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Results for “Model interpretability”

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PubMed1984

Spontaneous otoacoustic emissions in chinchilla ear canals: correlation with histopathology and suppression by external tones.

Two cases of spontaneous otoacoustic emissions (SOAEs) have been found among a sample of 28 chinchilla ears after noise exposure, and no cases of SOAEs have been found among 28 unexposed ears. Further observations of the characteristics of SOAEs recorded in the ear canals of two chinchillas after noise exposure are described. These signals were tonal, robust, and could be suppressed by presenting external tones to the ear. Histopathological evaluation of the cochlea of emitting ears revealed discrete basal-turn lesions near the positions corresponding to the frequencies of the emissions. Behavioral threshold shifts measured in one animal after noise exposure and acoustic intermodulation distortion product behavior in the other both suggest a region of increased vibratory response of the cochlear partition near the location of the SOAE. Results from these emitting ears support a hypothesis that a punctate loss of the organ of Corti (OC) may facilitate the occurrence of an SOAE. We further hypothesize that the following conditions are both necessary and sufficient for an SOAE to occur: (1) functional disruption of a normally present biomechanical control mechanism in a region of the OC; (2) presence of functionally active OC (especially outer hair cells) adjacent to the region. The observations from ears possessing SOAEs provide strong, though indirect support for active and nonlinear models in interpreting cochlear biomechanical phenomena.

Acoustic Stimulation↗

PubMed1991

The plasma sex steroid binding protein (SBP or SHBG). A critical review of recent developments on the structure, molecular biology and function.

Significant developments have taken place within the past five years on the characterization, molecular biology and function of the plasma sex steroid-binding protein, SBP (or sex hormone binding globulin, SHBG). During the span of that time, amino acid sequences of two SBPs have been established, amino acid residues in the steroid-binding site have been identified, the structure of the human SBP gene has been deduced and evidence for the possible existence of a SBP membrane receptor has been presented. This review covers the salient aspects of these and other developments including a critical analysis of the various proposed models and interpretations with regards to the structure, evolution, molecular biology and function of SBP.

Amino Acid Sequence↗

PubMed2006

Cluster-crossover design: a method for limiting clusters level effect in community-intervention studies.

The cluster-crossover design can be used for clinical trials comparing two or more interventions in a naturally formed study population, i.e. a cluster. This design differs from that of a crossover study, in that the treatment sequence is allocated at the cluster level. A cluster-crossover study can thus be considered as a cluster-randomized controlled study with additional periodic cluster-randomization(s) or treatment permutation(s) during the study. The data must be analyzed with hierarchical models with random effects in order to allow for different outcome probabilities in each period, cluster and cluster-period. Original data from two published field studies of hospital infection control based on this design are used here to illustrate the impact of different statistical models on the interpretation of the results.

Clinical Trials as Topic↗

PubMed2004

Chromatographic and spectroscopic methods for the determination of solvent properties of room temperature ionic liquids.

Room temperature ionic liquids are novel solvents with favorable environmental and technical features. Synthetic routes to over 200 room temperature ionic liquids are known but for most ionic liquids physicochemical data are generally lacking or incomplete. Chromatographic and spectroscopic methods afford suitable tools for the study of solvation properties under conditions that approximate infinite dilution. Gas-liquid chromatography is suitable for the determination of gas-liquid partition coefficients and activity coefficients as well as thermodynamic constants derived from either of these parameters and their variation with temperature. The solvation parameter model can be used to define the contribution from individual intermolecular interactions to the gas-liquid partition coefficient. Application of chemometric procedures to a large database of system constants for ionic liquids indicates their unique solvent properties: low cohesion for ionic liquids with weakly associated ions compared with non-ionic liquids of similar polarity; greater hydrogen-bond basicity than typical polar non-ionic solvents; and a range of dipolarity/polarizability that encompasses the same range as occupied by the most polar non-ionic liquids. These properties can be crudely related to ion structures but further work is required to develop a comprehensive approach for the design of ionic liquids for specific applications. Data for liquid-liquid partition coefficients is scarce by comparison with gas-liquid partition coefficients. Preliminary studies indicate the possibility of using the solvation parameter model for interpretation of liquid-liquid partition coefficients determined by shake-flask procedures as well as the feasibility of using liquid-liquid chromatography for the convenient and rapid determination of liquid-liquid partition coefficients. Spectroscopic measurements of solvatochromic and fluorescent probe molecules in room temperature ionic liquids provide insights into solvent intermolecular interactions although interpretation of the different and generally uncorrelated "polarity" scales is sometimes ambiguous. All evidence points to the ionic liquids as a unique class of polar solvents suitable for technical development. In terms of designer solvents, however, further work is needed to fill the gaps in our knowledge of the relationship between ion structures and physicochemical properties.

Chemical Phenomena↗

PubMed2004

Perspective: stem cells react! Cell lineages as complex adaptive systems.

It may be argued that adult stem cell processes or, more precisely, the cell lineages that arise from them, represent complex reactive or adaptive systems. Approaching hematopoietic and other stem cell lineages from this perspective has direct bearing on current debates regarding the plasticity of these lineage systems as well as on interpretation and modeling of clinical data regarding many diseases.

Adaptation, Physiological↗

PubMed2026

Systematic evaluation of one-dimensional-to-two-dimensional near-infrared spectroscopy transformations with deep learning for quantifying coconut sap adulteration.

Near-infrared (NIR) spectroscopy have limitations when combined with deep learning (DL) algorithms because they rely on low-dimensional datasets. Therefore, we investigated the potential of transforming one-dimensional (1D) NIR spectra into two-dimensional (2D) spectrograms using synchronous and asynchronous techniques and the continuous wavelet transform (CWT) and their effectiveness by integrating with DL for detecting adulteration in coconut sap. NIR spectra (12,500-4000 cm-1) were collected from binary mixtures (0%-100%;w/w). The performance of all DL (convolutional neural networks-CNN, AlexNet and ResNet) models was compared with that of partial least squares (PLS). The models were ranked in the mentioned order based on their performances: 2D-CWT > 2D-asynchronous > 2D-synchronous > 1D/2D-PLS. The important features of the best model can be explained and visualized using gradient-weighted-class-activation-mapping. The findings highlight that the 1D-to-2D NIR data transformation combined with DL is a highly robust approach because it addresses the feature representation gap in NIR data and effectively captures the spatial-spectral correlations.

Spectroscopy, Near-Infrared↗

PubMed2005

Validation of a modified version of the brief pain inventory for painful diabetic peripheral neuropathy.

Neuropathic pain is the focus of current clinical research, clinical identification, and treatment. It is unique from nociceptive pain and requires evaluation of the relevance and utility of common pain measures created for other painful conditions. This study evaluated the psychometric properties of a modified Brief Pain Inventory (BPI) for patients with painful diabetic peripheral neuropathy (BPI-DPN). Participants were patients with painful DPN (n=255) enrolled in a DPN Burden of Illness survey referred through 17 outpatient settings (primary care physicians, endocrinologists, neurologists, and anesthesiologists). Patients completed the BPI-DPN, and self-report measures of health-related quality of life, mood sleep, and healthcare utilization. Construct, criterion and discriminant validity, and internal consistency reliability were evaluated. Principal axis factoring with oblimin rotation revealed two interpretable factors (eigenvalues>1.0), consistent with most published BPI validation studies; a severity scale comprising the four BPI Severity items and an interference scale comprising the seven Interference items, which satisfied criteria for interpretability and model fit. Cronbach's alpha was high (0.94) for both scales. Mean pain Severity was highly correlated with Bodily Pain from the Medical Outcomes Study Short Form-12, version 2 (rs=0.63, P < 0.001), the Pain/Discomfort item in the Euro-QoL (rs=0.58, P < 0.001), and a verbal rating scale measure of pain severity (rs=0.74, P < 0.001). Individual BPI-DPN Interference domains were moderately correlated (rs's >0.5, P < 0.001) with analogous measures, and the Sleep Interference item had a high, significant association with the three primary Medical Outcome Study-Sleep scale subscales (rs's=0.66-71, P < 0.001). Worst Pain and Interference ratings were significantly associated with hospital utilization and outpatient visits due to DPN. These results replicate, in a pure peripheral neuropathic pain condition, the BPI psychometric characteristics documented in populations with nociceptive or mixed pain conditions. The BPI-DPN is a promising instrument in the evaluation of painful DPN.

Adolescent↗

PubMed2005

Validation of a modified version of the Brief Pain Inventory for painful diabetic peripheral neuropathy.

Neuropathic pain is the focus of current clinical research, clinical identification, and treatment. It is unique from nociceptive pain and requires evaluation of the relevance and utility of common pain measures created for other painful conditions. This study evaluated the psychometric properties of a modified Brief Pain Inventory (BPI) for patients with painful diabetic peripheral neuropathy (BPI-DPN). Participants were patients with painful DPN (n = 255) enrolled in a DPN Burden of Illness survey referred through 17 outpatient settings (primary care physicians, endocrinologists, neurologists, and anesthesiologists). Patients completed the BPI-DPN and self-report measures of health-related quality of life, mood sleep, and health care use. Construct, criterion and discriminant validity, and internal consistency reliability were evaluated. Principal axis factoring with oblimin rotation revealed two interpretable factors (eigenvalues > 1.0), consistent with most published BPI validation studies: a severity scale comprising the four BPI Severity items and an interference scale comprising the seven Interference items, which satisfied criteria for interpretability and model fit. Cronbach's alpha was high (0.94) for both scales. Mean pain Severity was highly correlated with Bodily Pain from the Medical Outcomes Study Short Form-12, version 2 (r(s) = 0.63, P < .001), the Pain/Discomfort item in the Euro-QoL (r(s) = 0.58, P < .001), and a verbal rating scale measure of pain severity (r(s) = 0.74, P < .001). Individual BPI-DPN Interference domains were moderately correlated (r(s)'s > 0.5, P < .001) with analogous measures, and the Sleep Interference item had a high, significant association with the three primary Medical Outcome Study-Sleep scale subscales (r(s)'s = 0.66-71, P < .001). Worst Pain and Interference ratings were significantly associated with hospital use and outpatient visits because of DPN. These results replicate, in a pure peripheral neuropathic pain condition, the BPI psychometric characteristics documented in populations with nociceptive or mixed pain conditions. The BPI-DPN is a promising instrument in the evaluation of painful DPN.

Adolescent↗

PubMed2026

Comparison of phylogenetic metrics of transmission between symptomatic and asymptomatic tuberculosis in individuals who were incarcerated in Brazil in 2008-24: a retrospective genomic epidemiology study.

BACKGROUND: Tuberculosis control efforts have traditionally targeted symptomatic individuals; however, the role of asymptomatic cases in sustaining transmission is increasingly recognised. We aimed to quantify the contribution of asymptomatic tuberculosis to recent transmission using genomic and epidemiological data from a high-transmission setting. METHODS: We conducted a retrospective genomic epidemiology study of Mycobacterium tuberculosis isolates collected in Mato Grosso do Sul, Brazil, between Aug 25, 2008, and March 19, 2024. Available isolates underwent whole-genome sequencing. Demographic, clinical, incarceration history, and laboratory metadata were obtained from surveillance records. From Jan 1, 2017, to March 19, 2024, active case finding was conducted in the state's three largest prisons (all male-only facilities), during which sputum samples were collected from individuals irrespective of symptoms and tested using GeneXpert and culture. Comparisons of transmission between individuals with and without symptoms were restricted to individuals who were incarcerated and were identified through active case finding and for whom high-quality, M tuberculosis lineage 4 genomes were available. Metrics of recent transmission included phylogenetic clustering, time-scaled haplotype density (THD), local branching index (LBI), and transmission probabilities inferred using Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories. FINDINGS: 4448 tuberculosis cases were notified in Mato Grosso do Sul in 2008-24. After excluding cases for which M tuberculosis isolates were not available or had low sequencing quality, who had contaminated cultures or mixed infection, or who were infected with non-lineage 4 M tuberculosis, we included 2362 lineage 4 M tuberculosis isolates with high-quality genome sequences. 1849 (78·3%) of 2362 isolates were part of a genomic cluster. Among 2362 individuals with tuberculosis, 1137 (48·1%) were incarcerated at diagnosis. Of these individuals, 505 were identified through active case finding in three male-only prisons. The median age was 30 years (IQR 25-37); 304 (60·2%) had mixed ethnicity, 90 (17·8%) were White, 56 (11·1%) were Black, 13 (2·6%) were Indigenous, and six (1·2%) were Asian. 277 (54·9%) had symptomatic disease and 228 (45·1%) had asymptomatic tuberculosis. There were no significant differences between symptomatic and asymptomatic individuals in phylogenetic clustering (213 [76·9%] of 277 vs 195 [85·5%] of 228; p=0·37), THD (median 0·39 [IQR 0·06-0·62] vs 0·50 [0·09-0·65]; p=0·12), or LBI (0·00863 [0·00810-0·00988] vs 0·00871 [0·00829-0·01020]; p=0·088). Bayesian transmission trees showed no significant difference in the number of secondary infections inferred from symptomatic compared with asymptomatic individuals (p=0·56). These findings were consistent across genomic clusters and robust to model assumptions. INTERPRETATION: We identified no differences in transmission between individuals who were symptomatic and those who were asymptomatic using multiple genomic measures. In this high-transmission setting, where systematic screening is implemented, our findings indicate that asymptomatic tuberculosis substantially contributes to tuberculosis transmission at the population level. These results suggest that symptom-based case detection alone is likely to be insufficient to interrupt transmission and highlight the importance of expanded screening strategies in high-risk populations. FUNDING: US National Institutes of Health and the Brazilian National Research Council (CNPq).

Humans↗

PubMed2004

Psychology and neurobiology of simple decisions.

Patterns of neural firing linked to eye movement decisions show that behavioral decisions are predicted by the differential firing rates of cells coding selected and nonselected stimulus alternatives. These results can be interpreted using models developed in mathematical psychology to model behavioral decisions. Current models assume that decisions are made by accumulating noisy stimulus information until sufficient information for a response is obtained. Here, the models, and the techniques used to test them against response-time distribution and accuracy data, are described. Such models provide a quantitative link between the time-course of behavioral decisions and the growth of stimulus information in neural firing data.

Action Potentials↗

PubMed2004

Adequate immunotoxicity testing in drug development.

Modulation of the immune system can lead to either immunostimulation or immunosuppression and can be either intended or unintended. While many effects on the immune system's components can be found as a result of a drug treatment or chemical exposure, true immunotoxicity occurs when such treatment results in adverse effects or defects in the immune response. Regulatory expectations to evaluate potential adverse effects of pharmaceuticals warrants a need for reliable and readily standardized methods. Moreover, criteria to classify a drug as an "immunotoxicant" need to be established. Examples of studies using a modified approach to measure T-cell-dependent antibody responses (the rat KLH model) and interpretation of the results in the context of immunotoxicity evaluation are discussed in this paper.

Animals↗

PubMed2026

Jingjing Zhai and Edward S. Buckler.

Dr. Laura Zahn asked the authors, Dr. Jingjing Zhai and Dr. Edward (Ed) S. Buckler, to tell us about their research relating to their Cell Genomics paper, "PlantCAD2: A DNA foundation model for interpreting genomes across flowering plants."

Genomics↗

PubMed1996

Assessment of reversible dyssynergic segments after acute myocardial infarction: Dobutamine echocardiography versus thallium-201 single photon emission computed tomography.

Only a moderate degree of concordance has been reported between stress-redistribution-reinjection thallium-201 single photon emission computed tomography (SPECT) and dobutamine echocardiography for the identification of myocardial viability after acute myocardial infarction. SPECT with rest-reinjection performed 4 hours after exercise testing and digitized two-dimensional (2-D) ultrasound reconstruction of the left ventricle at baseline and after low-dose dobutamine (5 to 10 microg/kg/min) infusion were compared in 50 patients > or = 8 days (12 +/- 7 days) after acute myocardial infarction. Five patients were excluded because of technically inadequate echocardiograms. Both SPECT and dobutamine echocardiography were assessed in a 16-segment model and interpreted in the remaining 45 patients. Digitized 2-D reconstruction of the left ventricle in each wall motion was scored from 1 (normal) to 4 (dyskinesia). Myocardial viability was identified on ultrasound wall-motion improvement of one or more grades from baseline to echocardiography performed > or = 30 days (60 +/- 41 days) after systematic revascularization procedure of the infarct-related artery. Reversible defect under thallium-201 SPECT and wall-motion improvement under dobutamine echocardiography were concordant in 163 (69 percent) of the 235 baseline dyssynergic segments and in 30 (67 percent) patients. Myocardial viability was identified after angioplasty (n=37) or surgery (n=8) in 29 patients and 109 segments. Positive and negative predictive values per patient in the diagnosis of myocardial viability were 86 percent and 57 percent, respectively, for stress thallium-201 SPECT with reinjection, and 100 percent and 62 percent for dobutamine echocardiography. Positive and negative predictive values per segment were 80 percent and 69 percent for the isotopic method and 91 percent and 70 percent for dobutamine echocardiography. We conclude that dobutamine echocardiography and stress thallium-201 SPECT with reinjection have similar accuracies to identify myocardial viability after acute myocardial infarction, with excellent positive but relatively low negative predictive values.

Adrenergic beta-Agonists↗

PubMed2001

Electron-beam computed tomography: a Bayesian approach to risk assessment.

The epidemic of coronary artery disease continues to affect a large number of individuals who often experience sudden and unexpected events. This underscores the need to develop more effective programs to detect silent atherosclerosis, with the ultimate goal of preventing coronary events. The use of conventional risk factors is helpful in assessing the median risk of a population, but it is often unsatisfactory in estimating the actual risk of an individual patient. As a consequence, newer imaging modalities are being developed to detect atherosclerosis in its early developmental phases. Technologies such as electron-beam computed tomography (EBCT) may render risk stratification more accurate if used in the appropriate patient populations and with the right diagnostic approach. Several studies have already demonstrated the power of coronary calcification as a strong predictor of future cardiovascular events. Nonetheless, the medical literature is currently pervaded by an animated debate, as some investigators still have concerns about the effectiveness of a preventive approach driven by technology. The use of Bayesian models to interpret data acquired with EBCT screening may provide practitioners with valuable evidence to aid in their decision making.

Bayes Theorem↗

PubMed1983

Neutron diffraction analysis of cytochrome b5 reconstituted in deuterated lipid multilayers.

Cytochrome b5 was reconstituted with a highly deuterated phospholipid to form ordered multilayers consisting of repeated centrosymmetric pairs of asymmetric lipid-protein bilayers. Lamellar neutron diffraction data were collected to approximately 29 A resolution, and have been interpreted using models for the interaction of the membrane-binding domain of cytochrome b5 with the lipid bilayer. A range of different models was examined, and those in which the protein penetrates well into the bilayer, possibly spanning it, are favored.

Animals↗

PubMed1984

Oxygen distribution and migration within Mbdes Fe and Hbdes Fe. Multifrequency phase and modulation fluorometry study.

Quenching of the intensity and lifetime of porphyrin fluorescence from Mbdes Fe and Hbdes Fe (iron-free myoglobin and hemoglobin) by oxygen was investigated using a multifrequency cross-correlation phase fluorometer. The single exponential decay characteristic of porphyrin emission of Mbdes Fe and Hbdes Fe became doubly exponential upon application of oxygen pressure. The results were interpreted in terms of a general model of dynamic quenching of fluorescence in globular proteins. The model accounted for the rate k+ of acquisition of quencher by the protein, the exit rate k- of quencher from the protein, and the migration rate chi of quencher in the protein interior. The values of k+, k-, and chi were different for Mbdes Fe and Hbdes Fe. The addition of 40% sucrose, which increased the bulk viscosity sixfold, modified these rates. These results are discussed and compared with previous quenching studies on proteins. The significance of these results and the model for the interpretation of protein quenching studies is emphasized.

Animals↗

PubMed2003

The inverse relationship between species diversity and body mass: do primates play by the "rules"?

Evolutionary biologists have long commented on a seemingly universal "rule" of nature-that in large taxonomic assemblages from groups as diverse as bacteria, plants, insects, marine invertebrates, fish, reptiles, amphibians, birds, and mammals, there exists a frequency distribution of body sizes among species that is highly skewed to the right (positive skewness). This distribution reflects the strong inverse, or negative, relationship often noted between mean body size of taxa and the number of species they contain--i.e., the observation that small body size is often associated with high species diversity (speciosity). This is sometimes "explained" by recourse to the idea that smaller-bodied taxa are able to subdivide their environments more finely than larger-bodied taxa. With but few exceptions, the applicability of this "rule" to the Order Primates has not been studied in any detail. In this study I address the following questions of (paleo)anthropological interest: (1) How speciose is the Order Primates? (2) Does this biological "rule" characterize the Order Primates (at any taxonomic level) in any meaningful way? (3) Does the association between speciosity and body mass within the Order Primates provide any useful models for interpreting and/or predicting speciosity in the fossil primate record? Using phylogenetically independent contrasts methods, I conclude that the answers to those three questions are: (1) not very; (2) no; and (3) not particularly (with the possible exception of larger-bodied taxa).

Animals↗

PubMed1998

Pairing sites and the role of chromosome pairing in meiosis and spermatogenesis in male Drosophila.

Mechanistic and regulatory aspects of meiotic chromosome pairing and segregation have received increasing attention in recent years. This review is concerned with the role of chromosomal sites and chromosome organization in pairing and sperm development in Drosophila. Two major topics are reviewed. The first concerns the distribution and identification of meiotic pairing sites in male Drosophila. Cytogenetic data show that pairing sites are distributed widely in the euchromatin of autosomes but are absent from centromeric heterochromatin. The reverse distribution holds for the X, where the major pairing site is located in the central region of the centric heterochromatin, co-mapping with the rDNA locus. Recent transgenic studies have demonstrated that this pairing site consists mainly of a 240-bp repeated sequence in the intergenic spacers of the rDNA repeats. These spacer repeats contain RNA polymerase I promoters, which must be functional for the repeats to have pairing activity, suggesting a mechanistic connection between pairing and transcription. The general idea that pairing sites coincide with transcribed sequences is discussed. The second major topic involves the effects of sex chromosome rearrangements on spermiogenesis. A variety of rearrangements involving the sex chromosomes, including heterochromatic deletions and translocations with autosomes, have been shown to lead either to meiotic drive or to sterility. Recent evidence strongly implicates the X chromosome pairing site in the etiology of these effects. These findings are discussed in terms of a novel model that interprets the spermiogenic disruptions associated with sex chromosome rearrangements as resulting from disabling of spermatids due to triggering of a checkpoint concerned with monitoring chromosome alignment at meiotic metaphase.

Animals↗