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Brain tumor demarcation by applying a LAMSTAR neural network to spectroscopy data.

The application of optical spectroscopy for intra-operatively delineating brain tumors has been studied in this paper. The classification of tissue as normal, tumor and boundary is done using the LAMSTAR neural network (NN). The objective is to combine both fluorescence and reflectance as attributes to be used for the demarcation, thus giving the identification greater specificity and sensitivity. The input word has seven sub-words, five with autofluorescence parameters and two with reflectance values. The mean and standard deviation for the fluorescence parameters that were used for setting the weights of the NN were obtained from previous work. The reflectance value was used with the fluorescence parameters through a two-step discrimination algorithm. The neural network was trained with 10 sets of each tumor, normal and boundary type of tissue parameters. The network was then tested with 15 complete input sets and 10 incomplete sets for the identification. A 100% success rate was obtained for the complete testing sets and 80% for the incomplete ones. The most significant self-organizing map layers of the network were also identified for each decision. A sensitivity of 97.1% and specificity of 94.73% were achieved, which is much higher than earlier published results of 89 and 76%, respectively.

Brain Neoplasms↗

Motility analysis of pancreatic adenocarcinoma cells reveals a role for the atypical zeta isoform of protein kinase C in cancer cell movement.

The acquisition of an invasive and metastatic phenotype is accompanied by profound alterations of intracellular mechanisms controlling cell movement. Analysis of quantitative parameters of cell motility in cancer cells may help in the identification of intracellular signaling events determining invasion and metastasis. Here we developed a novel procedure of quantification of cell motility based on time-lapse video microscopy and digital image analysis. Three kinetic parameters, including area change, plasma membrane remodeling, and speed of linear movement, are quantified and combined in one single, time-normalized value we defined motility score (MS). Through calculation of the MS for various human pancreatic adenocarcinoma cell subclones, we identified clones characterized by low or high spontaneous motility in vitro. Analysis of the signaling mechanisms involved in the regulation of pancreatic adenocarcinoma cell motility showed that the atypical zeta isozyme of the serine-threonine protein kinase C (PKC) plays a critical role in maintaining a high MS in motile subclones, as demonstrated by the inhibitory effect of cell permeable peptides with sequence corresponding to the pseudosubstrate inhibitory region of the atypical zeta PKC. Other PKC isozymes, either classic or novel, seem not involved. Furthermore, biochemical analysis showed that in motile cells, zeta PKC is constitutively associated with the plasma membrane, whereas in nonmotile cells, zeta PKC is totally excluded from the plasma membrane. These data suggest that the disregulation of the function of atypical zeta PKC might be involved in the acquisition of an invasive and metastatic phenotype in pancreatic adenocarcinoma cells.

3T3 Cells↗

Modelling the relationship between peripheral blood pressure and blood volume pulses using linear and neural network system identification techniques.

The relationships between peripheral blood pressure and blood volume pulse waveforms can provide valuable physiological data about the peripheral vascular system, and are the subject of this study. Blood pressure and volume pulse waveforms were collected from 12 normal male subjects using non-invasive optical techniques, finger arterial blood pressure (BP, Finapres: Datex-Ohmeda) and photoelectric plethysmography (PPG) respectively, and captured to computer for three equal (1 min) measurement phases: baseline, hand raising and hand elevated. This simple physiological challenge was designed to induce a significant drop in peripheral blood pressure. A simple first order lag transfer function was chosen to study the relationship between blood pressure (system input) and blood volume pulse waveforms (system output), with parameters describing the dynamics (time constant, tau) and input-output gain (K). Tau and K were estimated for each subject using two different system identification techniques: a recursive parameter estimation algorithm which calculated tau and K from a linear auto-regressive with exogenous variable (ARX) model, and an artificial neural network which was trained to learn the non-linear process input-output relationships and then derive a linearized ARX model of the system. The identification techniques allowed the relationship between the blood pressure and blood volume pulses to be described simply, with the neural network technique providing a better model fit overall (p < 0.05, Wilcoxon). The median falls in tau following the hand raise challenge were 26% and 31% for the linear and neural network based techniques respectively (both p < 0.05, Wilcoxon). This preliminary study has shown that the time constant and gain parameters obtained using these techniques can provide physiological data for the clinical assessment of the peripheral circulation.

Adult↗

Parameterization of multivariate random effects models for categorical data.

Alternative parameterizations and problems of identification and estimation of multivariate random effects models for categorical responses are investigated. The issues are illustrated in the context of the multivariate binomial logit-normal (BLN) model introduced by Coull and Agresti (2000, Biometrics 56, 73-80). We demonstrate that the BLN model is poorly identified unless proper restrictions are imposed on the parameters. Moreover, estimation of BLN models is unduly computationally complex. In the first application considered by Coull and Agresti, an identification problem results in highly unstable, highly correlated parameter estimates and large standard errors. A probit-normal version of the specified BLN model is demonstrated to be underidentified, whereas the BLN model is empirically underidentified. Identification can be achieved by constraining one of the parameters. We show that a one-factor probit model is equivalent to the probit version of the specified BLN model and that a one-factor logit model is empirically equivalent to the BLN model. Estimation is greatly simplified by using a factor model.

Biometry↗

Improving automatic peptide mass fingerprint protein identification by combining many peak sets.

An automated peak picking strategy is presented where several peak sets with different signal-to-noise levels are combined to form a more reliable statement on the protein identity. The strategy is compared against both manual peak picking and industry standard automated peak picking on a set of mass spectra obtained after tryptic in gel digestion of 2D-gel samples from human fetal fibroblasts. The set of spectra contain samples ranging from strong to weak spectra, and the proposed multiple-scale method is shown to be much better on weak spectra than the industry standard method and a human operator, and equal in performance to these on strong and medium strong spectra. It is also demonstrated that peak sets selected by a human operator display a considerable variability and that it is impossible to speak of a single "true" peak set for a given spectrum. The described multiple-scale strategy both avoids time-consuming parameter tuning and exceeds the human operator in protein identification efficiency. The strategy therefore promises reliable automated user-independent protein identification using peptide mass fingerprints.

Cell Line↗

Hypocalcemia response following calcitonin administration: lack of correlation with osteoclast number determined after histoenzymologic identification in osteoporosis.

The relationship between calcitonin-induced hypocalcemia and histomorphometric parameters of bone resorption was examined in iliac crest biopsies of 30 osteoporotic patients aged 55-86 years all of whom had received a single injection of 100 UI of salmon calcitonin. Number of osteoclasts and active resorption surfaces were determined after histoenzymologic staining based on osteoclastic tartrate resistant acid phosphatase content. No significant correlation could be demonstrated between the drop of hypocalcemia and the different histomorphometric parameters. It can be concluded that the calcitonin test is useless in osteoporosis.

Aged↗

Phonocardiographic approach to the detection of right ventricular myocardial infarction.

Right ventricular myocardial infarction (RVMI) is not as rare as was previously thought and, if present, is almost always complicated with inferior myocardial infarction (IMI). On the basis of hemodynamic criteria, RVMI was identified in 33.7 percent of 98 cases with IMI. RVMI may induce a low cardiac output, if not often, resulting in cardiogenic shock. It is clearly desirable therefore to have an early and sensitive diagnostic clue to the presence or possibility of RVMI. Although much investigative attention in the diagnosis of RVMI has been focused on electrocardiography, echocardiography, radionuclide ventriculography, technetium-99 m stannous pyrophosphate scintigraphy, and thallium-201 scintigraphy, there has been little study of phonocardiography (PCG). The present study was therefore undertaken in an attempt to assess whether or not PCG information is useful for the identification of RVMI. PCG recordings were made during unforced natural respiration for at least 8 consecutive beats. From among several PCG parameters, the delta QP2 interval was found to be the most reliable for the identification of RVMI in patients with IMI. The delta QP2 interval was defined as the difference between Max QP2 and Min QP2, where Max QP2 and Min QP2 represent the maximal and minimal interval between Q and P2, respectively. Using delta QP2 less than or equal to 10 msec, the sensitivity and specificity for the diagnosis of RVMI were 90.9% and 84.6%, respectively. These results were superior to those obtained by radionuclide ventriculography, electrocardiography and echocardiography. We consider therefore that PCG should be recorded as soon as possible in the presence of IMI, and conclude that a small range (less than or equal to 10 msec) of delta QP2 carries a reasonably high sensitivity and specificity for the diagnosis of RVMI.

Adult↗

Slow oscillations of psychophysiological parameters in human operators during monotony.

Objective estimation of the human operator's functional state is an urgent problem in applied psychophysiology. It helps to forecast the reliability and efficiency of the operator's activity. Slow (minute) changes in the functional state of 22 subjects were recorded and analysed in experiments simulating the long-term operator's activity. Spatial synchronization of the electroencephalogram (EEG) and the heart-rate (HR) served as parameters. It was shown that the time of detection and identification of visual signals (geometrical figures) amid visual "noise" in a long-term observation naturally depends on the changes in a subject's state. These changes were estimated by slow (2-3 min) components of the changes in spatial synchronization of EEG and HR throughout 3 h of the experiment. These objective parameters of the human operator's state may be used to predict efficiency. The connection between minute oscillations of electrophysiological parameters and time of reaction is absent during the first 30 min of the experiment, then appears and increases throughout further stages, becoming clearly marked in its second half.

Boredom↗

Prediction of arrhythmia risk based on signal-averaged ECG in postinfarction patients.

In patients surviving acute MI, identification of those at high risk for life-threatening ventricular tachyarrhythmias and/or sudden death is of great importance. Numerous strategies based on indices such as the degree of left ventricular dysfunction, complex ventricular arrhythmias, or parameters of autonomic dysfunction have not yet led to an effective identification of the individual patient at risk. During the past decade, many investigators have recorded low amplitude, high frequency components in the terminal QRS complex (so-called late potentials) from patients prone to sustained ventricular tachycardia. The SAECG has been used to predict life-threatening tachyarrhythmias in patients after acute MI and to screen for inducible ventricular tachycardia in patients with unexplained syncope or sustained ventricular tachycardia. This review article describes the most frequently applied methodology and clinical applications of the SAECG in post-MI patients and discusses the usefulness of noninvasive recordings in various other clinical settings.

Arrhythmias, Cardiac↗

Characterisation and metabolic studies of Saccharomyces cerevisiae and Kluyveromyces fragilis by flow microcalorimetry.

The use of microcalorimetry in the routine identification of microorganisms is critically discussed and assessed. By use of flow microcalorimetric studies on Saccharomyces cerevisiae and Kluyveromyces fragilis the role of physical parameters and that of oxygen tension are discussed. The conclusion reached is that identification of microorganisms by microcalorimetry and subsequent discussion of metabolic events revealed by the thermogram, except under restrictive conditions, is inappropriate. However flow microcalorimetry, in contrast to batch microcalorimetry which has been used in the published material on microorganism identification, may allow characterization of yeasts suitable for particular industrial processes.

Ascomycota↗

Medical monitoring in long-term space missions.

The following principles, derived from the experience of medical support during past spaceflights, can provide a basis for a system of health monitoring and diagnosis during long-term and interplanetary missions: a system of preflight medical screening; medical screening on a systemic basis, which may include purposeful diagnosis in subsystems following the method of hierarchic structure; use of an individual approach; correction of the medical program with respect to the space crew status; assessment of the interrelations of the entire complex of parameters; utilization of the methods of correlation, classification and identification to elicit interrelations between different functions; evaluation of shifts in body functions and their adequacy to ambient conditions; continuity of medical examinations during all pre-flight stages, during flight and after completion of flight; analysis of information and anamnestic data by means of data bases; confidentiality of medical conclusions. Discussed are a classification of unfavorable microgravity-related syndromes, possible impairments due to abnormal situations, and some approaches to the prediction of the risk of various diseases, in relation to the construction of a conceptual diagnostic model for interplanetary missions. In the interest of medical monitoring special significance is attributed to the knowledge of individual norms for each crew member and of his unique peculiarities. Such data can be compiled by means of statistical analysis (single and multidimensional analysis) of the results of medical examinations and of observations during selection, training and tests. Selection of necessary physiological parameters, functional loads and data processing techniques which can be used in combination with other data sources for inflight diagnosis should be based on the following principles: the use of informative, non-invasively registered parameters and functional tests to reveal adverse states or most probable diseases; the possibility to assess the dynamics of physiological parameters and the status of the regulatory systems, and to predict possible developments in the body; the possibility to check the efficiency of countermeasures; the possibility to differentiate a physiological state adapted to the current environment from a pathological state; the possibility to differentiate between specific and non-specific reactions; the possibility to differentiate defensive, adaptive or compensatory phenomena from pathological manifestations. This paper describes the application of single- and multidimensional, statistical methods to process diagnostic information, to reduce the vector dimension of the chosen parameters, and to classify and identify individual and crew physiological standards providing the ability to assign an individual to a suitable team. Thus it will be possible to acquire comprehensive and statistically reliable information in compact format, and thus to perform a more incisive analysis and diagnosis of various states by comparing them with the baseline preflight data. These theoretical considerations constitute the basis for a conceptual model for medical diagnosis in long-term orbital and interplanetary missions. The paper contains a section dealing with the practical aspects of medical monitoring and diagnostic examinations during Mir missions. The program of medical monitoring for long-term Mir missions incorporates on-line monitoring during intravehicular and extravehicular activities, routine daily examinations, periodic extensive medical examinations accomplished on schedule or an indication. The Mir program includes cardiovascular investigations at rest and during functional loading, testing of the cosmonaut muscular systems, validation of the standard training protocols, occasional blood and urine analysis, incl. serum immunoglobulins, and blood cell counts. (ABSTRACT TRUNCATED)

Animals↗

Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations.

We here describe a simple, efficient DNA sequencing procedure for hemophilia A molecular diagnosis. In severe patients we first test for the presence of factor VIII gene intron 22 inversion using a recently described single-tube PCR method. In moderate, mild, or inversion-negative severe patients we systematically sequence the promoter, all exons and splice junctions of factor VIII gene. Specially designed primers allow amplification of 23 PCR products under the same salt conditions and thermocycling parameters. The whole sequencing procedure, from blood extraction to mutation identification, can be readily done within 42 h when using regular instruments or in just 14 h when using a high-throughput sequencer. Thus, this is a versatile and cost-effective strategy with little hands-on time requirements. Since its implementation we have identified mutations in 45/46 hemophilia A patients, 14 of which are novel. Once the genetic defect has been identified, accurate genetic counseling is then easily performed.

Amino Acid Substitution↗

How can the dynamics of the tundra-taiga boundary be remotely monitored?

This paper discusses some of the difficulties in establishing the location of the Arctic treeline and forest line on a circumpolar basis, and the contribution that remote sensing, particularly from spaceborne platforms, can make in resolving them. Spaceborne techniques can provide spatial resolutions as fine as a few meters, although the requirements for regional or global coverage are likely to limit the resolution to 30 to 100 m. Since this will preclude the identification of individual trees, the definition of the treeline will be based on statistical parameters estimated from satellite images. The optimum criteria for these parameters remain to be determined. Most remote-sensing observations that are suited to the measurement of the distribution of vegetation, and identification of its type, are based on the visible and near-infrared (VIR) parts of the electromagnetic spectrum, although there is increasing interest in the use of active microwave (radar) techniques. We discuss the basis of both types of approach and the techniques that follow from them, and present 3 case studies from the Russian Arctic.

Arctic Regions↗

Changes of carbohydrate-deficient transferrin in chronic alcoholism.

Compared with other well established liver enzyme parameters, carbohydrate-deficient transferrin (CDT) offers a new method for the identification of chronic alcoholism. The dependence of CDT and alcoholism/abstinence was studied in 29 controls and 64 alcoholics (both groups comprising men and women). In contrast to the currently used parameters GOT, GPT, gammaGT, LDH and MCV, CDT measures chronic alcoholism exclusively. CDT is dependent on sex but not age. In chronic alcoholism its rate increases significantly, but drops quickly after a short time of abstinence. CDT variations may be a specific and sensitive indicator of alcoholism or abstinence and possibly the duration.

Adult↗

Splenomegaly and reticulocytosis caused by Babesia microti infections in natural populations of the montane vole, Microtus montanus.

A survey for Babesia microti in rodents was conducted at six sites within Grand Teton National Park, Wyoming. Blood and spleen smears, hematocrits, and reticulocyte counts were made on all of the animals to evaluate parameters for the diagnosis of babesiosis. Ticks were removed for identification. Of 257 Microtus montanus, 103 were infected with B. microti. In addition, five of 12 Microtus pennsylvanicus and one of three Arvicola richardsoni were parasitized by B. microti. Peromyscus maniculatus (n = 40) were not infected. Concurrent infections by Hepatozoon sp., Trypanosoma sp., and the bacterium, Grahamella sp., were noted in blood smears from a number of M. montanus. Splenomegaly and reticulocytosis were significant parameters associated with babesiosis while decreased hematocrit was not. Ticks removed from the voles were identified as Ixodes eastoni and were the probable vectors of the B. microti.

Animals↗

Bayesian estimation for species identification in single-molecule fluorescence microscopy.

In this article we describe a recursive Bayesian estimator for the identification of diffusing fluorophores using photon arrival-time data from a single spectral channel. We present derivations for all relevant diffusion and fluorescence models, and we use simulated diffusion trajectories and photon streams to evaluate the estimator's performance. We consider simplified estimation schemes that bin the photon counts within time intervals of fixed duration, and show that they can perform well in realistic parameter regimes. The latter results indicate the feasibility of performing identification experiments in real time. It will be straightforward to generalize our approach for use in more complicated scenarios, e.g., with multiple spectral channels or fast photophysical dynamics.

Algorithms↗

Automated identification of subpopulations in flow cytometric list mode data using cluster analysis.

The application of K-means (ISODATA) cluster analysis to flow cytometric data is described. The results of analyses of flow cytometric data for mixtures of fluorescent microspheres and samples of peripheral blood mononuclear cells are presented. A method for simultaneously displaying list mode data for any number of parameters, which had previously been applied to a continuous set of parameters such as multi-angle light scattering data, is used to present the results of cluster analysis on physically unrelated parameters; this method allows rapid evaluation of the success of subpopulation identification. The factors that influence automated identification of subpopulations are examined, and methods for determining optimal values for these factors are described.

Flow Cytometry↗

Laboratory identification of familial thrombophilia: do the pitfalls exceed the benefits? A reassessment of ABO-blood group, gender, age, and other laboratory parameters on the potential influence on a diagnosis of protein C, protein S, and antithrombin deficiency and the potential high risk of a false positive diagnosis.

Laboratory testing for familial thrombophilia defines a large proportion of the modern hemostasis laboratory workload. As part of an ongoing assessment of our activities, we have re-evaluated our laboratory procedures for antithrombin (AT), Protein C (PC), and Protein S (PS), inclusive of normal reference ranges (NRR), the potential influence of ABO-blood group, gender and age, as well as other laboratory parameters, in order to help assess the effectiveness of testing as an aid to clinical diagnosis. We did not observe a significant influence of ABO-blood group on AT, PC, or PS. However, there were gender-related effects for PS (lower in females) and AT (higher in females), but not for PC. There were also age-related effects for AT, PC, and PS. Data is compared with literature findings. We also audited the positive detection rate for PC and/or PS deficiencies. In a 6-month period of testing, we identified that 18.9% of tested samples yielded low or near-low PC and/or PS levels. However, 33.3% of such samples were potentially derived from patients on oral anticoagulant therapy (ie, potential false positives). Additional pre-analytical variables, intra-assay, inter-assay, and inter-laboratory variability also contribute to the possibility of false positive detection. Thus, whilst NRR can be developed for test parameters, the likelihood of a false-positive test result can still be shown to exceed the likelihood of a true positive result, and this casts a shadow over the clinical value of such testing in some cases. In conclusion, laboratory testing for these markers of familial thrombophilia may or may not assist in the clinical diagnosis of this condition and clinical specialists should be made aware of laboratory test limitations, and consult with laboratories prior to making a definitive diagnosis of AT, PC, or PS deficiency.

ABO Blood-Group System↗