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PubMed2005

SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.

Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.

Algorithms↗
PubMed2001

Evaluating medical information systems: ethnomethodological and interactionist approaches.

This paper examines how qualitative research can contribute to the evaluation of medical information systems. Most qualitative studies of the use of medical computer systems adopt either an interactionist or, less commonly, an ethnomethodological perspective. The paper compares and contrasts the two approaches through the detailed discussion of two case studies, one rooted in each tradition. It identifies the implications of using these different analytical approaches and assesses their strengths and weaknessess. The paper argues that the preference for interactionism has led qualitative researchers to overlook important aspects of the social processess which surround the use of computer systems and that, consequently, a shift in emphasis towards ethnomethodological research is necessary. Nonetheless, it concludes by asserting that both strands of qualitative research can illuminate the organizational impact of medical computer systems.

Attitude of Health Personnel↗
PubMed1999

Scoring performance on computer-based patient simulations: beyond value of information.

As computer based clinical case simulations become increasingly popular for training and evaluating clinicians, approaches are needed to evaluate a trainee's or examinee's solution of the simulated cases. In 1997 we developed a decision analytic approach to scoring performance on computerized patient case simulations, using expected value of information (VOI) to generate a score each time the user requested clinical information from the simulation. Although this measure has many desirable characteristics, we found that the VOI was zero for the majority of information requests. We enhanced our original algorithm to measure potential decrements in expected utility that could result from using results of information requests that have zero VOI. Like the original algorithm, the new approach uses decision models, represented as influence diagrams, to represent the diagnostic problem. The process of solving computer based patient simulations involves repeated cycles of requesting and receiving these data from the simulations. Each time the user requests clinical data from the simulation, the influence diagram is evaluated to determine the expected VOI of the requested clinical datum. The VOI is non-zero only it the requested datum has the potential to change the leading diagnosis. The VOI is zero when the data item requested does not map to any node in the influence diagram or when the item maps to a node but does not change the leading diagnosis regardless of it's value. Our new algorithm generates a score for each of these situations by modeling what would happen to the expected utility of the model if the user changes the leading diagnosis based on the results. The resulting algorithm produces a non-zero score for all information requests. The score is the VOI when the VOI is non-zero It is a negative number when the VOI is zero.

Algorithms↗
PubMed1983

[Assessment of cancer risk in the work environment. Epidemiologic approach].

There are two essential steps in the analysis of carcinogenic risks in the work place: first, a descriptive approach which might raise the suspicion of an agent related to the frequency of a disease or mortality rate and then the analytical approach, based on retrospective and prospective cross-sectional studies. Such studies allow proof of the existence of a relation between a carcinogenic product and the frequency of lung cancer. The richer the contribution of such studies, the more difficult their accomplishment. All these studies assume that certain constraints are accepted: a precise protocol, collection of correct data, choice of a relevant population to be studied and controlled when necessary; rigorous supervision of each cohort under observation in the prospective studies, provision made for distorting factors. Such studies ought to result in averting occupational cancers rather than detecting them when clinically or radiologically apparent.

Adult↗
PubMed1999

Inverse planning for x-ray rotation therapy: a general solution of the inverse problem.

Rotation therapy with photons is currently under investigation for the delivery of intensity modulated radiotherapy (IMRT). An analytical approach for inverse treatment planning of this radiotherapy technique is described. The inverse problem for the delivery of arbitrary 2D dose profiles is first formulated and then solved analytically. In contrast to previously applied strategies for solving the inverse problem, it is shown that the most general solution for the fluence profiles consists of two independent solutions of different parity. A first analytical expression for both fluence profiles is derived. The mathematical derivation includes two different strategies, an elementary expansion of fluence and dose into polynomials and a more practical approach in terms of Fourier transforms. The obtained results are discussed in the context of previous work on this problem.

Mathematics↗
PubMed2001

Multiresolution analysis in fMRI: sensitivity and specificity in the detection of brain activation.

Multiresolution analysis of fMRI studies using wavelets is a new approach, previously reported to yield higher sensitivity in the detection of activation areas. No data are available, however, in the literature on the analytic approach and wavelet bases that produce optimum results. The present study was undertaken to assess the performance of different wavelet decomposition schemes by making use of a "gold standard," a realistic computer-simulated phantom. As activation areas are then known "a priori," accurate assessments of sensitivity, specificity, ROC curve area and spatial resolution can be obtained. This approach has allowed us to study the effect of different factors: the size of the activation area, activity level, signal-to-noise ratio (SNR), use of pre-smoothing, wavelet base function and order and resolution level depth. Activations were detected by performing t-tests in the wavelet domain and constructing the final image from those coefficients that passed the significance test at a given P-value threshold. In contrast to previously reported data, our simulation study shows that lower wavelet orders and resolution depths should be used to obtain optimum results (in terms of ROC curve area). The Gabor decomposition offers the maximum fidelity in preserving activation area shapes. No major differences were found between other wavelet bases functions. Data pre-smoothing increases ROC area for all but very small activation region sizes.

Algorithms↗
PubMed1998

A randomized nearest-neighbor approach for assessment of character displacement: the vulture guild as a model

Character displacement has been analysed in the past but not with an approach that considers nearest-neighbor distances between members of a guild. Vultures provide a model system in which to test a new analytical approach presented here to assess character displacement. Vultures are represented by two geographically isolated and taxonomically distinct groups: the Old World accipitrids and New World vultures. These two groups provide an excellent case of convergent evolution in which functional similarities can be compared among obligate carrion-feeding birds. The vulture guild was analysed from several geographic regions where species occur in a high diversity: East Africa, South Africa, the Indian subcontinent, Amazonia, and the pleistocene deposits from Rancho La Brea, California. A three-dimensional morphospace was constructed derived from features of the skull, beak, and mandible to assess feeding capabilities. Species packing and their distribution within the morphospace were compared using a nearest-neighbor approach through Monte Carlo simulations. Vultures seem to exhibit a similar array of ecomorphological types wherever they occur in a high diversity, even though there are phylogenetic differences among some regions. Phylogenetic effects appear to have little influence on the distribution of functional types in each region and evidence for character displacement was found only at Rancho La Brea where both Old and New World vultures were present.Copyright 1998 Academic Press Limited Copyright 1998 Academic Press Limited

Journal Article↗
PubMed2004

An approach to the residence time distribution for stochastic multi-compartment models.

Stochastic compartmental models are widely used in modeling processes such as drug kinetics in biological systems. This paper considers the distribution of the residence times for stochastic multi-compartment models, especially systems with non-exponential lifetime distributions. The paper first derives the moment generating function of the bivariate residence time distribution for the two-compartment model with general lifetimes and approximates the density of the residence time using the saddlepoint approximation. Then, it extends the distributional approach to the residence time for multi-compartment semi-Markov models combining the cofactor rule for a single destination and the analytic approach to the two-compartment model. This approach provides a complete specification of the residence time distribution based on the moment generating function and thus facilitates an easier calculation of high-order moments than the approach using the coefficient matrix. Applications to drug kinetics demonstrate the simplicity and usefulness of this approach.

Anticholesteremic Agents↗
PubMed2000

Discrimination between NK and LAK cytotoxic activities of murine spleen cells by MTT assay: differential inhibition by PGE(2) and EDTA.

In the present study we propose a mathematical approach to improve the analysis of NK and LAK activities measured by MTT assay adapted for murine cells. We found that to calculate NK activity, high E:T ratios should be used (up to 50:1) and the phenomenon fits to a linear least-squares analysis. However, 5-fold less effector cells (10:1, E:T) should be used to detect LAK activity and the phenomenon has a nonlinear exponential behavior. Using this approach, we showed that EDTA inhibits LAK but not NK activity whereas PGE(2) inhibits NK but not LAK activity. In conclusion, this analytical approach allowed the discrimination between NK and LAK activities and exposed differences between these two cytotoxic activities.

Animals↗
PubMed2002

Now you see it, now you don't: statistical and methodological considerations in fMRI.

We illustrate the effects of statistical threshold, spatial clustering, voxel size, and two approaches to multiple comparison correction on fMRI results. We first analyzed fMRI images obtained from a single subject during a noun-verb matching task. Data were analyzed with Statistical Parametric Mapping (SPM) using two different voxel sizes, and results were displayed at three different levels of statistical significance. At each statistical threshold, results were first uncorrected for multiple comparisons and spatial extent and then presented using a spatial extent cluster of 20 voxels. We then statistically controlled the Type I error rate associated with multiple comparisons by using the false discovery rate and by the random field adjustment for false-positive rate used by SPM. We also examined group results from language and graphesthesia paradigms at three levels of statistical significance. In all circumstances, apparent random activations decreased as more conservative statistical approaches were employed, but activation in areas considered to be functionally significant was also reduced. These issues are important in the choice of analytic approach and interpretation of fMRI results, with clear implications for the surgical management of individual patients when fMRI results are used to delineate specific areas of eloquent cortex.

Journal Article↗
PubMed2003

Pharmacokinetic and pharmacodynamic properties of insulin aspart and human insulin.

The preferred approach to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties of insulin analogues is the euglycemic glucose clamp. Currently non-compartmental data analytical approaches are used to analyze data. The purpose of the present study is to propose a novel compartmental-model for analysis of data from glucose clamp studies. Data used in this trial only involved 18 of the 20 originally treated subjects. Data was obtained from a crossover trial where 18 healthy subjects each received a single subcutaneous (s.c.) dose of 1.2 nmol/kg (body weight) insulin aspart (IAsp) or 1.2 nmol/kg human insulin (HI) during a euglycemic glucose clamp after overnight fast. Serum insulin and glucose concentrations were measured and the glucose infusion rate (GIR) was adjusted after dosing, to maintain blood glucose near basal levels. Individual model parameters were estimated for IAsp, HI, and the corresponding glucose and GIR data. We found statistically significant differences between most of the HI and IAsp pharmacokinetic parameters, including the sigmoidicity of the time course of absorption (1.5 for HI vs. 2.1 for IAsp (unit less), P = 0.0005, Wilcoxon Signed-rank test), elimination rate constant (0.010 min-1 for HI vs. 0.016 min-1 for IAsp (P = 0.002)). The PD model parameters were mostly not different, except for the rate of insulin action (0.012 min-1 for HI vs. 0.017 min-1 for IAsp (P = 0.03)). The model may provide a framework to account for different PK properties when estimating the PD properties of insulin and insulin analogues in glucose clamp experiments.

Adult↗
PubMed1993

Assessing neurobehavioral changes in HIV+ infants and children. A methodological approach.

The rationale and development of a developmental approach to assessing neurobehavioral changes in infants and children exposed to or infected with the HIV-1 virus is presented. Methodological problems in earlier approaches to assessment are reviewed. Among these are measures employed, impact of different treatments on measures of outcome, multicultural differences between samples, and analytic approaches to developmental data. The assessment protocol developed by the Pediatric Neurobehavioral Study Group of NIMH/NICHD/NIAID is described.

Adolescent↗
PubMedDate not supplied

[Effect of mycotoxin T-2 on bioluminescence intensity of bacteria].

The acute and chronic toxicity of T-2 was studied by bioluminescent method with the use of two strains of luminous bacteria--P. phosphorum Sq3 u V. fischeri F1 as biological objects. It was shown that in acute experiments after 10 min incubation of bacteria in the presence of T-2 the bioluminescence inhibition on the 50% level was observed at the toxin concentration equal to 12 mg/mL. In chronic experiments such a level of bioluminescence inhibition was registered after 16 hours incubation at the toxin concentration of 18 mg/mL. T-2 toxicity was also investigated in the presence of different serum albumin concentrations. It decreases with the increase of albumin concentration at the short term of incubation (5 min) of the mixture to be analyzed. In case of the longer term of incubation (up to 30 min) of this mixture T-2 toxicity was restored. Probably, it is a result of destruction of protein-toxin complex, which is, evidently, reversible and may be characterized by some index. It is necessary to emphasize that the sensitivity of T-2 analysis increases under the decrease of pH value up to lower bacterial physiological level, i.e. to 5-5.5. The revealed abilities of T-2 toxin effect on the intensity of bacterial bioluminescence may be used under the development of instrumental analytical approach on the basis of biosensor technology for testing this toxin in the environment. Taking into account the analysis simplicity and rapidity, such analytical device may have a perspective for wide practical application.

Environmental Monitoring↗
PubMed2004

Molecular clock fork phylogenies: closed form analytic maximum likelihood solutions.

Maximum likelihood (ML) is increasingly used as an optimality criterion for selecting evolutionary trees, but finding the global optimum is a hard computational task. Because no general analytic solution is known, numeric techniques such as hill climbing or expectation maximization (EM) are used in order to find optimal parameters for a given tree. So far, analytic solutions were derived only for the simplest model-three-taxa, two-state characters, under a molecular clock. Quoting Ziheng Yang, who initiated the analytic approach,"this seems to be the simplest case, but has many of the conceptual and statistical complexities involved in phylogenetic estimation."In this work, we give general analytic solutions for a family of trees with four-taxa, two-state characters, under a molecular clock. The change from three to four taxa incurs a major increase in the complexity of the underlying algebraic system, and requires novel techniques and approaches. We start by presenting the general maximum likelihood problem on phylogenetic trees as a constrained optimization problem, and the resulting system of polynomial equations. In full generality, it is infeasible to solve this system, therefore specialized tools for the molecular clock case are developed. Four-taxa rooted trees have two topologies-the fork (two subtrees with two leaves each) and the comb (one subtree with three leaves, the other with a single leaf). We combine the ultrametric properties of molecular clock fork trees with the Hadamard conjugation to derive a number of topology dependent identities. Employing these identities, we substantially simplify the system of polynomial equations for the fork. We finally employ symbolic algebra software to obtain closed formanalytic solutions (expressed parametrically in the input data). In general, four-taxa trees can have multiple ML points. In contrast, we can now prove that each fork topology has a unique(local and global) ML point.

Animals↗
PubMed2005

A novel approach for nontargeted data analysis for metabolomics. Large-scale profiling of tomato fruit volatiles.

To take full advantage of the power of functional genomics technologies and in particular those for metabolomics, both the analytical approach and the strategy chosen for data analysis need to be as unbiased and comprehensive as possible. Existing approaches to analyze metabolomic data still do not allow a fast and unbiased comparative analysis of the metabolic composition of the hundreds of genotypes that are often the target of modern investigations. We have now developed a novel strategy to analyze such metabolomic data. This approach consists of (1) full mass spectral alignment of gas chromatography (GC)-mass spectrometry (MS) metabolic profiles using the MetAlign software package, (2) followed by multivariate comparative analysis of metabolic phenotypes at the level of individual molecular fragments, and (3) multivariate mass spectral reconstruction, a method allowing metabolite discrimination, recognition, and identification. This approach has allowed a fast and unbiased comparative multivariate analysis of the volatile metabolite composition of ripe fruits of 94 tomato (Lycopersicon esculentum Mill.) genotypes, based on intensity patterns of >20,000 individual molecular fragments throughout 198 GC-MS datasets. Variation in metabolite composition, both between- and within-fruit types, was found and the discriminative metabolites were revealed. In the entire genotype set, a total of 322 different compounds could be distinguished using multivariate mass spectral reconstruction. A hierarchical cluster analysis of these metabolites resulted in clustering of structurally related metabolites derived from the same biochemical precursors. The approach chosen will further enhance the comprehensiveness of GC-MS-based metabolomics approaches and will therefore prove a useful addition to nontargeted functional genomics research.

Automation↗
PubMedDate not supplied

Bayesian networks for knowledge discovery in large datasets: basics for nurse researchers.

The growth of nursing databases necessitates new approaches to data analyses. These databases, which are known to be massive and multidimensional, easily exceed the capabilities of both human cognition and traditional analytical approaches. One innovative approach, knowledge discovery in large databases (KDD), allows investigators to analyze very large data sets more comprehensively in an automatic or a semi-automatic manner. Among KDD techniques, Bayesian networks, a state-of-the art representation of probabilistic knowledge by a graphical diagram, has emerged in recent years as essential for pattern recognition and classification in the healthcare field. Unlike some data mining techniques, Bayesian networks allow investigators to combine domain knowledge with statistical data, enabling nurse researchers to incorporate clinical and theoretical knowledge into the process of knowledge discovery in large datasets. This tailored discussion presents the basic concepts of Bayesian networks and their use as knowledge discovery tools for nurse researchers.

Artificial Intelligence↗
PubMed2006

Scaling and normalization effects in NMR spectroscopic metabonomic data sets.

Considerable confusion appears to exist in the metabonomics literature as to the real need for, and the role of, preprocessing the acquired spectroscopic data. A number of studies have presented various data manipulation approaches, some suggesting an optimum method. In metabonomics, data are usually presented as a table where each row relates to a given sample or analytical experiment and each column corresponds to a single measurement in that experiment, typically individual spectral peak intensities or metabolite concentrations. Here we suggest definitions for and discuss the operations usually termed normalization (a table row operation) and scaling (a table column operation) and demonstrate their need in 1H NMR spectroscopic data sets derived from urine. The problems associated with "binned" data (i.e., values integrated over discrete spectral regions) are also discussed, and the particular biological context problems of analytical data on urine are highlighted. It is shown that care must be exercised in calculation of correlation coefficients for data sets where normalization to a constant sum is used. Analogous considerations will be needed for other biofluids, other analytical approaches (e.g., HPLC-MS), and indeed for other "omics" techniques (i.e., transcriptomics or proteomics) and for integrated studies with "fused" data sets. It is concluded that data preprocessing is context dependent and there can be no single method for general use.

Algorithms↗
PubMed2002

Measurement of the scattering of a Lamb wave by a through hole in a plate.

Flexural waves propagating in an aluminum plate containing a circular hole are studied. In the experiments the first antisymmetric Lamb wave mode A0 is excited selectively by a piezoelectric transducer. The scattered field around a circular cavity is measured pointwise using a heterodyne laser interferometer. The measurements are compared with theoretical calculations. Different approximate analytical approaches, employing Kirchhoff and Mindlin types of plate theories to describe the scattered field, are used. Good agreement between the experimental data and the analytical solutions is found within the ranges of validity of the different models. Introduction of a small imperfection, like a notch, at the boundary of the cavity changes the measured scattered field

Journal Article↗