Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment, and disease progression and control

Although assessment of asthma control is important to guide treatment, it is difficult since the temporal pattern and risk of exacerbations are often unpredictable. In this Review, we summarise the classic methods to assess control with unidimensional and multidimensional approaches. Next, we show how ideas from the science of complexity can explain the seemingly unpredictable nature of bronchial asthma and emphysema, with implications for chronic obstructive pulmonary disease. We show that fluctuation analysis, a method used in statistical physics, can be used to gain insight into asthma as a dynamic disease of the respiratory system, viewed as a set of interacting subsystems (eg, inflammatory, immunological, and mechanical). The basis of the fluctuation analysis methods is the quantification of the long-term temporal history of lung function parameters. We summarise how this analysis can be used to assess the risk of future asthma episodes, with implications for asthma severity and control both in children and adults.

Dynamic modeling, simulation and control design of a parafoil-payload system for ship launched aerial delivery system (SLADS)

The objective of this research was to develop a high-fidelity dynamic model of a parafoilpayload system with respect to its application for the Ship Launched Aerial Delivery System (SLADS). SLADS is a concept in which cargo can be transfered from ship to shore using a parafoil-payload system. It is accomplished in two phases: An initial towing phase when the glider follows the towing vessel in a passive lift mode and an autonomous gliding phase when the system is guided to the desired point. While many previous researchers have analyzed the parafoil-payload system when it is released from another airborne vehicle, limited work has been done in the area of towing up the system from ground or sea. One of the main contributions of this research was the development of a nonlinear dynamic model of a towed parafoil-payload system. After performing an extensive literature review of the existing methods of modeling a parafoil-payload system, a five degree-of-freedom model was developed. The inertial and geometric properties of the system were investigated to predict accurate results in the simulation environment. Since extensive research has been done in determining the aerodynamic characteristics of a paraglider, an existing aerodynamic model was chosen to incorporate the effects of air flow around the flexible paraglider wing. During the towing phase, it is essential that the parafoil-payload system follow the line of the towing vessel path to prevent an unstable flight condition called ‘lockout’. A detailed study of the causes of lockout, its mathematical representation and the flight conditions and the parameters related to lockout, constitute another contribution of this work. A linearized model of the parafoil-payload system was developed and used to analyze the stability of the system about equilibrium conditions. The relationship between the control surface inputs and the stability was investigated. In addition to stability of flight, one more important objective of SLADS is to tow up the parafoil-payload system as fast as possible. The tension in the tow cable is directly proportional to the rate of ascent of the parafoil-payload system. Lockout instability is more favorable when tow tensions are large. Thus there is a tradeoff between susceptibility to lockout and rapid deployment. Control strategies were also developed for optimal tow up and to maintain stability in the event of disturbances.

Adaptive control of sinusoidal brushless DC motor actuators

Electrical Power Assisted Steering system (EPAS) will likely be used on future automotive power steering systems. The sinusoidal brushless DC (BLDC) motor has been identified as one of the most suitable actuators for the EPAS application. Motor characteristic variations, which can be indicated by variations of the motor parameters such as the coil resistance and the torque constant, directly impart inaccuracies in the control scheme based on the nominal values of parameters and thus the whole system performance suffers. The motor controller must address the time-varying motor characteristics problem and maintain the performance in its long service life. In this dissertation, four adaptive control algorithms for brushless DC (BLDC) motors are explored. The first algorithm engages a simplified inverse dq-coordinate dynamics controller and solves for the parameter errors with the q-axis current (iq) feedback from several past sampling steps. The controller parameter values are updated by slow integration of the parameter errors. Improvement such as dynamic approximation, speed approximation and Gram-Schmidt orthonormalization are discussed for better estimation performance. The second algorithm is proposed to use both the d-axis current (id) and the q-axis current (iq) feedback for parameter estimation since id always accompanies iq. Stochastic conditions for unbiased estimation are shown through Monte Carlo simulations. Study of the first two adaptive algorithms indicates that the parameter estimation performance can be achieved by using more history data. The Extended Kalman Filter (EKF), a representative recursive estimation algorithm, is then investigated for the BLDC motor application. Simulation results validated the superior estimation performance with the EKF. However, the computation complexity and stability may be barriers for practical implementation of the EKF. The fourth algorithm is a model reference adaptive control (MRAC) that utilizes the desired motor characteristics as a reference model. Its stability is guaranteed by Lyapunov’s direct method. Simulation shows superior performance in terms of the convergence speed and current tracking. These algorithms are compared in closed loop simulation with an EPAS model and a motor speed control application. The MRAC is identified as the most promising candidate controller because of its combination of superior performance and low computational complexity. A BLDC motor controller developed with the dq-coordinate model cannot be implemented without several supplemental functions such as the coordinate transformation and a DC-to-AC current encoding scheme. A quasi-physical BLDC motor model is developed to study the practical implementation issues of the dq-coordinate control strategy, such as the initialization and rotor angle transducer resolution. This model can also be beneficial during first stage development in automotive BLDC motor applications.

Optimal game theoretic distributed control methodologies in small scale power systems

This dissertation presents the competitive control methodologies for small-scale power system (SSPS). A SSPS is a collection of sources and loads that shares a common network which can be isolated during terrestrial disturbances. Micro-grids, naval ship electric power systems (NSEPS), aircraft power systems and telecommunication system power systems are typical examples of SSPS. The analysis and development of control systems for small-scale power systems (SSPS) lacks a defined slack bus. In addition, a change of a load or source will influence the real time system parameters of the system. Therefore, the control system should provide the required flexibility, to ensure operation as a single aggregated system. In most of the cases of a SSPS the sources and loads must be equipped with power electronic interfaces which can be modeled as a dynamic controllable quantity. The mathematical formulation of the micro-grid is carried out with the help of game theory, optimal control and fundamental theory of electrical power systems. Then the micro-grid can be viewed as a dynamical multi-objective optimization problem with nonlinear objectives and variables. Basically detailed analysis was done with optimal solutions with regards to start up transient modeling, bus selection modeling and level of communication within the micro-grids. In each approach a detail mathematical model is formed to observe the system response. The differential game theoretic approach was also used for modeling and optimization of startup transients. The startup transient controller was implemented with open loop, PI and feedback control methodologies. Then the hardware implementation was carried out to validate the theoretical results. The proposed game theoretic controller shows higher performances over traditional the PI controller during startup. In addition, the optimal transient surface is necessary while implementing the feedback controller for startup transient. Further, the experimental results are in agreement with the theoretical simulation. The bus selection and team communication was modeled with discrete and continuous game theory models. Although players have multiple choices, this controller is capable of choosing the optimum bus. Next the team communication structures are able to optimize the players’ Nash equilibrium point. All mathematical models are based on the local information of the load or source. As a result, these models are the keys to developing accurate distributed controllers.

Red blood cell lifespan, erythropoiesis and hemoglobin control

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

EVALUATION OF INTELLIGENT COMPACTION CONTROL IN THE M-189 RECONSTRUCTION PROJECT AT IRON RIVER, MICHIGAN

This research evaluated an Intelligent Compaction (IC) unit on the M-189 highway reconstruction project at Iron River, Michigan. The results from the IC unit were compared to several traditional compaction measurement devices including Nuclear Density Gauge (NDG), Geogauge, Light Weight Deflectometer (LWD), Dynamic Cone Penetrometer (DCP), and Modified Clegg Hammer (MCH). The research collected point measurements data on a test section in which 30 test locations on the final Class II sand base layer and the 22A gravel layer. These point measurements were compared with the IC measurements (ICMVs) on a point-to-point basis through a linear regression analysis. Poor correlations were obtained among different measurements points using simple regression analysis. When comparing the ICMV to the compaction measurements points. Factors attributing to the weak correlation include soil heterogeneity, variation in IC roller operation parameters, in-place moisture content, the narrow range of the compaction devices measurement ranges and support conditions of the support layers. After incorporating some of the affecting factors into a multiple regression analysis, the strength of correlation significantly improved, especially on the stiffer gravel layer. Measurements were also studied from an overall distribution perspective in terms of average, measurement range, standard deviation, and coefficient of variance. Based on data analysis, on-site project observation and literature review, conclusions were made on how IC performed in regards to compaction control on the M-189 reconstruction project.

Effects of cognitive behavioral stress management on HIV-1 RNA, CD4 cell counts and psychosocial parameters of HIV-infected persons

OBJECTIVE: To determine the effects of cognitive-behavioral stress management (CBSM) training on clinical and psychosocial markers in HIV-infected persons. METHODS: A randomized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy (cART), measuring HIV-1 surrogate markers, adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training. RESULTS: Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group: HIV-1 RNA < 50 copies/ml in 81.1% [95% confidence interval (CI), 68.0-90.6] and 74.5% (95% CI, 60.4-85.7), respectively (P = 0.34), and mean CD4 cell change from baseline of 53.0 cells/microl (95% CI, 4.1-101.8) and 15.5 cells/microl (95% CI, -34.3 to 65.4), respectively (P = 0.29). Self-reported adherence to therapy did not differ between groups at baseline (P = 0.53) or at 12 month's post-intervention (P = 0.47). Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores: physical health 2.9 (95% CI, 0.7-5.1) and -0.2 (95% CI, -2.1 to 1.8), respectively (P = 0.05); mental health 4.8 (95% CI, 1.8-7.3) and -0.5 (95% CI, -3.3 to 2.2) (P = 0.02); anxiety -2.1 (95% CI, -3.6 to -1.0) and 0.3 (95% CI, -0.7 to 1.4), respectively (P = 0.002); and depression -2.1 (95% CI, -3.2 to -0.9) and 0.02 (95% CI, -1.0 to 1.1), respectively (P = 0.001). Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline. CONCLUSION: CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being.

STATE OF CHARGE BASED DROOP SURFACE FOR OPTIMAL CONTROL OF DC MICROGRIDS

For a microgrid with a high penetration level of renewable energy, energy storage use becomes more integral to the system performance due to the stochastic nature of most renewable energy sources. This thesis examines the use of droop control of an energy storage source in dc microgrids in order to optimize a global cost function. The approach involves using a multidimensional surface to determine the optimal droop parameters based on load and state of charge. The optimal surface is determined using knowledge of the system architecture and can be implemented with fully decentralized source controllers. The optimal surface control of the system is presented. Derivations of a cost function along with the implementation of the optimal control are included. Results were verified using a hardware-in-the-loop system.

Reaction Control in Quiescent Systems of Free-Radical Retrograde-Precipitation Polymerization

Free-radical retrograde-precipitation polymerization, FRRPP in short, is a novel polymerization process discovered by Dr. Gerard Caneba in the late 1980s. The current study is aimed at gaining a better understanding of the reaction mechanism of the FRRPP and its thermodynamically-driven features that are predominant in controlling the chain reaction. A previously developed mathematical model to represent free radical polymerization kinetics was used to simulate a classic bulk polymerization system from the literature. Unlike other existing models, such a sparse-matrix-based representation allows one to explicitly accommodate the chain length dependent kinetic parameters. Extrapolating from the past results, mixing was experimentally shown to be exerting a significant influence on reaction control in FRRPP systems. Mixing alone drives the otherwise severely diffusion-controlled reaction propagation in phase-separated polymer domains. Therefore, in a quiescent system, in the absence of mixing, it is possible to retard the growth of phase-separated domains, thus producing isolated polymer nanoparticles (globules). Such a diffusion-controlled, self-limiting phenomenon of chain growth was also observed using time-resolved small angle x-ray scattering studies of reaction kinetics in quiescent systems of FRRPP. Combining the concept of self-limiting chain growth in quiescent FRRPP systems with spatioselective reaction initiation of lithography, microgel structures were synthesized in a single step, without the use of molds or additives. Hard x-rays from the bending magnet radiation of a synchrotron were used as an initiation source, instead of the more statistally-oriented chemical initiators. Such a spatially-defined reaction was shown to be self-limiting to the irradiated regions following a polymerization-induced self-assembly phenomenon. The pattern transfer aspects of this technique were, therefore, studied in the FRRP polymerization of N-isopropylacrylamide (NIPAm) and methacrylic acid (MAA), a thermoreversible and ionic hydrogel, respectively. Reaction temperature increases the contrast between the exposed and unexposed zones of the formed microgels, while the irradiation dose is directly proportional to the extent of phase separation. The response of Poly (NIPAm) microgels prepared from the technique described in this study was also characterized by small angle neutron scattering.

Reliability of intraoperative high-resolution 2D ultrasound as an alternative to high-field strength MR imaging for tumor resection control: a prospective comparative study

OBJECT: Ultrasound may be a reliable but simpler alternative to intraoperative MR imaging (iMR imaging) for tumor resection control. However, its reliability in the detection of tumor remnants has not been definitely proven. The aim of the study was to compare high-field iMR imaging (1.5 T) and high-resolution 2D ultrasound in terms of tumor resection control. METHODS: A prospective comparative study of 26 consecutive patients was performed. The following parameters were compared: the existence of tumor remnants after presumed radical removal and the quality of the images. Tumor remnants were categorized as: detectable with both imaging modalities or visible only with 1 modality. RESULTS: Tumor remnants were detected in 21 cases (80.8%) with iMR imaging. All large remnants were demonstrated with both modalities, and their image quality was good. Two-dimensional ultrasound was not as effective in detecting remnants<1 cm. Two remnants detected with iMR imaging were missed by ultrasound. In 2 cases suspicious signals visible only on ultrasound images were misinterpreted as remnants but turned out to be a blood clot and peritumoral parenchyma. The average time for acquisition of an ultrasound image was 2 minutes, whereas that for an iMR image was approximately 10 minutes. Neither modality resulted in any procedure-related complications or morbidity. CONCLUSIONS: Intraoperative MR imaging is more precise in detecting small tumor remnants than 2D ultrasound. Nevertheless, the latter may be used as a less expensive and less time-consuming alternative that provides almost real-time feedback information. Its accuracy is highest in case of more confined, deeply located remnants. In cases of more superficially located remnants, its role is more limited.

Influence of rubber dam on objective and subjective parameters of stress during dental treatment of children and adolescents - a randomized controlled clinical pilot study

BACKGROUND Rubber dam is recommended for isolating the working field during adhesive dentistry procedures; however, dentists often omit rubber dam, particularly in paediatric dentistry, supposing that it would stress the patient. AIM The aim of this study was to evaluate stress parameters during a standardized dental treatment procedure performed with or without rubber dam. The treatment time was measured as a secondary outcome variable. DESIGN This study was designed as a randomized, controlled, clinical study with 72 patients (6-16 years; mean age, 11.1). During standardized fissure sealing procedures, objective parameters of stress (e.g., skin resistance, breath rate) were recorded. The operator's stress level was measured by pulse rate. Subjective pain (patients) and stress perception (operator) were evaluated by an interview. RESULTS The breath rate was significantly (P<0.05) lower and the skin resistance level was significantly higher during treatment with rubber dam compared to the control group. Subjective pain perception was significantly lower for the test group. The treatment time needed for the fissure sealing procedure was 12.4% less in the test group. CONCLUSION Isolation with rubber dam caused less stress in children and adolescents compared to relative isolation with cotton rolls if applied by an experienced dentist.

Evaluation of control and surveillance strategies for classical swine fever using a simulation model

Classical swine fever (CSF) outbreaks can cause enormous losses in naïve pig populations. How to best minimize the economic damage and number of culled animals caused by CSF is therefore an important research area. The baseline CSF control strategy in the European Union and Switzerland consists of culling all animals in infected herds, movement restrictions for animals, material and people within a given distance to the infected herd and epidemiological tracing of transmission contacts. Additional disease control measures such as pre-emptive culling or vaccination have been recommended based on the results from several simulation models; however, these models were parameterized for areas with high animal densities. The objective of this study was to explore whether pre-emptive culling and emergency vaccination should also be recommended in low- to moderate-density areas such as Switzerland. Additionally, we studied the influence of initial outbreak conditions on outbreak severity to improve the efficiency of disease prevention and surveillance. A spatial, stochastic, individual-animal-based simulation model using all registered Swiss pig premises in 2009 (n=9770) was implemented to quantify these relationships. The model simulates within-herd and between-herd transmission (direct and indirect contacts and local area spread). By varying the four parameters (a) control measures, (b) index herd type (breeding, fattening, weaning or mixed herd), (c) detection delay for secondary cases during an outbreak and (d) contact tracing probability, 112 distinct scenarios were simulated. To assess the impact of scenarios on outbreak severity, daily transmission rates were compared between scenarios. Compared with the baseline strategy (stamping out and movement restrictions) vaccination and pre-emptive culling neither reduced outbreak size nor duration. Outbreaks starting in a herd with weaning piglets or fattening pigs caused higher losses regarding to the number of culled premises and were longer lasting than those starting in the two other index herd types. Similarly, larger transmission rates were estimated for these index herd type outbreaks. A longer detection delay resulted in more culled premises and longer duration and better transmission tracing increased the number of short outbreaks. Based on the simulation results, baseline control strategies seem sufficient to control CSF in low-medium animal-dense areas. Early detection of outbreaks is crucial and risk-based surveillance should be focused on weaning piglet and fattening pig premises.

A paleoclimate record with tephrochronological age control for the last glacial-interglacial cycle from Lake Ohrid, Albania and Macedonia

Abstract Lake Ohrid is probably of Pliocene age, and the oldest extant lake in Europe. In this study climatic and environmental changes during the last glacial-interglacial cycle are reconstructed using lithological, sedimentological, geochemical and physical proxy analysis of a 15-m-long sediment succession from Lake Ohrid. A chronological framework is derived from tephrochronology and radiocarbon dating, which yields a basal age of ca. 136 ka. The succession is not continuous, however, with a hiatus between ca. 97.6 and 81.7 ka. Sediment accumulation in course of the last climatic cycle is controlled by the complex interaction of a variety of climate-controlled parameters and their impact on catchment dynamics, limnology, and hydrology of the lake. Warm interglacial and cold glacial climate conditions can be clearly distinguished from organic matter, calcite, clastic detritus and lithostratigraphic data. During interglacial periods, short-term fluctuations are recorded by abrupt variations in organic matter and calcite content, indicating climatically-induced changes in lake productivity and hydrology. During glacial periods, high variability in the contents of coarse silt to fine sand sized clastic matter is probably a function of climatically-induced changes in catchment dynamics and wind activity. In some instances tephra layers provide potential stratigraphic markers for short-lived climate perturbations. Given their widespread distribution in sites across the region, tephra analysis has the potential to provide insight into variation in the impact of climate and environmental change across the Mediterranean.

Health control beliefs in old age - relationship with subjective and objective health and health behavior

The main purpose of this paper is to explore health control beliefs (internality, powerful others, chance) in different age cohorts of elderly people and to examine the relationship between health control beliefs and objective and subjective health, and health behaviour. This contribution shows data from an interdisciplinary longitudinal ageing study: (a) a descriptive analysis of age- and time-correlated changes in health control beliefs of different cohorts of elderly people by taking into account gender as a differential aspect; (b) group comparisons between objectively and subjectively healthy or sick people and their health control beliefs and health relevant behaviour. Participants are 442 community elderly, 309 men, 133 women, aged 65± 94 years (mean age: 74.95 years). Our data demonstrate the dominance of chance control beliefs over internality and powerful others in all age cohorts. It can be concluded that internal control remains stable well into old age, whereas a signi® cant age-correlated increase of externality can be observed. Our results show the signi® cant relationship of subjective health self-evaluations with health control beliefs and health behaviour which is not the case for objective health parameters. Strong gender effects are found for internality and social externality: women have signi® cantly lower internality and powerful others scores than men.

Robust meta-analytic-predictive priors in clinical trials with historical control information.

Historical information is always relevant for clinical trial design. Additionally, if incorporated in the analysis of a new trial, historical data allow to reduce the number of subjects. This decreases costs and trial duration, facilitates recruitment, and may be more ethical. Yet, under prior-data conflict, a too optimistic use of historical data may be inappropriate. We address this challenge by deriving a Bayesian meta-analytic-predictive prior from historical data, which is then combined with the new data. This prospective approach is equivalent to a meta-analytic-combined analysis of historical and new data if parameters are exchangeable across trials. The prospective Bayesian version requires a good approximation of the meta-analytic-predictive prior, which is not available analytically. We propose two- or three-component mixtures of standard priors, which allow for good approximations and, for the one-parameter exponential family, straightforward posterior calculations. Moreover, since one of the mixture components is usually vague, mixture priors will often be heavy-tailed and therefore robust. Further robustness and a more rapid reaction to prior-data conflicts can be achieved by adding an extra weakly-informative mixture component. Use of historical prior information is particularly attractive for adaptive trials, as the randomization ratio can then be changed in case of prior-data conflict. Both frequentist operating characteristics and posterior summaries for various data scenarios show that these designs have desirable properties. We illustrate the methodology for a phase II proof-of-concept trial with historical controls from four studies. Robust meta-analytic-predictive priors alleviate prior-data conflicts ' they should encourage better and more frequent use of historical data in clinical trials.