = 9). Motor capacity was measured by a modification of the scoring system of Hoehn and Yahr, which reports motor capacity as percent. All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed. The data show that the proposed treatment improves the clinical condition of PD patients. Riboflavin-sensitive mechanisms involved in PD may include glutathione depletion, cumulative mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. More studies are required to identify the mechanisms involved.

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This thesis presents an analysis of recently enacted Russian renewable energy policy based on capacity mechanism. Considering its novelty and poor coverage by academic literature, the aim of the thesis is to analyze capacity mechanism influence on investors’ decision-making process. The current research introduces a number of approaches to investment analysis. Firstly, classical financial model was built with Microsoft Excel® and crisp efficiency indicators such as net present value were determined. Secondly, sensitivity analysis was performed to understand different factors influence on project profitability. Thirdly, Datar-Mathews method was applied that by means of Monte Carlo simulation realized with Matlab Simulink®, disclosed all possible outcomes of investment project and enabled real option thinking. Fourthly, previous analysis was duplicated by fuzzy pay-off method with Microsoft Excel®. Finally, decision-making process under capacity mechanism was illustrated with decision tree. Capacity remuneration paid within 15 years is calculated individually for each RE project as variable annuity that guarantees a particular return on investment adjusted on changes in national interest rates. Analysis results indicate that capacity mechanism creates a real option to invest in renewable energy project by ensuring project profitability regardless of market conditions if project-internal factors are managed properly. The latter includes keeping capital expenditures within set limits, production performance higher than 75% of target indicators, and fulfilling localization requirement, implying producing equipment and services within the country. Occurrence of real option shapes decision-making process in the following way. Initially, investor should define appropriate location for a planned power plant where high production performance can be achieved, and lock in this location in case of competition. After, investor should wait until capital cost limit and localization requirement can be met, after that decision to invest can be made without any risk to project profitability. With respect to technology kind, investment into solar PV power plant is more attractive than into wind or small hydro power, since it has higher weighted net present value and lower standard deviation. However, it does not change decision-making strategy that remains the same for each technology type. Fuzzy pay-method proved its ability to disclose the same patterns of information as Monte Carlo simulation. Being effective in investment analysis under uncertainty and easy in use, it can be recommended as sufficient analytical tool to investors and researchers. Apart from described results, this thesis contributes to the academic literature by detailed description of capacity price calculation for renewable energy that was not available in English before. With respect to methodology novelty, such advanced approaches as Datar-Mathews method and fuzzy pay-off method are applied on the top of investment profitability model that incorporates capacity remuneration calculation as well. Comparison of effects of two different RE supporting schemes, namely Russian capacity mechanism and feed-in premium, contributes to policy comparative studies and exhibits useful inferences for researchers and policymakers. Limitations of this research are simplification of assumptions to country-average level that restricts our ability to analyze renewable energy investment region wise and existing limitation of the studying policy to the wholesale power market that leaves retail markets and remote areas without our attention, taking away medium and small investment into renewable energy from the research focus. Elimination of these limitations would allow creating the full picture of Russian renewable energy investment profile.

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Phytotherapies have offered alternative sources of therapy for migraine and gained much importance in prophylactic treatment. Sapindus trifoliatus is a medium-sized deciduous tree growing wild in south India that belongs to the family Sapindaceae. The pericarp is reported for various medicinal properties. A thick aqueous solution of the pericarp is used for the treatment of hemicrania, hysteria or epilepsy in folklore medicine. We have investigated the antihyperalgesic effects of the lyophilized aqueous extract of S. trifoliatus in animal models predictive of experimental migraine models using morphine withdrawal-induced hyperalgesia on the hot-plate test and on 0.3% acetic acid-induced abdominal constrictions in adult male Swiss albino mice. The extract significantly (N = 10, P < 0.05) increased the licking latency in the hot-plate test when administered ip at 10 mg/kg (6.70 ± 0.39 s in saline control vs 18.76 ± 0.96 s in S. trifoliatus-treated animals) and significantly (N = 10, P < 0.001) reduced the abdominal constrictions when administered ip at 2 and 10 mg/kg (40.20 ± 1.36 in saline control vs 30.20 ± 1.33 and 23.00 ± 0.98 for 2 and 10 mg/kg, ip, respectively, in S. trifoliatus-treated animals). Furthermore, when administered ip at 20 and 100 mg/kg, the extract significantly (N = 10, P < 0.05) inhibited the apomorphine-induced climbing behavior in mice (climbing duration 15.75 ± 5.0 min for saline control vs 11.4 ± 1.28 and 3.9 ± 1.71 min for 20 and 100 mg/kg, respectively, in S. trifoliatus-treated animals). In receptor radioligand-binding studies, the extract exhibited affinity towards D2 receptors. The findings suggest that dopamine D2 antagonism could be the mechanism involved in the antihyperalgesic activity of the aqueous extract of S. trifoliatus.

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Asthma is a common chronic illness that imposes a heavy burden on all aspects of the patient's life, including personal and health care cost expenditures. To analyze the direct cost associated to uncontrolled asthma patients, a cross-sectional study was conducted to determine costs related to patients with uncontrolled and controlled asthma. Uncontrolled patient was defined by daytime symptoms more than twice a week or nocturnal symptoms during two consecutive nights or any limitations of activities, or need for relief rescue medication more than twice a week, and an ACQ score less than 2 points. A questionnaire about direct cost stratification in health services, including emergency room visits, hospitalization, ambulatory visits, and asthma medications prescribed, was applied. Ninety asthma patients were enrolled (45 uncontrolled/45 controlled). Uncontrolled asthmatics accounted for higher health care expenditures than controlled patients, US$125.45 and US$15.58, respectively [emergency room visits (US$39.15 vs US$2.70) and hospitalization (US$86.30 vs US$12.88)], per patient over 6 months. The costs with medications in the last month for patients with mild, moderate and severe asthma were US$1.60, 9.60, and 25.00 in the uncontrolled patients, respectively, and US$6.50, 19.00 and 49.00 in the controlled patients. In view of the small proportion of uncontrolled subjects receiving regular maintenance medication (22.2%) and their lack of resources, providing free medication for uncontrolled patients might be a cost-effective strategy for the public health system.

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In this thesis properties and influence of modification techniques of porous silicon were studied by Atomic Force Microscope (AFM). This device permits to visualize the surface topography and to study properties of the samples on atomic scale, which was necessary for recent investigation. Samples of porous silicon were obtained by electrochemical etching. Nickel particles were deposited by two methods: electrochemical deposition and extracting from NiCl2 ethanol solution. Sample growth was conducted in Saint-Petersburg State Electrotechnical University, LETI. Kelvin probe force microscopy (KPFM) and Magnetic force microscopy (MFM) were utilized for detailed information about surface properties of the samples. Measurements showed the difference in morphology correlating with initial growth conditions. Submicron size particles were clearly visible on surfaces of the treated samples. Although their nature was not clarified due to limitations of AFM technique. It is expected that surfaces were covered by nanometer scale Ni particles, which can be verified by implication of RAMAN device.

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Personalized pharmacogenomics aims to use individual genotypes to direct medical treatment. Unfortunately, the loci relevant for the pharmacokinetics and especially the pharmacodynamics of most drugs are still unknown. Moreover, we still do not understand the role that individual genotypes play in modulating the pathogenesis, the clinical course and the susceptibility to drugs of human diseases which, although appearing homogeneous on the surface, may vary from patient to patient. To try to deal with this situation, it has been proposed to use interpopulational variability as a reference for drug development and prescription, leading to the development of "race-targeted drugs". Given the present limitations of genomic knowledge and of the tools needed to fully implement it today, some investigators have proposed to use racial criteria as a palliative measure until personalized pharmacogenomics is fully developed. This was the rationale for the FDA approval of BiDil for treatment of heart failure in African Americans. I will evaluate the efficacy and safety of racial pharmacogenomics here and conclude that it fails on both counts. Next I shall review the perspectives and the predicted rate of development of clinical genomic studies. The conclusion is that "next-generation" genomic sequencing is advancing at a tremendous rate and that true personalized pharmacogenomics, based on individual genotyping, should soon become a clinical reality.

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Electrical stimulation has been used for more than 100 years in neuroscientific and biomedical research as a powerful tool for controlled perturbations of neural activity. Despite quickly driving neuronal activity, this technique presents some important limitations, such as the impossibility to activate or deactivate specific neuronal populations within a single stimulation site. This problem can be avoided by pharmacological methods based on the administration of receptor ligands able to cause specific changes in neuronal activity. However, intracerebral injections of neuroactive molecules inherently confound the dynamics of drug diffusion with receptor activation. Caged compounds have been proposed to circumvent this problem, for spatially and temporally controlled release of molecules. Caged compounds consist of a protecting group and a ligand made inactive by the bond between the two parts. By breaking this bond with light of an appropriate wavelength, the ligand recovers its activity within milliseconds. To test these compounds in vivo, we recorded local field potentials (LFPs) from the cerebral cortex of anesthetized female mice (CF1, 60-70 days, 20-30 g) before and after infusion with caged γ-amino-butyric-acid (GABA). After 30 min, we irradiated the cortical surface with pulses of blue light in order to photorelease the caged GABA and measure its effect on global brain activity. Laser pulses significantly and consistently decreased LFP power in four different frequency bands with a precision of few milliseconds (P < 0.000001); however, the inhibitory effects lasted several minutes (P < 0.0043). The technical difficulties and limitations of neurotransmitter photorelease are presented, and perspectives for future in vivo applications of the method are discussed.