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ROC analysis of an erythroblast morphologic scoring system to improve identification of fetal cells in maternal blood.

OBJECTIVES: Nucleated red blood cells are used in research settings as a target cell type for investigations of noninvasive prenatal diagnosis, and these cells have a characteristic nuclear morphology and hemoglobin staining pattern that makes them distinguishable from maternal cells. Recently, we developed an erythroblast scoring system based on these characteristics. Here, we employ statistical analyses to further characterize the utility of this scoring system. METHODS: A total of 170 nucleated red blood cells isolated from peripheral blood of four women undergoing elective termination of a trisomy 21 male fetus were analyzed. Each of the four scoring system parameters, whose values range from 0 to 3 points, served as an independent variable to determine its significance for the correct identification of a cell as fetal or maternal. A logistic regression was used as a multivariable statistical tool. RESULTS: Forty-four patterns of the four parameters were found in the overall series. Some patterns were exclusively associated with maternal cells (e.g. 1-1-1-1 and 1-1-2-2), and others were exclusively associated with fetal cells (e.g. 3-2-2-2 and 3-2-3-2). A detection rate of 73.9% at a false-positive rate of 5% resulted from a random simulation model performed with a 1:5 case:control matched set. The variables most predictive of a cell being fetal were gamma hemoglobin staining intensity of cytoplasm and nuclear roundness. CONCLUSIONS: The modified scoring system presented here improves upon the previously reported, unmodified erythroblast scoring system. These statistical analyses suggest that the scoring system is a promising method that aids in distinguishing fetal and maternal NRBCs for prenatal diagnostic applications and that it may be amenable to automated microscopy by applying the discrete morphological parameters as computational classifiers.

Cell Nucleus↗

Simultaneously multi-parameter determination of hematonosis cell apoptosis by two-photon and confocal laser scanning microscopy.

Flow cytometry (FCM), TdT-mediated dUTP Nick End Labeling (TUNEL), and DNA ladder are conventional methods to detect apoptosis of drug-treated cells. However, the assumption of cell number restricts their applications in clinics. In this paper, we report a cell-saving imaging method for quick identification of the hematonosis cell apoptosis induced by chemotherapeutic drugs. By the combination of two-photon and confocal microscopy, three main apoptosis parameters (the change of nuclear morphology, collapse of mitochondrial membrane potential, and increase of intracellular calcium) were recorded simultaneously for single As2O3-induced Molt-4 cells. The results are highly in accordance with those produced by classical flow cytometry. This work suggests that this new imaging method would be promising in the quick identification of hematonosis cell apoptosis.

Apoptosis↗

Traditional ribotyping shows a higher discrimination than the automated RiboPrinter system in typing Vibrio cholerae O1.

Sixteen clinical Vibrio cholerae O1 strains from four different countries were selected for comparison by traditional ribotyping and an automated RiboPrinter system for identification and discrimination purposes. Automated ribotyping, which routinely uses the restriction enzyme EcoRI for typing all bacterial species, produced only five different ribotypes compared with 10 different EcoRI ribotypes obtained by the traditional method. Traditional and automated ribotyping using the restriction enzyme BglI, which is recommended for the ribotyping of V. cholerae, produced 10 and seven different ribotypes, respectively. The lower discrimination shown by the RiboPrinter system was caused mainly by an inability to differentiate closely located fragments due to a lower resolution and electrophoresis conditions, a parameter which cannot be changed in the automated system. The RiboPrinter system includes a database for bacterial identification. However, none of the V. cholerae O1 strains studied showed EcoRI ribotype patterns which matched any of the patterns included in the database. In conclusion, the existing RiboPrinter system is not adequate for taxonomic identification and classification of V. cholerae O1.

Automation↗

[Ultrasonographic diagnosis of the pathology of the rotator cuff and subacromial bursa: criteria].

Shoulder soft tissues echographic evaluation depends on the availability of well established echographic diagnostic criteria, which hasn't been fully accepted until nowadays, as results in that field have been controversial. The main purpose of the present study has been to determine the echographic criteria of the most frequent shoulder periarticular soft tissue pathology. A prospective study has been carried out, comparing the right to the left shoulder of 37 normals in order to determine the normal characteristics and limits of the selected echographic parameters (echogenicity, echostructure, dimensions in terms of width, rhythm of movement and rotator cuff competence ratio). Afterwards, the relative role of these variables in the identification of three different nosological groups determined through suitable gold standard diagnostic methods (36 suprasinatus tears, 20 supraspinatus tendinitis and 22 subacromial bursitis) has been determined. Lastly, the discriminant power of some echographic parameters association was tested, thus suggesting the echographic criteria to be selected. Results support the following criteria: 1) supraspinatus tears: cuff competence ratio less than 1, the difference value between the affected and the sound tendon thickness less than -1,8 mm associated with asymmetries of one of the remaining parameters (echogenicity, echostructure or rhythm); 2) supraspinatus tendinitis: the difference between the affected and the sound tendon thickness bigger than 1 mm associated with asymmetries of one of the remaining parameters (echogenicity, echostructure or rhythm); cuff competence ratio equal or above 1;3) subacromial bursitis: the difference between the affected and the sound bursa thickness bigger than 1 mm associated with asymmetries of one of the following parametres: echogenicity, echostruture or rhythm.

Acromioclavicular Joint↗

Risk stratification by the "EPA+DHA level" and the "EPA/AA ratio" focus on anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty acids.

The identification of risks associated with sudden cardiac death requires further investigations. The question was addressed whether parameters can be established which not only describe an increased risk for an enhanced electrical instability of the heart but also of inflammatory events underlying plaque rupture. Emphasis is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of EPA and DHA are required for most of their biological effects, it appears essential not only to build up stores in the body for release of these fatty acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters are taken up more slowly within 24 h. For the administration of 1 g/day highly purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from 2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 35 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for sudden cardiac death and that the administration of 840 mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with a marked protection from sudden cardiac death. For reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl esters. For assessing influences from pro-inflammatory eicosanoids and cytokines, the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in fish dishes of the cafeteria of the Philipps University Hospital Marburg, Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100 g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA administered in the GISSI Prevention Study in the form of ethyl ester which markedly reduced the risk of sudden cardiac death in postmyocardial infarction patients. Nonetheless, at least two preferably oily fish meals per week should be consumed as preventive measure by persons without coronary artery disease. With documented coronary heart disease, it was advised to consume approximately 1 g/day of EPA+DHA.

Administration, Oral↗

[Prediction of individual radio-resistance in animals by the parameters of initial endocrine functioning of the organism].

Predictability of individual radioresistance by initial parameters of endocrine functions, i.e. peripheral blood levels of adrenal hormones (corticosterone) and thyroid hormones (triiodthyronin and thyroxin) was tested. An integral logarithmic index of parameter deviation from the mean statistical norm was used as a predictive criterion. The initial corticosterone content was found to be very informative of future radioresistance and allowed identification of subgroups of animals whose survivability reached 92.3% against group-average 57.2%. Triiodthyronin also turned to be a predictor as survivability of animals positively qualified by the parameter made up 83.5%. In the experiment with irradiation of rats with a higher dose resulting in group-average survivability of 28.7%, a subgroup with 2.2-fold higher survivability was identified.

Adaptation, Physiological↗

Digital videomicroscopy and image analysis with automatic classification for detection of thin melanomas.

The aim of our investigation was to evaluate the usefulness of a system composed of a digital videomicroscope equipped with a dedicated program for the quantitative characterization of various parameters of the clinically significant features of pigmented skin lesion (PSL) images, forming the basis for automatic differentiation of naevi and thin melanomas. In total 424 naevi and 37 melanomas (including 23 thinner than 0.75 mm) were considered. All the digital images were acquired, framed and analysed using the DBDermo-MIPS program (Biomedical Engineering Dell'Eva-Burroni), which calculates different parameters related to the geometry, the colour distribution and the internal pattern of the lesion. We also assessed the efficacy of an automatic classifier, trained for 100% sensitivity using a subset of PSL images (59 naevi and 19 melanomas), on a test set including 365 naevi and 18 melanomas thinner than 0.75 mm. Significant differences between values from benign and malignant PSLs were observed for most of the numerical parameters. Values from the training set underwent elaboration by means of multivariate discriminant analysis, enabling the identification of variables that are important for distinguishing between the groups in order to develop a procedure for predicting group membership for new cases (test set) in which group membership is undetermined. Going on the training set data, a threshold score was established, enabling each melanoma to be attributed to the right group. When the same threshold value was employed for discriminating between benign and malignant lesions in the test set, all the melanomas were correctly classified, whereas 30 out of the 365 benign lesions were attributed to the wrong group. Thus the specificity of the system reached 92%, whereas the sensitivity was 100%. Our data suggest that elaboration of videomicroscopic images by means of dedicated software improves diagnostic accuracy for thin melanoma. Since elaboration of an image requires only 60s using our system, all the parameter data are available in real time and can be immediately examined by the classifier, providing an instant aid to clinical diagnosis.

Databases, Factual↗

Identification of time-varying stiffness, damping, and equilibrium position in human forearm movements.

Knowledge of how stiffness, damping, and the equilibrium position of specific limbs change during voluntary motion is important for understanding basic strategies of neuromotor control. Presented here is an algorithm for identifying time-dependent changes in joint stiffness, damping, and equilibrium position of the human forearm. The procedure requires data from only a single trial. The method relies neither on an analysis of the resonant frequency of the arm nor on the presence of an external bias force. Its validity was tested with a simulated forward model of the human forearm. Using the parameter estimations as forward model input, the angular kinematics (model output) were reconstructed and compared to the empirically measured data. Identification of mechanical impedance is based on a least-squares solution of the model equation. As a regularization technique and to improve the temporal resolution of the identification process, a moving temporal window with a variable width was imposed. The method's performance was tested by (a) identifying a priori known hypothetical time-series of stiffness, damping, and equilibrium position, and (b) determining impedance parameters from recorded single-joint forearm movements during a hold and a goal-directed movement task. The method reliably reconstructed the original angular kinematics of the artificial and human data with an average positional error of less than 0.05 rad for movement amplitudes of up to 0.9 rad, and did not yield hypermetric trajectories like previous procedures not accounting for damping.

Acceleration↗

Modeling of the pyruvate production with Escherichia coli in a fed-batch bioreactor.

A family of 10 competing, unstructured models has been developed to model cell growth, substrate consumption, and product formation of the pyruvate producing strain Escherichia coli YYC202 ldhA::Kan strain used in fed-batch processes. The strain is completely blocked in its ability to convert pyruvate into acetyl-CoA or acetate (using glucose as the carbon source) resulting in an acetate auxotrophy during growth in glucose minimal medium. Parameter estimation was carried out using data from fed-batch fermentation performed at constant glucose feed rates of q(VG)=10 mL h(-1). Acetate was fed according to the previously developed feeding strategy. While the model identification was realized by least-square fit, the model discrimination was based on the model selection criterion (MSC). The validation of model parameters was performed applying data from two different fed-batch experiments with glucose feed rate q(VG)=20 and 30 mL h(-1), respectively. Consequently, the most suitable model was identified that reflected the pyruvate and biomass curves adequately by considering a pyruvate inhibited growth (Jerusalimsky approach) and pyruvate inhibited product formation (described by modified Luedeking-Piret/Levenspiel term).

Bioreactors↗

Robustness of MetaNet graph models: predicting control of urea production in humans.

Urea production in human liver was described by a MetaNet graph, a flowchart-like representation of metabolic pathways that includes parameters for the kinetic constants of the constituent enzymes. Formal operations on the graph facilitate the identification of ligand-binding equilibria that participate in feedback regulation in the network of biochemical reactions. The state of the biochemical network is specified by the concentrations of the intermediates. At any particular time, the influence of an identified locus of regulation is proportional to the respective fractional saturation of the corresponding binding site. Enzymes that make or consume the feedback chemicals share in the control of the strength of the feedback signal in proportion to their fractional saturation. This model predicts control of urea production by the processes that deliver amino groups to the urea cycle enzymes more than by the cycle enzymes themselves. Mitochondrial membrane transport processes are important for transmission of information through the network, but irreversible enzymes and processes far from equilibrium control the strength of the feedback signal. Systematic variation of the parameter values by amounts comparable to the expected variability of their measured values indicated a high probability of invariance in the identities of the predicted control points. The properties of the model are consistent with those of error-tolerant scale-free networks. These results demonstrate the robustness of a MetaNet model's predictions with respect to uncertainties in the values of its parameters.

Computer Simulation↗

A simple model for predicting nodal metastasis in patients with clinical stage I nonseminomatous germ cell testicular tumors undergoing retroperitoneal lymph node dissection only.

PURPOSE: In patients with clinical stage I nonseminomatous germ cell testicular tumor the identification of risk categories for nodal metastases and/or distant metastases could permit selective management. We built 2 models for distinguishing these risk categories. MATERIALS AND METHODS: Data on 322 consecutive patients with clinical stage I nonseminomatous germ cell testicular tumor patients treated with retroperitoneal lymphadenectomy (RPLND) alone between 1985 and 1995 were analyzed. The interval between orchiectomy and RPLND, vascular invasion (VI), pT stage, percent embryonal carcinoma (ECa) and teratoma in the primary tumor were considered clinically relevant for their association with nodal or distant metastases. Two logistic models were constructed. Model 1 was meant to discriminate 2 patient categories, namely those with and without nodal metastases at RPLND. Model 2 was meant to discriminate 3 patient categories, namely those without any metastases, with nodal metastases only and with distant metastases independent of retroperitoneal metastases. The models were based on these above variables, which were inserted as categorical and then processed through a backward selection procedure. RESULTS: At RPLND nodal metastases were found in 60 patients (18.6%). During followup distant metastases were observed in 43 patients (13.4%) and retroperitoneal recurrences were noted in 6 (1.9%). Of all recurrences 93.8% were within 2 years since RPLND. RPLND had a high curative rate since 73% of all pN+ cases were cured by surgery alone. The final logistic model 1, including percent ECa and VI, was reassessed in 202 patients with available data. Absent VI and ECa 90% or greater identified a category of 110 patients at low risk for nodal metastasis (14%), while VI and/or ECa greater than 90% identified a category of 92 at higher risk (35%). The identified categories were also related to distant metastases, which occurred in 9.3% of low risk and in 23.1% of high risk cases. Model 2 was not clinically suitable because it did not allow us to distinguish patients at risk for nodal metastases only from those at risk for distant metastases. CONCLUSIONS: Simplicity is the main advantage of model 1 since only 2 well-known prognostic parameters are involved. Although the model must be validated in an independent case series, the identification of a low risk category with few expected nodal metastases could permit us to replace traditional RPLND with a less invasive staging procedure.

Adolescent↗

[Identification of Tougucao derived from Clematis species].

Comparative studies were carried out on the morphology and histology of 5 Clematis species, namely, C. intricata, C. aethusifolia, C. glauca, C. tangutica and C. hexapetala, allegedly used as "Tougucao". New characteristics, a sclerenchymatous ring composed of primary phloem fibers and lignified parenchyma cells, and a parenchymatous tertiary ring were discovered. A parameter representing the ratio of the diameter of cambium ring to the diameter of the stem (RCR) is created. A key for identification of the stems of the above five species is made according to the presence or absence of the sclerenchymatous ring, the diameter and numbers of hair cells, the thickness of fiber wall and the value of RCR, etc.

Magnoliopsida↗

Simultaneous parameter compensation in the replication of programmed temperature gas chromatographic retention measurements.

Tables of relative retention times, retention indices or emergence temperatures obtained under one set of chromatographic conditions can be used for the tentative identification of unknowns determined under an entirely different set of conditions. This can be accomplished for a particular liquid phase if the emergence temperature of a reference compound is maintained while one or more chromatographic parameters are changed to compensate for the changes in other parameters. The advantage of using proximal standards for the determination of both relative retention times and emergence temperatures is demonstrated in this report.

Chlorpyrifos↗

Designed strength identification of concrete by ultrasonic signal processing based on artificial intelligence techniques.

This paper presents a pattern recognition method to identify the designed strength of concrete by evidence accumulation based on artificial intelligence techniques with multiple feature parameters. Concrete specimens in this experiment, which were designed to have the strengths of 180, 210, 240, 300, and 400 kg/cm2, respectively, have been considered. Variance, zero-crossing, mean frequency, autoregressive (AR) model coefficients, and linear cepstrum coefficients are extracted as feature parameters from ultrasonic signals of concretes. Pattern recognition is carried out through the evidence accumulation procedure using the distances measured with reference parameters. A fuzzy mapping function is introduced to transform the distance for the application of the evidence accumulation method. Results are presented to support the feasibility of the suggested approach for concrete pattern identification.

Journal Article↗

Hemodynamic correlates of atrial natriuretic peptide concentration in unselected patients with heart disease of different etiologies.

BACKGROUND: Although a large number of studies have investigated the relationship between atrial natriuretic peptide (ANP) concentrations and circulatory abnormalities, it is presently unsettled as to whether this parameter provides valuable information in unselected patients with heart disease of different etiologies regardless of the presence of left ventricular dysfunction or heart failure. AIM OF THE STUDY: The aim was to evaluate the correlation between ANP, hemodynamics and parameters of ventricular function in a large series of consecutive patients and to define the predictive value of ANP for the identification of specific circulatory abnormalities. METHODS: Cardiac catheterization was performed in 167 consecutive patients (62% males; mean age 62 yrs; range 18-85) and ANP serum levels were determined concomitantly by single antibody immune assay. Underlying etiology was: ischemic (67), valvular (72), idiopathic (12) and miscellaneous (16). Data management included: comparison of patients according to ANP values > or < 50% percentile of the cumulative distribution curve (i.e. 140 pg/ml); analysis of ANP concentrations according to the presence of normal or abnormal ventricular filling pressures; correlation between hemodynamic parameters and ANP concentrations; correlation of ANP with ventricular function in the whole population and in subgroups; calculation of sensitivity and specificity of ANP for the identification of abnormal filling pressures. RESULTS: Mean ANP concentration was 181 +/- 139 pg/ml. Patients with ANP < 140 had significantly lower right-sided pressures but similar ventricular volumes and ejection fractions. By multivariate analysis, the single independent predictor of ANP was wedge pressure (p < 0.0001). Regarding etiology, severe mitral regurgitation was associated with the highest ANP levels (259 +/- 122 pg/ml), although the difference was not significant. The presence of abnormal left and right ventricular filling pressures was associated with significantly higher levels of ANP (p < 0.0001). A level of 125 pg/ml proved to be fairly sensitive (79%) but poorly specific (66%) for the detection of an abnormal wedge pressure. ANP was related to ventricular function only in the small subgroup of patients with dilated cardiomyopathy, where a significant negative correlation was found with both left ventricular (r = -0.72; p = 0.008) and right ventricular ejection fraction (-0.71; p = 0.01). CONCLUSIONS: In unselected cardiac patients, ANP is confirmed to be a marker of left ventricular filling pressure in spite of poor specificity. Ventricular function appears to be related to ANP concentrations only in the subgroup of patients with pure heart-muscle disease.

Adolescent↗

Predictive factors for sacral neuromodulation in chronic lower urinary tract dysfunction.

OBJECTIVES: To investigate data from 211 patients who underwent a trial stimulation (percutaneous nerve evaluation [PNE]) to determine the clinical parameters that can enhance the prediction of PNE success. The advantageous effect of sacral neuromodulation depends on the accurate identification of suitable candidates during the preimplantation PNE. METHODS: A total of 211 patients (161 women and 50 men), with refractory urge incontinence, urgency-frequency syndrome, and urinary retention, underwent a PNE. Patient data (demographics, medical history, urologic investigations, and diagnosis) were collected. The PNE results were evaluated from a voiding diary and patient history. More than 50% improvement of voiding parameters was considered a successful PNE, and those patients were selected for implantation. Logistic regression analysis was performed. The factors tested for predicting the test result were sex, patient age, diagnosis, previous surgery, neurogenic bladder dysfunction, duration of complaints, and previous treatments. RESULTS: The PNEs were positive in 85 patients (40.3%) and negative in 105 patients (49.8%). In 18 patients (8.5%), the test electrode had migrated; 3 more patients were not assessable and were also excluded. Missing data on the variable "duration of complaints" reduced the number of patients in the analyses from 190 to 174 patients. CONCLUSIONS: Intervertebral disk prolapse, duration of complaints, neurogenic bladder dysfunction, and urge incontinence were found to be significant predictive factors. However, a PNE remains necessary to evaluate a patient's chance of implant success objectively.

Adult↗

Tympanic ECochG and conventional ABR: a combined approach for the identification of wave I and the I-V interwave interval.

Identification of wave I and measurement of the I-V interwave interval (IWI) are important parameters of the auditory brain stem response (ABR). However, at low stimulus sensation levels, wave I may be absent in the presence of wave V when the ABR is recorded conventionally with scalp electrodes. Several studies have shown that the amplitude and detectability of wave I (or N1) can be enhanced via extratympanic electrocochleography (ECochG), and even more so with tympanic ECochG. In the present study, tympanic ECochG was combined with conventional ABR to compare the amplitude and sensitivity of N1, wave I, and wave V in normally hearing subjects, and to identify the N1-V IWI in hearing impaired subjects whose conventional ABRs did not contain a reliable wave I. For the normally hearing subjects, the amplitude of the N1 was considerably larger than the amplitudes of waves I and V of the conventional ABR and there was no significant difference between N1 and wave V thresholds. For the hearing impaired group, the combined ECochG-ABR approach allowed for the identification of N1 and measurement of the N1-V IWI in all subjects. Our results support the use of tympanic ECochG in combination with conventional ABR for certain audiological and neurological applications.

Audiometry, Evoked Response↗

Influence of data filtering on reliability of respiratory impedance and derived parameters in children.

Forced oscillation impedance (Zrs) measurements are frequently corrupted by noisy data in children. Our aim was to improve the reliability of respiratory resistance (Rrs) and routine identification of its flow (V') and volume (V) dependence during tidal breathing, according to Rrs = K1 + K2 x /V'/ + K3 x V. Zrs was measured at 12 Hz, using a head generator in 23 children aged 4-13 years undergoing methacholine (Mch) challenge. Rrs, K1, K2, K3, and residual mean square error (RMSD), as well as reproducibility of the parameters, were obtained. Calculations were performed separately in inspiration and expiration on the raw data, and after eliminating values lying outside confidence intervals ranging from 99% (F3SD) to 95% (F2SD) of the mean Zrs. Filtering decreased RMSD and Rrs, F3SD improved reproducibility of Rrs in expiration compared to raw data. F2SD increased K1 and decreased the amplitude of K2 and K3 before and after Mch compared to F3SD. Rrs and K2 were significantly larger and K3 significantly more negative in expiration than in inspiration at all levels of filtering, probably because of the upper airways. F3SD appeared efficient in eliminating aberrant data, while allowing the identification of physiological variations of Rrs.

Adolescent↗