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PubMed1986

Identification of 11-dehydro-TXB2 as a suitable parameter for monitoring thromboxane production in the human.

In order to identify suitable parameters for measurement of thromboxane production in vivo, the metabolism of TXB2 was studied in the human. [3H8]-TXB2 was given intravenously to a healthy human volunteer. Blood samples were collected for 50 min after the injection, and urine was collected for 24 hours. The urinary and blood metabolic profiles were visualized by the use of two-dimensional TLC and autoradiography. Identification of metabolites was achieved with GC/MS and in some cases by cochromatography with reference compounds in TLC and GC. In blood, unmetabolized TXB2 was the dominating compound during the first 30 min. Three less polar metabolites appeared, two of which were identified as 11-dehydro-TXB2 and 11,15-didehydro-13,14-dihydro-TXB2, respectively. The third compound was tentatively identified as 15-dehydro-13,14-dihydro-TXB2. Since 11-dehydro-TXB2 was one of the major metabolites in blood as well as urine, it was deemed suitable as target for measurement of thromboxane production in vivo. The advantages of 11-dehydro-TXB2 over its parent compound, TXB2, were demonstrated in experiments where unlabeled TXB2 was injected i.v. to a human volunteer, and the blood and urinary levels of both compounds were then followed by radioimmunoassay. Measured levels of 11-dehydro-TXB2 were found to give a more reliable picture of metabolic events than TXB2, the latter compound to a large extent reflecting technical difficulties during blood sample collection.

Autoradiography↗

PubMed1984

Spectral analysis of biochemical reactions used for identification of bacteria.

To define parameters for optimizing automated discrimination of bacterial biochemical reactions certain theoretical considerations of spectrophotometric analysis were explored. One-hundred and one recent clinical isolates of gram-negative bacilli (21 species) were inoculated into AP1 20 E strips and read manually after 24 hours. With spectrophotometric scanning, the AP1 reactions could be classified into three analytical categories: pH change, production of new products, and darkening of the medium. Whereas single wavelength analysis gave 2.9% disagreement from the visual, multiple wavelength analyses were uniformly more accurate. The best results for pH change reactions were obtained by calculating a ratio of two wavelengths. New color reactions were best interpreted by demonstration of the new peak, whereas darkening reactions required quantitation of the area under the entire curve. With these methods, a 99.3% overall agreement of individual reactions and a 97% agreement of identification were achieved. Multiple-point analysis of spectra coupled with computerized interpretation of the data should help resolve the problem of equivocal reactions in bacterial identification schemes optimized for spectral analysis.

Bacteriological Techniques↗

PubMed2005

Inter-operator variability in perfusion assessment of tumors in MRI using automated AIF detection.

A method is presented for the calculation of perfusion parameters in dynamic contrast enhanced MRI. This method requires identification of enhancement curves for both tumor tissue and plasma. Inter-operator variability in the derived rate constant between plasma and extra-cellular extra-vascular space is assessed in both canine and human subjects using semi-automated tumor margin identification with both manual and automated arterial input function (AIF) identification. Experimental results show a median coefficient of variability (CV) for parameter measurement with manual AIF identification of 21.5% in canines and 11% in humans, with a median CV for parameter measurement with automated AIF identification of 6.7% in canines and 6% in humans.

Animals↗

PubMed1995

Evaluation of a long-range adaptive predictive controller for computerized drug delivery systems.

A closed-loop adaptive control system, based on the generalized predictive control law with a terminal matching condition, has been developed for computerized drug delivery. The control law is a minimization of the squares of prediction errors over a small future prediction horizon plus weighted square of the prediction error at steady-state. A control-relevant, long-range identification algorithm is used for on-line parameter estimation. Since the control and identification are mutually compatible, the system truly satisfies the approximate dual control criterion. The system has been applied to the control of mean arterial pressure (MAP) by automatic infusion of sodium nitroprusside in the presence of physical and physiological constraints. Experimental evaluation on six mongrel dogs, in an ethics-approved manner, included setpoint tracking and regulation of MAP in the presence of unpredictable disturbances. The system was found to be capable of inducing hypotension in an average of 2.44 +/- 0.31 min (mean +/- standard error of mean) after probing without any overshoots in mean arterial pressure. The nitroprusside infusion was also free of any ringing. When the subjects were not disturbed, 96.2% of mean arterial pressure remained within 5 mm Hg of the target pressure. A series of disturbances introduced in the presence and absence of closed-loop control affirms the robustness and effectiveness of this control system.

Algorithms↗

PubMed2003

[Cellular and neoplastic otorhinolaryngologic changes, molecular markers and therapeutic potential].

Head and neck cancer is believed to arise after accumulation of genetic alterations resulting at least partially from chronic exposure of the upper aerodigestive tract to tobacco carcinogens. Accumulation of somatic genetic events in genes implicated in cell growth and differentiation lead to cell transformation and to the acquisition of cancer phenotype. The most frequent alterations in head and neck cancer results from chromosomal instability with amplification and deletion of recurrent chromosome arms. Among the genes that drives head and neck carcinogenesis, TP53 mutations, p16 deletion or hypermethylation, amplification of cyclinD1 and overexpression of the epidermal growth factor receptor are of the most importance and will be discuss in this review. Correlation between genetic alterations and clinical parameters will be underlined. Indeed, the identification of molecular alterations linked to specific tumor parameters may be of help in the management of head and neck cancer patients or useful in the development of new therapeutic strategies. Finally, studies have shown that in some part, constitutional genetic background could also interfere with the development of head and neck cancer through the existence of polymorphisms in carcinogens metabolizing enzymes and/or DNA repair enzymes. Individuals with low carcinogens elimination or DNA repair capacities could therefore be at risk of head and neck cancer. In this review both aspects of head and neck carcinogenesis will be discuss and relation between fundamental research and clinical practice will be mentioned.

Chromosome Aberrations↗

PubMed2004

Rapid identification of environmental bacterial strains by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

In recent years, various mass spectrometry procedures have been developed for bacterial identification. The accuracy and speed with which data can be obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) could make this a powerful tool for environmental monitoring. However, minor variations in the sample preparation can influence the mass spectra significantly. Therefore, the first objectives of this study were the adjustment and the optimization of experimental parameters allowing a rapid identification of whole bacterial cells without laborious sample preparation. The tested experimental parameters were matrix, extraction solvent, salt content, deposition method, culture medium and incubation time. This standardized protocol was applied to identify reference and environmental bacterial strains of Escherichia coli, Salmonella and Acinetobacter. The environmental bacterial strains were isolated from sewage sludge using an original microextraction procedure based on repeated sonications and enzymatic treatments. The bacterial identification was realized by the observation of the respective genus-, species- and strain-specific biomarkers. This bacterial taxonomy could be completed within one hour, with minimal sample preparation, provided that sufficient bacteria had been collected prior to MALDI-TOF analysis.

Actinobacteria↗

PubMed1993

Relationship between subjective sleep rating and objective sleep parameters: a case study.

The subjective sleep of a male subject was related to 22 objective polygraphic sleep parameters on 39 experimental nights. Subjective sleep was rated by the sleeper himself as "good," "moderate," or "poor" upon arising, for 10, 24, and 5 nights, respectively. Differences in the 22 sleep parameters for these three ratings were examined, and poor sleep showed a significant increase in stage W (waking), an elongation of sleep latency, a decrease in mean sleep depth during the night and 2 hr after going to bed, a decrease in integrated value of sleep depth during the night, an increase in the gradient and decrease in the intercept of regression line of sleep depth against time, and a shortening of total sleep time. The average delta wave percentage per epoch was greater for a subjective rating of "moderate" than for the other groups. Canonical discriminant analysis was conducted using 16 sleep parameters, and the overall correct identification rate of three subjective sleep ratings by the objective sleep parameters was 89.7%. Variables of the first or second axis with large standard coefficients were stages 1, 2, REM (rapid eye movement), integrated voltage of electromyogram, and sleep latency. From the above two sets of analyses, sleep latency was the most useful parameter for predicting subjective sleep.

Adult↗

PubMed2003

NARMAX representation and identification of ankle dynamics.

Representation and identification of a parallel pathway description of ankle dynamics as a model of the nonlinear autoregressive, moving average exogenous (NARMAX) class is considered. A nonlinear difference equation describing this ankle model is derived theoretically and shown to be of the NARMAX form. Identification methods for NARMAX models are applied to ankle dynamics and its properties investigated via continuous-time simulations of experimental conditions. Simulation results show that 1) the outputs of the NARMAX model match closely those generated using continuous-time methods and 2) NARMAX identification methods applied to ankle dynamics provide accurate discrete-time parameter estimates. Application of NARMAX identification to experimental human ankle data models with high cross-validation variance accounted for.

Ankle↗

PubMed2003

The minimal model: an evolving methodology.

After more than 20 years, minimal model analysis of intravenous glucose tolerance test glucose and insulin concentrations continues to be widely employed in studies of insulin sensitivity and insulin resistance. Moreover, problems encountered in solving the minimal model equations continue to find new solutions. Bayesian techniques enable prior knowledge to be incorporated into parameter estimation routines. They offer particular advantages in the measurement of insulin sensitivity with the minimal model, and provide an elegant means of improving model identification success rates and parameter precision. This comment describes the study by Agbaje and colleagues in this issue of Clinical Science that exemplifies a new phase in the evolution of minimal model practice.

Bayes Theorem↗

PubMed2001

Sex determination from the head of the femur of South African whites and blacks.

The current practice whereby criminals dismember the remains of their victims in an attempt to make their identification difficult requires that simple methods of sex determination from fragmented skeletal remains are available to forensic anthropologists and skeletal biologists. The head of the femur is an example of such bone fragments. Identification and demarking points have been derived from the diameters of the head of the femur and used to determine the sex of individuals. It has been shown, however, that the numerical values of these parameters that permit sex identification vary between races. The objectives of the present study were therefore to establish the standard numerical values of the identification and demarking points for sex determination in South African whites and blacks and to see if these standards are different in the two races. A total of 520 femurs of white (160 males and 100 females) and black (160 males and 100 females) South Africans were obtained from the Raymond Dart Skeletal Collection in the Department of Anatomical Sciences of the University of the Witwatersrand, Johannesburg, South Africa. The vertical and transverse diameters of the heads of the femurs were measured by means of a stainless steel vernier caliper. Identification and demarking points were derived from the values of these diameters. The head diameter identification point and demarking point were found to be sexually dimorphic in both white and black South Africans. The mean head diameter of the male femur was significantly greater than the mean head diameter of the female femur in both population groups (significant at P<0.001). These values were correspondingly greater in the white than the black population. The numerical values of the male identification and demarking points were higher than the corresponding female values in the two population. In both sexes, these values were greater in the whites than the blacks South Africans. It is concluded that the diameters of the head of the femur and the identification and demarking points that are derived from them are sexually dimorphic in South African white and black populations. However, the numerical values of these sex-determining bone parameters defer between the two population groups. Therefore, it is necessary to determine race-specific standards of these parameters.

Aged↗

PubMed1989

Segmentation of EEG during sleep using time-varying autoregressive modeling.

Time-varying AR modeling is applied to sleep EEG signal, in order to perform parameter estimation and detect changes in the signal characteristics (segmentation). Several types of basis functions have been analyzed to determine how closely they can approximate parameter changes characteristic of the EEG signal. The TV-AR model was applied to a large number of simulated signal segments, in order to examine the behaviour of the estimation under various conditions such as variations in the EEG parameters and in the location of segment boundaries, and different orders of the basis functions. The set of functions that is the basis for the Discrete Cosine Transform (DCT), and the Walsh functions were found to be the most efficient in the estimation of the model parameters. A segmentation algorithm based on an "Identification function" calculated from the estimated model parameters is suggested.

Algorithms↗

PubMedDate not supplied

Reverberation as a parameter in clinical testing.

Word identification was measured binaurally and monaurally using the Modified Rhyme Test under noise and reverberation. Normally hearing and hearing-impaired subjects were tested. A change in reverberation time from 0.25 to 0.50 s in a small audiometric room caused a significant change in word identification scores in both groups of subjects. A simulated reverberation composed of five distinct reflections did not affect word identification. The binaural advantage (difference between the binaural and monaural scores) was significant for normally hearing subjects, while it was not significant for hearing-impaired subjects.

Acoustic Stimulation↗

PubMedDate not supplied

Simultaneous detection of cellular ras p21 oncogene product and DNA content by two-parameter flow cytometry.

The rapid identification of the expression of oncogene products in specific cell types could be useful to investigate normal and malignant cell proliferation. We have developed a sensitive fixation - permeabilization technique (with 70% ethanol and 0.01% Triton x 100) for the detection of p21 ras oncoprotein and DNA content. Cell suspensions with negligible cell clumping, bright specific immunofluorescent staining were obtained with this method. Bivariate flow cytometry was then used to quantitate simultaneously the distribution of anti p21 ras oncoprotein (with a specific FITC-labeled antibody) and of total DNA (with propidium iodide). The study was carried out in human leukemic cell lines HL-60 and K562, human breast carcinoma cell line MCF-7 and fresh neoplastic cells from human acute leukemia. The p21 ras oncoprotein was found in all phases of cell cycle. The degree of its expression, however, varied widely in diploid (C0/G1) cells from different samples, which could be related to differences in the relative proportion of G0 and G1 cells. Compared to the conventional gel electrophoretic technique, the use of bivariate FCM is feasible, fast, requires fewer cells per sample (2 x 10(6] and allows both the ras oncogene expression in intact cell populations as well as its relationship with cell cycle phases to be studied.

Cell Cycle↗

PubMed1979

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

Two physical parameters were investigated to automatically recognize cells in sputum from human squamous cell carcinoma of the lung and to separate them for preparation by the Papanicolaou methods, for human interactive identification and for automated high resolution image analysis. The two parameters, 0.5-15.0 degrees forward argon-ion laser light scatter to estimate total cell size and 546 nm Acridine orange fluorescence to approximate total cell DNA content, were measured in a flow-through fluorescence activated cell sorting system. Enrichment for neoplastic cells in three cases of squamous cell carcinoma of the lung averaged 7.8-fold over the original sputum when only green fluorescence was used and 10.5-fold using green fluorescence and forward light scatter. The average enrichment for neoplastic cells was 65.6-fold relative to polymorphonuclear deenrichment.

Carcinoma, Squamous Cell↗

PubMed2002

Estimation of kinetic parameters without input functions: analysis of three methods for multichannel blind identification.

Compartment modeling of dynamic medical image data implies that the concentration of the tracer over time in a particular region of the organ of interest is well modeled as a convolution of the tissue response with the tracer concentration in the blood stream. The tissue response is different for different tissues while the blood input is assumed to be the same for different tissues. The kinetic parameters characterizing the tissue responses can be estimated by multichannel blind identification methods. These algorithms use the simultaneous measurements of concentration in separate regions of the organ; if the regions have different responses, the measurement of the blood input function may not be required. Three blind identification algorithms are analyzed here to assess their utility in medical imaging: eigenvector-based algorithm for multichannel blind deconvolution; cross relations; and iterative quadratic maximum-likelihood (IQML). Comparisons of accuracy with conventional (not blind) identification techniques where the blood input is known are made as well. Tissue responses corresponding to a physiological two-compartment model are primarily considered. The statistical accuracies of estimation for the three methods are evaluated and compared for multiple parameter sets. The results show that IQML gives more accurate estimates than the other two blind identification methods.

Algorithms↗

PubMed2002

A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma.

PURPOSE: In patients with an osteosarcoma, the prognosis is still poor. The aim of the present study was to investigate whether routinely tested biochemical parameters or additional parameters on bone scintigraphy could be identified which can select prognostic subgroups at the time of diagnosis. METHODS: A retrospective study was performed in 115 consecutive patients (70 male, 45 female) (mean age: 25.6 years; range: 3.50-78.0 years) who were referred for bone scintigraphy prior to treatment from March 1986 to September 2000 because of a newly diagnosed osteosarcoma. All bone scans were reassessed for the intensity and pattern of uptake and a bone-scan index. All pre-treatment general, histological, biochemical, and scintigraphic data were correlated with clinical outcome during follow-up. RESULTS: During follow-up 54 patients died. Tumour volume and GGT showed significance as independent variables for metastases. Patients with metastases demonstrated a significantly lower survival rate (23% 5-year survival) than patients without metastases (98% 5-year survival). Tumours of the humerus and femur had a significantly lower survival rate. With respect to significant biochemical parameters (ALP, GGT, ASAT), it was not possible to determine a cut-off value that could be used to differentiate between high- and low-risk patients. Additional parameters assessed on bone scintigraphy were not important for prognostic stratification. CONCLUSION: The strongest predictor of survival in osteosarcoma is the presence or absence of metastasis. Some biochemical parameters have prognostic value, but they cannot be used for the unequivocal identification of subgroups. Additional scintigraphic parameters are irrelevant for prognostic stratification.

Adolescent↗

PubMed1996

What parameters can be used for individual acoustic recognition by the greater flamingo?

The greater flamingo Phoenicopterus ruber is a colonial bird for which acoustic communication plays a great role, in particular during the mating period. The study of contact calls emitted by the adults allow enables identification of some acoustic parameters which may be used for individual recognition. It appears that the frequential values of the harmonics, the distribution of energy in the spectrum as well as beats (mimicking amplitude modulations) are susceptible to represent individual markers. On the contrary, the coding of the individual identity does not depend on frequency modulation since this latter is practically lacking. These results are remarkably similar to those obtained from another colonial bird species, the emperor penguin Aptenodytes forsteri, and may correspond to signal adaptations to special acoustic constraints of the colonial way of life.

Animal Communication↗

PubMed2024

optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material.

Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.

Humans↗