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Linear and nonlinear approaches to the analysis of R-R interval variability.

Analysis techniques derived from linear and non-linear dynamics systems theory qualify and quantify physiological signal variability. Both clinicians and researchers use physiological signals in their scopes of practice. The clinician monitors patients with signal-analysis technology, and the researcher analyzes physiological data with signal-analysis techniques. Understanding the theoretical basis for analyzing physiological signals within one's scope of practice ensures proper interpretation of the relationship between physiolgical function and signal variability. This article explains the concepts of linear and nonlinear signal analysis and illustrates these concepts with descriptions of power spectrum analysis and recurrence quantification analysis. This article also briefly describes the relevance of these 2 techniques to R-to-R wave interval (i.e., heart rate variability) signal analysis and demonstrates their application to R-to-R wave interval data obtained from an isolated rat heart model.

Animals↗

Extra-transference interpretation. A defense of classical technique.

New psychoanalytic techniques stemming from various object relations and Kleinian frameworks have increasingly diverged from many of the principles of classical analysis, such as interpretations of genetic transference, resistances and reconstructions of the past. In contrast to the wide-ranging foci of classical technique, the so-called modern analysis is narrowly focused on the interpretation of transference in the here-and-now analytic relationship. This change in technique is attributed to paradigm shifts from Freud's intrapsychic metapsychology to two-person theories about internal object relationships, infantile phantasies and countertransference. This paper examines important elements of this broad issue through a specific focus on the controversy over the therapeutic value of extra-transference interpretations vs. here-and-now transference interpretations. An extensive review of the literature is followed by excerpts from published analyses to illustrate the different clinical styles of classical vs. modern analysis. Freud's actual analytic work with a patient is presented to show his natural, rule-free clinical style is very different from his early technique papers. Classical technique is also illustrated by a description of relevant aspects of the author's own training analysis with Anna Freud. Finally, a clinical vignette illustrates the author's approach to extra-transference material and its interpretation.

Humans↗

CT and MR imaging in the local staging of primary malignant musculoskeletal neoplasms: Report of the Radiology Diagnostic Oncology Group.

PURPOSE: To assess the relative accuracies of computed tomography (CT) and magnetic resonance (MR) imaging in the local staging of primary malignant bone and soft-tissue tumors. MATERIALS AND METHODS: At four institutions, 367 eligible patients (aged 6-89 years) with malignant bone or soft-tissue neoplasms in selected anatomic sites were enrolled. Patients underwent both CT and MR imaging within 4 weeks before surgery. In each patient, CT scans were interpreted independently by two radiologists and MR images by two other radiologists at the enrolling institution. The CT and MR images were then interpreted together by two of those radiologists and subsequently reread at the other institutions. Imaging and histopathologic findings were compared and were supplemented when needed with surgical findings. Receiver operating characteristic curve analysis and descriptive statistical analysis were performed. RESULTS: Cases were analyzable in 316 patients: 183 had primary bone tumors; 133 had primary soft-tissue tumors. There was no statistically significant difference between CT and MR imaging in determining tumor involvement of muscle, bone, joints, or neurovascular structures. The combined interpretation of CT and MR images did not statistically significantly improve accuracy. Interreader variability was similar for both modalities. CONCLUSION: CT and MR imaging are equally accurate in the local staging of malignant bone and soft-tissue neoplasms in the specific anatomic sites studied.

Adolescent↗

Attachment of the tectorial membrane revealed by scanning electron microscope.

Our present-day descriptions of the causes of many forms of sensorineural deafness are based on what is known about the morphology of the organ of Corti. Unfortunately, this information is still woefully inadequate for a complete interpretation of normal events within this structure. Nevertheless there has been no shortage of theories based, in part at least, on assumptins of what the unknown morphology might be. One of the least understood structures is the tectorial membrane, for which the extent and position have had many descriptions. A review of these reveals that the observations vary with the techniques used, and different techniques have various effects on the sticky gel of the tectorial membrane which is reported to be 90% water. Here is described a technique whereby the bulk frozen-hydrated tectorial membrane is viewed by scanning microscopy. In its natural living state the tectorial membrane is sealed to the Hensen's cells, protecting the reticular lamina from endolymph.

Animals↗

Combining qualitative and quantitative sampling, data collection, and analysis techniques in mixed-method studies.

Researchers have increasingly turned to mixed-method techniques to expand the scope and improve the analytic power of their studies. Yet there is still relatively little direction on and much confusion about how to combine qualitative and quantitative techniques. These techniques are neither paradigm- nor method-linked; researchers' orientations to inquiry and their methodological commitments will influence how they use them. Examples of sampling combinations include criterion sampling from instrument scores, random purposeful sampling, and stratified purposeful sampling. Examples of data collection combinations include the use of instruments for fuller qualitative description, for validation, as guides for purposeful sampling, and as elicitation devices in interviews. Examples of data analysis combinations include interpretively linking qualitative and quantitative data sets and the transformation processes of qualitizing and quantitizing.

Data Collection↗

The origin of mesoderm in phoronids.

Descriptive studies of phoronid development have concluded that the mesoderm of these animals originates from the endoderm during gastrulation. This interpretation has been tested by labeling one blastomere of 4- through 16-cell embryos and examining the position and germ layers occupied by the labeled clones of cells in the larva. No 2 injections gave rise to identical clones of cells, suggesting that the cleavage program does not generate cells of unique identity and that cell fates are established at later developmental time points. In many cases, a relatively large sector composed of ectodermal cells was labeled. When these labeled cells were adjacent to the mouth or anus of the larva, muscle and mesenchyme cells originated from the labeled clones. Under these circumstances, nerve cells also originated from these labeled sectors. These labeling studies also showed that endodermal cells can give rise to mesodermal and neural cells. These results suggest that nerve and muscle cells are induced to form at ectodermal-endodermal boundaries from both germ layers. These marking experiments also confirmed the observation that nerve cells originate both from the apical organ and the trunk region and show for the first time that the intestine originates by ingression of posterior ectoderm.

Animals↗

Evaluation of effect profiles: Functional Observational Battery outcomes.

The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects.

Animals↗

Analysis of a model of bovine brucellosis using singular perturbations.

In this paper a model of bovine brucellosis spread is analyzed. This model consider four epidemiological classes: susceptibles, aborting infectious, infectious carriers and immune by vaccination. The per capita death rates of susceptibles, aborting and carriers are interpreted as slaughtering rates and they are time variable in order to maintain the size of the herd constant. A description of the evolution of the disease at the beginning of the epizootiological outbreak is given by means of singular perturbation techniques. We obtain a threshold parameter for the outbreak of the disease and a description of the asymptotic behavior of the model by using a theorem of Markus on asymptotically autonomous systems.

Abortion, Veterinary↗

[18F]-FDG uptake in soft tissue dermatome prior to herpes zoster eruption: an unusual pitfall.

Authors report on a case of [18F]-fluorodeoxyglucose ([18F]-FDG) uptake in the soft tissue of a patient referred for [18F]-FDG coincidence detection emission tomography (CDET) in a search for recurrence of colorectal cancer. A herpes zoster eruption occurred in the same site within two days, but was spontaneously resolved. To the best of our knowledge this is the first description of a false positive [18F]-FDG result in relation to a viral infection of soft tissue. It shows that interpretation of subcutaneous foci has to be cautious in patients with or without a past history of herpes zoster even in pain-free areas and prior to skin eruption.

Adenocarcinoma↗

A stochastic model of radiation carcinogenesis: latent time distributions and their properties.

A stochastic model of radiation carcinogenesis is proposed that has much in common with the ideas suggested by M. Pike as early as 1966. The model allows us to obtain a parametric family of substochastic-type distributions for the time of tumor latency that provides a description of the rate of tumor development and the number of affected individuals. With this model it is possible to interpret data on tumor incidence in terms of promotion and progression processes. The basic model is developed for a prolonged irradiation at a constant dose rate and includes short-term irradiation as a special case. A limiting form of the latent time distribution for short-term irradiation at high doses is obtained. This distribution arises in the extreme value theory within the random minima framework. An estimate for the rate of convergence to a limiting distribution is given. Based on the proposed latent time distributions, long-term predictions of carcinogenic risk do not call for information about irradiation dose. As shown by computer simulation studies and real data analysis, the parametric estimation of carcinogenic risk appears to be robust to the loss of statistical information caused by the right-hand censoring of time-to-tumor observations. It seems likely that this property, although revealed by means of a purely empirical procedure, may be useful in selecting a model for the practical purpose of risk prediction.

Animals↗

Simulating visibility during language comprehension.

In this study, participants performed a sentence-picture verification task in which they read sentences about an agent viewing an object (e.g., moose) through a differentially occlusive medium (e.g., clean vs. fogged goggles), and then verified whether a subsequently pictured object was mentioned in the previous sentence. Picture verification latencies were shorter when the resolution of the pictured object and the resolution implied by the sentence matched than when they did not. These results suggest that the degree of visibility implied in linguistic context can influence immediate object interpretation. These data suggest that readers mentally simulate the visibility of objects during language comprehension. Thus, the simulation of linguistic descriptions is not limited to the activation of intrinsic object properties (e.g., object shape), but also invokes the perceptibility of referential objects given implied environmental context.

Child↗

Do vibrational spectroscopies uniquely describe protein dynamics? The case for myoglobin.

We develop a quasi-harmonic description of protein dynamics and apply this description to the anomalous Mössbauer, infrared, x-ray diffraction, and EXAFS (extended x-ray absorption fine structure spectroscopy) data that are available for myoglobin (Mb) and its interactions with carbon monoxide (CO). In the quasi-harmonic approximation the dynamical parameters derived from these spectroscopic data are relevant in the calculation of reaction rates, and we give a quantitative description of the nonexponential kinetics of Mb-CO binding observed at low temperatures. All these data have previously been interpreted in terms of the more complex conformational substates model for protein dynamics. We point out several problems with this model and propose experiments that can provide detailed tests of the quasi-harmonic theory proposed here.

Iron↗

Investigation of phase transitions in bilayer membranes.

This article described three techniques used to study phase transitions in phospholipid bilayers. The complementarity of the three techniques in characterizing the thermotropic and structural properties of phospholipid bilayers has been demonstrated by describing their use to characterize a series of mixed-chain-length PCs. It has been shown that an understanding of the energetics that govern the packing of phospholipid chains in the gel phase can be used to construct a model to interpret thermodynamic data of the PCs. This model, in turn, provided a framework for designing and interpreting the Raman spectroscopic and X-ray diffraction experiments on this series of phospholipids. The result was a complete description of the phase transitions and gel phase packing properties of the mixed-chain-length PCs. The phase diagram of Fig. 5B has been expanded to include the mixed-chain-length PC series C18C18PC through C18C0PC. Furthermore, the phase diagram and the chain inequivalence parameter have been shown to describe the behavior of any mixed-chain-length PC, irrespective of the lengths of the hydrocarbon chains or the position of the chains on the glycerol backbone. This is demonstrated by the additional mixed-chain-length PCs plotted in Fig. 5B. With minor modifications, the phase diagram also accurately describes the behavior of mixed-chain-length phosphatidylethanolamines, sphingomyelins, and unsaturated PCs. Finally, it has been demonstrated that a correlation exists between the thermodynamic and the Raman spectroscopic parameters determined for the phase transition of phospholipid bilayers. This correlation is based on the common chain energetics being measured by these two techniques.

Calorimetry, Differential Scanning↗

Evaluating quality-of-life and health status instruments: development of scientific review criteria.

The Medical Outcomes Trust is a depository and distributor of high-quality, standardized, health outcomes measurement instruments to national and international health communities. Every instrument in the Trust library is reviewed by the Scientific Advisory Committee against a rigorous set of eight attributes. These attributes consist of the following: (1) conceptual and measurement model; (2) reliability; (3) validity; (4) responsiveness; (5) interpretability; (6) respondent and administrative burden; (7) alternative forms; and (8) cultural and language adaptations. In addition to a full description of each attribute, we discuss uses of these criteria beyond evaluation of existing instruments and lessons learned in the first few rounds of instrument review against these criteria.

Health Status↗

Clinical trials in veterinary oncology: a clinician's viewpoint.

Review of the veterinary oncology literature is important for keeping up-to-date, but it can be time-consuming and sometimes frustrating. Results of clinical trials are published in a variety of formats, including case descriptions, review articles, retrospective studies, and prospective trials. They may be found as abstracts, which usually present preliminary data and interpretation, as interesting items or commentary in a newsletter, or as articles in referred journals. In this "clinician's viewpoint," a practical approach to sifting through the mountains of literature is offered.

Animals↗

Evaluation of links in heroin seizures.

The evaluation of a link between two heroin seizures using a descriptive method is presented. It is based on the measure of the angles between two chromatograms assimilated to vectors, and interpreted using a continuous approach based on the likelihood ratio of Bayes' theorem. A complete evaluation model thus avoids the drawbacks of decision thresholds used until now to establish a link. Validation is obtained through tests and simulation methods.

Forensic Medicine↗

Methods to reveal domain networks.

The development and application of high-throughput technology to study protein interactions has led to the construction of complex interaction maps, the correct interpretation of which is crucial to the identification of targets for drug development. Here we propose that a more informative description of protein interaction networks can be achieved by considering explicitly the modular nature of proteins. In this representation, proteins are drawn as covalently linked modular domains binding to their target sites in partner proteins. Families of conserved modules that bind to relatively short peptides mediate a large fraction of the non-covalent interactions linking different proteins in the network. As these interactions are often involved in the propagation of signal transduction, determining the recognition specificity of each domain family member is an essential step toward a functional description of the global interactome.

Peptide Library↗

Highly optimised global organisation of metabolic networks.

High-level, mathematically precise descriptions of the global organisation of complex metabolic networks are necessary for understanding the global structure of metabolic networks, the interpretation and integration of large amounts of biologic data (sequences, various -omics) and ultimately for rational design of therapies for disease processes. Metabolic networks are highly organised to execute their function efficiently while tolerating wide variation in their environment. These networks are constrained by physical requirements (e.g. conservation of energy, redox and small moieties) but are also remarkably robust and evolvable. The authors use well-known features of the stoichiometry of bacterial metabolic networks to demonstrate how network architecture facilitates such capabilities, and to develop a minimal abstract metabolism which incorporates the known features of the stoichiometry and respects the constraints on enzymes and reactions. This model shows that the essential functionality and constraints drive the tradeoffs between robustness and fragility, as well as the large-scale structure and organisation of the whole network, particularly high variability. The authors emphasise how domain-specific constraints and tradeoffs imposed by the environment are important factors in shaping stoichiometry. Importantly, the consequence of these highly organised tradeoffs and tolerances is an architecture that has a highly structured modularity that is self-dissimilar and scale-rich.

Animals↗