Coordinated semi-adaptive closed-loop control for infusion of two interacting medications

This paper presents a coordinated and semi‐adaptive closed‐loop control approach to the infusion of 2 interacting medications. The proposed approach consists of an upper‐level coordination controller and a lower‐level semi‐adaptive controller. The coordination controller recursively adjusts the reference targets based on the estimated dose‐response relationship of a patient to ensure that they can be achieved by the patient. The semi‐adaptive controller drives the patient outputs to the reference targets while estimating the patient's dose‐response relationship online. In this way, the controller is resilient to unachievable caregiver‐specified reference targets and responsive to the medication needs of individual patients. To establish the proposed approach, we developed the following: (1) a linear two‐input–two‐output dose‐response model; (2) a two‐input–two‐output semi‐adaptive controller to regulate the patient outputs while adapting high‐sensitivity parameters in the patient model; and (3) a coordination controller to adjust the reference targets that reconcile caregiver inputs and medication use. The proposed approach was applied to an example scenario in which cardiac output and respiratory rate are regulated via infusion of propofol and remifentanil in an in silico simulation setting. The results show that the coordinated semi‐adaptive control could (1) track achievable reference targets with consistent transient and steady‐state performance and (2) resiliently adjust the unachievable reference targets to achievable ones

A system identification approach to non-invasive central cardiovascular monitoring

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (leaves 180-187).This thesis presents a new system identification approach to non-invasive central cardiovascular monitoring problem. For this objective, this thesis will develop and analyze blind system identification and input signal reconstruction algorithms for a class of 2-channel IIR and Wiener systems. In particular, this thesis will present blind identifiability conditions for a class of 2-channel IIR and Wiener wave propagation systems and develop the associated blind identification algorithms. It will be shown that the blind identifiability conditions can be achieved in many real-world applications by appropriate selection of channel lengths, sensor locations, and sampling frequency which are the specifications that the system design can exploit for blind identifiability In addition, this thesis will develop a novel input signal reconstruction algorithm that is applicable to general class of multi-channel IIR and Wiener systems. Furthermore, this thesis will rigorously analyze and evaluate three analytic measures for determining the system order and other key parameters of the black-box dynamics as well as for quantifying the quality of the identified gray-box dynamics, without any direct use of unknown input signal: persistent excitation, model identifiability and asymptotic variance. The blind identification and input signal reconstruction algorithms will first be applied to 2-sensor central cardiovascular monitoring problem using two distinct peripheral blood pressure measurements, where the cardiovascular wave propagation dynamics is blindly identified and the aortic blood pressure and flow signals are reconstructed by exploiting black-box and physics-based gray-box model structures of the cardiovascular system.(cont.) The validity of the 2-sensor central cardiovascular monitoring methodology will be illustrated by experimental data from swine subjects and simulation data from a full-scale human cardiovascular simulator across diverse physiologic conditions. The 2-sensor central cardiovascular monitoring methodology will then be extended to address noninvasive, 1-sensor cardiovascular monitoring problem, where the specific challenges involved are 1) identifying the cardiovascular wave propagation dynamics and reconstructing the aortic blood pressure signal by exploiting the measurement from a single peripheral sensor, and 2) identifying the scale for calibrating the blood pressure signal. In order to address these challenges, this thesis will propose a heuristics-based system order estimation algorithm and a model-based blood pressure calibration algorithm, which will be combined with the blind identification of the cardiovascular wave propagation dynamics to realize the non-invasive 1-sensor central cardiovascular monitoring. The non-invasive 1-sensor central cardiovascular monitoring methodology will be illustrated by experimental data from swine subjects, simulation data from a full-scale human cardiovascular simulator, and experimental data from human subjects across diverse physiologic conditions.by Jin-Oh Hahn.Ph.D

Nine-Year Survival of Lymphoblastic Lymphoma Patients

This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p = 0.25). The age at presentation influenced the outcome of the patients (p = 0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p = 0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes

Closed-Loop Fluid Resuscitation Control Via Blood Volume Estimation

This paper presents a closed-loop control of fluid resuscitation to overcome hypovolemia based on model-based estimation of relative changes in blood volume (BV). In this approach, the control system consists of a model-based relative BV (RBV) estimator and a feedback controller. The former predicts relative changes in the BV response to augmented fluid by analyzing an arterial blood pressure (BP) waveform and the electrocardiogram (ECG). Then, the latter determines the amount of fluid to be augmented by comparing target versus predicted relative changes in BV. In this way, unlike many previous methods for fluid resuscitation based on controlled variable(s) nonlinearly correlated with the changes in BV, fluid resuscitation can be guided by a controlled variable linearly correlated with the changes in BV. This paper reports initial design of the closed-loop fluid resuscitation system and its in silico evaluation in a wide range of hypovolemic scenarios. The results suggest that closed-loop fluid resuscitation guided by a controlled variable linearly correlated with the changes in BV can be effective in overcoming hypovolemia: across 100 randomly produced hypovolemia cases, it resulted in the BV regulation error of 7.98 6 171.6 ml, amounting to 0.18 6 3.04% of the underlying BV. When guided by pulse pressure (PP), a classical controlled variable nonlinearly correlated with the changes in BV; the same closed-loop fluid resuscitation system resulted in persistent under-resuscitation with the BV regulation error of À779.1 6 147.4 ml, amounting to À13.9 6 2.65% of the underlying BV

Hypotension in ICU Patients Receiving Vasopressor Therapy

Vasopressor infusion (VPI) is used to treat hypotension in an ICU. We studied compliance with blood pressure (BP) goals during VPI and whether a statistical model might be efficacious for advance warning of impending hypotension, compared with a basic hypotension threshold alert. Retrospective data were obtained from a public database. Studying adult ICU patients receiving VPI at submaximal dosages, we analyzed characteristics of sustained hypotension episodes (>15 min) and then developed a logistic regression model to predict hypotension episodes using input features related to BP trends. The model was then validated with prospective data. In the retrospective dataset, 102-of-215 ICU stays experienced >1 hypotension episode (median of 2.5 episodes per day in this subgroup). When trained with 75% of retrospective dataset, testing with the remaining 25% of the dataset showed that the model and the threshold alert detected 99.6% and 100% of the episodes, respectively, with median advance forecast times (AFT) of 12 and 0 min. In a second, prospective dataset, the model detected 100% of 26 episodes with a median AFT of 22 min. In conclusion, episodes of hypotension were common during VPI in the ICU. A logistic regression model using BP temporal trend features predicted the episodes before their onset

Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86±0.15 to 0.58±0.12 ng/mL in the controls, and from 2.38±0.76 to 1.12±0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82±44.4 vs. -10.41±2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS

The genome sequence of Xanthomonas oryzae pathovar oryzae KACC10331, the bacterial blight pathogen of rice

The nucleotide sequence was determined for the genome of Xanthomonas oryzae pathovar oryzae (Xoo) KACC10331, a bacterium that causes bacterial blight in rice (Oryza sativa L.). The genome is comprised of a single, 4 941 439 bp, circular chromosome that is G + C rich (63.7%). The genome includes 4637 open reading frames (ORFs) of which 3340 (72.0%) could be assigned putative function. Orthologs for 80% of the predicted Xoo genes were found in the previously reported X.axonopodis pv. citri (Xac) and X.campestris pv. campestris (Xcc) genomes, but 245 genes apparently specific to Xoo were identified. Xoo genes likely to be associated with pathogenesis include eight with similarity to Xanthomonas avirulence (avr) genes, a set of hypersensitive reaction and pathogenicity (hrp) genes, genes for exopolysaccharide production, and genes encoding extracellular plant cell wall-degrading enzymes. The presence of these genes provides insights into the interactions of this pathogen with its gramineous host