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Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders.

OBJECTIVE: To describe the different clinical and laboratory diagnostic methods (basal and dynamic tests) available to identify poor-, good-, and high-responder patients undergoing treatment with in vitro fertilization (IVF). DESIGN: Analytical review. SETTING: IVF program. PATIENTS: Women in different age groups undergoing IVF treatment. INTERVENTION(S): Assessment of clinical and laboratory parameters and correlation with outcomes. MAIN OUTCOME MEASURE(S): Response to ovarian stimulation and success of the assisted reproductive technologies (ART). RESULT(S): Age, basal follicle-stimulating hormone (FSH), estradiol and inhibin-B levels, and dynamic testing serve to predict individual response to ovarian stimulation for ART. CONCLUSION(S): Markers of ovarian reserve (day 3 FSH, inhibin B and E(2)) are particularly predictive and useful in guiding the choice of the optimal protocol for ART. However, no tests are absolutely predictive of a successful outcome. For the younger individual, and for the patient at risk of developing ovarian hyperstimulation syndrome (OHSS), assessment and identification of clinical and laboratory parameters predictive of a high response to ovarian stimulation should guide the clinician in choosing an appropriate stimulation protocol, thus attenuating the risk of OHSS.

Adult↗

Realistic modeling of entorhinal cortex field potentials and interpretation of epileptic activity in the guinea pig isolated brain preparation.

Mechanisms underlying epileptic activities recorded from entorhinal cortex (EC) were studied through a computational model based on review of cytoarchitectonic and neurobiological data about this structure. The purpose of this study is to describe and use this model to interpret epileptiform discharge patterns recorded in an experimental model of ictogenesis (guinea pig isolated brain perfused with bicuculline). A macroscopic modeling approach representing synaptic interactions between cells subpopulations in the EC was chosen for its adequacy to mimic field potentials reflecting overall dynamics rising from interconnected cells populations. Therefore intrinsic properties of neurons were not included in the modeling design. Model parameters were adjusted from an identification procedure based on quantitative comparison between real and simulated signals. For both EC deep and superficial layers, results show that the model generates very realistic signals regarding temporal dynamics, spectral features, and cross-correlation values. These simulations allowed us to infer information about the evolution of synaptic transmission between principal cell and interneuronal populations and about connectivity between deep and superficial layers during the transition from background to ictal activity. In the model, this transition was obtained for increased excitation in deep versus superficial layers. Transitions between epileptiform activities [interictal spikes, fast onset activity (25 Hz), ictal bursting activity] were explained by changes of parameters mainly related to GABAergic interactions. Notably, the model predicted an important role of GABAa,fast- and GABAb-receptor-mediated inhibition in the generation of ictal fast onset and burst activities, respectively. These findings are discussed with respect to experimental data.

Action Potentials↗

[Identification of pelvic autonomic nerves during partial and total mesorectal excision--influence parameters and significance for neurogenic bladder].

INTRODUCTION: The objective of the present prospective study was to determine the frequency of pelvic autonomic nerve preservation (PANP) during total mesorectal excision (TME) for rectal carcinoma, and to identify a possible link between PANP and postoperative micturition disturbances. METHODS: Between March 1997 and February 2003, 229 patients with adenocarcinoma of the rectum were operated on with sphincter preservation in 178 (78%) cases. In 101 (48%) patients, the tumor did not invade the muscularis propria. To determine influence parameters on the achievement of complete PANP, a multivariate analysis was performed. The number of complete-partial-or nonidentification of the nerves (superior hypogastric plexus up to the neurovascular bundles) was documented and correlated with micturition disturbances. RESULTS: The pelvic autonomic nerves were identified completely in 169 (74%), partially in 25 (11%), and could not be demonstrated in 35 (15%) patients. Multivariate analysis showed multivisceral resection ( p<0.001), gender ( p<0.001), surgeon (<25 operations >, p<0.001), and tumor site (middle/upper third vs lower third of rectum, p= 0.011) to exert an independent influence on the achievement of complete PANP. Twenty (8.8%) patients needed a long-term urinary catheter. Preservation of the parasympathetic nerves was associated with low bladder dysfunction rates (4.1 vs 22.4%, p<0.001). CONCLUSIONS: To minimize the risk of postoperative micturition disturbances due to neurogenic bladder, pelvic autonomic nerves should be identified during TME. Neurogenic bladder after TME is a useful parameter to assess the quality of surgical treatment for rectal carcinoma.

Adult↗

Identification of compartmental models for perturbed cell populations using state-space parameter estimation techniques.

Multiple compartment models for describing synchronous cell kinetics in which cell populations are characterized by DNA content are reviewed. These models are useful for understanding and predicting a cell population's dynamic response to perturbations induced by drugs or radiation. A practical approach is proposed for determining the parameters of these models from empirical cell-cycle data. Specifically, a state-space parameter estimation algorithm based on the maximum likelihood method--developed and coded primarily for engineering applications and commercially available for personal computers and minicomputers--can be applied to DNA specific cell-cycle measurements from synchronized cell populations to produce model parameter estimates. This is demonstrated using published data from a cell-cycle experiment. The results show that the procedure works well, and that with careful experimental planning even better results should be possible. Since the compartmental model is often used to represent biological systems, this approach is widely applicable.

Algorithms↗

Automatic cell identification and enrichment in lung cancer. III. Light scatter and two fluorescence parameters.

Two fluorescence parameters and size are used in a flow through system to enrich sputum specimens for cancer cells. Human cells in sputum which are stained with acridine orange show a characteristic distribution of red and green fluorescence from which cancer cells can be localized. The peak enrichment is obtained by selectively sorting cells with the largest values of red and green fluorescence. Cancer cells located in other distribution regions having smaller fluorescence intensities show progressively diminished nuclear and cytoplasmic tinctorial features by Papanicolaou stain, consistent with the decreased intensity of red and green fluorescence.

Carcinoma, Squamous Cell↗

Monitoring the quality of psychiatric care.

Modern medical quality assurance depends on the identification and continual monitoring of important parameters or indicators of care. Indicators are defined as measurable clinical variables, often related to high volume, high risk, or problem-prone areas of medical care. Although the identification and monitoring of indicators is often a complex task, there are several areas in psychiatry where effective indicators can be developed. The process of indicator development is discussed and several suggestions are made for effective clinical parameters to monitor.

Goals↗

Modeling the internal dynamics of energy and mass transfer in an imperfectly mixed ventilated airspace.

UNLABELLED: The present paper outlines a modeling approach, which has been developed to model the internal dynamics of heat and moisture transfer in an imperfectly mixed ventilated airspace. The modeling approach, which combines the classical heat and moisture balance differential equations with the use of experimental time-series data, provides a physically meaningful description of the process and is very useful for model-based control purposes. The paper illustrates how the modeling approach has been applied to a ventilated laboratory test room with internal heat and moisture production. The results are evaluated and some valuable suggestions for future research are forwarded. PRACTICAL IMPLICATIONS: The modeling approach outlined in this study provides an ideal form for advanced model-based control system design. The relatively low number of parameters makes it well suited for model-based control purposes, as a limited number of identification experiments is sufficient to determine these parameters. The model concept provides information about the air quality and airflow pattern in an arbitrary building. By using this model as a simulation tool, the indoor air quality and airflow pattern can be optimized.

Air Movements↗

Dealing with the genotype x environment interaction via a modelling approach: a comparison of QTLs of maize leaf length or width with QTLs of model parameters.

Quantitative genetics of adaptive traits is made difficult by the genotypexenvironment interaction. A classical assumption is that QTLs identified in both stressed and control conditions correspond to constitutive traits whereas those identified only in stressed treatments are stress-specific and correspond to adaptive traits. This hypothesis was tested by comparing, in the same set of experiments, two ways of analysing the genetic variability of the responses of maize leaf growth to water deficit. One QTL detection was based on raw phenotypic traits (length and width of leaf 6) of 100 recombinant inbred lines (RILs) in four experiments with either well-watered or stressing conditions in the field or in the greenhouse. Another detection followed a method proposed recently which consists of analysing intrinsic responses of the same RILs to environmental conditions, determined jointly over several experiments. QTLs of three responses were considered: (i) leaf elongation rate per unit thermal time in the absence of stress, (ii) its response to evaporative demand in well-watered plants, and (iii) its response to soil water status in the absence of evaporative demand. The QTL of leaf length differed between experiments, but colocalized in seven cases out of 13 with QTLs of the intrinsic leaf elongation rate, even in experiments with stressing conditions. No colocalization was found between QTLs of leaf length under water deficit and QTLs of responses to air or soil water status. By contrast, QTLs of leaf width colocalized in all experiments, regardless of environmental conditions. The classical method of identifying the QTL of constitutive versus adaptive traits therefore did not apply to the experiments presented here. It is suggested that identification of the QTL of parameters of response curves provides a promising alternative for dealing with the genetic variability of adaptive traits.

Circadian Rhythm↗

Quantitative analysis of the phenotypic variability of shoot architecture in two grapevine (Vitis vinifera) cultivars.

BACKGROUND AND AIMS: Plant architecture and its interaction with agronomic practices and environmental constraints are determinants of the structure of the canopy, which is involved in carbon acquisition and fruit quality development. A framework for the quantitative analysis of grapevine (Vitis vinifera) shoot architecture, based on a set of topological and geometrical parameters, was developed for the identification of differences between cultivars and the origins of phenotypic variability. METHODS: Two commercial cultivars ('Grenache N', 'Syrah') with different shoot architectures were grown in pots, in well-irrigated conditions. Shoot topology was analysed, using a hidden semi-Markov chain and variable-order Markov chains to identify deviations from the normal pattern of succession of phytomer types (P0-P1-P2), together with kinematic analysis of shoot axis development. Shoot geometry was characterized by final internode and individual leaf area measurements. KEY RESULTS: Shoot architecture differed significantly between cultivars. Secondary leaf area and axis length were greater for 'Syrah'. Secondary leaf area distribution along the main axis also differed between cultivars, with secondary leaves preferentially located towards the basal part of the shoot in 'Syrah'. The main factors leading to differences in leaf area between the cultivars were: (a) slight differences in main shoot structure, with the supplementary P0 phytomer on the lower part of the shoot in 'Grenache N', which bears a short branch; and (b) an higher rate and duration of development of branches bearing by P1-P2 phytomers related to P0 ones at the bottom of the shoot in 'Syrah'. Differences in axis length were accounted for principally by differences in individual internode morphology, with 'Syrah' having significantly longer internodes. This trait, together with a smaller shoot diameter, may account for the characteristic 'droopy' habit of 'Syrah' shoots. CONCLUSIONS: This study highlights the architectural parameters involved in the phenotypic variability of shoot architecture in two grapevine cultivars. Differences in primary shoot structure and in branch development potential accounted for the main differences in leaf area distribution between the two cultivars. By contrast, shoot shape seemed to be controlled by differences in axis length due principally to differences in internode length.

Kinetics↗

Acoustic parameters in human speaker recognition.

Four speaker identification tests were conducted using five female speakers known to the listeners. Starting from acoustic recordings of reiterant "ma" syllables, the perceptual importance of the following three factors was investigated: F0 height, F0 contour, and speech rhythm. For speakers with typically low or high voices F0 height turned out to be a highly relevant cue in speaker identification. For all speakers F0 contour was of secondary importance, whereas speech rhythm had a small but consistent influence on recognition rates. It could be inferred that remaining factors alone (mainly global spectral information) would yield recognition scores of approximately 50%. Consistent with previous investigations, the relevance of perceptual cues in the recognition of familiar voices was shown to be not hierarchically fixed, but to depend on speaker-specific voice characteristics.

Cues↗

Diagnostic parameters of vascular neoplasms by immunohistochemistry.

Immunohistochemical identification of Factor VIII-related antigen and Ulex Europaeus A-I lectin as endothelial markers were studied in a series of 103 cases, comprising of benign and malignant vascular tumours, and few undifferentiated sarcomas. The results are correlated with that of others in this area and emphasizes the utility of these markers in surgical pathological diagnosis, especially to confirm the difficult diagnosis of angiosarcoma from other poorly differentiated sarcomas.

Antigens↗

A least-squares parameter estimation algorithm for switched hammerstein systems with applications to the VOR.

A "Multimode" or "switched" system is one that switches between various modes of operation. When a switch occurs from one mode to another, a discontinuity may result followed by a smooth evolution under the new regime. Characterizing the switching behavior of these systems is not well understood and, therefore, identification of multimode systems typically requires a preprocessing step to classify the observed data according to a mode of operation. A further consequence of the switched nature of these systems is that data available for parameter estimation of any subsystem may be inadequate. As such, identification and parameter estimation of multimode systems remains an unresolved problem. In this paper, we 1) show that the NARMAX model structure can be used to describe the impulsive-smooth behavior of switched systems, 2) propose a modified extended least squares (MELS) algorithm to estimate the coefficients of such models, and 3) demonstrate its applicability to simulated and real data from the Vestibulo-Ocular Reflex (VOR). The approach will also allow the identification of other nonlinear bio-systems, suspected of containing "hard" nonlinearities.

Algorithms↗

Quantum chemistry predicted correlations between geometric isomerism (conformation) of -OH and =NH substituents and typical group frequencies of nucleic acid bases: cytosine.

Results of a search for correlations between typical group mode frequencies and conformation of -OH and =NH substituents is reported. The study is based on quantum chemical data (HF/6-31G (d, p) and MP2 (full)/6-31G (d, p) approximations) of 13 isomers of cytosine. It is closely related to investigations of stability and energetics of all isomers of the more common nucleic acid bases, which revealed correlations between conformation (geometric isomerism) of OH and =NH substituents on the one hand and conversion energies, relaxation of internal structural parameters, electric field gradients, etc. on the other hand. In the majority of cases alteration of conformation of these substituents is accompanied by systematic frequency shifts of stretching, in-plane and out-of-plane bending (torsional) modes conventionally assigned to such groups and by alteration of quantum chemically predicted estimates of harmonic valence force constants and structural parameters dominating the mode frequencies. For identification of group modes 'fractional' mass (other than 'natural' mass) isotope shifts of frequency and normal vectors proved useful. Likewise, estimation of effects of force constant and structural parameter alterations on frequency shifts by first order perturbation theory of the FG problem of partial structures contributed valuable insight into the origin of the shifts.

Adenine↗

System identification for the ECG using CZT.

A new approach for extraction of clinically useful parameters from the ECG signal is presented using the system identification technique of CZT on the DCT-transformed signal. A one to one relationship between the model singularities and the significant points in the time signal is arrived at. The method allows the determination of R-R interval needed in rhythm analysis. The complex cepstrum is used for identifying and removing the effect of zeros outside the unit circle. A significant data compression of 1 in 10 is achieved. A large number of continuous strips of ECG data are analyzed and the results are presented.

Algorithms↗

[Pre-operative identification of patients at risk for septic complications after surgery for neoplasms of the digestive system. A multiphasic multicenter study].

One hundred ninety-six patients undergoing surgical treatment for digestive tract cancer were recruited in a polycentric, multistep study to value significant differences of pre-operative nutritional and immunologic parameters between patients with or without post-operative infections. Such parameters might be useful for the identification of "septic risk" patients. Primarily, 63 patients were given a complete anthropometric evaluation, laboratory screening and immunologic assessment (surface marker analysis of peripheral blood mononuclear cells, polymorphonuclears in vitro chemotaxis and phagocytosis). Only a few serologic parameters were significantly reduced in patients with post-operative infections, namely: total serum proteins (p less than 0.02), albumin (p less than 0.02), beta-globulins (p less than 0.01), and C3c (p less than 0.05). These parameters were elaborated with Fisher's linear discriminant function to detect the optimal discriminant threshold able to identify "septic risk" patients. The predictivity of this discriminant function was validated in a second group of patients (n = 49) in which total serum protein with electrophoresis were pre-operatively assayed as well as skin test reactivity to intradermal injection of recall antigens (Multitest skin-testing); discriminant sensitivity was 80%, the specificity 50%, and positive predictivity 62%. This low discriminant power of the equation based only on serum proteins assessment coupled with the significant negative relationship between skin testing and post-operative infections (male, p less than 0.005; female, less than 0.025) suggested a re-elaboration of the discriminant function, including the skin-testing score. The definite assessment of this new discriminant equation was evaluated in the third sample of patients (n = 84) which showed 67% sensitivity, 88% specificity, and 76% positive predictivity, thus suggesting the high reliability of this test for the pre-operative selection of "septic risk" patients.

Aged↗

Localization of p53 and proliferating cell nuclear antigen in fine-needle aspirates of benign and primary malignant tumors of the human breast: an immunocytochemical study using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method.

p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine-needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of six fibroadenomas and 50 primary breast carcinomas using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous immunostaining for PCNA was seen in all benign and malignant tumors examined. p53 expression in relation to nuclear plemorphism and lymph-node status showed weak correlation only as to nuclear grade (r = 0.28; P < 0.01). No direct or inverse correlation was found to exist between PCNA score and the evaluated prognostic parameters. In conclusion, although the identification of p53 in FNAs of breast tumors may assist in the diagnosis of malignancy, its application in the laboratory practice of cytopathology appears to be limited, since only 28% of primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can be used as an alternative to traditional methods of evaluating the proliferative rate of tumors in FNAs.

Adult↗

Frequency difference gating: a multivariate method for identifying subsets that differ between samples.

BACKGROUND: In multivariate distributions (for example, in 3- or more color flow cytometric datasets), it can become difficult or impossible to identify populations that differ between samples based only on a combination of univariate or bivariate displays. Indeed, it is possible that such differences can only be identified in "n"-dimensional space, where "n" is the number of parameters measured. Therefore, computer assisted identification of such differences is necessary. Such a method could be used to identify responses (i.e., by comparing cell samples before and after stimulation) in exquisite detail by allowing complete analysis of the collected data on only those events which have responded. METHODS: Multivariate Probability Binning can be used to compare different datasets to identify the distance and statistical significance of a difference between the distributions. An intermediate step in the algorithm provides access to the actual locations within the n-dimensional comparison which are most different between the distributions. Gates based on collections of hyper-rectangular bins can then be applied to datasets, thereby selecting those events (or clusters of events) that are different between samples. We term this process Frequency Difference Gating. RESULTS: Frequency Difference Gating was used in several test scenarios to evaluate its utility. First, we compared PBMC subsets identified by solely by immunofluorescence staining: based on this training data set, the algorithm automatically generated an accurate forward and side-scatter gate to identify lymphocytes. Second, we applied the algorithm to identify subtle differences between CD4 memory subsets based on 8-color immunophenotyping data. The resulting 3-dimensional gate could resolve cells subsets much more frequent in one subset compared to the other; no combination of two-dimensional gates could accomplish this resolution. Finally, we used the algorithm to compare B cell populations derived from mice of different ages or strains, and found that the algorithm could find very subtle differences between the populations. CONCLUSION: Frequency Difference Gating is a powerful tool that automates the process of identifying events comprising underlying differences between samples. It is not a clustering tool; it is not meant to identify subsets in multidimensional space. Importantly, this method may reveal subtle changes in small populations of cells, changes that only occur simultaneously in multiple dimensions in such a way that identification by univariate or bivariate analyses is impossible. Finally, the method may significantly aid in the analysis of high-order multivariate data (i.e., 6-12 color flow cytometric analyses), where identification of differences between datasets becomes so time-consuming as to be impractical. Published 2001 Wiley-Liss, Inc.

Algorithms↗

A method for simultaneous nuclear immunofluorescence and DNA content quantitation using monoclonal antibodies and flow cytometry.

A preparative technique for the two-parameter flow cytometric study of nuclear antigen expression is reported. This method employs a brief sequential treatment of cells at 4 degrees C first with 0.5% paraformaldehyde and second with 0.1% Triton X-100 in phosphate-buffered saline followed by cellular staining with indirect immunofluorescence and propidium iodide. Using this technique, cellular morphology is preserved, cell clumping is minimized, and high-quality indirect immunofluorescence and DNA staining are obtained with a minimum of nonspecific labeling. Utilizing nuclear antigen-specific monoclonal antibodies in conjunction with this technique, the cell-cycle phase-dependent expression of such antigens is examined. From these data, the utility of two-parameter flow cytometry in the identification and quantification of cell-cycle-dependent modulation of nuclear antigens is discussed.

Antibodies, Monoclonal↗