Morphological changes of the jejunal mucosa in protracted diarrhea and their correlation with disease duration, weight loss and serum albumin levels

The pathogenesis of protracted diarrhea is multifactorial. In developing countries, intestinal infectious processes seem to play an important role in triggering the syndrome. Thirty-four children aged 1 to 14 months, mean 6.5 months, with protracted diarrhea were studied clinically and in terms of small intestinal mucosal morphology. Mild, moderate or severe hypotrophy of the jejunal mucosa was detected in 82% of cases, and mucosal atrophy was observed in 12%. The intensity of the morphological changes of the jejunal mucosa correlated negatively with serum albumin levels. No correlation was detected between mucosal grading and duration of diarrhea or between mucosal grading and weight reported as percentile. After nutritional support was instituted, serial jejunal biopsies were obtained from 12 patients: five patients submitted to parenteral nutrition for 7 to 38 days, mean 17 days, and 7 patients receiving a hypoallergenic oral diet (semi-elemental formula, 3; chicken formula, 3; human milk, 1). In seven cases (58%) a progressive increase in villus height and a decrease in the number of inflammatory cells were noted. Recovery of the morphologic pattern was accompanied by clinical improvement in all patients

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 ± 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 ± 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 ± 6.6 years (mean ± SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

Annual changes in serum calcium and inorganic phosphate levels and correlation with gonadal status of a freshwater murrel, Channa punctatus (Bloch)

Adult Channa punctatus murrels of both sexes (60-80 g) were collected locally from Ramgarh Lake during the second week of every month (10 individuals of each sex/month) throughout the year. Blood samples were collected and analyzed for serum calcium and phosphate levels by the methods of Trinder (1960) and Fiske and Subbarow (1925), respectively. Gonads were fixed to judge the state of maturation of the fish. Males exhibited no change in serum calcium levels throughout the year in correlation with testicular maturation. However, serum phosphate levels exhibited a rise in correlation with the increased gonadosomatic index. Females showed marked seasonal changes in serum calcium and phosphate levels which were associated with ovarian maturation (vitellogenesis).

Electro-oscillographic correlation between dorsal raphe nucleus, neocortex and hippocampus during wakefulness before and after serotoninergic inactivation

Theta rhythm in many brain structures characterizes wakefulness and desynchronized sleep in most subprimate mammalian brains. In close relation to behaviors, theta frequency and voltage undergo a fine modulation which may involve mobilization of dorsal raphe nucleus efferent pathways. In the present study we analyzed frequency modulation (through instantaneous frequency variation) of theta waves occurring in three cortical areas, in hippocampal CA1 and in the dorsal raphe nucleus of Wistar rats during normal wakefulness and after injection of the 5-HT1a receptor agonist 8-OH-DPAT into the dorsal raphe. We demonstrated that in attentive states the variation of theta frequency among the above structures is highly congruent, whereas after 8-OH-DPAT injection, although regular signals are present, the variation is much more complex and shows no relation to behaviors. Such functional uncoupling after blockade demonstrates the influence of dorsal raphe nucleus efferent serotoninergic fibers on the organization of alertness, as evaluated by electro-oscillographic analysis.

Intima-media thickness evaluation by B-mode ultrasound: Correlation with blood pressure levels and cardiac structures

The aim of this study was to analyze the thickness of the intima-media complex (IMC) using a noninvasive method. The carotid and femoral common arteries were evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52 hypertensive subjects and the thickness of the IMC was tested for correlation with blood pressure, cardiac structures and several clinical and biological parameters. The IMC was thicker in hypertensive than in normotensive subjects (0.67 ± 0.13 and 0.62 ± 0.16 vs 0.54 ± 0.09 and 0.52 ± 0.11 mm, respectively, P<0.0001). In normotensive patients, the simple linear regression showed significant correlations between IMC and age, body mass index and 24-h systolic blood pressure for both the carotid and femoral arteries. In hypertensives the carotid IMC was correlated with age and 24-h systolic blood pressure while femoral IMC was correlated only with 24-h diastolic blood pressure. Forward stepwise regression showed that age, body mass index and 24-h systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in normotensives. On the other hand, the femoral IMC relationship was influenced by 24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h systolic blood pressure were the most important determinants of carotid IMC (r2 = 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure (r2 = 0.10). There was an association between carotid IMC and echocardiographic findings in normotensives, while in hypertensives only the left posterior wall and interventricular septum were associated with femoral IMC. We conclude that age and blood pressure influence the intima-media thickness, while echocardiographic changes are associated with the IMC.

Application and development of numerical methods for the modelling of innovative gas cooled fission reactors

Innovative gas cooled reactors, such as the pebble bed reactor (PBR) and the gas cooled fast reactor (GFR) offer higher efficiency and new application areas for nuclear energy. Numerical methods were applied and developed to analyse the specific features of these reactor types with fully three dimensional calculation models. In the first part of this thesis, discrete element method (DEM) was used for a physically realistic modelling of the packing of fuel pebbles in PBR geometries and methods were developed for utilising the DEM results in subsequent reactor physics and thermal-hydraulics calculations. In the second part, the flow and heat transfer for a single gas cooled fuel rod of a GFR were investigated with computational fluid dynamics (CFD) methods. An in-house DEM implementation was validated and used for packing simulations, in which the effect of several parameters on the resulting average packing density was investigated. The restitution coefficient was found out to have the most significant effect. The results can be utilised in further work to obtain a pebble bed with a specific packing density. The packing structures of selected pebble beds were also analysed in detail and local variations in the packing density were observed, which should be taken into account especially in the reactor core thermal-hydraulic analyses. Two open source DEM codes were used to produce stochastic pebble bed configurations to add realism and improve the accuracy of criticality calculations performed with the Monte Carlo reactor physics code Serpent. Russian ASTRA criticality experiments were calculated. Pebble beds corresponding to the experimental specifications within measurement uncertainties were produced in DEM simulations and successfully exported into the subsequent reactor physics analysis. With the developed approach, two typical issues in Monte Carlo reactor physics calculations of pebble bed geometries were avoided. A novel method was developed and implemented as a MATLAB code to calculate porosities in the cells of a CFD calculation mesh constructed over a pebble bed obtained from DEM simulations. The code was further developed to distribute power and temperature data accurately between discrete based reactor physics and continuum based thermal-hydraulics models to enable coupled reactor core calculations. The developed method was also found useful for analysing sphere packings in general. CFD calculations were performed to investigate the pressure losses and heat transfer in three dimensional air cooled smooth and rib roughened rod geometries, housed inside a hexagonal flow channel representing a sub-channel of a single fuel rod of a GFR. The CFD geometry represented the test section of the L-STAR experimental facility at Karlsruhe Institute of Technology and the calculation results were compared to the corresponding experimental results. Knowledge was gained of the adequacy of various turbulence models and of the modelling requirements and issues related to the specific application. The obtained pressure loss results were in a relatively good agreement with the experimental data. Heat transfer in the smooth rod geometry was somewhat under predicted, which can partly be explained by unaccounted heat losses and uncertainties. In the rib roughened geometry heat transfer was severely under predicted by the used realisable k − epsilon turbulence model. An additional calculation with a v2 − f turbulence model showed significant improvement in the heat transfer results, which is most likely due to the better performance of the model in separated flow problems. Further investigations are suggested before using CFD to make conclusions of the heat transfer performance of rib roughened GFR fuel rod geometries. It is suggested that the viewpoints of numerical modelling are included in the planning of experiments to ease the challenging model construction and simulations and to avoid introducing additional sources of uncertainties. To facilitate the use of advanced calculation approaches, multi-physical aspects in experiments should also be considered and documented in a reasonable detail.

Analysis and modelling of chemical looping combustion process with and without oxygen uncoupling

Effective control and limiting of carbon dioxide (CO₂) emissions in energy production are major challenges of science today. Current research activities include the development of new low-cost carbon capture technologies, and among the proposed concepts, chemical combustion (CLC) and chemical looping with oxygen uncoupling (CLOU) have attracted significant attention allowing intrinsic separation of pure CO₂ from a hydrocarbon fuel combustion process with a comparatively small energy penalty. Both CLC and CLOU utilize the well-established fluidized bed technology, but several technical challenges need to be overcome in order to commercialize the processes. Therefore, development of proper modelling and simulation tools is essential for the design, optimization, and scale-up of chemical looping-based combustion systems. The main objective of this work was to analyze the technological feasibility of CLC and CLOU processes at different scales using a computational modelling approach. A onedimensional fluidized bed model frame was constructed and applied for simulations of CLC and CLOU systems consisting of interconnected fluidized bed reactors. The model is based on the conservation of mass and energy, and semi-empirical correlations are used to describe the hydrodynamics, chemical reactions, and transfer of heat in the reactors. Another objective was to evaluate the viability of chemical looping-based energy production, and a flow sheet model representing a CLC-integrated steam power plant was developed. The 1D model frame was succesfully validated based on the operation of a 150 kWth laboratory-sized CLC unit fed by methane. By following certain scale-up criteria, a conceptual design for a CLC reactor system at a pre-commercial scale of 100 MWth was created, after which the validated model was used to predict the performance of the system. As a result, further understanding of the parameters affecting the operation of a large-scale CLC process was acquired, which will be useful for the practical design work in the future. The integration of the reactor system and steam turbine cycle for power production was studied resulting in a suggested plant layout including a CLC boiler system, a simple heat recovery setup, and an integrated steam cycle with a three pressure level steam turbine. Possible operational regions of a CLOU reactor system fed by bituminous coal were determined via mass, energy, and exergy balance analysis. Finally, the 1D fluidized bed model was modified suitable for CLOU, and the performance of a hypothetical 500 MWth CLOU fuel reactor was evaluated by extensive case simulations.

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.

Correlation of mixed lymphocyte culture with chronic graft-versus-host disease following allogeneic stem cell transplantation

The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR <=4.5%. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.

Bone mineral density in young women of the city of São Paulo, Brazil: correlation with both collagen type I alpha 1 gene polymorphism and clinical aspects

Osteoporosis is a multifactorial disease with great impact on morbidity and mortality mainly in postmenopausal women. Although it is recognized that factors related to life-style and habits may influence bone mass formation leading to greater or lower bone mass, more than 85% of the variation in bone mineral density (BMD) is genetically determined. The collagen type I alpha 1 (COLIA1) gene is a possible risk factor for osteoporosis. We studied a population of 220 young women from the city of São Paulo, Brazil, with respect to BMD and its correlation with both COLIA1 genotype and clinical aspects. The distribution of COLIA1 genotype SS, Ss and ss in the population studied was 73.6, 24.1 and 2.3%, respectively. No association between these genotypes and femoral or lumbar spine BMD was detected. There was a positive association between lumbar spine BMD and weight (P<0.0001), height (P<0.0156), and body mass index (BMI) (P<0.0156), and a negative association with age at menarche (P<0.0026). There was also a positive association between femoral BMD and weight (P<0.0001), height (P<0.0001), and BMI (P<0.0001), and a negative correlation with family history for osteoporosis (P<0.041). There was no association between the presence of allele s and reduced BMD. We conclude that a family history of osteoporosis and age at menarche are factors that may influence bone mass in our population.

Time Varying Conditional Correlation Between Stock And Bond Returns: Evidence From CIVETS Nations

This thesis estimates long-run time variant conditional correlation between stock and bond returns of CIVETS (Colombia, Indonesia, Vietnam, Egypt, Turkey, and South Africa) nations. Further, aims to analyse the presence of asymmetric volatility effect in both asset returns, as well as, obverses increment or decrement in conditional correlation during pre-crisis and crisis period, which lead to make a reliable diversification decision. The Constant Conditional Correlation (CCC) GARCH model of Bollerslev (1990), the Dynamic Conditional Correlation (DCC) GARCH model (Engle 2002), and the Asymmetric Dynamic Conditional Correlation (ADCC) GARCH model of Cappiello, Engle, and Sheppard (2006) were implemented in the study. The analyses present strong evidence of time-varying conditional correlation in CIVETS markets, excluding Vietnam, during 2005-2013. In addition, negative innovation effects were found in both conditional variance and correlation of the asset returns. The results of this study recommend investors to include financial assets from these markets in portfolios, in order to obtain better stock-bond diversification benefits, especially during high volatility periods.

Fluvio-morphological processes of meander bends - Combining conventional field measurements, close-range remote sensing and computational modelling

Meandering rivers have been perceived to evolve rather similarly around the world independently of the location or size of the river. Despite the many consistent processes and characteristics they have also been noted to show complex and unique sets of fluviomorphological processes in which local factors play important role. These complex interactions of flow and morphology affect notably the development of the river. Comprehensive and fundamental field, flume and theoretically based studies of fluviomorphological processes in meandering rivers have been carried out especially during the latter part of the 20th century. However, as these studies have been carried out with traditional field measurements techniques their spatial and temporal resolution is not competitive to the level achievable today. The hypothesis of this study is that, by exploiting e increased spatial and temporal resolution of the data, achieved by combining conventional field measurements with a range of modern technologies, will provide new insights to the spatial patterns of the flow-sediment interaction in meandering streams, which have perceived to show notable variation in space and time. This thesis shows how the modern technologies can be combined to derive very high spatial and temporal resolution data on fluvio-morphological processes over meander bends. The flow structure over the bends is recorded in situ using acoustic Doppler current profiler (ADCP) and the spatial and temporal resolution of the flow data is enhanced using 2D and 3D CFD over various meander bends. The CFD are also exploited to simulate sediment transport. Multi-temporal terrestrial laser scanning (TLS), mobile laser scanning (MLS) and echo sounding data are used to measure the flow-based changes and formations over meander bends and to build the computational models. The spatial patterns of erosion and deposition over meander bends are analysed relative to the measured and modelled flow field and sediment transport. The results are compared with the classic theories of the processes in meander bends. Mainly, the results of this study follow well the existing theories and results of previous studies. However, some new insights regarding to the spatial and temporal patterns of the flow-sediment interaction in a natural sand-bed meander bend are provided. The results of this study show the advantages of the rapid and detailed measurements techniques and the achieved spatial and temporal resolution provided by CFD, unachievable with field measurements. The thesis also discusses the limitations which remain in the measurement and modelling methods and in understanding of fluvial geomorphology of meander bends. Further, the hydro- and morphodynamic models’ sensitivity to user-defined parameters is tested, and the modelling results are assessed against detailed field measurement. The study is implemented in the meandering sub-Arctic Pulmanki River in Finland. The river is unregulated and sand-bed and major morphological changes occur annually on the meander point bars, which are inundated only during the snow-melt-induced spring floods. The outcome of this study applies to sandbed meandering rivers in regions where normally one significant flood event occurs annually, such as Arctic areas with snow-melt induced spring floods, and where the point bars of the meander bends are inundated only during the flood events.

Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.

Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies?

Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N = 12), grade I invasive ductal carcinoma (N = 15), grade II invasive ductal carcinoma (N = 15), grade III invasive ductal carcinoma (N = 15), tubular carcinoma (N = 8), lobular carcinoma (N = 10), and medullary carcinoma (N = 10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P < 0.001), but not between EBNA-1 and p53 (P = 0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.

Semantic and fuzzy modelling for human behaviour recognition in smart spaces : a case study on ambient assisted living.

Human activity recognition in everyday environments is a critical, but challenging task in Ambient Intelligence applications to achieve proper Ambient Assisted Living, and key challenges still remain to be dealt with to realize robust methods. One of the major limitations of the Ambient Intelligence systems today is the lack of semantic models of those activities on the environment, so that the system can recognize the speci c activity being performed by the user(s) and act accordingly. In this context, this thesis addresses the general problem of knowledge representation in Smart Spaces. The main objective is to develop knowledge-based models, equipped with semantics to learn, infer and monitor human behaviours in Smart Spaces. Moreover, it is easy to recognize that some aspects of this problem have a high degree of uncertainty, and therefore, the developed models must be equipped with mechanisms to manage this type of information. A fuzzy ontology and a semantic hybrid system are presented to allow modelling and recognition of a set of complex real-life scenarios where vagueness and uncertainty are inherent to the human nature of the users that perform it. The handling of uncertain, incomplete and vague data (i.e., missing sensor readings and activity execution variations, since human behaviour is non-deterministic) is approached for the rst time through a fuzzy ontology validated on real-time settings within a hybrid data-driven and knowledgebased architecture. The semantics of activities, sub-activities and real-time object interaction are taken into consideration. The proposed framework consists of two main modules: the low-level sub-activity recognizer and the high-level activity recognizer. The rst module detects sub-activities (i.e., actions or basic activities) that take input data directly from a depth sensor (Kinect). The main contribution of this thesis tackles the second component of the hybrid system, which lays on top of the previous one, in a superior level of abstraction, and acquires the input data from the rst module's output, and executes ontological inference to provide users, activities and their in uence in the environment, with semantics. This component is thus knowledge-based, and a fuzzy ontology was designed to model the high-level activities. Since activity recognition requires context-awareness and the ability to discriminate among activities in di erent environments, the semantic framework allows for modelling common-sense knowledge in the form of a rule-based system that supports expressions close to natural language in the form of fuzzy linguistic labels. The framework advantages have been evaluated with a challenging and new public dataset, CAD-120, achieving an accuracy of 90.1% and 91.1% respectively for low and high-level activities. This entails an improvement over both, entirely data-driven approaches, and merely ontology-based approaches. As an added value, for the system to be su ciently simple and exible to be managed by non-expert users, and thus, facilitate the transfer of research to industry, a development framework composed by a programming toolbox, a hybrid crisp and fuzzy architecture, and graphical models to represent and con gure human behaviour in Smart Spaces, were developed in order to provide the framework with more usability in the nal application. As a result, human behaviour recognition can help assisting people with special needs such as in healthcare, independent elderly living, in remote rehabilitation monitoring, industrial process guideline control, and many other cases. This thesis shows use cases in these areas.