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Background : Despite the known impact of propofol and remifentanil on hemodynamics and patient outcomes, there is a lack of comprehensive quantitative analysis, particularly in surgical settings, considering the influence of noxious stimuli. The aim of this study was to develop a quantitative semi-mechanistic population model that characterized the time course changes in mean arterial pressure (MAP) and heart rate (HR) due to the effects of propofol, remifentanil, and different types of noxious stimulation related to the clinical routine. Methods : Data from a prospective study were used; the study analyzed the effects of propofol and remifentanil general anesthesia on female patients in physical status of I-II according to the American Society of Anesthesiologists (ASA I-II) undergoing gynecology surgery. Patients were consecutively assigned to different administration schemes of propofol and remifentanil targeted at different effect-site concentrations. Esophageal instrumentation, laryngeal mask airway insertion, hysteroscopy, and tetanus stimuli were applied. Data from patients with chronic hypertension were discarded. Results : MAP and HR observations from 77 patients were analyzed. The hemodynamic effects were described using turn-over models incorporating feedback mechanisms. Analyses revealed that propofol and remifentanil elicited effects on the turn-over of MAP and HR, respectively, with estimates of plasma drug concentrations causing an inhibition-half of the maximum effect ( C 50) of 8.79 µg∙mL -1 and 4.57 ng∙mL -1 . Hysteroscopy exerted an increase in MAP (but not in HR), which was well-characterized by the model, with a predicted typical increase of 28 mmHg and a dissipation half-life of 33 min. The impact of other noxious stimuli on MAP or HR could not be identified. Model simulations indicated that propofol and remifentanil, titrated to inhibit the motor response to noxious stimuli, regardless of dose combinations, cause a significant risk of hypotension, especially following induction and at the end of surgery (when surgical intervention is completed, before the awakening phase). Conclusions : The developed semi-mechanistic and fully identifiable model provides quantitative information on how propofol, remifentanil, and surgical stimulus (hysteroscopy) interact to produce the hemodynamic changes (of MAP and HR) commonly observed in clinical practice.

The performance of catalysts prepared from hierarchical Y zeolites has been studied during the conversion of vacuum gas oil (VGO) into higher-value products. Two different catalysts have been studied: CatY.0.00 was obtained from the standard zeolite (Y-0.00-M: without alkaline treatment) and CatY.0.20 was prepared from the desilicated zeolite (Y-0-20-M: treated with 0.20 M NaOH). The cracking tests were carried out in a microactivity test (MAT) unit with a fixed-bed reactor at 550 °C in the 20-50 s reaction time range, with a catalyst mass of 3 g and a mass flow rate of VGO of 2.0 g/min. The products obtained were grouped according to their boiling point range in dry gas (DG), liquefied petroleum gas (LPG), naphtha, and coke. The results showed a greater conversion and selectivity to gasoline with the CatY.0.20 catalyst, along with improved quality (RON) of the C 5 -C 12 cut. Conversely, the CatY.0.00 catalyst (obtained from the Y-0.00-M zeolite) showed greater selectivity to gases (DG and LPG), attributable to the electronic confinement effect within the microporous channels of the zeolite. The nature of coke has been studied using different analysis techniques and the impact on the catalysts by comparing the properties of the fresh and deactivated catalysts. The coke deposited on the catalyst surfaces was responsible for the loss of activity; however, the CatY.0.20 catalyst showed greater resistance to deactivation by coke, despite showing the highest selectivity. Given that the reaction occurs in the acid sites of the zeolite and not in the matrix, the increased degree of mesoporosity of the zeolite in the CatY.0.20 catalyst facilitated the outward diffusion of products from the zeolitic channels to the matrix, thereby preserving greater activity.

Background: The aim of this observational study was to determine whether bilateral bispectral index (BIS) monitoring can detect seizures in epileptic patients., Methods: Four-channel frontal BIS monitoring and standard 40-channel electroencephalography monitoring were conducted in epileptic patients undergoing evaluation for epilepsy surgery. The BIS numerical value, signal quality index, electromyography, suppression ratio, and color density spectral array were continuously recorded. In patients with electroencephalography-confirmed seizures, the mean value and trend (slope of linear regression) of bilateral BIS monitor parameters were analyzed from 1 minute before to 1 minute after seizure onset., Results: Of 48 patients included in the study, 21 (43.8%) had at least 1 seizure. BIS numerical value was not able to detect focal or focal to bilateral tonic-clonic seizures. Considering all seizures, the only significant differences between recordings 1 minute before and 1 minute after seizure onset were a decrease in the signal quality index slope from 1 hemisphere (0.039±0.297 vs. -0.085±0.321, respectively; P =0.029) and in the mean signal quality index recorded from both hemispheres (left hemisphere: 65.775±30.599 vs. 61.032±26.285; P =0.016 and right hemisphere: 63.244±31.985 vs. 59.837±27.360; 0.029); these differences were not maintained after Hochberg adjustment for multiple comparisons. In seizures occurring during sleep, there was a change in the electromyography slope of 1 hemisphere before and after seizure onset (-0.141±0.176 vs. 0.162±0.140, respectively; P =0.038). There were variable responses in BIS parameters in the 3 patients who developed focal nonconvulsive seizure clusters., Conclusion: Bilateral BIS monitoring was not able to detect the occurrence of seizures in epileptic patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%., (© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Psychosocial risks, also present in educational processes, are stress factors particularly critical in state-schools, affecting the efficacy, stress, and job satisfaction of the teachers. This study proposes an intelligent algorithm to improve the prediction of psychosocial risk, as a tool for the generation of health and risk prevention assistance programs., Methods: The proposed approach, Physical Surface Tension-Neural Net (PST-NN), applied the theory of superficial tension in liquids to an artificial neural network (ANN), in order to model four risk levels (low, medium, high and very high psychosocial risk). The model was trained and tested using the results of tests for measurement of the psychosocial risk levels of 5,443 teachers. Psychosocial, and also physiological and musculoskeletal symptoms, factors were included as inputs of the model. The classification efficiency of the PST-NN approach was evaluated by using the sensitivity, specificity, accuracy and ROC curve metrics, and compared against other techniques as the Decision Tree model, Naïve Bayes, ANN, Support Vector Machines, Robust Linear Regression and the Logistic Regression Model., Results: The modification of the ANN model, by the adaptation of a layer that includes concepts related to the theory of physical surface tension, improved the separation of the subjects according to the risk level group, as a function of the mass and perimeter outputs. Indeed, the PST-NN model showed better performance to classify psychosocial risk level on state-school teachers than the linear, probabilistic and logistic models included in this study, obtaining an average accuracy value of 97.31%., Conclusions: The introduction of physical models, such as the physical surface tension, can improve the classification performance of ANN. Particularly, the PST-NN model can be used to predict and classify psychosocial risk levels among state-school teachers at work. This model could help to early identification of psychosocial risk and to the development of programs to prevent it., Competing Interests: The authors declare there are no competing interests., (©2021 Mosquera Navarro et al.)

It has been suggested that a viable strategy to improve complexity estimation based on the assessment of pattern similarity is to increase the pattern matching rate without enlarging the series length. We tested this hypothesis over short simulations of nonlinear deterministic and linear stochastic dynamics affected by various noise amounts. Several transformations featuring a different ability to increase the pattern matching rate were tested and compared to the usual strategy adopted in sample entropy (SampEn) computation. The approaches were applied to evaluate the complexity of short-term cardiac and vascular controls from the beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP) in 12 Parkinson disease patients and 12 age- and gender-matched healthy subjects at supine resting and during head-up tilt. Over simulations, the strategies estimated a larger complexity over nonlinear deterministic signals and a greater regularity over linear stochastic series or deterministic dynamics importantly contaminated by noise. Over short HP and SAP series the techniques did not produce any practical advantage, with an unvaried ability to discriminate groups and experimental conditions compared to the traditional SampEn. Procedures designed to artificially increase the number of matches are of no methodological and practical value when applied to assess complexity indexes.

The refined multiscale entropy (RMSE) approach is commonly applied to assess complexity as a function of the time scale. RMSE is normally based on the computation of sample entropy (SampEn) estimating complexity as conditional entropy. However, SampEn is dependent on the length and standard deviation of the data. Recently, fuzzy entropy (FuzEn) has been proposed, including several refinements, as an alternative to counteract these limitations. In this work, FuzEn, translated FuzEn (TFuzEn), translated-reflected FuzEn (TRFuzEn), inherent FuzEn (IFuzEn), and inherent translated FuzEn (ITFuzEn) were exploited as entropy-based measures in the computation of RMSE and their performance was compared to that of SampEn. FuzEn metrics were applied to synthetic time series of different lengths to evaluate the consistency of the different approaches. In addition, electroencephalograms of patients under sedation-analgesia procedure were analyzed based on the patient's response after the application of painful stimulation, such as nail bed compression or endoscopy tube insertion. Significant differences in FuzEn metrics were observed over simulations and real data as a function of the data length and the pain responses. Findings indicated that FuzEn, when exploited in RMSE applications, showed similar behavior to SampEn in long series, but its consistency was better than that of SampEn in short series both over simulations and real data. Conversely, its variants should be utilized with more caution, especially whether processes exhibit an important deterministic component and/or in nociception prediction at long scales.

The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation., (Copyright © 2016 the American Physiological Society.)

Respiratory depression is a common adverse effect of propofol and remifentanil. We aimed to develop a model for respiratory depressant effects of propofol with remifentanil in patients undergoing endoscopy with sedation. Data were available for 136 patients undergoing endoscopy with sedation. Participants randomly received infusions of propofol and remifentanil. Predicted plasma concentrations, outputted by infusion pumps, were available. Transcutaneous arterial pressure of carbon dioxide (pCO2) was measured. Data were analyzed using nonlinear mixed-effects modeling methods. Covariate relationships were investigated for age, noxious stimuli (endoscopy tube insertion), and A118G genotype for the µ-opioid receptor (OPRM1). Participants had a median (range) age of 64.0 (25.0-88.0) years, weight of 70.0 (35.0-98.0) kg, and height of 164.0 (147.0-190.0) cm. Seven percent were recessive homozygous for OPRM1 polymorphism. An indirect-effect model with a "modulator" compartment best described pCO2 data (P < 0.001) over a direct-effect model. Remifentanil inhibited pCO2 removal with an IC50 of 1.13 ng/ml and first-order rate constant (ke 0) of 0.28 minute(-1). Propofol affected the modulator compartment with an IC50 of 4.97 µg/ml (no effect-site compartment). Propofol IC50 and remifentanil ke 0 were reduced with increasing age. Noxious stimuli and genotype were not significant covariates. An indirect-effect model with a rebound mechanism can describe remifentanil- and propofol-induced changes in pCO2 in patients undergoing noxious procedures. The model may be useful for identifying optimal dosing schedules for these drugs in a combination that provides adequate sedation but avoids respiratory depression., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope., Methods: Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use., Results: One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively., Conclusions: We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

The level of sedation in patients undergoing medical procedures evolves continuously, affected by the interaction between the effect of the anesthetic and analgesic agents and the pain stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. However, the quantification of analgesia still remains an open problem. The purpose of this work is to improve the prediction of nociceptive responses with linear and non-linear measures calculated from EEG signal filtered in frequency bands higher than the traditional bands. Power spectral density and auto-mutual information function was applied in order to predict the presence or absence of the nociceptive responses to different stimuli during sedation in endoscopy procedure. The proposed measures exhibit better performances than the bispectral index (BIS). Values of prediction probability of Pk above 0.75 and percentages of sensitivity and specificity above 70% were achieved combining EEG measures from the traditional frequency bands and higher frequency bands.

Myocardial ischaemia is hypothesized to stimulate the cardiac sympathetic excitatory afferents and, therefore, the spontaneous changes of heart period (approximated as the RR interval), and the QT interval in ischaemic dilated cardiomyopathy (IDC) patients might reflect this sympathetic activation. Symbolic analysis is a nonlinear and powerful tool for the extraction and classification of patterns in time-series analysis, which implies a transformation of the original series into symbols and the construction of patterns with the symbols. The aim of this work was to investigate whether symbolic transformations of RR and QT cardiac series can provide a better separation between IDC patients and healthy control (HC) subjects compared with traditional linear measures. The variability of these cardiac series was studied during daytime and night-time periods and also during the complete 24 h recording over windows of short data sequences of approximately 5 min. The IDC group was characterized by an increase in the occurrence rate of patterns without variations (0 V%) and a reduction in the occurrence rate of patterns with one variation (1 V%) and two variations (2 V%). Concerning the RR variability during the daytime, the highest number of patterns had 0 V%, whereas the rates of 1 V% and 2 V% were lower. During the night, 1 V% and 2 V% increased at the expense of diminishing 0 V%. Patterns with and without variations between consecutive symbols were able to increase the separation between the IDC and HC groups, allowing accuracies higher than 80%. With regard to entropy measures, an increase in RR regularity was associated with cardiac disease described by accuracy >70% in the RR series and by accuracy >60% in the QTc series. These results could be associated with an increase in the sympathetic tone in IDC patients., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)

The aim of the present study was to investigate the suitability of the Phase-Rectified Signal Averaging (PRSA) method for improved risk prediction in cardiac patients. Moreover, this technique, which separately evaluates acceleration and deceleration processes of cardiac rhythm, allows the effect of sympathetic and vagal modulations of beat-to-beat intervals to be characterized. Holter recordings of idiopathic dilated cardiomyopathy (IDC) patients were analyzed: high-risk (HR), who suffered sudden cardiac death (SCD) during the follow-up; and low-risk (LR), without any kind of cardiac-related death. Moreover, a control group of healthy subjects was analyzed. PRSA indexes were analyzed, for different time scales T and wavelet scales s, from RR series of 24 h-ECG recordings, awake periods and sleep periods. Also, the behavior of these indexes from simulated data was analyzed and compared with real data results. Outcomes demonstrated the PRSA capacity to significantly discriminate healthy subjects from IDC patients and HR from LR patients on a higher level than traditional temporal and spectral measures. The behavior of PRSA indexes agrees with experimental evidences related to cardiac autonomic modulations. Also, these parameters reflect more regularity of the autonomic nervous system (ANS) in HR patients., (Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of the present study was to validate the qCON index of hypnotic effect and the qNOX index of nociception. Both indices are derived from the frontal electroencephalogram (EEG) and implemented in the qCON 2000 monitor (Quantium Medical, Barcelona, Spain)., Methods: The study was approved by the local ethics committee, including data from 60 patients scheduled for ambulatory surgery undergoing general anaesthesia with propofol and remifentanil, using TCI. The Bis (Covidien, Boulder, CO, USA) was recorded simultaneously with the qCON. Loss of eyelash reflex [loss of consciousness (LOC)] was recorded, and prediction probability for Bis and qCON was calculated. Movement as a response to noxious stimulation [laryngeal mask airway (LMA) insertion, laryngoscopy and tracheal intubation] was registered. The correlation coefficient between qCON and Bis was calculated. The patients were divided into movers/non-movers as a response to noxious stimulation. A paired t-test was used to assess significant difference for qCON and qNOX for movers/non-movers., Results: The prediction probability (Pk) and the standard error (SE) for qCON and Bis for detecting LOC was 0.92 (0.02) and 0.94 (0.02) respectively (t-test, no significant difference). The R between qCON and Bis was 0.85. During the general anaesthesia (Ce propofol > 2 μg/ml, Ce remifentanil > 2 ng/ml), the mean value and standard deviation (SD) for qCON was 45 (8), while for qNOX it was 40 (6). The qNOX pre-stimuli values were significantly different (P < 0.05) for movers/non-movers as a response to LMA insertion [62.5 (24.0) vs. 45.5 (24.1)], tracheal intubation [58.7 (21.8) vs. 41.4 (20.9)], laryngoscopy [54.1 (21.4) vs. 41.0 (20.8)]. There were no significant differences in remifentanil or propofol effect-site concentrations for movers vs. non-movers., Conclusion: The qCON was able to reliably detect LOC during general anaesthesia with propofol and remifentanil. The qNOX showed significant overlap between movers and non-movers, but it was able to predict whether or not the patient would move as a response to noxious stimulation, although the anaesthetic concentrations were similar., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population.

The level of sedation in patients undergoing medical procedures is affected by the interaction between the effect of the anesthetic and analgesic agents and the pain stimuli. The presence of the A118G single nucleotide polymorphism (SNP) in the OPRM1 gene affects the requirements of opioids for patients undergoing sedation-analgesia. The purpose of this work is to evaluate the influence of the SNP A118G in OPRM1 on EEG measures for the prediction of the response to pain stimulation during endoscopy procedure. The proposed measures were based on power spectral density and auto-mutual information function. It was found that the statistical performances of the EEG measures improved when the presence of the SNP was taken into account (prediction probability Pk>0.9).

During the early stages of human papillomavirus (HPV) infections, the innate immune system creates a pro-inflammatory microenvironment by recruiting innate immune cells to eliminate the infected cells, initiating an effective acquired immune response. However, HPV exhibits a wide range of strategies for evading immune-surveillance, generating an anti-inflammatory microenvironment. The administration of new adjuvants, such as TLR (Toll-like receptors) agonists and alpha-galactosylceramide, has been demonstrated to reverse the anti-inflammatory microenvironment by down-regulating a number of adhesion molecules and chemo-attractants and activating keratinocytes, dendritic (DC), Langerhans (LC), natural killer (NK) or natural killer T (NKT) cells; thus, promoting a strong specific cytotoxic T cell response. Therefore, these adjuvants show promise for the treatment of HPV generated lesions and may be useful to elucidate the unknown roles of immune cells in the natural history of HPV infection. This review focuses on HPV immune evasion mechanisms and on the proposed response of the innate immune system, suggesting a role for the surrounding pro-inflammatory microenvironment and the NK and NKT cells in the clearance of HPV infections.

Background: The presence of the A118G single nucleotide polymorphism in the OPRM1 gene as well as noxious stimulation might affect the requirements of remifentanil for patients undergoing ultrasonographic endoscopy under sedation-analgesia with propofol and remifentanil. Bispectral index (BIS) was used as a surrogate measure of effect., Method: A total of 207 patients were screened for A118G and randomly received different combinations of propofol and remifentanil, changed depending on the nausea response to endoscopy tube introduction. Nonlinear mixed effects modelling was used to establish the relation between propofol and remifentanil with respect to BIS and to investigate the influence of A118G or noxious stimulation. The value of k e0 for propofol and remifentanil was estimated to avoid the hysteresis between predicted effect site concentration (Ce) and BIS., Results: Data from 176 patients were analysed. Eleven were recessive homozygous for A118G (OPRM = 1). A total of 165 patients were either dominant homozygous or heterozygous and considered normal (OPRM = 0). The estimated values of k e0 for propofol and remifentanil were 0.122 and 0.148 min(-1). Propofol and remifentanil were synergistic with respect to the BIS (α = 1.85). EC50 estimate for propofol was 3.86 µg/ml and for remifentanil 19.6 ng/ml in normal patients and 326 ng/ml in OPRM = 1 patients. BIS increases around 4% for the same effect site concentrations with noxious stimulation., Conclusions: Predicted effect site concentration of remifentanil ranging 1-5 ng/ml synergistically potentiates the effects of propofol on the BIS but has no effect in A118G patients. Noxious stimulation increases BIS values by 4% at the same concentrations of propofol and remifentanil.

In this work, a univariate and multivariate statistical analysis of indexes derived from heart rate variability (HRV) was conducted to stratify patients with ischemic dilated cardiomyopathy (IDC) in cardiac risk groups. Indexes conditional entropy, refined multiscale entropy (RMSE), detrended fluctuation analysis, time and frequency analysis, were applied to the RR interval series (beat-to-beat series), for single and multiscale complexity analysis of the HRV in IDC patients. Also, clinical parameters were considered. Two different end-points after a follow-up of three years were considered: (i) analysis A, with 151 survivor patients as a low risk group and 13 patients that suffered sudden cardiac death as a high risk group; (ii) analysis B, with 192 survivor patients as a low risk group and 30 patients that suffered cardiac mortality as a high risk group. A univariate and multivariate linear discriminant analysis was used as a statistical technique for classifying patients in risk groups. Sensitivity (Sen) and specificity (Spe) were calculated as diagnostic criteria in order to evaluate the performance of the indexes and their linear combinations. Sen and Spe values of 80.0% and 72.9%, respectively, were obtained during daytime by combining one clinical parameter and one index from RMSE, and during nighttime Sen = 80% and Spe = 73.4% were attained by combining one clinical factor and two indexes from RMSE. In particular, relatively long time scales were more relevant for classifying patients into risk groups during nighttime, while during daytime shorter scales performed better. The results suggest that the left atrial size, indexed to body surface and RMSE indexes are those that allow enhanced classification of ischemic patients in their respective risk groups, confirming that a single measurement is not enough to fully characterize ischemic risk patients and the clinical relevance of HRV complexity measures.

The level of sedation in patients undergoing medical procedures evolves continuously, such as the effect of the anesthetic and analgesic agents is counteracted by pain stimuli. The monitors of depth of anesthesia, based on the analysis of the electroencephalogram (EEG), have been progressively introduced into the daily practice to provide additional information about the state of the patient. However, the quantification of analgesia still remains an open problem. The purpose of this work is to analyze the capability of prediction of nociceptive responses based on the time-frequency representation (TFR) of EEG signal. Functions of spectral entropy, instantaneous power and instantaneous frequency were calculated in order to predict the presence or absence of the nociceptive responses to different stimuli during sedation in endoscopy procedure. Values of prediction probability of Pk above 0.75 and percentages of sensitivity and specificity above 70% and 65% respectively were achieved combining TFR functions with bispectral index (BIS) and with concentrations of propofol (CeProp) and remifentanil (CeRemi).

This study assesses complexity of cardiovascular control in patients affected by type-1 variant of long QT (LQT1) syndrome. Complexity was assessed by refined multiscale entropy of heart period (HP) and QT interval variabilities. HP was taken as the time distance between two consecutive R peaks (RR) and QT interval was approximated as the time distance between the R-peak and T-wave apex (RTa) and between R-peak and T-wave end (RTe). RR, RTa and RTe intervals were automatically extracted from 24h Holter recordings and the daytime period was analyzed (from 02:00 to 06:00 PM). Non mutation carrier (NMC) individuals (n=11), utilized as a control group, were taken from the same family line of the mutation carrier (MC) subjects (n=26). We found that, while NMC and MC groups were indistinguishable based on time domain and complexity analyses of RR dynamics, complexity analysis of RTa and RTe variabilities clearly separates the two populations and suggests an impairment in the cardiac control mechanisms acting on the ventricles.

The use of more abstract language to describe expected behaviors as opposed to unexpected behaviors has traditionally been considered a way of stereotype maintenance. This tendency is known as linguistic expectancy bias. Two experiments examined the influence of approach and avoidance motivational orientations on the production of this linguistic expectancy bias. It was predicted that approach strategic orientation is likely to describe expectancy consistent behaviors at a higher level of linguistic abstraction than expectancy inconsistent behaviors. In contrast, avoidance strategic orientation is likely to describe both expectancy consistent behaviors and expectancy inconsistent behaviors at a lower level of linguistic abstraction, thus facilitating the disappearance of linguistic expectancy bias. Two experiments confirmed these expectations, using strategic orientation manipulations based either on communication goals or on motor action, and measuring linguistic abstraction either on forced-choice answer format or on free descriptions. Implications for the generalisation of linguistic expectancy bias are discussed.

Background: The increasing demand for anesthetic procedures in the gastrointestinal endoscopy area has not been followed by a similar increase in the methods to provide and control sedation and analgesia for these patients. In this study, we evaluated different combinations of propofol and remifentanil, administered through a target-controlled infusion system, to estimate the optimal concentrations as well as the best way to control the sedative effects induced by the combinations of drugs in patients undergoing ultrasonographic endoscopy., Methods: One hundred twenty patients undergoing ultrasonographic endoscopy were randomized to receive, by means of a target-controlled infusion system, a fixed effect-site concentration of either propofol or remifentanil of 8 different possible concentrations, allowing adjustment of the concentrations of the other drug. Predicted effect-site propofol (C(e)pro) and remifentanil (C(e)remi) concentrations, parameters derived from auditory evoked potential, autoregressive auditory evoked potential index (AAI/2) and electroencephalogram (bispectral index [BIS] and index of consciousness [IoC]) signals, as well as categorical scores of sedation (Ramsay Sedation Scale [RSS] score) in the presence or absence of nociceptive stimulation, were collected, recorded, and analyzed using an Adaptive Neuro Fuzzy Inference System. The models described for the relationship between C(e)pro and C(e)remi versus AAI/2, BIS, and IoC were diagnosed for inaccuracy using median absolute performance error (MDAPE) and median root mean squared error (MDRMSE), and for bias using median performance error (MDPE). The models were validated in a prospective group of 68 new patients receiving different combinations of propofol and remifentanil. The predictive ability (P(k)) of AAI/2, BIS, and IoC with respect to the sedation level, RSS score, was also explored., Results: Data from 110 patients were analyzed in the training group. The resulting estimated models had an MDAPE of 32.87, 12.89, and 8.77; an MDRMSE of 17.01, 12.81, and 9.40; and an MDPE of -1.86, 3.97, and 2.21 for AAI/2, BIS, and IoC, respectively, in the absence of stimulation and similar values under stimulation. P(k) values were 0.82, 0.81, and 0.85 for AAI/2, BIS, and IoC, respectively. The model predicted the prospective validation data with an MDAPE of 34.81, 14.78, and 10.25; an MDRMSE of 16.81, 15.91, and 11.81; an MDPE of -8.37, 5.65, and -1.43; and P(k) values of 0.81, 0.8, and 0.8 for AAI/2, BIS, and IoC, respectively., Conclusion: A model relating C(e)pro and C(e)remi to AAI/2, BIS, and IoC has been developed and prospectively validated. Based on these models, the (C(e)pro, C(e)remi) concentration pairs that provide an RSS score of 4 range from (1.8 μg·mL(-1), 1.5 ng·mL(-1)) to (2.7 μg·mL(-1), 0 ng·mL(-1)). These concentrations are associated with AAI/2 values of 25 to 30, BIS of 71 to 75, and IoC of 72 to 76. The presence of noxious stimulation increases the requirements of C(e)pro and C(e)remi to achieve the same degree of sedative effects.

This work has proposed a methodology based on the concept of entropy rates to study the complexity of the short-term heart-rate variability (HRV) for improving risk stratification to predict sudden cardiac death (SCD) of patients with established ischemic-dilated cardiomyopathy (IDC). The short-term HRV was analyzed during daytime and nighttime by means of RR series. An entropy rate was calculated on the RR series, previously transformed to symbol sequences by means of an alphabet. A statistical analysis permitted to stratify high- and low-risk patients of suffering SCD, with a specificity (SP) of 95% and sensitivity (SE) of 83.3%.

Multiscale entropy (MSE) was proposed to characterize complexity as a function of the time-scale factor tau. Despite its broad use, this technique suffers from two limitations: 1) the artificial MSE reduction due to the coarse graining procedure and 2) the introduction of spurious MSE oscillations due to the suboptimal procedure for the elimination of the fast temporal scales. We propose a refined MSE (RMSE), and we apply it to simulations and to 24-h Holter recordings of heart rate variability (HRV) obtained from healthy and aortic stenosis (AS) groups. The study showed that the refinement relevant to the elimination of the fast temporal scales was more helpful at short scales (spanning the range of short-term HRV oscillations), while that relevant to the procedure of coarse graining was more useful at large scales. In healthy subjects, during daytime, RMSE was smaller at short scales (i.e., tau = 1-2) and larger at longer scales (i.e., tau = 4-20) than during nighttime. In AS population, RMSE was smaller during daytime both at short and long time scales (i.e., tau = 1 -11) than during nighttime. RMSE was larger in healthy group than in AS population during both daytime (i.e., tau = 2 -9) and nighttime (i.e., tau = 2). RMSE overcomes two limitations of MSE and confirms the complementary information that can be derived by observing complexity as a function of the temporal scale.

In the present document the multiscale entropy (MSE) methodology has been applied to analyze the complex behavior of the heart rate variability (HRV), in patients with aortic stenosis (AS). A set of healthy voluntaries have been used as a control group. MSE analysis calculates an entropy rate over different time scales to assess the complexity of time series, evaluating short-term and long-term correlations. Daytime and nighttime have been considered to study variations of the complexity inside the same group of population. A statistical analysis showed that entropy was significantly higher in healthy subjects than in AS subjects in all the scales during daytime, with exception at scale 1. During nighttime, entropy in healthy subjects was significantly higher than in AS subjects only in scales from 1 to 7. Multiscale entropy is helpful to characterize AS patients and distinguish them from healthy subjects.

Subjects with ischemic dilated cardiomiopathy tend to suffer episodes of sudden cardiac death, thus risk stratification is essential to establish an adequate therapy for the patients. In this work, a new methodology was proposed for the study of the heart rate variability by using a multiscale analysis based on the concept of entropy rates, for improving risk prediction in cardiac patients. Symbolic dynamics were applied to RR time series and sets of words in several scales were constructed. The multiscale regularity analysis was proposed by comparing the entropies, calculated using Shannon and Renyi definitions, of the series of words in different scales. The study considered the selection of the best parameters for the length of the words (l) and the order of the entropies (q). Statistical analysis with repeated measures and discriminant analysis revealed statistically significant differences (p-value<0.05) and a high percentage of well classified subjects in their different risk groups, with sensitivity, specificity and positive predictive values of 100%.

In 3 experiments, the authors investigated how strategic inclinations associated with promotion versus prevention orientations--that is, eager approach versus vigilant avoidance, respectively--affect the use of language. It is hypothesized that eager promotion strategies used to attain desired end states entail using more abstract language than used with vigilant prevention strategies. This is shown to hold for experimentally induced relationship goals (Experiment 1) and communication goals (Experiment 2). In the 3rd experiment, the authors examined the impact of abstractly and concretely worded messages upon the behavioral intentions of chronically prevention- and promotion-oriented individuals and found support for the hypothesis that behavioral intentions to engage in specific activities are stronger when there is a fit between message wording and chronic orientation than when there is no fit. The broader implications of these findings are discussed.