Anti-Windup Design for Internal Model Control

This paper considers linear control design for systems with input magnitude saturation. A general anti-windup scheme which optimizes nonlinear performance, applicable to MIMO systems, is developed. Several examples, including an ill-conditioned plant, show that the scheme provides graceful degradation of performance. The attractive features of this scheme are its simplicity and effectiveness

Robust Constrained Model Predictive Control using Linear Matrix Inequalities

The primary disadvantage of current design techniques for model predictive control (MPC) is their inability to deal explicitly with plant model uncertainty. In this paper, we present a new approach for robust MPC synthesis which allows explicit incorporation of the description of plant uncertainty in the problem formulation. The uncertainty is expressed both in the time domain and the frequency domain. The goal is to design, at each time step, a state-feedback control law which minimizes a "worst-case" infinite horizon objective function, subject to constraints on the control input and plant output. Using standard techniques, the problem of minimizing an upper bound on the "worst-case" objective function, subject to input and output constraints, is reduced to a convex optimization involving linear matrix inequalities (LMIs). It is shown that the feasible receding horizon state-feedback control design robustly stabilizes the set of uncertain plants under consideration. Several extensions, such as application to systems with time-delays and problems involving constant set-point tracking, trajectory tracking and disturbance rejection, which follow naturally from our formulation, are discussed. The controller design procedure is illustrated with two examples. Finally, conclusions are presented

A Unified Framework for the Study of Anti-Windup Designs

We present a unified framework for the study of linear time-invariant (LTI) systems subject to control input nonlinearities. The framework is based on the following two-step design paradigm: "Design the linear controller ignoring control input nonlinearities and then add anti-windup bumpless transfer (AWBT) compensation to minimize the adverse eflects of any control input nonlinearities on closed loop performance". The resulting AWBT compensation is applicable to multivariable controllers of arbitrary structure and order. All known LTI anti-windup and/or bumpless transfer compensation schemes are shown to be special cases of this framework. It is shown how this framework can handle standard issues such as the analysis of stability and performance with or without uncertainties in the plant model. The actual analysis of stability and performance, and robustness issues are problems in their own right and hence not detailed here. The main result is the unification of existing schemes for AWBT compensation under a general framework

Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals

An Uncommon Case of Pediatric Neurobrucellosis Associated with Intracranial Hypertension

We present the case of a 4-year-old boy who was admitted to hospital with intracranial hypertension, headache, diplopia, papilledema, and a normal brain MRI. Brucella melitensis in the cerebrospinal fluid was confirmed with PCR assay. We believe that neurobrucellosis should be included in the differential diagnosis when headaches persist following brucellosis. In addition, we suggest that when cerebrospinal fluid culture is negative, PCR may prove to be an optimal alternative tool for an immediate and accurate diagnosis

The Role of Phenytoin in the Treatment of Localization Related Epilepsy: An International Internet-Based Survey of Neurologists and Epileptologists

Phenytoin (PHT) has been the most widely used medication to treat both partial and generalized seizures. However, over the past twenty years, a variety of new compounds have been released with comparable efficacy, fewer adverse effects, and more predictable pharmacokinetic properties. We surveyed neurologists and epileptologists to determine current practice patterns relating to the use of PHT using an online survey instrument. A total of 200 responses were obtained though response rates for each survey question varied. Of the respondents, 78.1% were epilepsy specialists; 60% were adult practitioners; and the remainder saw either, only children or both adults and children. For new onset partial seizures only 10 respondents said PHT would be their first or second choice, while 45% reported that they would not consider PHT. This study shows that in the era of newer medications, the role of PHT has been placed in the category of a reserve medication in intractable epilepsy

Risk Factors Associated with Death in In-Hospital Pediatric Convulsive Status Epilepticus

Objective: To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort. Patients and Methods: We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant. Results: We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE. Conclusion: Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management

Robust constrained model predictive control based on parameter-dependent Lyapunov functions

The problem of robust constrained model predictive control (MPC) of systems with polytopic uncertainties is considered in this paper. New sufficient conditions for the existence of parameter-dependent Lyapunov functions are proposed in terms of linear matrix inequalities (LMIs), which will reduce the conservativeness resulting from using a single Lyapunov function. At each sampling instant, the corresponding parameter-dependent Lyapunov function is an upper bound for a worst-case objective function, which can be minimized using the LMI convex optimization approach. Based on the solution of optimization at each sampling instant, the corresponding state feedback controller is designed, which can guarantee that the resulting closed-loop system is robustly asymptotically stable. In addition, the feedback controller will meet the specifications for systems with input or output constraints, for all admissible time-varying parameter uncertainties. Numerical examples are presented to demonstrate the effectiveness of the proposed techniques

Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial

BACKGROUND: Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (C(max)). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. METHODS: This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30(®)]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. RESULTS: Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) C(max )reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in C(max )reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the most common adverse events observed during the trial. CONCLUSIONS: The observed reduction in C(max )is likely of limited importance given the unaltered oral contraceptive bioavailability and trough concentrations; however, for oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before exenatide injection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00254800