SEARCH · PubMed Health

Results for “Model explainability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,747 records · Page 97Linked to original sources

PubMed1993

Chemoattraction of neutrophils by substance P and transforming growth factor-beta 1 is inadequately explained by current models of lipid remodeling.

"Classical" chemoattractants, such as FMLP, C5a, or leukotriene B4, not only elicit directed motility but also activate neutrophils (degranulation, release of active oxygen species). Signal transduction after ligation of receptors for these classical chemoattractants is mediated by pertussis toxin (PT)-sensitive, heterotrimeric G proteins and the early production of lipid messengers via phospholipases. In contrast, we have previously shown that substance P (SP) and transforming growth factor-beta 1 (TGF-beta 1) are "pure" chemoattractants in that they elicit chemotaxis without activating neutrophils. Paradoxically, pure chemoattractants also activate G proteins (plasmalemmal GTPase activity) without eliciting increments in cytosolic calcium ([Ca]i) and thus inositol trisphosphate. We therefore determined lipid remodeling and signal transduction in response to pure chemoattractants. Increments in plasmalemmal GTPase activated by SP (0.1 microM) and TGF-beta 1 (40 fM), like that after FMLP, were PT-sensitive (SP = 6.6 +/- 2 pm/mg/min vs SP + PT = 1.1 +/- 0.9 over basal activity; TGF-beta 1 = 4.3 +/- 1.6 vs TGF-beta 1 + PT = 2.3 +/- 0.9). In parallel, treatment of PMN with PT (1 microgram/ml, 30 min) inhibited chemotaxis (under agarose) after FMLP (2175 +/- 176 (SEM) microns vs 726 +/- 267) and SP (411 +/- 99 microns vs 103 +/- 62 microns) and TGF-beta 1 (40 fM, 375 +/- 53 microns vs 83 +/- 47). However, G proteins coupled to receptors for SP and TGF-beta 1, unlike FMLP, did not appear to be linked to phospholipases in that neither increments in diacylglycerol were detected after receptor ligation (FMLP = 152 +/- 22% resting levels; SP = 101 +/- 5%; TGF-beta 1 = 105 +/- 4%) nor was alkylacylglycerol increased by exposure to SP or TGF-beta 1 (SP = 92 +/- 4%; TGF-beta 1 = 101 +/- 8%; FMLP = 226 +/- 40%). Moreover, polymorphonuclear leukocytes failed to generate phosphatidates (PA) of either species after SP (DA-PA = 79 +/- 9% resting at 60 s; EA-PA = 103 +/- 4%) or TGF-beta 1 (DA-PA = 101 +/- 5%; EA-PA = 98 +/- 9%) in contrast to FMLP (DA-PA = 155 +/- 22%; EA-PA = 149 +/- 16%). The data clearly contravene the current dogma that all chemoattractants use inositol trisphosphate and diglycerides as intracellular signals and suggest the presence of a unique subset of PT-sensitive G proteins, not coupled to "classical" phospholipases, transduce chemoattraction.

Adult↗

PubMed2000

On measures of explained variance in nonrecursive structural equation models.

Whereas measures of explained variance in a regression and an equation of a recursive structural equation model can be simply summarized by a standard R2 measure, this is not possible in nonrecursive models in which there are reciprocal interdependencies among variables. This article provides a general approach to defining variance explained in latent dependent variables of nonrecursive linear structural equation models. A new method of its estimation, easily implemented in EQS or LISREL and available in EQS 6, is described and illustrated.

Analysis of Variance↗

PubMed1989

Kinetics of phototransduction in retinal rods of the newt Triturus cristatus.

1. The kinetics of photoresponses to flashes and steps of light of rods, from the retina of the newt Triturus cristatus, were analysed by recording the membrane current with a suction electrode. 2. In dark-adapted conditions the relation between the normalized amplitude of the photoresponse at a fixed time 1 s after the onset of light and the light intensity could be fitted by an exponential or a polynomial relation. In the presence of a steady bright light the same relation could be fitted by a Michaelis-Menten relation. 3. The kinetics of photoresponses to light stimuli was reconstructed using a model in which: (i) three molecules of guanosine 3'.5'-cyclic monophosphate (cyclic GMP) open a light-sensitive channel; (ii) light activates the enzyme phosphodiesterase, which hydrolyses cyclic GMP, thus closing light-sensitive channels: (iii) Ca2+ ions permeate through light-sensitive channels: and (iv) intracellular Ca2+ inhibits, in a co-operative way, the enzyme cyclase, which synthesizes cyclic GMP. 4. The model reproduces the shortening of the time to peak of brief flash photoresponses from about 1080 ms to about 690 ms with brighter lights. The model also explains the shortening of the time to peak to 350 ms observed in the presence of a steady light and the lack of a further acceleration with brighter flashes of lights. 5. The presence in the model of an intracellular calcium buffer accounts for the partial reactivation of the photocurrent following a step of light, lasting several seconds. The time course of this reactivation is not accelerated by a steady bright light both experimentally and in the model. 6. After the extinction to a long step of light the photocurrent showed a rapid partial reactivation, which was followed by a slow component of the photoresponse which extinguished with a rate constant of about 0.05 s-1. The model explains the origin of this slow component by assuming that the inactivation of excited rhodopsin is partially reversible. 7. The model is also able to explain the particular changes of kinetics when different amounts of exogenous calcium buffers are incorporated into rods (Torre, Matthews & Lamb, 1986).

Animals↗

PubMed2006

Why kin and group selection models may not be enough to explain human other-regarding behaviour.

Models of kin or group selection usually feature only one possible fitness transfer. The phenotypes are either to make this transfer or not to make it and for any given fitness transfer, Hamilton's rule predicts which of the two phenotypes will spread. In this article we allow for the possibility that different individuals or different generations face similar, but not necessarily identical possibilities for fitness transfers. In this setting, phenotypes are preference relations, which concisely specify behaviour for a range of possible fitness transfers (rather than being a specification for only one particular situation an animal or human can be in). For this more general set-up, we find that only preference relations that are linear in fitnesses can be explained using models of kin selection and that the same applies to a large class of group selection models. This provides a new implication of hierarchical selection models that could in principle falsify them, even if relatedness--or a parameter for assortativeness--is unknown. The empirical evidence for humans suggests that hierarchical selection models alone are not enough to explain their other-regarding or altruistic behaviour.

Altruism↗

PubMed1985

Cardiovascular changes and hearing threshold shifts in men under complex exposures to noise, whole body vibrations, temperatures and competition-type psychic load.

This study deals with changes in the temporary hearing threshold (TTS2), heart rate (HR), R-wave amplitude (RWA), diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP) and reaction time (RT) in subjects (n = 108) who, while working on a choice reaction apparatus, were exposed in an exposure chamber to combinations of noise and vibration at dry bulb temperatures of 20 degrees and 30 degrees C. The study was carried out as a type 2-3-3 factorial experiment, the number of the exposure combinations thus being 18. To find out the effects of competition-type psychic stress, some of the subjects were placed in a competitive group and some in a non-competitive group. The members of the competitive group were given financial encouragement and information on their progress during the test, whereas those in the non-competitive group worked at the rate they considered best without any monetary rewards or interim information. The noise classes were: no noise, a stable broadband (bandwidth 0.2-16.0 kHz) A-weighted noise of 90 dB not related to competition, and a stable broadband A-weighted noise of 90 dB related to competition about the fastest reaction time. The vibration classes were: no vibration, sinusoidal whole body vibration (Z-axis) at a frequency of 5 Hz, and stochastic broadband (bandwidth 2.8-11.2 Hz) whole body vibration (Z-axis). The acceleration (rms) of both vibrations was 2.12 m/s2. One experiment consisted of a control period of 30 min, three consecutive exposure periods of 16 min with an interval of 4 min, and a 15-min recovery period. The variance analysis model best explained the variation in TTS2 values at 4 kHz and second best the variation in TTS2 values at 6 kHz; it explained the variation in HR values third best, the variation in SBP values fourth best and the variation in PP values fifth best. On the other hand, the model explained least well the variation in DBP and RWA values. In general, the explanatory power of the model increased together with the number of exposures. The psychic stress caused by competition accelerated the growth of the TTS2 values, HR values and SBP values, when the subjects were simultaneously exposed to noise or to a combination of noise and vibration. An interesting finding for the continuation of the research project was that sinusoidal and stochastic vibration affected the cardiovascular changes, temporary hearing threshold and reaction times in different ways.

Adolescent↗

PubMed2006

Recent relative sea-level trends: an attempt to quantify the forcing factors.

Local sea-level is affected by a number of forcing factors, which all contribute to the trends observed by tide gauges. Here we use the fingerprints of main factors contributing to secular sea-level trends to construct an initial empirical model that explains best the trends in sea-level as recorded by the large number of coastal tide gauges over the last 50 years. The forcing factors considered include steric changes derived from observations, post-glacial rebound as predicted by geophysical models and mass changes in the Greenland and Antarctic ice sheets as predicted by the static sea-level equation. The approximation of the observed spatial pattern of sea-level trends through a model based on the spatial fingerprints of the main forcing factors fully utilizes the information contents of the available observations and models and allows the interpolation of the sea-level trends between the tide gauges. As a result, we obtain the global picture of sea-level trends due to the forcing factors accounted for in the analysis. Moreover, we derive constraints on the mass changes of the large ice sheets. The empirical models explain about 15% of the variance of the sea-level trends. Nevertheless, the models are correlated with the observations on the level of 0.38+/-0.07, indicating that most of the unexplained variance is due to contributions with small spatial scales. Averaged over the last five decades, the results indicate that the Antarctic and Greenland ice sheets have been melting with an equivalent contribution to global sea-level rise of 0.39+/-0.11 and 0.10+/-0.05 mm yr(-1), respectively. The steric signal derived from observations is clearly identified in the sea-level trends and is found to be at a minimum of 0.2 mm yr(-1), with the most likely value being close to 0.35 mm yr(-1). The global tide gauge network, which covers only a small fraction of the ocean surface, appears to sense an average sea-level rise larger than the global average. Extrapolating the regression models to the global ocean and taking into account the uncertainties in the extrapolation results in a most likely global average of the order of 1.05+/-0.75 mm yr(-1).

Climate↗

PubMed1997

Clonality and life cycles of intestinal crypts explained by a state dependent stochastic model of epithelial stem cell organization.

The organization and control of stem cells is a key issue in epithelial cell biology. The small intestinal murine crypt is a useful tissue to study such problems since stem cells are known to be located at specific positions at the bottom of the crypt where they are self maintaining. Recent data suggest, that (1) the number of active stem cells in a crypt can fluctuate, (2) the immediate progeny of a single stem cell can replace other stem cells eventually leading to monoclonality and (3) the life cycle of crypts may be linked to stem cell dynamics. It is the objective of this paper to suggest a stochastic state-dependent model of stem cell and crypt growth which can explain and-link these phenomena into one comprehensive framework. Monte Carlo simulations are performed to show consistently with available data. The model explains the size distribution of small intestinal crypts in steady state, the observations of stem cell fluctuations and monoclonality conversion, recovery of the crypt population after moderate damage and the rate of crypt fission and extinction. The key assumption of this model is an autoregulatory control of stem cell growth.

Animals↗

PubMed2000

Mucous granule exocytosis and CFTR expression in gallbladder epithelium.

A mechanistic model of mucous granule exocytosis by columnar epithelial cells must take into account the unique physical-chemical properties of mucin glycoproteins and the resultant mucus gel. In particular, any model must explain the intracellular packaging and the kinetics of release of these large, heavily charged species. We studied mucous granule exocytosis in gallbladder epithelium, a model system for mucus secretion by columnar epithelial cells. Mucous granules released mucus by merocrine exocytosis in mouse gallbladder epithelium when examined by transmission electron microscopy. Spherules of secreted mucus larger than intracellular granules were noted on scanning electron microscopy. Electron probe microanalysis demonstrated increased calcium concentrations within mucous granules. Immunofluorescence microscopic studies revealed intracellular colocalization of mucins and the cystic fibrosis transmembrane conductance regulator (CFTR). Confocal laser immunofluorescence microscopy confirmed colocalization. These observations suggest that calcium in mucous secretory granules provides cationic shielding to keep mucus tightly packed. The data also suggests CFTR chloride channels are present in granule membranes. These observations support a model in which influx of chloride ions into the granule disrupts cationic shielding, leading to rapid swelling, exocytosis and hydration of mucus. Such a model explains the physical-chemical mechanisms involved in mucous granule exocytosis.

Animals↗

PubMed1993

A topochemical approach to explain morphiceptin bioactivity.

A topochemical model to explain the bioactivity of morphiceptin (Tyr1-Pro2-Phe3-Pro4-NH2) was developed by taking account of accessible conformations around rotatable bonds which define relative spatial arrangements of opioid pharmacophores, the amine and phenolic groups of tyrosine and the aromatic ring of phenylalanine, necessary for receptor recognition. For this purpose, 1H-NMR measurements and computer simulations were extensively carried out on 10 stereoisomeric analogs related to morphiceptin: Tyr-Pro-(L and D)-Phe- (L and D)-Pro-NH2; Tyr-Pro-(L and D)-(NMe)Phe-(L and D)-Pro-NH2; Tyr-(NMe)Ala-Phe-D-Pro-NH2; and Tyr-Ala-Phe-D-Pro-NH2. These analogs are structurally close to one another but display various opiate potencies from highly active to inactive. The conformation of each rotatable bond has been specifically identified by measuring accessible space for the analogs, in which the difference in composition is observed in the specific site affecting only the conformation around the target bond. The most interesting characteristic of the model is a requirement of a cis amide bond linking residues 1 and 2. The model also requires the side chains in a trans conformation (chi 1 = 180 degrees) for the Tyr and Phe residues. The distances between the three pharmacophores, d1 (Tyr N to Tyr OH), d2 (Tyr N to the center of the aromatic ring of the third residue), and d3 (Tyr OH to the center of the aromatic ring of the third residue), were found to be approximately 8, approximately 7, and approximately 11-13 A, respectively. This model should aid in pharmaceutical design of peptide and nonpeptide ligands with opioid potencies.

Analgesics↗

PubMed2000

Sources of cortical responses to painful CO(2) laser skin stimulation of the hand and foot in the human brain.

OBJECTIVES: To investigate whether the same dipolar model could explain the scalp CO(2) laser evoked potential (LEP) distribution after either hand or foot skin stimulation. METHODS: LEPs were recorded in 14 healthy subjects after hand and foot skin stimulation and brain electrical source analysis of responses obtained in each individual was performed. RESULTS: A 5 dipolar sources model explained the scalp LEP topography after both hand and foot stimulation. In particular, we showed that the co-ordinates of the two earliest activated dipoles were compatible with source locations in the upper bank of the Sylvian fissure on both sides. These sources did not change their location when the stimulation site was moved from the upper to the lower limb. The other 3 dipoles of our model were activated in the late LEP latency range with a biphasic profile and a location compatible with activation of the cingulate gyrus and deep temporo-insular structures. CONCLUSIONS: The dipolar model previously proposed for the hand stimulation LEPs can also satisfactorily explain the LEP distribution obtained after foot stimulation. The earliest activated Sylvian dipolar sources did not change their location when the upper or lower limb was stimulated, as expected from the close projections of hand and foot in the second somatosensory area. No source in the primary somatosensory area was necessary to model the scalp topography of LEPs to hand and foot stimulation.

Adult↗

PubMed2006

Factors explaining career satisfaction among psychiatrists and surgeons in Canada.

BACKGROUND: The career satisfaction of specialists is affected by many variables ranging from family responsibilities, stress, the quality of services and facilities available to patients, professional rewards, and how the work is organized. OBJECTIVE: To articulate models that explain a substantial portion of the variance associated with career satisfaction among surgeons and psychiatrists in Canada. METHODS: Of 4958 eligible physicians across Canada, 2810 (56.7%) completed a 12-page survey between January and March 2004, following which the responding 148 surgeons and 231 psychiatrists were selected for this study. We checked response bias and found it was negligible. Hierarchical regression analysis was used to record cumulative R2, Standardized beta, and significance levels as each predictor was entered. We applied weighting factors to reflect the actual physician population in Canada. RESULTS: The models explained 90.4% of the variance in career satisfaction for surgeons and 81.0% of the variance in career satisfaction for psychiatrists. The explanatory variables consisted of distress and coping, role in community activities, access to and quality of health care services, intrinsic and extrinsic rewards, workload, and organizational structure. CONCLUSIONS: The study demonstrated that variance associated with career satisfaction can be explained using various factors reported directly by physicians. The study also confirmed that relative differences in the importance of these factors do occur among specialties. Surgeons prefer to delegate more responsibility in the management of their practices on an informal basis, whereas psychiatrists prefer to be more involved in the management of their practices and use more formal structures.

Adaptation, Psychological↗

PubMed2005

Explaining educational-related inequalities in health: Mediation and moderator models.

This paper studies how education and certain lifestyle factors affect people's self-reported health. In addition to the assessment of the effects of education and lifestyle, the study contrasts two models of explaining educational-related health inequalities: the mediation model and the moderator model. The mediation model posits that well-educated people's better health, as compared to the poorly educated, is caused by their more 'healthy' lifestyles. The moderator model suggests, by contrast, that the effects of the lifestyle variables on health are dependent upon educational level. Several analyses are carried out on two large data sets comprising of middle-aged men and women in two Norwegian counties, Rogaland and Nordland. Two main findings are presented: (1) Both education and lifestyle factors have the expected effects on health. (2) The results do not permit a clear-cut conclusion as to which of the two models of educational-related health inequalities should be preferred: whereas the results support the mediation model in the data from Rogaland, the moderator model is partially supported in the Nordland data.

Adult↗

PubMed2001

THOMAS MCMAHON: A Dedication in Memoriam.

Thomas A. McMahon (1943-1999) was a pioneer in the field of biomechanics. He made primary contributions to our understanding of terrestrial locomotion, allometry and scaling, cardiac assist devices, orthopedic biomechanics, and a number of other areas. His work was frequently characterized by the use of simple mathematical models to explain seemingly complex phenomena. He also validated these models through creative experimentation. McMahon was a successful inventor and also published three well-received novels. He was raised in Lexington, Massachussetts, attended Cornell University as an undergraduate, and earned a PhD at MIT. From 1970 until his death, he was a member of the faculty of Harvard University, where he taught biomedical engineering. He is fondly remembered as a warm and gentle colleague and an exemplary mentor to his students.

Journal Article↗

PubMed1996

Atrazine retention and transport in soils.

No pesticide has been studied as extensively as atrazine. The study of atrazine has contributed to our general understanding of the behavior of pesticides in soils. New knowledge and concepts were evaluated, such as atrazine adsorption kinetics, desorption hysteresis, and preferential flow. Corresponding conceptual models were also proposed to explain the behavior of atrazine in soils. Atrazine adsorption-desorption is the major process affecting atrazine behavior in soils and is mainly affected by organic matter and soil pH. Atrazine in soils is subject to biological and chemical degradations. Hydroxyatrazine, the chemical degradation product, is more strongly adsorbed to soil than atrazine. Deethylatrazine and deisopropylatrazine, the major biological degradation products, are more mobile than atrazine. Hydrolysis of atrazine is soil-surface catalyzed and favored by low soil pH. The overall dissipation rate of atrazine was found to be pseudo first-order. Two distinct and different processes are involved in atrazine movement: slow transport through the soil matrix and rapid movement through macropores. The first process is controlled by adsorption kinetics and degradation reactions and can be well explained by models based on chemical heterogeneity, such as the two-site models and second-order models. The second flow process results from preferential flow through large pores and can be explained by physical nonequilibrium models such as the mobile-immobile and two-flow domain models. Because both processes coexist in atrazine transport, coupling of physical and chemical nonequilibrium models is often necessary and has shown promise in atrazine transport modeling. However, more efforts are needed in estimating model parameters and in developing management-oriented models.

Adsorption↗

PubMed2002

A model for regulation of ColE1-like plasmid replication by uncharged tRNAs in amino acid-starved Escherichia coli cells.

It has been previously observed that various ColE1-like plasmids replicate differentially in Escherichia coli cells during the relaxed response to amino acid starvation. Here we develop a kinetic model to explain these observations based on the possibility of interaction of the 3' CCA-OH sequence with the UGG triplets in loops of RNA I and RNA II encoded by ColE1-like plasmids. According to our model, when the interaction of uncharged CCA with RNA I is possible, the replication of the ColE1-like plasmid is affected by differences in the concentration of various tRNAs in the starved cell, but it is not affected by the tRNA concentration if the hypothetical pairing occurs between the CCA-OH and RNA II. Using the previously determined parameters for the pBR322 plasmid, the concentration of uncharged tRNAs in the amino acid starved relaxed strains and the assumed efficiency of binding of tRNA and RNA I, we show that our model explains the differences in pBR322 copy number in the relaxed strain starved for several amino acids.

Amino Acids↗

PubMed2002

Neurophysiological mechanisms of induction of meditation: a hypothetico-deductive approach.

A detailed analysis of methods of induction of meditation and meditative experience encountered therein implicates involvement of several mechanisms in inducing 'meditative effect'. 'Efferent attenuation', 'sensory attenuation' and 'cognitive restructuring' appear three possible mechanisms employed in varying degree of combinations to produce the 'meditative effect' during different types of meditations. Using hypothetico-deductive approach, it is possible to generate a neural model for explaining the 'meditative effect'. Primarily, the meditation is produced by disengaged association cortices driven by thalamus or other older group of reticular nuclei. Secondarily, there may be involvement of some more phylogenetically older structures depending upon depth and types of meditation. This model explains induction, maintenance and long-term effects of meditation.

Attention↗

PubMed1988

Explaining adolescent drug use: an elaboration strategy for structural equations modeling.

We report a series of analyses designed to estimate increasingly elaborated theoretical models that explain adolescent drug use. Each of the successive elaborations adds a theoretical construct to the explanatory model in order to increase our understanding of drug use by specifying in greater detail the nature of the structural relationships among the latent variables. The more detailed specification is accomplished by 1) specifying new direct effects that increase explained variance in drug use, 2) decomposing direct effects through the interpolation of hypothesized intervening variables, 3) specifying antecedents of variables that modify their direct effects, and 4) exposing suppressor effects. Where indicated, we evaluate alternative explanations of the observed relationships. We do this by controlling for common antecedent effects to reduce spuriousness or by examining different specifications of causal linkages among the explanatory constructs.

Adolescent↗

PubMed2001

Performance and race in evaluating minority mayors.

This research compares a performance model to a racial model in explaining approval of a black mayor. The performance model emphasizes citizen evaluations of conditions in the city and the mayor's perceived effectiveness in dealing with urban problems. The racial model stipulates that approval of a black mayor is based primarily on racial identification or racism. A model of mayoral approval is tested with two surveys over different years of citizens in a city that has had 20 years' experience with black mayors. Findings indicate that performance matters when evaluating black mayors, indicating that the national performance models of presidential approval are generalizable to local settings with black executives. Implications for black officeholders are discussed. However, the racial model is alive and well, as indicated by its impact on approval and the finding that, in this context, performance matters more to white voters than to black voters. A final, highly tentative conclusion is offered that context conditions the relative power of these models. The performance model may explain more variation in approval of the black mayor than the racial model in a context of rapidly changing city conditions that focuses citizen attention on performance, but during a period of relative stability the two models are evenly matched.

Journal Article↗