Recovery time of a plasma-wakefield accelerator.

The interaction of intense particle bunches with plasma can give rise to plasma wakes1,2 capable of sustaining gigavolt-per-metre electric fields3,4, which are orders of magnitude higher than provided by state-of-the-art radio-frequency technology5. Plasma wakefields can, therefore, strongly accelerate charged particles and offer the opportunity to reach higher particle energies with smaller and hence more widely available accelerator facilities. However, the luminosity and brilliance demands of high-energy physics and photon science require particle bunches to be accelerated at repetition rates of thousands or even millions per second, which are orders of magnitude higher than demonstrated with plasma-wakefield technology6,7. Here we investigate the upper limit on repetition rates of beam-driven plasma accelerators by measuring the time it takes for the plasma to recover to its initial state after perturbation by a wakefield. The many-nanosecond-level recovery time measured establishes the in-principle attainability of megahertz rates of acceleration in plasmas. The experimental signatures of the perturbation are well described by simulations of a temporally evolving parabolic ion channel, transferring energy from the collapsing wake to the surrounding media. This result establishes that plasma-wakefield modules could be developed as feasible high-repetition-rate energy boosters at current and future particle-physics and photon-science facilities.

Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure.

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.

Classification of patients undergoing weaning from mechanical ventilation using the coherence between heart rate variability and respiratory flow signal.

Weaning from mechanical ventilation is still one of the most challenging problems in intensive care. Unnecessary delays in discontinuation and weaning trials that are undertaken too early are both undesirable. This study investigated the contribution of spectral signals of heart rate variability (HRV) and respiratory flow, and their coherence to classifying patients on weaning process from mechanical ventilation. A total of 121 candidates for weaning, undergoing spontaneous breathing tests, were analyzed: 73 were successfully weaned (GSucc), 33 failed to maintain spontaneous breathing so were reconnected (GFail), and 15 were extubated after the test but reintubated within 48 h (GRein). The power spectral density and magnitude squared coherence (MSC) of HRV and respiratory flow signals were estimated. Dimensionality reduction was performed using principal component analysis (PCA) and sequential floating feature selection. The patients were classified using a fuzzy K-nearest neighbour method. PCA of the MSC gave the best classification with the highest accuracy of 92% classifying GSucc versus GFail patients, and 86% classifying GSucc versus GRein patients. PCA of the respiratory flow signal gave the best classification between GFail and GRein patients (79% accuracy). These classifiers showed a good balance between sensitivity and specificity. Besides, the spectral coherence between HRV and the respiratory flow signal, in patients on weaning trial process, can contribute to the extubation decision.

Auditory and Nociceptive Stimuli Responses in the Electroencephalogram. A Non-linear Measures and Time-frequency Representation Based Analysis.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and Images". OBJECTIVES: An efficient way to investigate the neural basis of nociceptive responses is the analysis of the event-related brain potentials (ERPs). The main objective of this work was to study how adaptation and fatigue affect the ERPs to stimuli of different modalities, by characterizing the responses to infrequent and frequent stimulation in different recording periods. METHODS: In this work, series of averaged EEG epochs recorded after thermal, electrical and auditory stimulation were analyzed with time-frequency representation and non-linear measures as spectral entropy and auto-mutual information function. The study was performed by considering the traditional EEG frequency bands. RESULTS: The defined measures presented a statistical significance p-value < 0.01 and accuracy higher than 60% by differentiating windows of response to infrequent (I) and frequent (F) stimuli between the start and end of the EEG recording. CONCLUSIONS: These measures permitted to observe some aspects of the subject's adaptation and the nociceptive response.

Complexity of the autonomic heart rate control in coronary artery occlusion in patients with and without prior myocardial infarction.

Autonomic nervous system (ANS) is governed by complex interactions arising from feedback loops of nonlinear systems that operate over a wide range of temporal and spatial scales, enabling the organism to adapt to stress, metabolic changes and diseases. This study is aimed to assess multifractal and nonlinear characteristics of the ANS during ischemic events provoked by a prolonged percutaneous coronary intervention (PCI) procedure. Eighty-seven patients from the STAFF III database were used. Patients were classified into 2 groups: (1) with prior myocardial infarction (MI) and (2) without MI (noMI). R-R signals during three 3-min stages of the procedures were analyzed using multifractal and surrogate data techniques. Multifractal indices increased significantly from the pre-inflation stage to the post-deflation stage. These variations were more marked for the noMI group. Multifractal changes significantly correlated with both the decreased parasympathetic and the increased sympathetic modulations accounted by classical linear indices. Multifractal measures resulted to be a more powerful indicator than linear HRV indices in quantifying the ischemia-induced changes. Right coronary artery (RCA) occlusions provoke greater multifractal reactions throughout the PCI procedure. Our findings suggest reduced complex multifractal and nonlinear reactions of ANS activity in patients with prior MI in comparison to the noMI group, possibly due to degradation in the complexity of control mechanism of heart rate generation.

Modeling the effect of propofol and remifentanil combinations for sedation-analgesia in endoscopic procedures using an Adaptive Neuro Fuzzy Inference System (ANFIS).

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.

Symbolic dynamic analysis of relations between cardiac and breathing cycles in patients on weaning trials.

Traditional time-domain techniques of data analysis are often not sufficient to characterize the complex dynamics of the cardiorespiratory interdependencies during the weaning trials. In this paper, the interactions between the heart rate (HR) and the breathing rate (BR) were studied using joint symbolic dynamic analysis. A total of 133 patients on weaning trials from mechanical ventilation were analyzed: 94 patients with successful weaning (group S) and 39 patients that failed to maintain spontaneous breathing (group F). The word distribution matrix enabled a coarse-grained quantitative assessment of short-term nonlinear analysis of the cardiorespiratory interactions. The histogram of the occurrence probability of the cardiorespiratory words presented a higher homogeneity in group F than in group S, measured with a higher number of forbidden words in group S as well as a higher number of words whose probability of occurrence is higher than a probability threshold in group S. The discriminant analysis revealed the best results when applying symbolic dynamic variables. Therefore, we hypothesize that joint symbolic dynamic analysis provides enhanced information about different interactions between HR and BR, when comparing patients with successful weaning and patients that failed to maintain spontaneous breathing in the weaning procedure.

Multifractal and nonlinear assessment of autonomous nervous system response during transient myocardial ischaemia.

We assess autonomic nervous system response during prolonged percutaneous transluminal coronary angioplasty (PTCA) using heart rate variability analysis with multifractal indices. These indices are used to evaluate the effects of the PTCA procedures at different arteries and locations. A total of 55 patients from the Staff3 database, with no prior history of myocardial infarction, were included in the study. The indices increased significantly during the transient ischaemia and reperfusion periods, indicating an increase in nonlinear multifractal characteristics and a change in temporal correlations in heartbeat fluctuations. This indicates that significant multifractal and nonlinear complex reactions in the autonomic control of the heart rate occurred during coronary artery occlusions and suggests that the multifractal indices may be a promising nonlinear technique for evaluating autonomic nervous system response in the presence of transient myocardial ischaemia.

DNA binding site characterization by means of Rényi entropy measures on nucleotide transitions.

In this work, parametric information-theory measures for the characterization of binding sites in DNA are extended with the use of transitional probabilities on the sequence. We propose the use of parametric uncertainty measures such as Rényi entropies obtained from the transition probabilities for the study of the binding sites, in addition to nucleotide frequency-based Rényi measures. Results are reported in this work comparing transition frequencies (i.e., dinucleotides) and base frequencies for Shannon and parametric Rényi entropies for a number of binding sites found in E. Coli, lambda and T7 organisms. We observe that the information provided by both approaches is not redundant. Furthermore, under the presence of noise in the binding site matrix we observe overall improved robustness of nucleotide transition-based algorithms when compared with nucleotide frequency-based method.

Heart rate variability analysis based on time-frequency representation and entropies in hypertrophic cardiomyopathy patients.

In hypertrophic cardiomyopathy (HCM) patients there is an increased risk of premature death, which can occur with little or no warning. Furthermore, classification for sudden cardiac death on patients with HCM is very difficult. The aim of our study was to improve the prognostic value of heart rate variability (HRV) in HCM patients, giving insight into changes of the autonomic nervous system. In this way, the suitability of linear and nonlinear measures was studied to assess the HRV. These measures were based on time-frequency representation (TFR) and on Shannon and Rényi entropies, and compared with traditional HRV measures. Holter recordings of 64 patients with HCM and 55 healthy subjects were analyzed. The HCM patients consisted of two groups: 13 high risk patients, after aborted sudden cardiac death (SCD); 51 low risk patients, without SCD. Five-hour RR signals, corresponding to the sleep period of the subjects, were considered for the analysis as a comparable standard situation. These RR signals were filtered in the three frequency bands: very low frequency band (VLF, 0-0.04 Hz), low frequency band (LF, 0.04-0.15 Hz) and high frequency band (HF, 0.15-0.45 Hz). TFR variables based on instantaneous frequency and energy functions were able to classify HCM patients and healthy subjects (control group). Results revealed that measures obtained from TFR analysis of the HRV better classified the groups of subjects than traditional HRV parameters. However, results showed that nonlinear measures improved group classification. It was observed that entropies calculated in the HF band showed the highest statistically significant levels comparing the HCM group and the control group, p-value < 0.0005. The values of entropy measures calculated in the HCM group presented lower values, indicating a decreasing of complexity, than those calculated from the control group. Moreover, similar behavior was observed comparing high and low risk of premature death, the values of the entropy being lower in high risk patients, p-value < 0.05, indicating an increase of predictability. Furthermore, measures from information entropy, but not from TFR, seem to be useful for enhanced risk stratification in HCM patients with an increased risk of sudden cardiac death.

SNP sets selection under mutual information criterion, application to F7/FVII dataset.

One of the main goals of human genetics is to find genetic markers related to complex diseases. In blood coagulation process, it is known that genetic variability in F7 gene is the most responsible for observed variations in FVII levels in blood. In this work, we propose a method for selecting sets of Single Nucleotide Polymorphisms (SNPs) significantly correlated with a phenotype (FVII levels). This method employs a feature selection algorithm (variant of Sequential Forward Selection, SFS) based on a criterion of statistical significance of a mutual information functional. This algorithm is applied to a sample of independent individuals from the GAIT project. Main SNPs found by the algorithm are in correspondence with previous results published using family-based techniques.

Multiscale regularity analysis of the Heart Rate Variability: stratification of cardiac death risk.

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%.

Hidden Markov models based on symbolic dynamics for statistical modeling of cardiovascular control in hypertensive pregnancy disorders.

Discrete hidden Markov models (HMMs) were applied to classify pregnancy disorders. The observation sequence was generated by transforming RR and systolic blood pressure time series using symbolic dynamics. Time series were recorded from 15 women with pregnancy-induced hypertension, 34 with preeclampsia and 41 controls beyond 30th gestational week. HMMs with five to ten hidden states were found to be sufficient to characterize different blood pressure variability, whereas significant classification in RR-based HMMs was found using fifteen hidden states. Pregnancy disorders preeclampsia and pregnancy induced hypertension revealed different patho-physiological autonomous regulation supposing different etiology of both disorders.

Patients on weaning trials from mechanical ventilation classified with neural networks and feature selection.

One of the challenges in intensive care is the process of weaning from mechanical ventilation. We studied the differences in respiratory pattern variability between patients capable of maintaining spontaneous breathing during weaning trials and patients that fail to maintain spontaneous breathing. In this work, neural networks were applied to study these differences. 64 patients from mechanical ventilation are studied: Group S with 32 patients with Successful trials and Group F with 32 patients that Failed to maintain spontaneous breathing and were reconnected. A performance of 64.56% of well classified patients was obtained using a neural network trained with the whole set of 35 features. After the application of a feature selection procedure (backward selection) 84.56% was obtained using only 8 of the 35 features.

Association between short term and long term communication in pathological autonomic control.

Autonomic Information Flow (AIF) reflects the time scale dependence of autonomic communications such as vagal, sympathetic, and slower rhythms and their complex interplay. We investigated the hypothesis that pathologically disturbed short term control is associated with simplified complex long term control. This particular characteristic of altered autonomic communication was evaluated in different medical patient groups. Holter recordings were assessed in patients with multiple organ dysfunction (MODS) (26 survivors, 10 non-survivors); with heart failure (14 low risk-without history of aborted cardiac arrest (CA), 13 high risk--with history of CA); with idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk of CA), after myocardial infarction (MI) (1221 low risk--survivors, 55 high risk--non-survivors); after abdominal aorta surgery (AAS, 32 length of stay in hospital LOS>7 days, 62 LOS < or =7 days). AIF of short and long time scales was investigated. We found a fundamental association of increased short term randomness and decreased long term randomness due to pathology. Concerning risk, high risk patients were characterized by increased short term complexity and decreased long term complexity in all patients groups with the exception of the IDC patients. We conclude that different time scales of AIF represent specific pathophysiological aspects of altered autonomic communication and control. The association of altered short term control with simplified long term behavior might be a pathophysiologically relevant compensation mechanism in the case of a disturbed fastest actuator. This knowledge might be useful for the development of comprehensive therapeutic strategies besides the predictive implications.

Information flow to assess cardiorespiratory interactions in patients on weaning trials.

Nonlinear processes of the autonomic nervous system (ANS) can produce breath-to-breath variability in the pattern of breathing. In order to provide assess to these nonlinear processes, nonlinear statistical dependencies between heart rate variability and respiratory pattern variability are analyzed. In this way, auto-mutual information and cross-mutual information concepts are applied. This information flow analysis is presented as a short-term non linear analysis method to investigate the information flow interactions in patients on weaning trials. 78 patients from mechanical ventilation were studied: Group A of 28 patients that failed to maintain spontaneous breathing and were reconnected; Group B of 50 patients with successful trials. The results show lower complexity with an increase of information flow in group A than in group B. Furthermore, a more (weakly) coupled nonlinear oscillator behavior is observed in the series of group A than in B.

Optimized symbolic dynamics approach for the analysis of the respiratory pattern.

Traditional time domain techniques of data analysis are often not sufficient to characterize the complex dynamics of respiration. In this paper, the respiratory pattern variability is analyzed using symbolic dynamics. A group of 20 patients on weaning trials from mechanical ventilation are studied at two different pressure support ventilation levels, in order to obtain respiratory volume signals with different variability. Time series of inspiratory time, expiratory time, breathing duration, fractional inspiratory time, tidal volume and mean inspiratory flow are analyzed. Two different symbol alphabets, with three and four symbols, are considered to characterize the respiratory pattern variability. Assessment of the method is made using the 40 respiratory volume signals classified using clinical criteria into two classes: low variability (LV) or high variability (HV). A discriminant analysis using single indexes from symbolic dynamics has been able to classify the respiratory volume signals with an out-of-sample accuracy of 100%.

Joint symbolic dynamic analysis of cardiorespiratory interactions in patients on weaning trials.

Assessing autonomic control provides information about patho-physiological imbalances. Measures of variability of the cardiac interbeat duration RR(n) and the variability of the breath duration TTot(n) are sensitive to those changes. The interactions between RR(n) and TTot(n) are complex and strongly non-linear. A study of joint symbolic dynamics is presented as a new short-term non-linear analysis method to investigate these interactions in patients on weaning trials. 78 patients from mechanical ventilation are studied: Group A (patients that failed to maintain spontaneous breathing and were reconnected) and Group B (patients with successful trials). Using the concept of joint symbolic dynamics, cardiac and respiratory changes were transformed into a word series, and the probability of occurrence of each word type was calculated and compared between both groups. Significant differences were found in 13 words, and the most significant pn(Wc010, r010): 0.0041 ± 0.0036 (group A) against 0.0012 ± 0.0024 (group B), p-value = 0.00001. The number of seldom occurring word types (forbidden words) also presents significant differences fwcr: 6.9 ± 6.6 against 13.5 ± 5.3, p-value = 0.00004. Joint symbolic dynamics provides an efficient non-linear representation of cardiorespiratory interactions that offers simple physiological interpretations.

Hidden markov models and mutual information analysis to characterize nonlinear dynamics in heart rate variability.

A study of nonlinear dynamics of the heart rate variability (HRV) was performed using hidden Markov models (HMM) and Mutual Information (MI). A methodology based on HMM has been developed in the present work. Cardiac RR series were analyzed in the three frequency bands: HF (0.15-0.45Hz), high frequency band; LF (0.04-0.15Hz), low frequency band; VLF (0.003-0.04Hz), very low frequency band. These series (0, observations) were modeled using HMM. The model λ=(A,B,∏) was selected so that P(O/λ) was locally maximized. Ergodic topology and N=10 states were also considered for this analysis. Different measures based on HMM were defined and obtained from RR time series of 37 Idiopathic Dilated Crdiomyopathy (IDC) patients and 46 healthy subjects (NRM), during awake and sleep stages. Two groups of IDC patients were considered: 11 high risk (HR) patients, after aborted sudden cardiac death (SCD) or who died during the follow up; 26 low risk (LR) patients, without SCD. Some HMM measures showed high percentages (up to 100%) of well classified subjects in all groups.

Estimating respiratory pattern variability by symbolic dynamics.

OBJECTIVES: The traditional techniques of data analysis are often not sufficient to characterize the complex dynamics of respiration. In this study the respiratory pattern variability was analyzed using symbolic dynamics. METHODS: A group of 20 patients on weaning trials from mechanical ventilation were studied at two different pressure support ventilation levels. Breath duration (T(TOT)) time series and the relation T(I)/T(TOT), that contains the influence of inspiratory time (T(I)), were considered. Length-3 words and 3 different symbols were proposed. The incidence of the overlapping tau and the parameter alpha were analyzed. RESULTS: From the breath duration time series, the distribution of words with probability of occurrence higher than 6% was concentrated on one word for low respiratory variability, whereas high variability was characterized by 4 words, presenting a statistically significant difference (p