Predicting asthma control and exacerbations: chronic asthma as a complex dynamic model

PURPOSE OF REVIEW: Predicting asthma episodes is notoriously difficult but has potentially significant consequences for the individual, as well as for healthcare services. The purpose of this review is to describe recent insights into the prediction of acute asthma episodes in relation to classical clinical, functional or inflammatory variables, as well as present a new concept for evaluating asthma as a dynamically regulated homeokinetic system. RECENT FINDINGS: Risk prediction for asthma episodes or relapse has been attempted using clinical scoring systems, considerations of environmental factors and lung function, as well as inflammatory and immunological markers in induced sputum or exhaled air, and these are summarized here. We have recently proposed that newer mathematical methods derived from statistical physics may be used to understand the complexity of asthma as a homeokinetic, dynamic system consisting of a network comprising multiple components, and also to assess the risk for future asthma episodes based on fluctuation analysis of long time series of lung function. SUMMARY: Apart from the classical analysis of risk factor and functional parameters, this new approach may be used to assess asthma control and treatment effects in the individual as well as in future research trials.

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.

Ecology of larval fishes and large zooplankton in the Keweenaw Current region of Lake Superior, with special focus on lake herring, Coregonus artedi

I assessed the influence of the Keweenaw Current and spring thermal bar on the distribution of larval fishes and large zooplankton in Lake Superior. In 1998 and 1999, samples were collected from inshore (0.2 – 3.0 km from shore) and offshore (5.0 – 9.0 km from shore) locations on three transects off the western coast of the Keweenaw Peninsula, Michigan. For larval fishes, density and size distribution patterns of lake herring (Coregonus artedi), rainbow smelt (Osmerus mordax), burbot (Lota lota), deepwater sculpin (Myoxocephalus thompsoni), and spoonhead sculpin (Cottus ricei) suggest a seasonal inshore to offshore movement. For zooplankton, seasonal warming appeared to be the major factor that limited planktonic catches of the primarily benthic Mysisrelicta and Diporeia spp., while simultaneously stimulated growth and reproduction of the cladocerans Daphnia spp., Holopedium gibberum, and Bythotrephes cederstroemi. In contrast, calanoid copepods as a group were abundant throughout the entire sampling season. The greatest abundances of zooplankton were generally encountered offshore, even for the cladocerans, which apparently expanded from inshore to offshore locations with seasonal warming. In 2000, sampling efforts focused on lake herring. Samples were collected from surface waters at 0.1 – 17.0 km from shore on two transects. Lake herring larvae were also reared in the laboratory from eggs in order to validate the use of otolith microstructure for aging. Increment deposition was not statistically different from a daily rate starting from 28 days after hatching, near the time of yolk-sac absorption, but larvae with lower growth rates could not be aged as accurately. In Lake Superior, lake herring tended to be slightly more abundant, larger, and older at inshore locations, but a dense patch of younger larvae was also encountered 7 – 13 km from shore. The distribution iiipatterns suggest that larvae were transported by prevailing currents into the study region, possibly from the more productive spawning regions in western Lake Superior. Growth rates were suppressed at offshore locations where temperatures were less than 8°C. These results indicate that lake herring larvae may be transported far distances from spawning concentrations by longshore currents, and water temperatures may largely control their growth.

What do case-control studies estimate? Survey of methods and assumptions in published case-control research

To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate.

STUDY OF HYBRID ELECTRIC VEHICLE BATTERY MODELING AND CONTROL USING AUTONOMIE

This report presents the research results of battery modeling and control for hybrid electric vehicles (HEV). The simulation study is conducted using plug-and-play powertrain and vehicle development software, Autonomie. The base vehicle model used for testing the performance of battery model and battery control strategy is the Prius MY04, a power-split hybrid electric vehicle model in Autonomie. To evaluate the battery performance for HEV applications, the Prius MY04 model and its powertrain energy flow in various vehicle operating modes are analyzed. The power outputs of the major powertrain components under different driving cycles are discussed with a focus on battery performance. The simulation results show that the vehicle fuel economy calculated by the Autonomie Prius MY04 model does not match very well with the official data provided by the department of energy (DOE). It is also found that the original battery model does not consider the impact of environmental temperature on battery cell capacities. To improve battery model, this study includes battery current loss on coulomb coefficient and the impact of environmental temperature on battery cell capacity in the model. In addition, voltage losses on both double layer effect and diffusion effect are included in the new battery model. The simulation results with new battery model show the reduced fuel economy error to the DOE data comparing with the original Autonomie Prius MY04 model.

Predictive control of hybrid vehicle powertrain for intelligent energy management

This thesis studies the minimization of the fuel consumption for a Hybrid Electric Vehicle (HEV) using Model Predictive Control (MPC). The presented MPC – based controller calculates an optimal sequence of control inputs to a hybrid vehicle using the measured plant outputs, the current dynamic states, a system model, system constraints, and an optimization cost function. The MPC controller is developed using Matlab MPC control toolbox. To evaluate the performance of the presented controller, a power-split hybrid vehicle, 2004 Toyota Prius, is selected. The vehicle uses a planetary gear set to combine three power components, an engine, a motor, and a generator, and transfer energy from these components to the vehicle wheels. The planetary gear model is developed based on the Willis’s formula. The dynamic models of the engine, the motor, and the generator, are derived based on their dynamics at the planetary gear. The MPC controller for HEV energy management is validated in the MATLAB/Simulink environment. Both the step response performance (a 0 – 60 mph step input) and the driving cycle tracking performance are evaluated. Two standard driving cycles, Urban Dynamometer Driving Schedule (UDDS) and Highway Fuel Economy Driving Schedule (HWFET), are used in the evaluation tests. For the UDDS and HWFET driving cycles, the simulation results, the fuel consumption and the battery state of charge, using the MPC controller are compared with the simulation results using the original vehicle model in Autonomie. The MPC approach shows the feasibility to improve vehicle performance and minimize fuel consumption.

The blood-central nervous system barriers actively control immune cell entry into the central nervous system

Before entering the central nervous system (CNS) immune cells have to penetrate any one of its barriers, namely either the endothelial blood-brain barrier, the epithelial blood-cerebrospinal fluid barrier or the tanycytic barrier around the circumventricular organs, all of which maintain homeostasis within the CNS. The presence of these barriers in combination with the lack of lymphatic vessels and the absence of classical MHC-positive antigen presenting cells characterizes the CNS as an immunologically privileged site. In multiple sclerosis a large number of inflammatory cells gains access to the CNS parenchyma. Studies performed in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis, have enabled us to understand some of the molecular mechanisms involved in immune cell entry into the CNS. In particular, the realization that /alpha4-integrins play a predominant role in leukocyte trafficking to the CNS has led to the development of a novel drug for the treatment of relapsing-remitting multiple sclerosis, which targets /alpha4-integrin mediated immune cell migration to the CNS. At the same time, the involvement of other adhesion and signalling molecules in this process remains to be investigated and novel molecules contributing to immune cell entry into the CNS are still being identified. The entire process of immune cell trafficking into the CNS is strictly controlled by the brain barriers not only under physiological conditions but also during neuroinflammation, when some barrier properties are lost. Thus, immune cell entry into the CNS critically depends on the unique characteristics of the brain barriers maintaining CNS homeostasis.

MULTIDIMENSIONAL OPTIMAL DROOP CONTROL FOR WIND RESOURCES IN DC MICROGRIDS

Two important and upcoming technologies, microgrids and electricity generation from wind resources, are increasingly being combined. Various control strategies can be implemented, and droop control provides a simple option without requiring communication between microgrid components. Eliminating the single source of potential failure around the communication system is especially important in remote, islanded microgrids, which are considered in this work. However, traditional droop control does not allow the microgrid to utilize much of the power available from the wind. This dissertation presents a novel droop control strategy, which implements a droop surface in higher dimension than the traditional strategy. The droop control relationship then depends on two variables: the dc microgrid bus voltage, and the wind speed at the current time. An approach for optimizing this droop control surface in order to meet a given objective, for example utilizing all of the power available from a wind resource, is proposed and demonstrated. Various cases are used to test the proposed optimal high dimension droop control method, and demonstrate its function. First, the use of linear multidimensional droop control without optimization is demonstrated through simulation. Next, an optimal high dimension droop control surface is implemented with a simple dc microgrid containing two sources and one load. Various cases for changing load and wind speed are investigated using simulation and hardware-in-the-loop techniques. Optimal multidimensional droop control is demonstrated with a wind resource in a full dc microgrid example, containing an energy storage device as well as multiple sources and loads. Finally, the optimal high dimension droop control method is applied with a solar resource, and using a load model developed for a military patrol base application. The operation of the proposed control is again investigated using simulation and hardware-in-the-loop techniques.

Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia

BACKGROUND: Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. METHODS AND RESULTS: Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027). CONCLUSIONS: Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.

Low current and nadir CD4+ T-cell counts are associated with higher hepatitis C virus RNA levels in the Swiss HIV cohort study

BACKGROUND: The aim of this study was to evaluate the effect of CD4+ T-cell counts and other characteristics of HIV-infected individuals on hepatitis C virus (HCV) RNA levels. METHODS: All HIV-HCV-coinfected Swiss HIV Cohort Study participants with available HCV RNA levels and concurrent CD4+ T-cell counts before starting HCV therapy were included. Potential predictors of HCV RNA levels were assessed by multivariate censored linear regression models that adjust for censored values. RESULTS: The study included 1,031 individuals. Low current and nadir CD4+ T-cell counts were significantly associated with higher HCV RNA levels (P = 0.004 and 0.001, respectively). In individuals with current CD4+ T-cell counts < 200/microl, median HCV RNA levels (6.22 log10 IU/ml) were +0.14 and +0.24 log10 IU/ml higher than those with CD4+ T-cell counts of 200-500/microl and > 500/microl. Based on nadir CD4+ T-cell counts, median HCV RNA levels (6.12 log10 IU/ml) in individuals with < 200/microl CD4+ T-cells were +0.06 and +0.44 log10 IU/ml higher than those with nadir T-cell counts of 200-500/microl and > 500/microl. Median HCV RNA levels were also significantly associated with HCV genotype: lower values were associated with genotype 4 and higher values with genotype 2, as compared with genotype 1. Additional significant predictors of lower HCV RNA levels were female gender and HIV transmission through male homosexual contacts. In multivariate analyses, only CD4+ T-cell counts and HCV genotype remained significant predictors of HCV RNA levels. Conclusions: Higher HCV RNA levels were associated with CD4+ T-cell depletion. This finding is in line with the crucial role of CD4+ T-cells in the control of HCV infection.

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.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Better conduct of clinical trials: the control group in critical care trials

OBJECTIVE: To review trial design issues related to control groups. DESIGN: Review of the literature with specific reference to critical care trials. MAIN RESULTS AND CONCLUSIONS: Performing randomized controlled trials in the critical care setting presents specific problems: studies include patients with rapidly lethal conditions, the majority of intensive care patients suffer from syndromes rather than from well-definable diseases, the severity of such syndromes cannot be precisely assessed, and the treatment consists of interacting therapies. Interactions between physiology, pathophysiology, and therapies are at best marginally understood and may have a major impact on study design and interpretation of results. Selection of the right control group is crucial for the interpretation and clinical implementation of results. Studies comparing new interventions with current ones or different levels of current treatments have the problem of the necessity of defining "usual care." Usual care controls without any constraints typically include substantial heterogeneity. Constraints in the usual therapy may help to reduce some variation. Inclusion of unrestricted usual care groups may help to enhance safety. Practice misalignment is a novel problem in which patients receive a treatment that is the direct opposite of usual care, and occurs when fixed-dose interventions are used in situations where care is normally titrated. Practice misalignment should be considered in the design and interpretation of studies on titrated therapies.

Marginalization of the Youth – a Current Societal Development?

The last two years a discussion on reforming the public sector has emerged. At its very heart we find important concepts like ‘quality reform’, ‘democracy’, and ‘development’. Recently I have presented an example of the ‘quality reform’ in SocMag, and this leads me to prolong that discussion on central themes on welfare state and democracy. Much energy is invested in arguing about management of the public sector: Do we need more competition from private companies? Do we need more control? Are more contracts concerning outcome needed? Can we be sure about the accountability needed from politicians? How much documentation, effectiveness measurement, bureaucracy, and evidence-based policy and practice are we looking for? A number of interesting questions – but strange enough we do not discuss the purpose of ‘keeping a welfare state’. What sort of understanding is lying behind the welfare state, and what kind of democracy are we drawing upon?

Increased parietal activity after training of interference control

Recent studies suggest that computerized cognitive training leads to improved performance in related but untrained tasks (i.e. transfer effects). However, most study designs prevent disentangling which of the task components are necessary for transfer. In the current study, we examined whether training on two variants of the adaptive dual n-back task would affect untrained task performance and the corresponding electrophysiological event-related potentials (ERPs). Forty three healthy young adults were trained for three weeks with a high or low interference training variant of the dual n-back task, or they were assigned to a passive control group. While n-back training with high interference led to partial improvements in the Attention Network Test (ANT), we did not find transfer to measures of working memory and fluid intelligence. ERP analysis in the n-back task and the ANT indicated overlapping processes in the P3 time range. Moreover, in the ANT, we detected increased parietal activity for the interference training group alone. In contrast, we did not find electrophysiological differences between the low interference training and the control group. These findings suggest that training on an interference control task leads to higher electrophysiological activity in the parietal cortex, which may be related to improvements in processing speed, attentional control, or both.