On the Design of Integral Observers for Unbiased Output Estimation in the Presence of Uncertainty

Integral observers are useful tools for estimating the plant states in the presence of non-vanishing disturbances resulting from plant-model mismatch and exogenous disturbances. It is well known that these observers can eliminate bias in all states, given that as many independent measurements are available as there are independent sources of disturbance. In the most general case, the dimensionality of the disturbance vector affecting the plant states corresponds to the order of the system and thus all states need to be measured. This condition, which is termed integral observability in the literature, represents a fairly restrictive situation. This study focuses on the more realistic case, where only the output variables are measured. Accordingly, the objective reduces to the unbiased estimation of the output variables. It is shown that both stability and asymptotically unbiased output estimation can be achieved if the system is observable, regardless of the dimensionality of the disturbance vector. Furthermore, a condition is provided under which, using output measurements, the errors in all states can be pushed to zero. It is also proposed to use off-line output measurements to tune the observer using a calibration-like approach. Integral observers and integral Kalman filters are evaluated via the simulation of a fourth-order linear system perturbed by unknown non-vanishing disturbances

Oxygen Control for an Industrial Pilot-Scale Fed-Batch Filamentous Fungal Fermentation

Industrial filamentous fungal fermentations are typically operated in fed- batch mode. Oxygen control represents an important operational challenge due to the varying biomass concentration. In this study, oxygen control is implemented by manipulating the substrate feed rate, i.e. the rate of oxygen consumption. It turns out that the setpoint for dissolved oxygen represents a trade-off since a low dissolved oxygen value favors productivity but can also induce oxygen limitation. This paper addresses the regulation of dissolved oxygen using a cascade control scheme that incorporates auxiliary measurements to improve the control performance. The computation of an appropriate setpoint profile for dissolved oxygen is solved via process optimization. For that purpose, an existing morphologically structured model is extended to include the effects of both low levels of oxygen on growth and medium rheological properties on oxygen transfer. Experimental results obtained at the industrial pilot-scale level confirm the efficiency of the proposed control strategy but also illustrate the shortcomings of the process model at hand for optimizing the dissolved oxygen setpoints

Association of symptoms of insomnia and sleep parameters among kidney transplant recipients

Objective: Insomnia complaints are frequent among kidney transplant (kTx) recipients and are associated with fatigue, depression, lower quality of life and increased morbidity. However, it is not known if subjective insomnia symptoms are associated with objective parameters of sleep architecture. Thus, we analyze the association between sleep macrostructure and EEG activity versus insomnia symptoms among kTx recipients. Methods: Participants (n1 = 100) were selected from prevalent adult transplant recipients (n0 = 1214) followed at a single institution. Insomnia symptoms were assessed by the Athens Insomnia Scale (AIS) and standard overnight polysomnography was performed. In a subgroup of patients (n2 = 56) sleep microstructure was also analyzed with power spectral analysis. Results: In univariable analysis AIS score was not associated with sleep macrostructure parameters (sleep latency, total sleep time, slow wave sleep, wake after sleep onset), nor with NREM and REM beta or delta activity in sleep microstructure. In multivariable analysis after controlling for covariables AIS score was independently associated with the proportion of slow wave sleep (β = 0.263; CI: 0.026–0.500) and REM beta activity (β = 0.323; CI = 0.041–0.606) (p < 0.05 for both associations). Conclusions: Among kTx recipients the severity of insomnia symptoms is independently associated with higher proportion of slow wave sleep and increased beta activity during REM sleep but not with other parameters sleep architecture. The results suggest a potential compensatory sleep protective mechanism and a sign of REM sleep instability associated with insomnia symptoms among this population

Depressive symptoms are associated with objectively measured sleep parameters in kidney transplant recipients

STUDY OBJECTIVES: Both depression and sleep complaints are very prevalent among kidney transplant (kTx) recipients. However, details of the complex relationship between sleep and depression in this population are not well documented. Thus, we investigated the association between depressive symptoms and sleep macrostructure parameters among prevalent kTx recipients.  METHODS: Ninety-five kTx recipients participated in the study (54 males, mean age 51 ± 13 y, body mass index 26 ± 4 kg/m2, estimated glomerular filtration rate 53 ± 19 ml/min/1.73 m2). Symptoms of depression were assessed by the Center for Epidemiologic Studies - Depression Scale (CES-D). After 1-night polysomnography each recording was visually scored and sleep macrostructure was analyzed.  RESULTS: The CES-D score was significantly associated with the amount of stage 2 sleep (r = 0.20, p 0.05). In multivariable linear regression models the CES-D score was independently associated with the amount of stage 2 sleep (β: 0.205; confidence interval: 0.001-0.409; p = 0.05) and REM latency (β: 0.234; confidence interval: 0.001-0.468; p = 0.05) after adjustment for potential confounders.  CONCLUSIONS: Depressive symptoms among kTx recipients are associated with increased amount of stage 2 sleep and prolonged REM latency. Further studies are needed to confirm our findings and understand potential clinical implications

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation.

RATIONALE: Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water ("flower pot") method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS. OBJECTIVES: We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons. METHODS: Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long "rebound sleep", electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry. RESULTS: During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound. CONCLUSIONS: These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders

Sleep in the Human Hippocampus: A Stereo-EEG Study

Background. There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. Methodology/Principal Findings. We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. Conclusions/Significance. Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonanc