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A theoretical model for estimating the margination constant of leukocytes.

BACKGROUND: Blood leukocytes constitute two interchangeable sub-populations, the marginated and circulating pools. These two sub-compartments are found in normal conditions and are potentially affected by non-normal situations, either pathological or physiological. The dynamics between the compartments is governed by rate constants of margination (M) and return to circulation (R). Therefore, estimates of M and R may prove of great importance to a deeper understanding of many conditions. However, there has been a lack of formalism in order to approach such estimates. The few attempts to furnish an estimation of M and R neither rely on clearly stated models that precisely say which rate constant is under estimation nor recognize which factors may influence the estimation. RESULTS: The returning of the blood pools to a steady-state value after a perturbation (e.g., epinephrine injection) was modeled by a second-order differential equation. This equation has two eigenvalues, related to a fast- and to a slow-component of the dynamics. The model makes it possible to identify that these components are partitioned into three constants: R, M and SB; where SB is a time-invariant exit to tissues rate constant. Three examples of the computations are worked and a tentative estimation of R for mouse monocytes is presented. CONCLUSIONS: This study establishes a firm theoretical basis for the estimation of the rate constants of the dynamics between the blood sub-compartments of white cells. It shows, for the first time, that the estimation must also take into account the exit to tissues rate constant, SB.

Animals↗

Psychosocial stress and prostate cancer: a theoretical model.

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage is more prevalent among African-American than among European-American men. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. Within the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively impact the immune system leaving the individual susceptible to malignancies. Behavioral responses to psychosocial stress are amenable to change. If psychosocial stress is found to negatively impact prostate cancer risk, interventions may be designed to modify reactions to environmental demands.

Black or African American↗

Health-related quality of life in youth with epilepsy: theoretical model for clinicians and researchers. Part I: the role of epilepsy and co-morbidity.

Children and adolescents with epilepsy are at increased risk for poor health-related quality of life (HRQL) even in the absence of active seizures. Clinicians who aim to achieve optimal seizure control also need to focus on improving HRQL. This can only be accomplished by recognizing how different features of the epilepsy itself, co-morbid conditions, as well as psychosocial factors can all make a difference to HRQL. These psychosocial factors include child, family and community/society variables that play a role in the well-being of these children. Conceptual models are relevant insofar as they provide us with a basis for hypothesizing the causal processes that lead to improved HRQL. They delineate what is meant by HRQL and highlight factors relevant to this important outcome. Researchers can use such models to test statistically and clinically relevant relationships. Clinicians can use this knowledge to direct the planning and implementation of services that are informed by these relationships, critically evaluate and then choose HRQL measures for use in clinical practice that most closely approximate what they understand HRQL is. The purpose of this review is to identify what is meant by HRQL as well as outline the theoretical and empirical basis for what it is about epilepsy, co-morbidity, and its treatment that we believe make a difference to HRQL.

Adolescent↗

A simple theoretical model for fluorescence polarization binding assay development.

Fluorescence polarization is a screening technology that is radioactivity free, homogeneous, and ratiometric. The signal measured with this technology is a weighted value of free and bound ligand. As a consequence, saturation curves are accessible only after calculation of the corresponding concentrations of free and bound ligand. To make this technology more accessible to assay development, the authors propose a simple mathematical model that predicts fluorescence polarization values from ligand and receptor total concentrations, depending on the corresponding dissociation constant. This model was validated using data of Bodipy-NDP-alphaMSH binding to MC(5), obtained after either ligand saturation of a receptor preparation or, conversely, receptor saturation of a ligand solution. These experimental data were also used to calculate the actual concentration of free and bound ligand and receptor and to obtain pharmacological constants by Scatchard analysis. A general method is proposed, which facilitates the design of fluorescence polarization binding assays by relying on the representation of theoretical polarization values. This approach is illustrated by the application to 2 systems of very different affinities.

Binding Sites↗

Experimental radiosurgery simulations using a theoretical model of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: A novel biomathematical arteriovenous malformation (AVM) model based on electric network analysis was used to investigate theoretically the potential role of intranidal hemodynamic perturbations in elevating the risk of rupture after simulated brain AVM radiosurgery. METHODS: The effects of radiation on 28 interconnected plexiform and fistulous AVM nidus vessels were simulated by predefined random or stepwise occlusion. Electric circuit analysis revealed the changes in intranidal flow, pressure, and risk of rupture at intervals of 3 months during a 3-year latency period after simulated partial/complete irradiation of the nidus using doses <25 and >/=25 Gy. An expression for risk of rupture was derived on the basis of the functional distribution of the critical radii of component vessels. The theoretical effects of radiation were also tested on AVM nidus vessels with progressively increasing elastic modulus (E:) and wall thickness during the latency period, simulating their eventual fibrosis. RESULTS: In an AVM with E=5. 0x10(4) dyne/cm(2), 4 (14.3%) of a total 28 sets of AVM radiosurgery simulations revealed theoretical nidus rupture (risk of rupture >/=100%). Three of these were associated with partial nidus coverage and 1 with complete treatment. All ruptures occurred after random occlusion of nidus vessels in AVMs receiving low-dose radiosurgery. Intranidal hemodynamic perturbations were observed in all cases of AVM rupture; the occlusion of a fistulous component resulted in intranidal rerouting of flow and escalation of the intravascular pressure in adjacent plexiform components. Risk of rupture was found to correlate with nidus vessel wall strength: a low E: of 1.9x10(4) dyne/cm(2) resulted in a 92.8% incidence of AVM rupture, whereas a higher E: of 7.0x10(4) dyne/cm(2) resulted in only a 3.6% incidence of AVM rupture. A dramatic reduction in rupture incidence was observed when increasing fibrosis of the nidus was modeled during the latency period. CONCLUSIONS: It was found that the theoretical occurrence of AVM hemorrhage after radiosurgery was low, particularly when radiation-induced fibrosis of nidus vessels was considered. When rupture does occur, it would appear from a theoretical standpoint that the occlusion of intranidal fistulas or larger-caliber plexiform vessels could be a significant culprit in the generation of critical intranidal hemodynamic surges resulting in nidus rupture. The described AVM model should serve as a useful research tool for further theoretical investigations of cerebral AVM radiosurgery and its hemodynamic sequelae.

Cerebral Hemorrhage↗

Extracting hydrophobic free energies from experimental data: relationship to protein folding and theoretical models.

Solubility and vapor pressure measurements of hydrocarbons in water are generally thought to provide estimates of the strength of the hydrophobic effect in the range 20-30 cal/(mol.A2). Our reassessment of the solubility data on the basis of new developments in solution thermodynamics suggests that the hydrophobic surface free energy for hydrocarbon solutes is 46-47 cal/(mol.A2), although the actual value depends strongly on curvature effects [Nicholls et al. (1991) Proteins (in press); Sharp et al. (1991) Science 252, 106-109]. The arguments to support such a significant increase in the estimate of the hydrophobic effect stem partly from theoretical considerations and partly from the experimental results of De Young and Dill [(1990) J. Phys. Chem. 94, 801-809] on benzene partition between water and alkane solvents. Previous estimates of the hydrophobic effect derive from an analysis of solute partition data, which does not fully account for changes in volume entropy. We show here how the ideal gas equations, combined with experimental molar volumes, can account for such changes. Revised solubility scales for the 20 amino acids, based on cyclohexane to water and octanol to water transfer energies, are derived. The agreement between these scales, particularly the octanol scale, and mutant protein stability measurements from Kellis et al. [(1989) Biochemistry 28, 4914-4922] and Shortle et al. [(1990) Biochemistry 29, 8033-8041] is good. The increased strength of the hydrophobic interaction has implications for the energetics of protein folding, substrate binding, and nucleic acid base stacking and the interpretation of computer simulations.

Alkanes↗

Theoretical model for the interpretation of BMD scans in patients stopping strontium ranelate treatment.

UNLABELLED: Strontium ranelate is a new treatment for osteoporosis that results in large increases in BMD, much of which is an artefact caused by high bone strontium content. We used clinical trial data and a model of long-term strontium kinetics to estimate the effect of past strontium treatment on future BMD measurements. INTRODUCTION: The oral administration of strontium ranelate causes a clinically significant overestimation of BMD because of the high attenuation of X-rays by strontium atoms in bone. As more patients are treated with strontium ranelate, questions will arise about the correct interpretation of their future BMD measurements. We performed a theoretical study to calculate the long-term effect of strontium treatment on BMD and establish the duration of past treatment for which the remaining bone strontium content (BSC) has a negligible effect on BMD. MATERIALS AND METHODS: The BMD changes measured at the spine and hip during strontium ranelate treatment were interpolated from clinical trial data. The long-term retention of strontium in bone was estimated using the International Commission on Radiological Protection (ICRP) strontium retention function modified for use in postmenopausal women. Estimates of the strontium BMD artefact after treatment has stopped were performed on the assumption that the BSC effect accounts for 75% of the total measured BMD change at 3 years. RESULTS: If 75% of the BMD changes are explained by BSC, in the average patient, 3-year treatment leads to a spine BMD artefact of 11.2%, decreasing to 3.8% 10 years after stopping treatment. The BMD artefacts at the total hip and femoral neck sites are smaller by factors of 0.65 and 0.53, respectively. If pre- and post-therapy BMD measurements are available, these predictions can be tailored to the individual patient. On average, 6-month treatment is required for the spine BMD artefact to exceed 3%, the figure adopted as the maximum BMD change caused by bone strontium that has a negligible effect on scan interpretation. Ten years after stopping treatment, 28 months of treatment are required for the residual BMD artefact to still exceed the 3% threshold. CONCLUSIONS: Strontium ranelate treatment lasting for >6 months can affect BMD measurements for many years afterward.

Bone Density↗

[A theoretical model study of open section effect on the mechanical properties of long bone].

The mechanical model of femur mid-diaphysis with a rectangular open section in the exterior cortex was developed and a finite element method was adopted in calculating and analysing the changes of torsional stiffness and the stress distribution when the dimension of the open section altered. It showed that the open section with a length of 1 OD (femur mid-diaphysis diameter) had little influence on the femur torsional stiffness or stress distribution. The torsional stiffness decreased most dramatically as the length increased from 2 to 4 OD. Shear stress peaked at the center of the open section. This conclusion provides an important theoretical ground for the operative methods and the dimension control of an open section in clinical orthopaedics.

Biomechanical Phenomena↗

Loneliness in older persons: a theoretical model and empirical findings.

BACKGROUND: This study examines predictors of loneliness among low-income older adults through a framework named MODEL (Model of Depression and Loneliness), which we developed to address the need for a comprehensive and intervention-oriented theory of loneliness in old age. The framework is rooted in a cognitive-behavioral theory that conceptualizes behaviors as resulting from an interaction of cognitive processes and environmental events. METHODS: 161 residents of five independent-living buildings for low-income older adults in Maryland were interviewed individually. The assessments were based on the theoretical framework, MODEL, which describes the influences that environmental resources, health, and psychological factors have on loneliness and depression. RESULTS: MODEL explained a large percentage of the variance of both loneliness and depressed affect. Of all the barriers examined in the present study, our findings suggest that psychosocial factors/barriers have the strongest influence in the etiology of loneliness. CONCLUSION: In this population of low-income older persons, the importance of new contacts, mobility, and financial resources in predicting loneliness suggests that preventive social services should target these factors in developing opportunities for socialization.

Activities of Daily Living↗

Extension of the Rorschach--Hazlewood theoretical model for spin-lattice relaxation in biological systems to low frequencies.

The water-biopolymer cross-relaxation model, proposed by H. E. Rorschach and C. F. Hazlewood (RH) [J. Magn. Reson. 70, 79 (1986)], explains the Larmor frequency dependence of T1 in many biological systems. However, the RH theory fails at low Larmor frequencies. In this paper, a more general version of the RH theory has been developed. This theory is valid at all frequencies. Use of the new expression for the spin-lattice relaxation rate (1/T1), earlier published experimental data in H2O/D2O bovine serum albumin, which had been measured over a wide frequency range (10 kHz to 100 MHz), were fitted over the entire frequency range. The agreement between theory and the experimental data is excellent. Theoretical expressions for the rotating-frame spin-lattice relaxation rate (1/T1(rho)) were also obtained.

Algorithms↗

Surface pH controls purple-to-blue transition of bacteriorhodopsin. A theoretical model of purple membrane surface.

We have developed a surface model of purple membrane and applied it in an analysis of the purple-to-blue color change of bacteriorhodopsin which is induced by acidification or deionization. The model is based on dissociation and double layer theory and the known membrane structure. We calculated surface pH, ion concentrations, charge density, and potential as a function of bulk pH and concentration of mono- and divalent cations. At low salt concentrations, the surface pH is significantly lower than the bulk pH and it becomes independent of bulk pH in the deionized membrane suspension. Using an experimental acid titration curve for neutral, lipid-depleted membrane, we converted surface pH into absorption values. The calculated bacteriohodopsin color changes for acidification of purple, and titrations of deionized blue membrane with cations or base agree well with experimental results. No chemical binding is required to reproduce the experimental curves. Surface charge and potential changes in acid, base and cation titrations are calculated and their relation to the color change is discussed. Consistent with structural data, 10 primary phosphate and two basic surface groups per bacteriorhodopsin are sufficient to obtain good agreement between all calculated and experimental curves. The results provide a theoretical basis for our earlier conclusion that the purple-to-blue transition must be attributed to surface phenomena and not to cation binding at specific sites in the protein.

Amino Acid Sequence↗

A theoretical model of the high-frequency arrhythmogenic depolarization signal following myocardial infarction.

Theoretical body-surface potentials were computed from single, branching and tortuous strands of Luo-Rudy dynamic model cells, representing different areas of an infarct scar. When action potential (AP) propagation either in longitudinal or transverse direction was slow (3-12 cm/s), the depolarization signals contained high-frequency (100-300 Hz) oscillations. The frequencies were related to macroscopic propagation velocity and strand architecture by simple formulas. Next, we extended a mathematical model of the QRS-complex presented in our earlier work to simulate unstable activation wavefront. It combines signals from different strands with small timing fluctuations relative to a large repetitive QRS-like waveform and can account for dynamic changes of real arrhythmogenic micropotentials. Variance spectrum of wavelet coefficients calculated from the composite QRS-complex contained the high frequencies of the individual abnormal signals. We conclude that slow AP propagation through fibrotic regions after myocardial infarction is a source of high-frequency arrhythmogenic components that increase beat-to-beat variability of the QRS, and wavelet variance parameters can be used for ventricular tachycardia risk assessment.

Arrhythmias, Cardiac↗

Testing a theoretical model for examining the relationship between family adjustment and expatriates' work adjustment.

Based on theoretical perspectives from the work/family literature, this study tested a model for examining expatriate families' adjustment while on global assignments as an antecedent to expatriates' adjustment to working in a host country. Data were collected from 110 families that had been relocated for global assignments. Longitudinal data, assessing family characteristics before the assignment and cross-cultural adjustment approximately 6 months into the assignment, were coded. This study found that family characteristics (family support, family communication, family adaptability) were related to expatriates' adjustment to working in the host country. As hypothesized, the families' cross-cultural adjustment mediated the effect of family characteristics on expatriates' host-country work adjustment.

Adult↗

[Scientific theoretical models in dentistry].

Developments leading to modern medicine only began about 150 years ago. The foundation of this progress was laid by the introduction of scientific working methods into practical and theoretical medicine. The principal methodical procedures are described in the present work, defined and examined as to its scientific basis. Examples from dental, oral, and maxillo-facial surgery are given as proof that the models used in the definition of present day biological research are helpful not only give accuracy to content recognized by scientific method but also to assure transition from theoretical to practical science.

Dental Articulators↗

Sexual addiction, sexual compulsivity, sexual impulsivity, or what? Toward a theoretical model.

We critically review the concepts of sexual addiction, sexual compulsivity, and sexual impulsivity and discuss their theoretical bases. A sample of 31 self-defined sex addicts were assessed by means of interview and questionnaires and compared with a large age-matched control group. A tendency to experience increased sexual interest in states of depression or anxiety was strongly characteristic of the sex addict group. Dissociative experiences were described by 45% of sex addicts and may have some explanatory relevance. Obsessive-compulsive mechanisms may be relevant in some cases, and the addiction concept may prove to be relevant with further research. Overall, results suggested that out of control sexual behavior results from a variety of mechanisms. We propose an alternative theoretical approach to investigating these mechanisms based on the dual control model and recent research on the relation between mood and sexuality.

Adult↗

Testing a theoretical model: correlates of parental stress responses in the pediatric intensive care unit.

This study was designed to evaluate a theoretical framework, based on stress theory, which identifies potential sources of stress in parents of children hospitalized in an intensive care unit (ICU). The framework suggests that personal, situational, and ICU environmental stress stimuli interactively impact on the overall parental stress response. Multiple regression techniques were used to evaluate the interaction of personal family factors, situational stimuli, and ICU environmental stressors and to assess their impact upon the overall parental stress response. Data were collected from 510 parents of children hospitalized in one of five midwestern ICUs. Instruments used were the Parental Stressor Scale: Pediatric ICU (Carter & Miles, 1984), the State-Trait Anxiety Scale (Spielberger, Gorsuch, & Luschene, 1970), the Review of Life Experiences Scale (Hurst, Jenkins, & Rose, 1978), and a personal-experiential questionnaire. Results indicate that a number of personal and situational variables were predictive of higher stress. In addition two aspects of the ICU environment contributed the most variance to the overall stress of parents: alterations in the parental role and the child's behavioral and emotional responses. In evaluating the full framework, one personal variable (Trait Anxiety); two situational variables (perception of severity and type of admission); and three ICU environmental dimensions, (parental role alteration, the child's behavior and emotional response, and the child's appearance) significantly predicted stress (State Anxiety). The findings support the theoretical framework underlying this study as a useful model for studying and evaluating parental stress during a child's admission to an ICU. Results also suggest that additional personal family and situational factors, such as uncertainty, may need to be added to the model to more fully predict parental stress responses.

Adolescent↗

Theoretical model of ruminant adipose tissue metabolism in relation to the whole animal.

Based on theoretical considerations and experimental data, estimates of contributions of adipose tissue to energy expenditures in a lactating cow and a growing steer were developed. The estimates indicate that adipose energy expenditures range between 5 and 10% of total animal heat production dependent on productive function and diet. These energy expenditures can be partitioned among maintenance (3%), lipogenesis (1-5%) and lipolysis and triglyceride resynthesis (less thatn 1.0%). Specific sites at which acute and chronic effectors can act to produce changes in adipose function, and changes in adipose function produced by diet and during pregnancy, lactation and aging were discussed with emphasis being placed on the need for additional, definitive studies of specific interactions among pregnancy, diet, age, lactation and growth in producing ruminants.

Adipose Tissue↗

Theoretical modeling of DNA-monocationic lexitropsin complexation: influence of ligand binding on DNA curvature.

A theoretical study is presented on the complexation to DNA of a monocationic lexitropsin. Energetics and the structures of the complexes formed are analyzed for three base pair sequences of a nucleic acid octamer. The influence of the ligand binding on the nucleic acid conformation is analysed in detail. It is found that whereas the uncomplexed nucleic acid segments have very irregular structures with an overall curvature varying between 15 degrees and 20 degrees, the DNA structure becomes more regular and the curvature is strongly reduced upon the binding of a monocationic lexitropsin.

Computer Simulation↗