Biomedical subjects

D Liberati

Publications and source records attributed to D Liberati.

At least 19 recordsLinked to original sources

PubMed2000

Comparison between human and artificial neural network detection of Laplacian-derived electroencephalographic activity related to unilateral voluntary movements.

A back-propagation artificial neural network (ANN) was tested to verify its capacity to select different classes of single trials (STs) based on the spatial information content of electroencephalographic activity related to voluntary unilateral finger movements. The rationale was that ipsilateral and contralateral primary sensorimotor cortex can be involved in a nonstationary way in the control of unilateral voluntary movements. The movement-related potentials were surface Laplacian-transformed (SL) to reduce head volume conductor effects and to model the response of the primary sensorimotor cortex. The ANN sampled the SL from four or two central channels overlying the primary motor area of both sides in the period of 80 ms preceding the electromyographic response onset in the active muscle. The performance of the ANN was evaluated statistically by calculating the percentage value of agreement between the STs classified by the ANN and those of two investigators (used as a reference). The results showed that both investigator and ANN were capable of selecting STs with the SL maximum in the central area contralateral to the movement (contralateral STs, about 25%), STs with considerable SL values also in the ipsilateral central area (bilateral STs, about 50%), and STs with neither the contralateral nor bilateral pattern ("spatially incoherent" single trials; about 25%). The maximum agreement (64-84%) between the ANN and the investigator was obtained when the ANN used four spatial inputs (P < 0.0000001). Importantly, the common means of all single trials showed a weak or absent ipsilateral response. These results may suggest that a back-propagation ANN could select EEG single trials showing stationary and nonstationary responses of the primary sensorimotor cortex, based on the same spatial criteria as the experimenter.

Electroencephalography↗

PubMed2000

Estimating germinability of Plasmopara viticola oospores by means of neural networks.

Neural networks are trained to estimate the germination percentages of Plasmopara viticola oospores, overwintered in natural conditions in two viticultural areas in northern Italy, by using climatic (temperature and rainfall) data, as well as the previous germination measurement, as input variables. The 288 available patterns consist of a set of selected independent variables associated with the corresponding germination percentage. All 12 networks investigated converge to a non-linear relationship between the selected independent variables and oospore germination. The highest correlation coefficient (equal to 0.83) between the real and estimated germination percentages is obtained by considering, as input to the network, the climatic data (both temperature and rainfall) recorded during the 40 days before sampling and the germination percentage assessed in the germination assay carried out immediately before the present sampling.

Germination↗

PubMed2000

Hamming clustering techniques for the identification of prognostic indices in patients with advanced head and neck cancer treated with radiation therapy.

The aim of the study is to demonstrate the usefulness of a new, non-linear classifier method, called Hamming clustering (HC), in selecting prognostic variables affecting overall survival in patients with head and neck cancer. In particular, the aim is to identify whether tumour proliferation parameters can be predictive factors of response in a set of 115 patients that receive either alternating chemo-radiotherapy or accelerated or conventional radiotherapy. HC is able to generate a set of understandable rules underlying the study objective; it can also select a subset of input variables that represent good prognostic factors. HC has been compared with other standard classifiers, providing better results in terms of classification accuracy. In particular, HC obtains the best accuracy of 74.8% (sensitivity of 51.1% and specificity of 91.2%) about survival. The rules found show that, besides the classical, well-known variables concerning the tumour dimension and the involved lymphonodes, some biological parameters, such as DNA ploidy, are also useful as predictive factors.

Aged↗

PubMed2000

Forecasting the growth of multicell tumour spheroids: implications for the dynamic growth of solid tumours.

The growth dynamics of multicell tumour spheroids (MTS) were analysed by means of mathematical techniques derived from signal processing theory. Volume vs. time trajectories of individual spheroids were fitted with the Gompertz growth equation and the residuals (i.e. experimental volume determinations minus calculated values by fitting) were analysed by fast fourier transform and power spectrum. Residuals were not randomly distributed around calculated growth trajectories demonstrating that the Gompertz model partially approximates the growth kinetics of three-dimensional tumour cell aggregates. Power spectra decreased with increasing frequency following a 1/f(delta) power-law. Our findings suggest the existence of a source of 'internal' variability driving the time-evolution of MTS growth. Based on these observations, a new stochastic Gompertzian-like mathematical model was developed which allowed us to forecast the growth of MTS. In this model, white noise is additively superimposed to the trend described by the Gompertz growth equation and integrated to mimic the observed intrinsic variability of MTS growth. A correlation was found between the intensity of the added noise and the particular upper limit of volume size reached by each spheroid within two MTS populations obtained with two different cell lines. The dynamic forces generating the growth variability of three-dimensional tumour cell aggregates also determine the fate of spheroid growth with a strong predictive significance. These findings suggest a new approach to measure tumour growth potential.

Animals↗

PubMed2000

Stimulated secretion of pituitary hormones in normal humans: a novel direct assessment from blood concentrations.

Gland responsiveness is usually assessed by administering suitable secretagogues and measuring the resulting hormone concentration in blood after the specific stimulus. Such response-to-stimulus tests are routinely conducted for the clinical diagnosis of pathologies involving the pituitary hormones growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone, adrenocorticotropic hormone, and thyrotropin hormone. However, the current evaluation approaches, based on the maximum peak value or the (normalized) area under the curve, are inadequate under several respects. A more physiologically based index of responsiveness is the amount of released hormone. This is not directly accessible but is typically estimated by (computationally expensive) deconvolution analysis. The present work derives a simple formula yielding the amount of released hormone as a linear combination of blood concentrations through proper weights depending on hormone kinetics and sampling protocol. The weights are derived and reported for all six pituitary hormones and the more common sampling protocols. A validation study involving 174 test experiments has been carried out. The use of the formula shows excellent agreement with the cumulative secretion estimates obtained through deconvolution analysis.

Adolescent↗

PubMed2000

Abnormal LH pulsatility in women with hyperprolactinaemic amenorrhoea normalizes after bromocriptine treatment: deconvolution-based assessment.

OBJECTIVE: The present study examines the LH secretory process in hyperprolactinaemic women before, during and after bromocriptine therapy, using restrictive clinical selection criteria as well as improved methodological tools. PATIENTS AND DESIGN: Six women (aged 20-40 years) with microprolactinomas (mean +/- SE prolactin, PRL: 2478 +/- 427 mU/l, range: 1370-3800 mU/l) and four age- and sex-matched healthy controls were admitted to the study. After an overnight fast, all patients and controls had blood samples withdrawn at 10 minute intervals for 6 h (during saline infusion) from 0800 h to 1400 h to determine serum LH and PRL concentrations. After baseline evaluation, patients were treated with bromocriptine, which was started at a daily dose of 1.25 mg for 7 days; the dose was then increased to 2.5 mg daily for the next 7 days and subsequently to 2.5 mg twice daily. PRL levels were evaluated at weekly intervals after the beginning of bromocriptine therapy for the duration of the study. The 6 h pulsatility study was repeated on four patients during treatment at a time when PRL levels were decreased, although not normalized (PRL range: 450-1350 mU/l) and, on four patients, with the attainment of normal serum PRL levels (PRL < 450 mU/l) in the early follicular phase of the menstrual cycle (days 2-5). The LH instantaneous secretion rate was reconstructed by a nonparametric deconvolution method. In addition to pulse analysis made using the program DETECT, the evaluation of the secretion rate yielded the pulse frequency as well as the pulse amplitude distribution. RESULTS: Each time series was submitted to deconvolution analysis using a nonparametric method in order to estimate the instantaneous secretion rate (ISR). Hyperprolactinaemic patients had very few high-amplitude LH pulses above 0.2 IU/(l minutes) before treatment (average frequency: 0.83 +/- 0.40 pulses/6 h) and at the intermediate evaluation (0.25 +/- 0.25 pulses/6 h). In both cases, the pulse frequency was significantly lower than in controls (P < 0.05 and P < 0.01, respectively). When PRL was normalized, the number of high-amplitude LH pulses (4.25 +/- 1.03 pulses/6 h), became statistically different from the pulse number before (P < 0.01) and during (P < 0.01) therapy; in particular the pulse frequency after therapy rose to a level not statistically different from that in controls. CONCLUSION: The present study shows the presence of reduced LH pulsatility in hyperprolactinaemic women that recovers completely to within the physiological distribution when PRL levels are normalized by bromocriptine therapy.

Adult↗

PubMed1999

Linear spectral deconvolution of catabolic plasma concentration decay in dialysis.

Deconvolution can be a useful step in the process of modelling biological data, as it produces an overview of the information content of the data, as well as directions about the structure of the mathematical model able to describe the generating system. This paper concerns the application of a deconvolution technique, spectral analysis, to the modelling process of the concentrations of metabolites sampled in plasma during dialysis: the spectral analysis consists in linearly identifying the whole spectrum of multi-exponential decays, describing the compartmental nature of the process. The application to urea and creatinin time series provides a careful determination of the spectra of the exponential decays, thus giving interesting insight into the system kinetics: a sharp, slow decay (about 0.23 h-1 for urea and 0.17 h-1 for creatinin) affects all the subjects, whereas a variable set of smaller and faster components accounts for interpatient variability as well as for the multicompartmental nature of the process. The power ratio of the components is an index of the relative amount of volume in the related compartments. The identified spectra provide a description of the data that, although computed in a very simple way, is consistent with the results of the classical identification techniques previously applied in building compartmental models of dialysis.

Computational Biology↗

PubMed1999

A non-parametric method for the analysis of experimental tumour growth data.

Analysis of tumour growth is required to investigate the biology of tumours and to determine the effects of new anti-tumour therapies. A non-parametric mathematical method for the analysis of a set of experimental tumour growth data is described. The method is based on the similarity between time series of tumour size measurements (e.g. tumour volume), similarity being defined as the Euclidean distance between data measured for each tumour at the same time. Subsets of similar time series are found for a given population of tumours. A biologically meaningful parameter H has been derived which is a measure of the scattering of experimental volume samples. The method has been applied to the analysis of the growth of (i) untreated multicellular tumour spheroids obtained with different cell lines and (ii) spheroids treated with cytotoxic drugs (immunotoxins). Results are compared with those previously obtained by applying the classical Gompertz growth model to the analysis of treated and untreated spheroids.

Animals↗

PubMed1999

LH and FSH secretory responses to GnRH in normal individuals: a non-parametric deconvolution approach.

OBJECTIVE: To reconstruct the instantaneous secretion rate (ISR) of LH and FSH after GnRH administration in normal volunteers using non-parametric deconvolution, and to derive a direct integration formula to evaluate the amount of LH and FSH secreted during the first 60 min after the stimulus. DESIGN AND METHODS: First, the deconvolution method was validated in vivo by reconstructing doses ranging from 7.5 IU to 75 IU injected in three healthy adult volunteers whose endogenous LH had previously been downregulated by pretreating them, 3-4 weeks earlier, with 3.75 mg GnRH agonist i.m. Then, 40 healthy adult male volunteers were tested with a single 100 microg GnRH bolus, administered at 0 min. LH and FSH concentrations were determined at -30, 0, 15, 30, 45, 60, 90, and 120 min. RESULTS AND CONCLUSIONS: The validation study, conducted over a 10-fold range of doses, demonstrated that non-parametric deconvolution provided a reasonably accurate estimate of the amount of hormone entering the circulation. Applying deconvolution to the LH and FSH responses to GnRH, the ISRs of both hormones were shown to have a similar pattern, with a clearly delimited pulse after the GnRH bolus. In conjunction with earlier analyses of estimates of GHRH-stimulated GH secretion, we conclude that secretagogues evoke discrete LH, FSH, and GH secretory bursts of about 60 min total duration, despite markedly unequal (glyco-)protein hormone half-lives (18-500 min). With respect to the assessment of total hormone release during the first 60 min after the stimulus, the integration formula provided a reliable approximation of the result obtained by deconvolution, and had a negligible dependence on the samples at times 90 and 120 min.

Adult↗

PubMed1999

Oscillating growth patterns of multicellular tumour spheroids.

The growth kinetics of 9L (rat glioblastoma cell line) and U118 (human glioblastoma cell line) multicellular tumour spheroids (MTS) have been investigated by non-linear least square fitting of individual growth curves with the Gompertz growth equation and power spectrum analysis of residuals. Residuals were not randomly distributed around calculated growth trajectories. At least one main frequency was found for all analysed MTS growth curves, demonstrating the existence of time-dependent periodic fluctuations of MTS volume dimensions. Similar periodic oscillations of MTS volume dimensions were also observed for MTS generated using cloned 9L cells. However, we found significant differences in the growth kinetics of MTS obtained with cloned cells if compared to the growth kinetics of MTS obtained with polyclonal cells. Our findings demonstrate that the growth patterns of three-dimensional tumour cell cultures are more complex than has been previously predicted using traditional continuous growth models.

Animals↗

PubMed1998

Measuring regularity by means of a corrected conditional entropy in sympathetic outflow.

A new method for measuring the regularity of a process over short data sequences is reported. This method is based on the definition of a new function (the corrected conditional entropy) and on the extraction of its minimum. This value is taken as an index in the information domain quantifying the regularity of the process. The corrected conditional entropy is designed to decrease in relation to the regularity of the process (like other estimates of the entropy rate), but it is able to increase when no robust statistic can be performed as a result of a limited amount of available samples. As a consequence of the minimisation procedure, the proposed index is obtained without an a-priori definition of the pattern length (i.e. of the embedding dimension of the reconstructed phase space). The method is validated on simulations and applied to beat-to-beat sequences of the sympathetic discharge obtained from decerebrate artificially ventilated cats. At control, regular, both quasiperiodic and periodic (locked to ventilation) dynamics are observed. During the sympathetic activation induced by inferior vena cava occlusion, the presence of phase-locked patterns and the increase in regularity of the sympathetic discharge evidence an augmented coupling between the sympathetic discharge and ventilation. The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation.

Animals↗

PubMed1998

EEG coherence in Alzheimer's disease.

EEG coherence can be used to evaluate the functionality of cortical connections and to get information about the synchronization of the regional cortical activity. We studied EEG coherence in patients affected by clinically probable Alzheimer's disease (AD) in order to quantify the modifications in the cortico-cortical or cortico-subcortical connections. The EEGs were recorded in 10 AD patients (with mild or moderate degrees of dementia) and in 10 normal age-matched subjects, at rest and eye-closed, from 16 electrodes with linked-ears reference. Spectral parameters and coherence were calculated by a multichannel autoregressive model using 50 artifact-free epochs, 1 s duration each. Alpha coherence was significantly decreased in 6 patients, the decrease being more accentuated in the area near the electrode taken into account; a significant delta coherence increase was found in a few patients between frontal and posterior regions. The AD group showed a significant decrease of alpha band coherence, in particular in temporo-parieto-occipital areas, more evident in patients with a more severe cognitive impairment. These abnormalities could reflect two different pathophysiological changes: the alpha coherence decrease could be related to alterations in cortico-cortical connections, whereas the delta coherence increase could be related to the lack of influence of subcortical cholinergic structures on cortical electrical activity.

Aged↗

PubMed1997

Total and partial coherence analysis of spontaneous and evoked EEG by means of multi-variable autoregressive processing.

The joint use of total and partial coherence between pairs of EEGs simultaneously recorded in a standard set, is shown to enhance what is caused by direct correlation between cortical subsystems and what is instead related to the spread of the electromagnetic field. A multi-variable autoregressive approach is employed in the computation, giving results even for a very short time window, thus allowing coherence to be investigated at the main cortical latencies of evoked potentials. In particular, when a combined visual and somatosensory stimulation is applied, cortical interactions are captured in the frequency domain.

Adult↗

PubMed1997

Non-parametric deconvolution provides an objective assessment of GH responsiveness to GH-releasing stimuli in normal subjects.

OBJECTIVE: Deconvolution analysis has been proposed as an effective method for analysing the physiology of GH secretion. In the literature, it has been applied to spontaneous secretion data characterized by long and uniform sampling paradigms. In the present study we investigated the applicability of non-parametric deconvolution to the analysis of response-to-stimuli (RTS) data characterized by infrequent and non-uniform sampling. PATIENTS: Thirty-six healthy adult male volunteers (age range 24-37 years) were randomly subdivided into two groups (group I, n = 30; group II, n = 6). DESIGN: Subjects of group I were tested with a single 1 microgram/kg body weight GH-releasing hormone (GHRH) bolus, administered at 0 minutes. Subjects of group II were tested, in random order, with a 4- or 5-day interval, with (1) two consecutive 1 microgram/kg body weight GHRH boluses at 0 and 120 minutes and (2) two consecutive 1 microgram/kg body weight hexarelin boluses, administered at 0 and 120 minutes. MEASUREMENTS: GH levels were determined at 0, 15, 30, 45, 60, 90 and 120 minutes (group I) and -30, 0, 15, 30, 45, 60, 120, 135, 150, 165, 180 and 240 minutes (group II). A numerically efficient regularization-based non-parametric deconvolution algorithm incorporating non-negativity constraints was used to estimate the time profile of the instantaneous secretion rate (ISR). Confidence limits allowing for both measurement error and kinetic model uncertainty were computed using a Monte-Carlo procedure. In order to validate the deconvolution method, a simulated benchmark problem was set up. RESULTS: The analysis of the benchmark problem showed that the proposed method is capable of providing an accurate reconstruction of the ISR (as measured by the root mean square (RMS) error). Moreover, it appeared that reliable confidence limits cannot be obtained unless the kinetic model uncertainty is taken into account. The analysis of the data showed a clear rise in the ISR subsequent to the first bolus (either GHRH or hexarelin), with most of the response occurring within 60 minutes of the stimulus. In group I, it was also seen that discarding the samples collected at times 90 and 120 minutes only marginally affected the estimate of the cumulated ISR over 0-60 minutes (the variation was always less than 3%). The analysis of GH responsiveness to repeated stimuli (group II) showed that the amount of hormone secreted after the second bolus was clearly reduced in comparison with the elicited by the first stimulus, most of the response occurring within 60 minutes of the injection. The amount of GH secreted after the second stimulus ranged from 13 to 36% (GHRH 17-36%; hexarelin 13-36%) of the overall amount of hormone secreted after time 0 minutes. CONCLUSIONS: Even with relatively few samples, non-parametric deconvolution of response-to-stimulus data is capable of providing a reliable, smooth and non-negative estimate of the GH instantaneous secretion rate that offers a realistic representation of the GH secretory dynamics. The non-parametric approach compares favourably with respect to discrete deconvolution methods, that yield discontinuous instantaneous secretion rates profiles, and parametric methods that would require more stringent assumptions on the shape of the instantaneous secretion rate. When assessing confidence limits it is essential to take into account both measurement error and kinetic model uncertainty. Using deconvolution in normal subjects, the estimated instantaneous secretion rate between 0 and 60 minutes is scarcely affected by samples taken after time 60 minutes. Since most of the secretory response takes place during this time interval, there is motivation for investigating the use of shorter sampling protocols in conjunction with deconvolution analysis. Although pulse detection and the assessment of the shape of spontaneous pulses have not been investigated, it could be interesting to apply non-parametric deconvolution to spontaneous sec

Adult↗

PubMed1996

Surface mechanomyogram reflects muscle fibres twitches summation.

The aim of this work is to define the pattern of summation of the muscle fibre twitches in the surface mechanomyogram (MMG) generation process. For this purpose, two groups of muscle fibres of the extensor digitorum communis (EDC) were stimulated using needle electrodes. To these two artificial (because made by different muscle fibre types) motor units (MU1 and MU2), we administered: (a) separate stimulations: 3 and 9 Hz (MU1), 8 and 20 Hz (MU2) for 5 s; (b) simultaneous stimulation: 3 Hz (MU1) + 8 Hz (MU2); 9 Hz (MU1) + 20 Hz (MU2) for 5 s. The mechanomyograms, recorded during separate stimulation of MU1 and MU2, were linearly summated for the generation of a mechanomyographic signal to be compared with the one detected during (b) stimulation procedure. The bispectrum and the bicoherence of the generated MMG (MMGg) and of the MMG recorded during simultaneous (MMGs) stimulation were calculated for the detection of the quadratic non-linearity in the system responses. It was found that the MMGg and MMGs presented difference in the bispectrum and bicoherence index only when the 9-20 Hz stimulation pair was considered In conclusion, our data indicate that the MMG derives from the summation of the active muscle fibres twitches and that the latter is linear only for very low firing rates. This is to be carefully considered when studies on MMG modelling will be undertaken.

Electric Stimulation↗

PubMed1995

Deconvolution of infrequently sampled data for the estimation of growth hormone secretion.

In this paper, the deconvolution of infrequently and nonuniformly sampled data is addressed. A nonparametric technique is worked out that provides a smooth estimate of the unknown input signal and takes into account nonnegativity constraints. In spite of the size of the problem, efficient algorithms for solving the constrained optimization problem and computing confidence intervals are proposed. The new technique is used to estimate growth hormone (GH) secretion after repeated GH-releasing hormone (GHRH) administration from samples of blood concentration.

Adult↗

PubMed1994

Analysis of single trial movement-related brain macropotential.

A parametric method of identification of movement-related brain macropotentials on a single trial basis through an ARX (autoregressive with exogenous inputs) algorithm is presented. The basic estimation of the information contained in the single trial is taken from an average carried out on a sufficient number of trials, while the noise sources, EEG and EOG are characterized as exogenous inputs in the model. The simulations as well as the experimental results confirm the capability of the model to drastically improve the signal/noise ratio in each single trial and to satisfactorily identify the contributions of signal and noise in the overall recording. This way, using the same algorithm, a particularly efficient reduction of ocular artifacts is also achieved. The movement-related brain macropotentials recorded in three subjects show a high degree of variability from trial and this effect seems to be related to programming processes and evaluation of errors.

Adult↗

PubMed1994

ARX filtering of single-sweep movement-related brain macropotentials in mono- and multi-channel recordings.

A technique of stochastic parametric identification and filtering is applied to the analysis of single-sweep event-related potentials. This procedure, called AutoRegressive with n eXogenous inputs (ARXn), models the recorded signal as the sum of n+1 signals: the background EEG activity, modeled as an autoregressive process driven by white noise, and n signals, one of which represents a filtered version of a reference signal carrying the average information contained in each sweep. The other (n-1) signals could represent various sources of noise (i.e., artifacts, EOG, etc.). An evaluation of the effects of both artifact suppression and accurate selection of the average signal on mono- or multi-channel scalp recordings is presented.

Brain Mapping↗