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Neighbourhood control policies and the spread of infectious diseases.

We present a model of a control programme for a disease outbreak in a population of livestock holdings. Control is achieved by culling infectious holdings when they are discovered and by the pre-emptive culling of livestock on holdings deemed to be at enhanced risk of infection. Because the pre-emptive control programme cannot directly identify exposed holdings, its implementation will result in the removal of both infected and uninfected holdings. This leads to a fundamental trade-off: increased levels of control produce a greater reduction in transmission by removing more exposed holdings, but increase the number of uninfected holdings culled. We derive an expression for the total number of holdings culled during the course of an outbreak and demonstrate that there is an optimal control policy, which minimizes this loss. Using a metapopulation model to incorporate local clustering of infection, we examine a neighbourhood control programme in a locally spreading outbreak. We find that there is an optimal level of control, which increases with increasing basic reproduction ratio, R(0); moreover, implementation of control may be optimal even when R(0) < 1. The total loss to the population is relatively insensitive to the level of control as it increases beyond the optimal level, suggesting that over-control is a safer policy than under-control.

Animals↗

Serum enzymes of lysosomal origin as indicators of the metabolic control in diabetes: comparison with glycated hemoglobin and albumin.

Several lysosomal enzymes (beta-N-D-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase, alpha-L-fucosidase, alpha-D-glucosidase, alpha-D-mannosidase, beta-D-glucosidase), glycated albumin and glycated hemoglobin (HbA1c) were determined in the serum of 81 insulin-dependent diabetics with different degrees of metabolic control (optimal, 21 patients; good, 39 patients; poor, 21 patients) and without signs of complications, and in 42 control subjects. All parameters examined increased in serum in inverse proportion to the degree of metabolic control. A highly significant correlation (p less than 0.01) was found between lysosomal enzymes and both glycated albumin and HbA1c. All parameters correlated with hyperglycemia, glycated albumin having the highest r-value (0.586) and lysosomal enzymes the lowest one. Unlike glycated albumin and HbA1c, serum levels of lysosomal enzymes in patients with optimal metabolic control were undistinguishable or even lower than those of controls. A 2-month longitudinal monitoring of a patient who was hospitalized in conditions of poor metabolic control and adequately treated, proved that lysosomal enzymes diminished in serum parallel to glycated albumin and HbA1c in relation to improvement of the metabolic situation. The conclusion is drawn that serum lysosomal enzymes are good indicators of the metabolic control of diabetic patients probably reflecting the overall metabolic state connected with insulin action rather than hyperglycemia.

Adolescent↗

Near-optimal human adaptive control across different noise environments.

A person learning to control a complex system needs to learn about both the dynamics and the noise of the system. We evaluated human subjects' abilities to learn to control a stochastic dynamic system under different noise conditions. These conditions were created by corrupting the forces applied to the system with noise whose magnitudes were either proportional or inversely proportional to the sizes of subjects' control signals. We also used dynamic programming to calculate the mathematically optimal control laws of an "ideal actor" for each noise condition. The results suggest that people learned control strategies tailored to the specific noise characteristics of their training conditions. In particular, as predicted by the ideal actors, they learned to use smaller control signals when forces were corrupted by proportional noise and to use larger signals when forces were corrupted by inversely proportional noise, thereby achieving levels of performance near the information-theoretic upper bounds. We conclude that subjects learned to behave in a near-optimal manner, meaning that they learned to efficiently use all available information to plan and execute control policies that maximized performances on their tasks.

Acclimatization↗

Quantum control mechanism analysis through field based Hamiltonian encoding.

Optimal control of quantum dynamics in the laboratory is proving to be increasingly successful. The control fields can be complex, and the mechanisms by which they operate have often remained obscure. Hamiltonian encoding (HE) has been proposed as a method for understanding mechanisms in quantum dynamics. In this context mechanism is defined in terms of the dominant quantum pathways leading to the final state of the controlled system. HE operates by encoding a special modulation into the Hamiltonian and decoding its signature in the dynamics to determine the dominant pathway amplitudes. Earlier work encoded the modulation directly into the Hamiltonian operators. This present work introduces the alternative scheme of field based HE, where the modulation is encoded into the control field and not directly into the Hamiltonian operators. This distinct form of modulation yields a new perspective on mechanism and is computationally faster than the earlier approach. Field based encoding is also an important step towards a laboratory based algorithm for HE as it is the only form of encoding that may be experimentally executed. HE is also extended to cover systems with noise and uncertainty and finally, a hierarchical algorithm is introduced to reveal mechanism in a stepwise fashion of ever increasing detail as desired. This new hierarchical algorithm is an improvement over earlier approaches to HE where the entire mechanism was determined in one stroke. The improvement comes from the use of less complex modulation schemes, which leads to fewer evaluations of Schrodinger's equation. A number of simulations are presented on simple systems to illustrate the new field based encoding technique for mechanism assessment.

Journal Article↗

Nominal and robust stability regions of optimization-based PID controllers.

In recent decades, several optimization-based methods have been developed for the proportional-integral-derivative (PID) controller design, and the common feature of these methods is that the controller has only one adjustable parameter. To keep the closed-loop systems stable is an essential requirement for the optimization-based PID controllers. In almost all these methods, however, no exact stability region for the single adjustable parameter was sketched. In this paper, using the proposed analytical procedure based on the dual-locus diagram technique, explicit stability regions of the optimization-based PID controllers are derived for stable, integrating, and unstable processes with time delay in the nominal and perturbed cases, respectively. It is revealed that the proposed analytical procedure is effective for the determination of the nominal and robust stability regions and it offers simplicity and ease of mathematical calculations over other available stability analysis methods. The results in this paper provide some insight into the tuning of the optimization-based PID controllers.

Algorithms↗

Stochastic optimal therapy for enhanced immune response.

Therapeutic enhancement of humoral immune response to microbial attack is addressed as the stochastic optimal control of a dynamic system. Without therapy, the modeled immune response depends upon the initial concentration of pathogens in a simulated attack. Immune response can be augmented by agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. Using a generic mathematical model of immune response to the infection (i.e., of the dynamic state of the system), previous papers demonstrated optimal (open-loop) and neighboring-optimal (closed-loop) control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal [Optimal Contr. Appl. Methods 23 (2002) 91, Bioinformatics 18 (2002) 1227]. Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and drug usage, providing implicit control over harmful side effects. Here, we focus on the effects that corrupted or incomplete measurements of the dynamic state may have on neighboring-optimal feedback control. Imperfect measurements degrade the precision of feedback adjustments to therapy; however, optimal state estimation allows the feedback strategy to be implemented with incomplete measurements and minimizes the expected effects of measurement error. Complete observability of the perturbed state for this four state example is provided by measurement of four of the six possible pairs of two variables, either set of three variables, or all four variables. The inclusion of state estimation extends the applicability of optimal control theory for developing new therapeutic protocols to enhance immune response.

Anti-Infective Agents↗

Diabetes education programs and the endocrinologist.

In the past, control of diabetes was considered important, but studies had not substantiated the effect of high-quality care on the outcome for patients with diabetes. Recently, however, published results of the Diabetes Control and Complications Trial indicated that optimal control of diabetes minimized the associated complications. As a consequence, educational efforts have focused on informing and encouraging patients with diabetes to help achieve and maintain the best possible medical care. This situation has created a market for products and services to assist patients with diabetes, and many nonphysicians have promoted their products without actual participation in a team effort to improve outcomes for patients with diabetes. Clinical endocrinologists, who are experts in the management of diabetes, should assume a leadership role on the diabetes-care team and should not relinquish this responsibility to those who are less qualified to provide care for the growing number of patients with diabetes who seek optimally effective treatment.

Journal Article↗

Semi-active control of a cable-stayed bridge under multiple-support excitations.

This paper presents a semi-active strategy for seismic protection of a benchmark cable-stayed bridge with consideration of multiple-support excitations. In this control strategy, Magnetorheological (MR) dampers are proposed as control devices, a LQG-clipped-optimal control algorithm is employed. An active control strategy, shown in previous researches to perform well at controlling the benchmark bridge when uniform earthquake motion was assumed, is also used in this study to control this benchmark bridge with consideration of multiple-support excitations. The performance of active control system is compared to that of the presented semi-active control strategy. Because the MR fluid damper is a controllable energy- dissipation device that cannot add mechanical energy to the structural system, the proposed control strategy is fail-safe in that bounded-input, bounded-output stability of the controlled structure is guaranteed. The numerical results demonstrated that the performance of the presented control design is nearly the same as that of the active control system; and that the MR dampers can effectively be used to control seismically excited cable-stayed bridges with multiple-support excitations.

Computer Simulation↗

Family conflict, adherence, and glycaemic control in youth with short duration Type 1 diabetes.

AIMS: Behavioural support around diabetes management tasks is linked to glycaemic outcomes. In this study we investigated the relationship between diabetes-related parental behaviours (conflict around and involvement in treatment tasks), adherence to blood glucose monitoring (BGM), and glycaemic control in youth with short duration Type 1 diabetes mellitus (DM). METHODS: In a cross-sectional study, 104 youth (aged 8-17 years, duration of Type 1 DM 0.5-6 years) along with a parent, completed the Diabetes Conflict Scale. Parental involvement in management tasks was assessed with structured interviews and the Diabetes Family Responsibility Questionnaire. Adherence to BGM was evaluated by family report and by independent clinician rating. Glycaemic control was assessed with glycosylated haemoglobin (HbA1c) (ref. range, 4-6%). RESULTS: Children (8-12 years; n = 69) and adolescents (13-17 years; n = 35), respectively, had similar durations of diabetes (x +/- sd; 2.7 +/- 1.69, 2.4 +/- 1.32 years) and similar glycaemic control (8.3 +/- 1.1%, 8.4 +/- 1.1%). In both age groups, parental involvement was a significant predictor of adherence to BGM (P = 0.01). Multivariate analyses, controlling for age, sex, disease duration, and BGM adherence, revealed that higher diabetes conflict significantly related to poorer glycaemic control (HbA1c) (R2 = 0.17; P < 0.01). CONCLUSIONS: These findings indicate that in this cohort, early in the course of diabetes, diabetes-specific conflict and adherence to BGM became strongly linked to the child's glycaemic control. This suggests that to insure optimal control, it may be beneficial to introduce targeted interventions to build positive family involvement and interaction around diabetes tasks early in the disease course, before negative behaviours become established.

Adolescent↗

Ultralente based insulin regimens--clinical applications, advantages and disadvantages.

The prolonged action of daily injections of beef ultralente insulin provides a source for the basal, steady state insulin supply which diabetics need in addition to their meal requirements. The complete distinction between basal and meal insulin requirements, provided by two or three injections of soluble insulin per day, allows simple rules to guide both the physician and patient. Thus, the required ultralente dose needs to be continued daily, irrespective of illness or missing meals, whereas the soluble insulin requirements are given according to meals. When starting ultralente insulin therapy a loading dose is required. The doses of ultralente and soluble insulin needed for different severities of diabetes and degrees of insulin resistance can be predicted. A simple regimen to cover the decreasing insulin requirements of newly presenting, ketotic juvenile-onset diabetics has been developed. During surgical operations the continued basal insulin supply, from ultralente insulin, greatly facilitates diabetes control. Whilst many patients have improved nocturnal blood glucose control after transfer to ultralente insulin, optimal control of diabetes sometimes remains difficult in view of the pre-breakfast plasma glucose rise and the longer action of subcutaneous soluble insulin than the physiological meal insulin response. Purified monocomponent beef ultralente insulin is antigenic, and human ultralente insulin might be advantageous.

Diabetes Mellitus↗

Improvement of renal function in patients with chronic gout after proper control of hyperuricemia and gouty bouts.

AIM: To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms. METHODS: Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period. RESULTS: 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function. CONCLUSIONS: Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.

Adult↗

Optimal strategy for cardiopulmonary resuscitation with continuous chest compression.

OBJECTIVES: To apply the mathematical techniques of optimal control theory (OCT) to a validated model of the human circulation during cardiopulmonary resuscitation (CPR), so as to discover improved waveforms for chest compression and decompression that maximize the coronary perfusion pressure (CPP). METHODS: The human circulatory system is represented by seven difference equations that describe the pressure changes in systemic vascular compartments that are caused by chest compression. The forcing term is the intrathoracic pressure that is generated by the external chest compression, which is taken as the control variable for the system. The optimum waveform of this forcing pressure as a function of time, determined from OCT, is that which maximizes the calculated CPP between the thoracic aorta and the superior vena cava over a period of 13.3 seconds of continuous chest compression. RESULTS: The optimal waveform included both compression and decompression of the chest to the maximum allowable extent. Compression-decompression waveforms were rectangular in shape. The frequency of optimal compression-decompression that was found by OCT was 90 per minute. The optimal duty cycle (compression duration per cycle time) was 40%. The CPP for the optimum control waveform was 36 mm Hg vs. 25 mm Hg for standard CPR. CONCLUSIONS: Optimal control theory suggests that both compression and decompression of the chest are needed for best hemodynamics during CPR.

Cardiopulmonary Resuscitation↗

Prevalence, treatment, and control of hypertension in the French population: data from a survey on high blood pressure in general practice, 1994.

A survey was conducted in a cohort of 235 general practitioners (GP) selected by Sofres Medical who were representative of the French medical population, to measure the percentage of patients with hypertension, treated hypertensives and patients with controlled hypertension. Data were collected over 1 week of office consultation. Practitioners were initially instructed to use the same type of mercury sphygmomanometer, equipped with pneumatic cuffs of different sizes. Three consecutive blood pressure (BP) measurements were made and the last two were recorded. Practitioners had to carry out their own survey over a period of 1 week on all patients > 18 years of age who visited their offices. Patients were considered as hypertensive (HP) if the mean of the two recorded BP measurements was > or = 140/90 mm Hg or if they were taking antihypertensive drug treatment. Three cutoff points were used to define controlled hypertension: < 140/90 mm Hg (overall population of HP), < 160/95 mm Hg (HP < 65 years of age), and < 160/90 mm Hg (HP > or = 65 years of age). Among 12,351 patients (mean age, 48.6 years; women, 58%), 5020 were HP, (41%) of whom 2035 were without treatment (41%) and 2985 were receiving antihypertensive drug treatment (59%). Two hundred-thirty patients (4.6%) remained at high risk with moderate or severe hypertension (BP > or = 180 [systolic] or 105 [diastolic] mm Hg), ie, 1 patient/week/GP. The study confirms the high prevalence of hypertension in general practice and shows that 7 of 10 patients have an acceptable control of their BP (< 160/95 or < 160/90 mm Hg according to age) but only 24% of treated HP achieved the target of a BP level < 140/90 mm Hg, representing 28% of the 18 to 64 year old group and 21% of the elderly group. French GP did not choose an optimal control, and the medical community is waiting for answers to crucial questions, ie, does optimal BP control significantly improve the absolute cardiovascular risk? How far should blood pressure be lowered?

Antihypertensive Agents↗

Predictors of metabolic control at one year in a population of pediatric patients with type 2 diabetes mellitus: a retrospective study.

BACKGROUND/OBJECTIVES: The rising prevalence of pediatric type 2 diabetes mellitus (DM2) and non-adherence to diabetes regimens pose challenges to obtaining optimal control. This study evaluated factors that may impact glycemic control (HbA1c): age, Tanner stage, body mass index (BMI), total daily insulin (TDD), metformin dose (MET), activity level, frequency of clinic visits and adherence. METHODS: One-year data from 72 patients (ages 8.6-17.8 years) were collected retrospectively. From that sample, 57 patients who continued to attend clinic for the entire year were assessed and divided into optimal and suboptimal HbA1c control groups. RESULTS: All factors measured were similar in the two groups, except for lower initial and 1.0-year HbA1c, TDD, and rates of missing MET and insulin in the optimal HbA1c control group. CONCLUSIONS: Initial glycemic status and adherence rate predicted metabolic control at one year. Early identification of DM2 may improve metabolic outcome, which may improve medical regimen adherence.

Adolescent↗

Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters.

The objective of this study was to evaluate the effect of some processing parameters on the release of lipid formulation from a tablet dosage form. A 17-run, face-centered cubic design was employed to evaluate the effect of colloidal silicates (X(1)), magnesium stearate mixing time (X(2)), and compression force (X(3)) on flow, hardness, and dissolution of Coenzyme Q(10) (CoQ(10)) lipid formulation from a tablet dosage form. The optimized formulation was subsequently subjected to a short-term accelerated stability study. All preparations had a flowability index values ranging from 77 to 90. The cumulative percent of CoQ(10) released within 8h (Y(5)) ranged from 40.6% to 90% and was expressed by the following polynomial equation: Y(5)=49.78-16.36X(1)+2.90X(2)-3.11X(3)-0.37X(1)X(2)+1.06X(1)X(3)-1.02X(2)X(3)+11.98X(1)(2)+10.63X(2)(2)-7.10X(3)(2). When stored at 4 degrees C, dissolution rates were retained for up to 3 months. Storage at higher temperatures, however, accelerated lipid release and caused leakage, and loss of hardness. Processing parameters have a profound effect on the release of lipid formulations from their solid carriers. While optimized controlled release formulations could be attained, further considerations should be made to prepare "liquisolids" that are physically stable at higher storage temperatures.

Coenzymes↗

Spinal motor control system incorporates an internal model of limb dynamics.

The existence and utilization of an internal representation of the controlled object is one of the most important features of the functioning of neural motor control systems. This study demonstrates that this property already exists at the level of the spinal motor control system (SMCS), which is capable of generating motor patterns for reflex rhythmic movements, such as locomotion and scratching, without the aid of the peripheral afferent feedback, but substantially modifies the generated activity in response to peripheral afferent stimuli. The SMCS is presented as an optimal control system whose optimality requires that it incorporate an internal model (IM) of the controlled object's dynamics. A novel functional mechanism for the integration of peripheral sensory signals with the corresponding predictive output from the IM, the summation of information precision (SIP) is proposed. In contrast to other models in which the correction of the internal representation of the controlled object's state is based on the calculation of a mismatch between the internal and external information sources, the SIP mechanism merges the information from these sources in order to optimize the precision of the controlled object's state estimate. It is demonstrated, based on scratching in decerebrate cats as an example of the spinal control of goal-directed movements, that the results of computer modeling agree with the experimental observations related to the SMCS's reactions to phasic and tonic peripheral afferent stimuli. It is also shown that the functional requirements imposed by the mathematical model of the SMCS comply with the current knowledge about the related properties of spinal neuronal circuitry. The crucial role of the spinal presynaptic inhibition mechanism in the neuronal implementation of SIP is elucidated. Important differences between the IM and a state predictor employed for compensating for a neural reflex time delay are discussed.

Animals↗

Optimal nonlocal boundary control of the wide-angle parabolic equation for inversion of a waveguide acoustic field.

This paper applies the concept of optimal boundary control for solving inverse problems in shallow water acoustics. To treat the controllability problem, a continuous analytic adjoint model is derived for the Claerbout wide-angle parabolic equation (PE) using a generalized nonlocal impedance boundary condition at the water-bottom interface. While the potential of adjoint methodology has been recently demonstrated for ocean acoustic tomography, this approach combines the advantages of exact transparent boundary conditions for the wide-angle PE with the concept of adjoint-based optimal control. In contrast to meta-heuristic approaches the inversion procedure itself is directly controlled by the waveguide physics and, in a numerical implementation based on conjugate gradient optimization, many fewer iterations are required for assessment of an environment that is supported by the underlying subbottom model. Furthermore, since regularization schemes are particularly important to enhance the performance of full-field acoustic inversion, special attention is devoted to the application of penalization methods to the adjoint optimization formalism. Regularization incorporates additional information about the desired solution in order to stabilize ill-posed inverse problems and identify useful solutions, a feature that is of particular importance for inversion of field data sampled on a vertical receiver array in the presence of measurement noise and modeling uncertainty. Results with test data show that the acoustic field and the bottom properties embedded in the control parameters can be efficiently retrieved.

Acoustics↗

Extramedullary skeletal traction for intramedullary femoral nailing.

The through-and-through forms of femoral skeletal traction that are often used during intramedullary nailing for femur fractures can present two problems: (a) impingement with the intramedullary nail, requiring repositioning of the traction pin intraoperatively under radiographic control, to a position that may not optimally control the fracture; and (b) the risk of contaminating the intramedullary canal that will soon contain the metallic fixation device, especially when placed in the emergency room or at the bedside. Two new forms of extramedullary skeletal femoral traction are presented. The pullout strength and optimal positioning of these devices on the distal femur were evaluated. The first form of extramedullary traction evaluated was the large AO/ASIF pinless clamp. The second form of extramedullary traction, the extramedullary skeletal clamp, was based on a modification of the Gardner-Wells tong. These two forms of skeletal traction were compared with standard tensioned Kirschner wire (K-wire) through-and-through traction. Six fresh-frozen distal femora from donors (average age 29 years) were used to test the three femoral traction devices. Five of these specimens were skeletally mature. A total of 38 pullout tests were conducted. The pullout strength of the tested devices was in the following descending order: (a) tensioned K-wire; (b) extramedullary skeletal clamp (in the optimal metadiaphyseal position, 77% the strength of the K-wire); and (c) large ASIF pinless clamp (in the optimal metaphyseal position, 46% the strength of the K-wire). The mode of failure for each device was cut out through or from the bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗