Evaluation of stunned and infarcted canine myocardium by real time myocardial contrast echocardiography

Differentiation between stunned and infarcted myocardium in the setting of acute ischemia is challenging. Real time myocardial contrast echocardiography allows the simultaneous assessment of myocardial perfusion and function. In the present study we evaluated infarcted and stunned myocardium in an experimental model using real time myocardial contrast echocardiography. Sixteen dogs underwent 180 min of coronary occlusion followed by reperfusion (infarct model) and seven other dogs were submitted to 20 min of coronary occlusion followed by reperfusion (stunned model). Wall motion abnormality and perfusional myocardial defect areas were measured by planimetry. Risk and infarct areas were determined by tissue staining. In the infarct model, the wall motion abnormality area during coronary occlusion (5.52 ± 1.14 cm²) was larger than the perfusional myocardial defect area (3.71 ± 1.45 cm²; P < 0.001). Reperfusion resulted in maintenance of wall motion abnormality (5.45 ± 1.41 cm²; P = 0.43 versus occlusion) and reduction of perfusional myocardial defect (1.51 ± 1.29 cm²; P = 0.004 versus occlusion). Infarct size determined by contrast echocardiography correlated with tissue staining (r = 0.71; P = 0.002). In the stunned model, the wall motion abnormality area was 5.49 ± 0.68 cm² during occlusion and remained 5.1 ± 0.63 cm² after reperfusion (P = 0.07). Perfusional defect area was 2.43 ± 0.79 cm² during occlusion and was reduced to 0.2 ± 0.53 cm² after reperfusion (P = 0.04). 2,3,5-Triphenyl tetrazolium chloride staining confirmed the absence of necrotic myocardium in all dogs in the stunned model. Real time myocardial contrast echocardiography is a noninvasive technique capable of distinguishing between stunned and infarcted myocardium after acute ischemia.

Valmistavan tehtaan tuotannon tehostaminen reaaliaikaisen tiedon avulla

Teollinen toimintaympäristö on muuttunut globalisaation seurauksena. Sisäisten ja ulkoisten asiakkaiden vaatimukset ovat entistä haastavampia toimitusajan, laadun ja kustannusten suhteen. Yritysten on automatisoitava toimintoja, jotta voidaan saavuttaa kilpailuetua ja parantaa yrityksen tehokkuutta. Diplomityön tarkoitus on kirjallisuus- ja vertailututkimuksen yhteenvetona koostaa asiakasyrityksen tarpeisiin soveltuva toimintomalli reaaliaikaisen tiedon hyödyntä-miseen valmistavan tehtaan tuotannon tehostamisessa. Kirjallisuustutkimusten avulla pyritään analysoimaan valmistavan teollisuuden erityispiirteet toimintaympäristön osalta, kartoittamaan soveltuvin teknologia haastavaan toimintaympäristöön sekä löytää keinot kuinka reaaliaikaista tietoa hyödynnetään tuotannon tehokkuuden toteutumisessa. Vertailututkimuksessa analysoidaan kahta reaaliaikaista tietoa toiminnoissaan hyödyntävää yritystä, joiden tuloksia verrataan kirjallisuustutkimuksen aineistoon. Työn soveltavassa osuudessa luotiin toimintomalli asiakasyrityksen tarpeisiin, huomioiden tehtaan toiminnot kokonaisuutena. Toimintomallin avulla yritys pystyy toteuttamaan reaaliaikaisen tiedon keräämisen sekä hyödyntämisen yrityksen toi-minnoista. Toimintomallin toimivuus todettiin soveltamalla pilot-projekti asiakasyrityksen tuotantoon ja analysoitiin saavutettuja tuloksia haastattelujen sekä kvalitatiivisten tulosten perusteella. Työn tutkimukset osoittivat haasteet valmistavan teollisuuden toimintaympäristön ja automaatioteknologian soveltamisessa. Yritysten tulee suunnitteella toimintamallin kokonaisuus ja pohtia järjestelmän toimivuutta ongelmatilanteissa. Reaaliaikaisen tiedonkeruun soveltaminen onnistuneesti mahdollistaa hyötyjä monella tapaa. Merkittävimmät ovat tehokkuuden kehittyminen toimintojen nopeutumisena sekä resurssisäästöt toimintojen automatisoinnin johdosta. Reaaliaikaista tietoa voidaan hyödyntää myös suorituskyvyn johtamisessa mittariston avulla.

Parameter identification in time series models

Time series analysis can be categorized into three different approaches: classical, Box-Jenkins, and State space. Classical approach makes a basement for the analysis and Box-Jenkins approach is an improvement of the classical approach and deals with stationary time series. State space approach allows time variant factors and covers up a broader area of time series analysis. This thesis focuses on parameter identifiablity of different parameter estimation methods such as LSQ, Yule-Walker, MLE which are used in the above time series analysis approaches. Also the Kalman filter method and smoothing techniques are integrated with the state space approach and MLE method to estimate parameters allowing them to change over time. Parameter estimation is carried out by repeating estimation and integrating with MCMC and inspect how well different estimation methods can identify the optimal model parameters. Identification is performed in probabilistic and general senses and compare the results in order to study and represent identifiability more informative way.

A new model for the population pharmacokinetics of didanosine in healthy subjects

Didanosine (ddI) is a component of highly active antiretroviral therapy drug combinations, used especially in resource-limited settings and in zidovudine-resistant patients. The population pharmacokinetics of ddI was evaluated in 48 healthy volunteers enrolled in two bioequivalence studies. These data, along with a set of co-variates, were the subject of a nonlinear mixed-effect modeling analysis using the NONMEM program. A two-compartment model with first order absorption (ADVAN3 TRANS3) was fitted to the serum ddI concentration data. Final pharmacokinetic parameters, expressed as functions of the co-variates gender and creatinine clearance (CL CR), were: oral clearance (CL = 55.1 + 240 x CL CR + 16.6 L/h for males and CL = 55.1 + 240 x CL CR for females), central volume (V2 = 9.8 L), intercompartmental clearance (Q = 40.9 L/h), peripheral volume (V3 = 62.7 + 22.9 L for males and V3 = 62.7 L for females), absorption rate constant (Ka = 1.51/h), and dissolution time of the tablet (D = 0.43 h). The intraindividual (residual) variability expressed as coefficient of variation was 13.0%, whereas the interindividual variability of CL, Q, V3, Ka, and D was 20.1, 75.8, 20.6, 18.9, and 38.2%, respectively. The relatively high (>30%) interindividual variability for some of these parameters, observed under the controlled experimental settings of bioequivalence trials in healthy volunteers, may result from genetic variability of the processes involved in ddI absorption and disposition.

Leishmania (Leishmania) chagasi-infected mice as a model for the study of glomerular lesions in visceral leishmaniasis

Renal involvement in visceral leishmaniasis (VL) is very frequent but the pathogenesis of this nephropathy is poorly understood. In previous studies using dogs with VL we have detected new immunopathological elements in the glomeruli such as T cells and adhesion molecules. Although Leishmania (Leishmania) chagasi-infected dogs and hamsters are considered to be good models for VL, their use is limited for immunopathologic studies. The use of isogenic mouse strains susceptible to L. (L.) chagasi infection was an alternative but, on the other hand, the renal lesions of these animals have not yet been characterized. Thus, our purpose in the present study was to characterize mice infected with L. (L.) chagasi as a suitable model to study VL nephropathy. Kidney samples were obtained from control mice (N = 12) and from BALB/c mice (N = 24) injected intraperitoneally with 20 million L. (L.) chagasi amastigotes 7, 15, and 30 days after injection and processed for histopathological studies and detection of IgG deposits. Glomerular hypercellularity was clearly visible and, upon Mason's trichrome and periodic acid methenamine silver staining, a pattern suggestive of mesangial proliferative glomerulonephritis was observed in mice with VL. Time-dependent IgG deposits were also seen in infected mice. We consider L. (L.) chagasi-infected mice to be a suitable model for studies of the immunopathogenesis of glomerular lesions in VL.

Comparison of the Polar S810i monitor and the ECG for the analysis of heart rate variability in the time and frequency domains

The aim of the present study was to compare heart rate variability (HRV) at rest and during exercise using a temporal series obtained with the Polar S810i monitor and a signal from a LYNX® signal conditioner (BIO EMG 1000 model) with a channel configured for the acquisition of ECG signals. Fifteen healthy subjects aged 20.9 ± 1.4 years were analyzed. The subjects remained at rest for 20 min and performed exercise for another 20 min with the workload selected to achieve 60% of submaximal heart rate. RR series were obtained for each individual with a Polar S810i instrument and with an ECG analyzed with a biological signal conditioner. The HRV indices (rMSSD, pNN50, LFnu, HFnu, and LF/HF) were calculated after signal processing and analysis. The unpaired Student t-test and intraclass correlation coefficient were used for data analysis. No statistically significant differences were observed when comparing the values analyzed by means of the two devices for HRV at rest and during exercise. The intraclass correlation coefficient demonstrated satisfactory correlation between the values obtained by the devices at rest (pNN50 = 0.994; rMSSD = 0.995; LFnu = 0.978; HFnu = 0.978; LF/HF = 0.982) and during exercise (pNN50 = 0.869; rMSSD = 0.929; LFnu = 0.973; HFnu = 0.973; LF/HF = 0.942). The calculation of HRV values by means of temporal series obtained from the Polar S810i instrument appears to be as reliable as those obtained by processing the ECG signal captured with a signal conditioner.

Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60% of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%), sham (95 ± 2.8 vs 59 ± 4.1%), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.

Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.

A time series analysis of meteorological factors and hospital outpatient admissions for cardiovascular disease in the Northern district of Guizhou Province, China

Findings on the effects of weather on health, especially the effects of ambient temperature on overall morbidity, remain inconsistent. We conducted a time series study to examine the acute effects of meteorological factors (mainly air temperature) on daily hospital outpatient admissions for cardiovascular disease (CVD) in Zunyi City, China, from January 1, 2007 to November 30, 2009. We used the generalized additive model with penalized splines to analyze hospital outpatient admissions, climatic parameters, and covariate data. Results show that, in Zunyi, air temperature was associated with hospital outpatient admission for CVD. When air temperature was less than 10°C, hospital outpatient admissions for CVD increased 1.07-fold with each increase of 1°C, and when air temperature was more than 10°C, an increase in air temperature by 1°C was associated with a 0.99-fold decrease in hospital outpatient admissions for CVD over the previous year. Our analyses provided statistically significant evidence that in China meteorological factors have adverse effects on the health of the general population. Further research with consistent methodology is needed to clarify the magnitude of these effects and to show which populations and individuals are vulnerable.

Model-based testing of software systems : functionality and performance

Software is a key component in many of our devices and products that we use every day. Most customers demand not only that their devices should function as expected but also that the software should be of high quality, reliable, fault tolerant, efficient, etc. In short, it is not enough that a calculator gives the correct result of a calculation, we want the result instantly, in the right form, with minimal use of battery, etc. One of the key aspects for succeeding in today's industry is delivering high quality. In most software development projects, high-quality software is achieved by rigorous testing and good quality assurance practices. However, today, customers are asking for these high quality software products at an ever-increasing pace. This leaves the companies with less time for development. Software testing is an expensive activity, because it requires much manual work. Testing, debugging, and verification are estimated to consume 50 to 75 per cent of the total development cost of complex software projects. Further, the most expensive software defects are those which have to be fixed after the product is released. One of the main challenges in software development is reducing the associated cost and time of software testing without sacrificing the quality of the developed software. It is often not enough to only demonstrate that a piece of software is functioning correctly. Usually, many other aspects of the software, such as performance, security, scalability, usability, etc., need also to be verified. Testing these aspects of the software is traditionally referred to as nonfunctional testing. One of the major challenges with non-functional testing is that it is usually carried out at the end of the software development process when most of the functionality is implemented. This is due to the fact that non-functional aspects, such as performance or security, apply to the software as a whole. In this thesis, we study the use of model-based testing. We present approaches to automatically generate tests from behavioral models for solving some of these challenges. We show that model-based testing is not only applicable to functional testing but also to non-functional testing. In its simplest form, performance testing is performed by executing multiple test sequences at once while observing the software in terms of responsiveness and stability, rather than the output. The main contribution of the thesis is a coherent model-based testing approach for testing functional and performance related issues in software systems. We show how we go from system models, expressed in the Unified Modeling Language, to test cases and back to models again. The system requirements are traced throughout the entire testing process. Requirements traceability facilitates finding faults in the design and implementation of the software. In the research field of model-based testing, many new proposed approaches suffer from poor or the lack of tool support. Therefore, the second contribution of this thesis is proper tool support for the proposed approach that is integrated with leading industry tools. We o er independent tools, tools that are integrated with other industry leading tools, and complete tool-chains when necessary. Many model-based testing approaches proposed by the research community suffer from poor empirical validation in an industrial context. In order to demonstrate the applicability of our proposed approach, we apply our research to several systems, including industrial ones.

Suitability of LiDAR technology for forest inventory in Russia

LiDAR is an advanced remote sensing technology with many applications, including forest inventory. The most common type is ALS (airborne laser scanning). The method is successfully utilized in many developed markets, where it is replacing traditional forest inventory methods. However, it is innovative for Russian market, where traditional field inventory dominates. ArboLiDAR is a forest inventory solution that engages LiDAR, color infrared imagery, GPS ground control plots and field sample plots, developed by Arbonaut Ltd. This study is an industrial market research for LiDAR technology in Russia focused on customer needs. Russian forestry market is very attractive, because of large growing stock volumes. It underwent drastic changes in 2006, but it is still in transitional stage. There are several types of forest inventory, both with public and private funding. Private forestry enterprises basically need forest inventory in two cases – while making coupe demarcation before timber harvesting and as a part of forest management planning, that is supposed to be done every ten years on the whole leased territory. The study covered 14 companies in total that include private forestry companies with timber harvesting activities, private forest inventory providers, state subordinate companies and forestry software developer. The research strategy is multiple case studies with semi-structured interviews as the main data collection technique. The study focuses on North-West Russia, as it is the most developed Russian region in forestry. The research applies the Voice of the Customer (VOC) concept to elicit customer needs of Russian forestry actors and discovers how these needs are met. It studies forest inventory methods currently applied in Russia and proposes the model of method comparison, based on Multi-criteria decision making (MCDM) approach, mainly on Analytical Hierarchy Process (AHP). Required product attributes are classified in accordance with Kano model. The answer about suitability of LiDAR technology is ambiguous, since many details should be taken into account.

Examining sport commitment and intentions to participate in intramural sports : application of the Sport Commitment Model and the Theory of Planned Behaviour in a campus recreational sport setting

Fifty-six percent of Canadians, 20 years of age and older, are inactive (Canadian Community Health Survey, 200012001). Research has indicated that one of the most dramatic declines in population physical activity occurs between adolescence and young adulthood (Melina, 2001; Stephens, Jacobs, & White, 1985), a time when individuals this age are entering or attending college or university. Colleges and universities have generally been seen as environments where physical activity and sport can be promoted and accommodated as a result of the available resources and facilities (Archer, Probert, & Gagne, 1987; Suminski, Petosa, Utter, & Zhang, 2002). Intramural sports, one of the most common campus recreational sports options available for post-secondary students, enable students to participate in activities that are suited for different levels of ability and interest (Lewis, Jones, Lamke, & Dunn, 1998). While intramural sports can positively affect the physical activity levels and sport participation rates of post-secondary students, their true value lies in their ability to encourage sport participation after school ends and during the post-school lives of graduates (Forrester, Ross, Geary, & Hall, 2007). This study used the Sport Commitment Model (Scanlan et aI., 1993a) and the Theory of Planned Behaviour (Ajzen, 1991) with post secondary intramural volleyball participants in an effort to examine students' commitment to intramural sport and 1 intentions to participate in intramural sports. More specifically, the research objectives of this study were to: (1.) test the Sport Commitment Model with a sample of postsecondary intramural sport participants(2.) determine the utility of the sixth construct, social support, in explaining the sport commitment of post-secondary intramural sport participants; (3.) determine if there are any significant differences in the six constructs of IV the SCM and sport commitment between: gender, level of competition (competitive A vs. B), and number of different intramural sports played; (4.) determine if there are any significant differences between sport commitment levels and constructs from the Theory of Planned Behaviour (attitudes, subjective norms, perceived behavioural control, and intentions); (5.) determine the relationship between sport commitment and intention to continue participation in intramural volleyball, continue participating in intramurals and continuing participating in sport and physical activity after graduation; and (6.) determine if the level of sport commitment changes the relationship between the constructs from the Theory of Planned Behaviour. Of the 318 surveys distributed, there were 302 partiCipants who completed a usable survey from the sample of post-secondary intramural sport participants. There was a fairly even split of males and females; the average age of the students was twenty-one; 90% were undergraduate students; for approximately 25% of the students, volleyball was the only intramural sport they participated in at Brock and most were part of the volleyball competitive B division. Based on the post-secondary students responses, there are indications of intent to continue participation in sport and physical activity. The participation of the students is predominantly influenced by subjective norms, high sport commitment, and high sport enjoyment. This implies students expect, intend and want to 1 participate in intramurals in the future, they are very dedicated to playing on an intramural team and would be willing to do a lot to keep playing and students want to participate when they perceive their pursuits as enjoyable and fun, and it makes them happy. These are key areas that should be targeted and pursued by sport practitioners.

Explaining the Transition Between Exchange Rate Regimes

This paper studies the transition between exchange rate regimes using a Markov chain model with time-varying transition probabilities. The probabilities are parameterized as nonlinear functions of variables suggested by the currency crisis and optimal currency area literature. Results using annual data indicate that inflation, and to a lesser extent, output growth and trade openness help explain the exchange rate regime transition dynamics.

The Transmission of Monetary Policy in a Multi-Sector Economy

This paper constructs and estimates a sticky-price, Dynamic Stochastic General Equilibrium model with heterogenous production sectors. Sectors differ in price stickiness, capital-adjustment costs and production technology, and use output from each other as material and investment inputs following an Input-Output Matrix and Capital Flow Table that represent the U.S. economy. By relaxing the standard assumption of symmetry, this model allows different sectoral dynamics in response to monetary policy shocks. The model is estimated by Simulated Method of Moments using sectoral and aggregate U.S. time series. Results indicate 1) substantial heterogeneity in price stickiness across sectors, with quantitatively larger differences between services and goods than previously found in micro studies that focus on final goods alone, 2) a strong sensitivity to monetary policy shocks on the part of construction and durable manufacturing, and 3) similar quantitative predictions at the aggregate level by the multi-sector model and a standard model that assumes symmetry across sectors.