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PubMed2007

Retention time prediction and protein identification.

Proteins are commonly identified through enzymatic digestion and generation of short sequence tags or fingerprints of peptide masses by mass spectrometry. Separation methods, such as liquid chromatography and electrophoresis, are often used to fractionate complex protein or peptide mixtures and these separations also provide information on the different species, such as molecular weight and isoelectric point from electrophoresis and hydrophobicity in reversed-phase chromatography. These are also properties that can be predicted from amino acid sequences derived from genomic sequences and used in protein identification. This chapter reviews recently introduced methods based on retention time prediction to extract information from chromatographic separations and the applications to protein identification in organisms with small and large genomes. Novel data on retention time prediction of posttranslationally modified peptides is also presented.

Amino Acid Sequence↗

PubMed1998

The role of biopsy pathology, quantitative nuclear morphometry, and biomarkers in the preoperative prediction of prostate cancer staging and prognosis.

The focus of this review is to survey pretreatment biopsy and patient-derived information applicable to predicting pathological stage and prognosis of men with a diagnosis of prostate cancer. Various sources of clinical and pathological information that may contribute to building decision support tools (DSTs) for application by the urologist to manage prostate cancer patients are presented. These DSTs use serum biomarkers and objective, well-established, pathology information extracted by experienced pathologists from needle-core tissue samples that describe tumor size, grade, and location. Other valuable data can be derived from the biopsy tissue, such as computer-assisted image cytometry-derived DNA ploidy and nuclear morphometry informatics, as well as select tissue biomarker results that may provide supplemental prognostic information. Also discussed are the technical and clinical limitations of these DSTs with respect to the prediction accuracy. A commercially available pretreatment prediction algorithm (UroScore, Oklahoma City, OK) was applied to predict the disease organ confinement status of the prostate cancer test case. Finally, the authors present existing and future applications of computer-derived computational solutions for incorporating all patient history, clinical laboratory, and pathology information into algorithms that can generate patient-specific predictive probability estimates of stage, recurrence, and progression.

Biomarkers, Tumor↗

PubMed2001

Informational and energetic masking effects in the perception of multiple simultaneous talkers.

Although many researchers have examined the role that binaural cues play in the perception of spatially separated speech signals, relatively little is known about the cues that listeners use to segregate competing speech messages in a monaural or diotic stimulus. This series of experiments examined how variations in the relative levels and voice characteristics of the target and masking talkers influence a listener's ability to extract information from a target phrase in a 3-talker or 4-talker diotic stimulus. Performance in this speech perception task decreased systematically when the level of the target talker was reduced relative to the masking talkers. Performance also generally decreased when the target and masking talkers had similar voice characteristics: the target phrase was most intelligible when the target and masking phrases were spoken by different-sex talkers, and least intelligible when the target and masking phrases were spoken by the same talker. However, when the target-to-masker ratio was less than 3 dB, overall performance was usually lower with one different-sex masker than with all same-sex maskers. In most of the conditions tested, the listeners performed better when they were exposed to the characteristics of the target voice prior to the presentation of the stimulus. The results of these experiments demonstrate how monaural factors may play an important role in the segregation of speech signals in multitalker environments.

Adult↗

PubMed2004

Cataract extraction and risk of breast cancer.

OBJECTIVE: To prospectively examine the association between cataract extraction and breast cancer risk among 66,782 postmenopausal women who were 50 years or older in the Nurses' Health Study cohort from 1984 to 1998. METHODS: Cataract extraction information was collected in each biennial questionnaire since 1984. A total of 2555 incident breast cancer cases were documented during 14 years of followup. The Mantel-Haenszel method and pooled logistic regression with two-year time increments were used to estimate the relative risk and 95% confidence interval. RESULTS: We found that cataract extraction was not significantly associated with increased risk of breast cancer; the relative risks were 1.08 (95% CI, 0.89-1.31) after controlling for age and 1.06 (95% CI, 0.88-1.29) after multivariate adjustment for other risk factors for breast cancer. Also, there were no significant differences in the association between cataract extraction and risk of breast cancer according to history of diabetes (p for interaction = 0.11), smoking status (p for interaction = 0.58), and family history of breast cancer (p for interaction = 0.22). CONCLUSION: These data suggest that cataract extraction is not associated with risk of breast cancer and may not be a good indicator of oxidative stress for breast cancer.

Aged↗

PubMed2000

Structural Interpretations of Static Light Scattering Patterns of Fractal Aggregates.

Information on the size and structure of aggregates is critical in predicting the formation kinetics, settling velocities, and reactivity of particle aggregates. For some systems, however, accessing this information may be very difficult. Light scattering measurements are among the most useful techniques for accessing such information. In the case of large primary particles forming aggregates, the common Rayleigh approximation is not valid. Instead, Mie scattering must be used and multiple scattering must be accounted for. Moreover, size polydispersity and structure of aggregates are combined in the scattered intensity measurements. This work presents an experimental validation of a new theoretical approach for extracting information on both aggregate structure and size when multiple scattering cannot be neglected. The chemically controlled aggregation of 0.8-µm latex particles demonstrates the following: (1) Polydispersity effects prevent the interpretation of data to obtain structural information from the Structure factor S(q). (2) The calculated optical contrast decreasing during the aggregation can be correlated with the structural changes in the growing aggregates independently of size polydispersity. We have shown that a strict correlation can be obtained between the fractal dimension D(f) and the scatterers' mean optical contrast calculated at large scattering angles. (3) The changes in the Form factor (F(q)) due to multiple scattering when particles are close together yield a predicted structure that is in agreement with expected fractal dimension values and therefore S(q) can be described in term of both structure and size polydispersity. Copyright 2000 Academic Press.

Journal Article↗

PubMedDate not supplied

From experimental units to unique experiments: chronobiologic pilots complement large trials.

The timing of treatment affects outcome. For mapping multi-frequency rhythm spectra first to optimize chronochemotherapy, 1000 marker determinations on the subject are more informative than a few determinations on each of hundreds of patients. N-of-6 subgroups should follow, with one subject assigned to each of 6 marker rhythm stages, 60 (e.g. 4 hours on a 24-hour scale) apart. Once the time structure has been mapped, minimal sampling requirements determined, and guidelines for treatment established, the information gained from chronobiologic n-of-1 and n-of-6 test pilot designs can be built cost-effectively into randomized controlled trials to benefit large patient populations. Sequential tests combined with marker rhythmometry and cosinor analysis on single test subjects, small groups and eventually on each patient are powerful tools that can extract information otherwise unattainable even at great cost and bring the P-value from publications to the patients.

Antineoplastic Agents↗

PubMed2006

Use of mixture distributions to deconvolute the behavior of "hits" and controls in high-throughput screening data.

The stochastic nature of high-throughput screening (HTS) data indicates that information may be gleaned by applying statistical methods to HTS data. A foundation of parametric statistics is the study and elucidation of population distributions, which can be modeled using modern spreadsheet software. The methods and results described here use fundamental concepts of statistical population distributions analyzed using a spreadsheet to provide tools in a developing armamentarium for extracting information from HTS data. Specific examples using two HTS kinase assays are analyzed. The analyses use normal and gamma distributions, which combine to form mixture distributions. HTS data were found to be described well using such mixture distributions, and deconvolution of the mixtures to the constituent gamma and normal parts provided insight into how the assays performed. In particular, the proportion of hits confirmed was predicted from the original HTS data and used to assess screening assay performance. The analyses also provide a method for determining how hit thresholds--values used to separate active from inactive compounds--affect the proportion of compounds verified as active and how the threshold can be chosen to optimize the selection process.

Chemistry, Pharmaceutical↗

PubMed2006

A powerful method for detecting differentially expressed genes from GeneChip arrays that does not require replicates.

BACKGROUND: Studies of differential expression that use Affymetrix GeneChip arrays are often carried out with a limited number of replicates. Reasons for this include financial considerations and limits on the available amount of RNA for sample preparation. In addition, failed hybridizations are not uncommon leading to a further reduction in the number of replicates available for analysis. Most existing methods for studying differential expression rely on the availability of replicates and the demand for alternative methods that require few or no replicates is high. RESULTS: We describe a statistical procedure for performing differential expression analysis without replicates. The procedure relies on a Bayesian integrated approach (BGX) to the analysis of Affymetrix GeneChips. The BGX method estimates a posterior distribution of expression for each gene and condition, from a simultaneous consideration of the available probe intensities representing the gene in a condition. Importantly, posterior distributions of expression are obtained regardless of the number of replicates available. We exploit these posterior distributions to create ranked gene lists that take into account the estimated expression difference as well as its associated uncertainty. We estimate the proportion of non-differentially expressed genes empirically, allowing an informed choice of cut-off for the ranked gene list, adapting an approach proposed by Efron. We assess the performance of the method, and compare it to those of other methods, on publicly available spike-in data sets, as well as in a proper biological setting. CONCLUSION: The method presented is a powerful tool for extracting information on differential expression from GeneChip expression studies with limited or no replicates.

Algorithms↗

PubMed2003

Manual versus powered toothbrushes: the Cochrane review.

BACKGROUND: In a report released in January 2003, The Cochrane Collaboration Oral Health Group provided a systematic review of the effectiveness of powered versus manual toothbrushes, which generated much interest in the popular press. METHODS: The Cochrane researchers developed and implemented search strategies for the Cochrane Oral Health Group's Trial Register, the Cochrane Central Register of Controlled Trials, MEDLINE and the Cumulative Index to Nursing and Allied Health Literature. They contacted manufacturers for additional information. Trials were selected if they met the following criteria: compared power versus manual toothbrushes, had a randomized design, drew participants from a general population without disabilities, provided data regarding plaque and gingivitis, and were at least 28 days in length. Reviewers evaluated only studies published in 2001 or earlier. Six reviewers from the Cochrane study independently extracted information in duplicate. Indexes for plaque and gingivitis were expressed as standardized values for data distillation. Data distillation was accomplished using a meta-analysis, with a mean difference between powered and manual toothbrushes serving as the measure of effectiveness. RESULTS: The searches identified 354 trials, only 29 of which met the inclusion criteria. These trials involved about 2,500 subjects and provided data for meta-analysis. The results indicated that only the rotating oscillating toothbrush consistently provided a statistically significant, although modest, clinical benefit over manual toothbrushes in reducing plaque and gingivitis. CONCLUSIONS AND CLINICAL IMPLICATIONS: Some powered toothbrushes with a rotation-oscillation action achieve a significant, but modest, reduction in plaque and gingivitis compared with manual toothbrushes.

Dental Plaque↗

PubMed2004

Multivariate approaches for efficient detection of potential metabolites from liquid chromatography/mass spectrometry data.

This work describes a novel method for rapid screening of unknown metabolites in urine samples that narrows down the list of potential metabolites. Prior to analysis by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS), urine samples were prepared using solid-phase extraction (SPE). Automatic curve resolution was used for deconvolution of the LC/MS data, followed by peak alignment. Preprocessed data were then used for metabolite pattern recognition using principal component analysis (PCA), parallel factor analysis (PARAFAC), and multilinear partial least squares (N-PLS). This approach enabled the rapid detection of metabolites of citalopram in urine by maximizing the information extracted. The metabolites thus identified were compared with earlier studies on the metabolism of citalopram. In addition, new, unreported metabolites were found and characterized by LC/MS/MS and accurate mass measurements. A combination of data from positive and negative ionization enhanced the identification of metabolites.

Animals↗

PubMed2002

Signalers and receivers in animal communication.

In animal communication natural selection favors callers who vocalize to affect the behavior of listeners and listeners who acquire information from vocalizations, using this information to represent their environment. The acquisition of information in the wild is similar to the learning that occurs in laboratory conditioning experiments. It also has some parallels with language. The dichotomous view that animal signals must be either referential or emotional is false, because they can easily be both: The mechanisms that cause a signaler to vocalize do not limit a listener's ability to extract information from the call. The inability of most animals to recognize the mental states of others distinguishes animal communication most clearly from human language. Whereas signalers may vocalize to change a listener's behavior, they do not call to inform others. Listeners acquire information from signalers who do not, in the human sense, intend to provide it.

Affect↗

PubMed2003

Quantitative image analysis: software systems in drug development trials.

Multi-dimensional image analysis is being used increasingly to arrive at surrogate end-points for drug development trials. Various imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound are used to analyze treatments for diseases such as cancer, multiple sclerosis, osteoarthritis, and Alzheimer's disease. However, extracting information from images can be tedious and is prone to high user variability. The medical image analysis community is moving towards advanced software systems specifically designed for drug development trials. These systems can automatically identify the anatomy of interest in medical images (segmentation methods), can compare the anatomy over time or between patients (registration methods) and allow the quantitative extraction of anatomical features and the integration of the data and results into a database management system, automatically tracking the changes made to the data (audit trail generation). In this article, we present a case study using a prototype system that is used for quantifying multiple sclerosis lesions from multivariate MRI.

Clinical Trials as Topic↗

PubMed1996

Schematic maps: cognitive tools for enhancing the early stages of counseling.

The purpose of the present studies was to explore the utility of schematic maps as tools for the early stages of both peer and self-counseling. In experiment 1 (self-counseling), 42 students from undergraduate general psychology classes participated to fulfill course requirements. Participants were assigned to either a schematic map or essay group. They first extracted information about their alcohol-related behavior patterns and then analyzed the patterns from the perspective of a counselor. In experiment 2 (peer counseling), 38 students from upper-division psychology courses participated for extra credit. Participants were asked to evaluate behavior patterns, in the form of maps or essays, which were presented either in the same form as they were extracted or were transposed to the other format. In both studies, assessment consisted of questionnaires that addressed the usefulness of the tools in the counseling process. Schematic maps are potentially powerful tools for both self- and peer counseling. For self-counseling, maps were preferred over traditional essay writing. In addition, the subjective reaction to maps as tools for peer counseling was positive.

Alcohol Drinking↗

PubMed2001

[Neonatal screening of deafness: evoked otoacoustic emissions or acoustic distortion products?].

Transiently evoked otoacoustic emissions (TEOAE) allows an auditory screening in neonates above 30 dB and between 2 kHz to 4 kHz. Another type of otoacoustic emissions, the distortion product (DP) allows a similar screening and provides more specific frequency information over a broader frequency range, including frequencies below 2 kHz and above 4 kHz. The goal of this study was to determine 1) the interest of distortion product in comparison with TEOAE in a auditory screening program in neonates; 2) The predictive value of information extracted from otoacoustic emissions recordings, on frequential parameters of distortion product (DP). In this prospective study, TEOAE and DP were successively recorded in 20 neonates (34 ears) with risk of hearing impairment, using the ILO92 software and hardware. When TEOAs were no detectable (9/34), the DPs were no detectable neither (10/34). When TEOAs were detectable, the Dps carried more specific frequency information above 1 kHz in 52 to 80% of the patients. DP amplitudes have been quantitatively correlated with TEOA energy bands. Correlations between DP and TEOA have been objectivized for DP2.5 and DP4 with OE2, and for DP4 and DP6 with OE5. The correlation predictive value was above 85%. In conclusion, this study demonstrated that analysis of TEOA spectrums procures frequential information without requiring DP recordings.

Audiometry, Evoked Response↗

PubMed1994

Turning medical data into decision-support knowledge.

Advances in information collection and analysis are reaching the point of providing physicians with the help of computer-based assistants. These systems will provide rapid second opinions to physicians in a clinical setting as well as assist them in the analysis of large sets of patient descriptions for research purposes. This paper presents INC2.5 as such a decision-support system. INC2.5 extracts information from databases of previously seen patients to build a decision tree which is used to predict the outcome of new patients on a chosen variable. The concept of matching new patients with the most similar previously seen patient, on which INC2.5 is based, can be easily understood by its users. Further adding to INC2.5's ease of use is its flexibility in allowing users to customize decision trees to their liking. In order to convey the uncertainty of the environment, INC2.5 presents all decisions with a confidence factor.

Classification↗

PubMed2006

Over-complete discrete wavelet transformation of the normal auditory brainstem response improves prediction of outcome following severe acute closed head injury.

Previous research has shown that complex statistical analysis (discriminant function analysis) of a 'normal' auditory brainstem response (ABR) result can improve this measure's ability to predict subject outcome following severe acute closed head injury (ACHI). We hypothesized that adding the ABR's time-frequency information to such an analysis would improve this predictive value even further. 'Normal' ABR results were sampled from 69 severe ACHI subjects (22 of whom died and 47 of whom lived) and their time-frequency information extracted using an over-complete discrete wavelet transformation (OCDWT). A series of logistic regression analyses then showed correct predictions of death and survival as follows: ABR measures only 72 and 89% (respectively), ABR OCDWT measures only 82 and 89% (respectively), and ABR and ABR OCDWT measures combined 86 and 93% (respectively). These results showed that the addition of time-frequency information can improve the ability of the 'normal' ABR result to predict outcome following severe ACHI.

Acoustic Stimulation↗

PubMed2001

From images to interactions: high-resolution phase imaging in tapping-mode atomic force microscopy.

In tapping-mode atomic force microscopy, the phase shift between excitation and response of the cantilever is used as a material-dependent signal complementary to topography. The localization of information in the phase signal is demonstrated with 1.4-nm lateral resolution on purple membrane of Halobacterium salinarum in buffer solution. In a first-order approximation, the phase signal is found to correlate with modulations of the tip oscillation amplitude, induced by topography. Extending the analysis to contributions of the tip-sample interaction area as a second-order approximation, a method is proposed to extract information about the interaction from the phase signal for surfaces with a roughness in the order of the tip radius.

Buffers↗

PubMed2000

Nanoscale EELS analysis of dielectric function and bandgap properties in gaN and related materials

The low loss region of an EEL spectrum (<50 eV) contains information about excitations of outer shell electrons and thus the electronic structure of a specimen which determines its optical properties. In this work, dedicated electron energy loss spectroscopy (EELS) methods for the experimental acquisition and analysis of spectra are described, which give improved information about the electronic structure near the bandgap region at a spatial resolution in the range of nanometers. For this purpose, we made use of a cold field emission scanning transmission electron microscope (STEM) equipped with a dedicated EELS system. This device provides a subnanometer electron probe and offers an energy resolution of 0.35 eV. Application of suitable deconvolution routines for removal of the zero loss peak extracts information on the bandgap region while the Kramers-Kronig transformation deduces the dielectric properties from the measured energy loss function. These methods have been applied to characterize the optical properties of wide-bandgap materials for the case of III-nitride compounds, which are currently the most promising material for applications on optoelectronic devices working in the blue and ultraviolet spectral range. The obtained results are in excellent agreement with experimental measurements by synchrotron ellipsometry and theoretical studies. The potential of the superior spatial resolution of EELS in a STEM is demonstrated by the analysis of dielectric properties of individual layers of heterostructures and individual defects within wurtzite GaN.

Journal Article↗