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PubMed2003

A model of physical factors in the structural adaptation of microvascular networks in normotension and hypertension.

Adequate function of the microcirculation is vital to any tissue. To maintain an optimal function, microvascular networks must be able to adapt structurally to changes in the physical environment. Here we present a mathematical network model based on vessel wall mechanics. We assume based on experimental observations that longstanding change in transmural pressure elicits a change in the vascular wall-to-lumen ratio for maintaining circumferential wall stress at a certain level. In addition, experimental observations show that chronic change in fluid shear stress at the vascular wall elicits a persistent change in luminal diameter. On this basis we hypothesize that wall influencing substances released from the endothelium in response to shear stress have a certain optimal level in the vascular wall. Deviation from this level will cause vascular remodeling, i.e. a structural change in luminal diameter, until equilibrium is restored. The model explains several of the key features observed experimentally in the microcirculation in normotension and hypertension. Most importantly, it suggests a scenario where overall network structure and network hemodynamics depend on adaptation to local hemodynamic stimuli in the individual vessel. Simulated results show emanating microvascular networks with properties similar to those observed in vivo. The model points to an altered endothelial function as a key factor in the development of vascular changes characteristic of hypertension.

Adaptation, Physiological↗
PubMed1980

Social adjustment of the elderly residing in institutional homes: a multivariate analysis.

An attempt was made to determine the order of magnitude of a number of variables which a bivariate analysis had demonstrated to show some degree of correlation with the way in which institutionalized elderly individuals adapt socially. To determine the multivariate impact of all these variables on the degree of social adjustment to life in a home, a path model was developed that permitted detection of both the direct and indirect effect of the variables. It was found that loneliness was the main factor underlying failure to adjust. Furthermore, widowhood and being alone seem to have a considerable influence. The degree of disability and the age of the individual proved to have a smaller impact than we had assumed to be the case. The operationalized model explains 27% of the variance of the social adjustment in a home for the elderly.

Aged↗
PubMed1999

Self-organized criticality in termite architecture: a role for crowding in ensuring ordered nest expansion

A cellular automaton model of the vertical and lateral growth that occurs in a termite nest expansion is formulated. The model consists of a lattice of building sites permeated by a trail network of termites. Termites are recruited from the network to build at these sites by an attractive pheromone which emanates from building pellets. The experimentally observed behaviour in which termites halt and then retreat from overcrowded sites is also incorporated along with the assumption that termites which retreat then build on nearby sites. Simulations without this response to crowding result in disordered, unrealistic nest structures, while its inclusion qualitatively reproduces two previously unexplained features of nest expansion. First, the active surface formed by joining the tips of growing pillars maintains a smooth appearance through time. Second, the model explains how building activity spreads laterally over the building domain. The competition between the attractive pheromone and inhibitory crowding stimuli drives the system to a critical state where the correlation length (distance over which building sites interact) diverges, i.e. all building sites interact with each other. An explicit mapping of a particular case of the model onto the sandpile model of self-organized criticality is exhibited. The criticality of the model determines power-law scalings of the system's dependence on the density of termites on the trail network and the size of the building domain. The model makes several experimentally testable predictions. Copyright 1999 Academic Press.

Journal Article↗
PubMed1989

A covariance structure model test of antecedents of adolescent alcohol misuse and a prevention effort.

As part of an alcohol misuse prevention evaluation, questionnaires were administered to 4,157 junior high school students to determine levels of alcohol misuse, exposure to peer use and misuse of alcohol, susceptibility to peer pressure, internal health locus of control, and self-esteem. A conceptual model of the antecedents of adolescent alcohol misuse and the effectiveness of a prevention effort was tested using covariance structure modeling techniques. The factor loadings for the model were all moderate to high, indicating that the observed variables served well as measurement instruments for the latent variables. The hypothesized structural relationships among the latent variables of alcohol misuse, exposure to peer use and misuse of alcohol, susceptibility to peer pressure, internal health locus of control, and self-esteem were supported by the data. The full model explained 45 percent of the variance in alcohol misuse in the analysis based on the total sample. The direct effect of the intervention on alcohol misuse was small but significant in the hypothesized direction. The direct effects of the intervention on susceptibility to peer pressure and internal health locus of control were not significant. The model was tested separately for groups of students who had high versus low scores on susceptibility to peer pressure in order to test the interaction between susceptibility to peer pressure and exposure to peer use and misuse of alcohol. The percentage of variance accounted for in alcohol misuse did not increase upon testing the model separately for students who had high versus low scores on susceptibility to peer pressure. Observed differences in the significance of the parameter estimates between the high and low susceptibility to peer pressure groups suggest that different approaches to the design and evaluation of substance abuse prevention programs may be necessary for different subgroups of students.

Alcoholism↗
PubMed1988

A thermodynamic model for force integration and microtubule assembly during axonal elongation.

We present here a thermodynamic model for tension and compression forces within axons (neurites) of the specific neural-cell line, PC 12, which seems generally applicable to neuronal growth. We suggest that these forces play a crucial role in microtubule assembly during axonal elongation. The Gibbs free energy change for the axonal elongation phase of neuronal growth is modeled as the sum of the extensional work for pulling on a random actin network, work of assembly for compressed microtubules and surface energy terms. This model explains the results of previously published experiments concerning axonal stability and microtubule polymerization and has been used to predict other phenomena.

Axons↗
PubMedDate not supplied

A panel study of physical activity in Taiwanese youth: testing the revised health-promotion model.

The rate of inactivity among young people in Taiwan remains high. However, few studies have explored physical activity patterns with a longitudinal approach in this population. Based on the revised health-promotion model, this study used 2-wave panel data to test a structural model of how individual characteristics, cognitions, and interpersonal influences predicted physical activity of Taiwanese adolescents. The findings suggest that gender, social support, modeling, self-efficacy, and perceived benefits and barriers to performing physical activity directly and indirectly influence the behavior of physical activity in Taiwanese adolescents. The hypothesized model explained 25% of the variance in physical activity. The implications for parents and policy are discussed.

Adolescent↗
PubMed1991

Herpes simplex virus latency in the nervous system--a new model.

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.

Animals↗
PubMed1981

Phrenic activity, respiratory pressures, and volume changes in cats.

In eight anesthetized cats we measured the integrated ("moving time average") phrenic activity [using phrenic electroneurogram (EPHR)] and the active transdiaphragmatic pressure [Pdi(mus)] during room air breathing, hypoxia, and hypercapnia. The relationship between Pdi(mus) and EPHR was unaffected by either hypoxic or hypercapnic stimulation of breathing, suggesting that in spontaneously breathing cats the pressure losses are negligible. In all cats, however, there was a substantial volume-related decrease in Pdi(mus), indicating that with increasing lung volume the effectiveness of the diaphragm as a pressure generator decreases. In addition, we have developed a model that allows prediction of the time course changes in lung volume for different morphology of inspiratory driving pressure. This model explains many of the features of control of breathing found experimentally in our cats.

Animals↗
PubMed1990

Depression among the homeless.

Very little is known about one of the most common mental health problems facing the homeless: high levels of depressive symptomatology. This paper explains variation in the prevalence of depressive symptoms (CES-D) for a random sample of 150 shelter- and street-based homeless persons in the Birmingham metropolitan area. Fifty-nine percent of the sample show the signs of "probable clinical caseness"; yet there is significant variation in the level of symptomatology. A modified version of the social resources model explains 31 percent of the variation in CES-D scores. Although psychological resources play an important role in the distress outcome, as predicted, social supports are found to have limited impact on depression. Life circumstances have significant direct effects on depression. Persons with previous histories of mental illness and with extensive life event histories are more susceptible to distress. Younger persons, the chronically homeless, the street-based homeless, the sick, and the less educated are also more likely to experience depression. This study suggests the importance of understanding homelessness both as a psychological condition and as a complex set of life circumstances and physical deprivations.

Adult↗
PubMed2004

Myometrial progesterone responsiveness and the control of human parturition.

OBJECTIVE: The goal of this review is to assess the body of literature addressing the mechanism of progesterone withdrawal in the control of human parturition and in particular the recent advances in testing the hypothesis that human parturition is initiated by decreased myometrial responsiveness to progesterone, ie, functional progesterone withdrawal. METHODS: Published studies of progesterone responsiveness of the pregnant human myometrium in the context of parturition control were reviewed. RESULTS: Advances in understanding the molecular basis for progesterone receptor (PR)-mediated control of progesterone responsiveness has led to the hypothesis that functional progesterone withdrawal in human parturition is mediated by specific changes in myometrial PR expression, function, or both. The human PR exists as two major subtypes, PR-A and PR-B. As PR-A represses progesterone actions mediated by PR-B, the extent of progesterone responsiveness is inversely related to the PR-A/PR-B expression ratio. In women, the onset of term labor is associated with a significant increase in the myometrial PR-A/PR-B expression ratio that may facilitate functional progesterone withdrawal. Interestingly, expression of the estrogen receptor-alpha (ERalpha) increases concordantly with the PR-A/PR-B expression ratio in nonlaboring myometrium. This finding indicates that functional estrogen activation and functional progesterone withdrawal are linked. CONCLUSION: Functional progesterone withdrawal in human parturition is likely mediated by an increase in the myometrial PR-A/PR-B expression ratio and possibly by modulation of coactivator and corepressor proteins. Functional progesterone withdrawal appears to induce functional estrogen activation. Thus, for most of pregnancy, progesterone may decrease myometrial estrogen responsiveness by inhibiting ERalpha expression. Such an interaction would explain why the human myometrium is refractory to the high levels of circulating estrogens for most of pregnancy. At term, functional progesterone withdrawal removes the suppression of ERalpha expression leading to an increase in ERalpha and a concomitant increase in myometrial estrogen responsiveness. Estrogen can then act to transform the myometrium to a contractile phenotype. This model explains why disruption of progesterone action alone triggers the full parturition cascade. The link between functional progesterone withdrawal and functional estrogen activation may be a critical mechanism for the endocrine control of human parturition.

Estrogens↗
PubMed2004

Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation.

Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG and PKC), to which PDK1 also belongs. Recent data suggests that PDK1 specificity is achieved by regulation of its interaction with substrates and supports a rather simple model explaining how PDK1 interacts with different substrates. The data further suggests that PDK1 interacts with its substrates when they are in a particular conformation (inactive). PDK1 has the ability to recognize, interact with and phosphorylate specific substrate conformations and thus sets PDK1 at the centre of a protein conformation sensor mechanism. The PDK1-substrate interaction model describes, at a molecular level, the mechanism used by PDK1 to sense the conformation of its substrates.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2000

A model of the perceived relative positions of moving objects based upon a slow averaging process.

We extend the local energy model of position detection to cope with temporally varying position signals and the perception of relative position. The extension entails two main components. First, a form of persistence for the position signal based on the temporal impulse response function of the visual system. Secondly, we hypothesise that the perceived relative position of two objects is determined by a slow average of the difference of the objects' position signals. The model explains why briefly flashed static dots are perceived to lag behind continuously visible moving dots, without the need for a motion extrapolation process [Nijhawan, R. (1994). Nature, 370, 256-257]. The dependence of this illusion on parameters such as the velocity, duration, frequency and number of flashes of the motion trajectories is accurately captured by the model. Furthermore, the model makes two predictions. First, briefly flashed dots on a staircase trajectory should lead dots with a long duration. Secondly, it should be possible to abolish the lag-effect between continuously visible and stroboscopically moving objects by halting the continuously visible dots during the interflash interval of the stroboscopic dots. Both predictions are corroborated in experiments.

Computer Simulation↗
PubMed2006

A land use regression model for predicting ambient concentrations of nitrogen dioxide in Hamilton, Ontario, Canada.

This paper reports on the development of a land use regression (LUR) model for predicting the intraurban variation of traffic-related air pollution in Hamilton, Ontario, Canada, an industrial city at the western end of Lake Ontario. Although land use regression has been increasingly used to characterize exposure gradients within cities, research to date has yet to test whether this method can produce reliable estimates in an industrialized location. Ambient concentrations of nitrogen dioxide (NO2) were measured for a 2-week period in October 2002 at > 100 locations across the city and subsequently at 30 of these locations in May 2004 to assess seasonal effects. Predictor variables were derived for land use types, transportation, demography, and physical geography using geographic information systems. The LUR model explained 76% of the variation in NO2. Traffic density, proximity to a highway, and industrial land use were all positively correlated with NO2 concentrations, whereas open land use and distance from the lake were negatively correlated with NO2. Locations downwind of a major highway resulted in higher NO2 levels. Cross-validation of the results confirmed model stability over different seasons. Our findings demonstrate that land use regression can effectively predict NO2 variation at the intraurban scale in an industrial setting. Models predicting exposure within smaller areas may lead to improved detection of health effects in epidemiologic studies.

Air Pollutants, Occupational↗
PubMed1997

Does case mix matter for substance abuse treatment? A comparison of observed and case mix-adjusted readmission rates for inpatient substance abuse treatment in the Department of Veterans Affairs.

OBJECTIVE: To develop a case mix model for inpatient substance abuse treatment to assess the effect of case mix on readmission across Veterans Affairs Medical Centers (VAMCs). DATA SOURCES/STUDY SETTING: The computerized patient records from the 116 VAMCs with inpatient substance abuse treatment programs between 1987 and 1992. STUDY DESIGN: Logistic regression was used on patient data to model the effect of demographic, psychiatric, medical, and substance abuse factors on readmission to VAMCs for substance abuse treatment within six months of discharge. The model predictions were aggregated for each VAMC to produce an expected number of readmissions. The observed number of readmissions for each VAMC was divided by its expected number to create a measure of facility performance. Confidence intervals and rankings were used to examine how case mix adjustment changed relative performance among VAMCs. DATA COLLECTION/EXTRACTION METHODS: Ward where care was provided and ICD-9-CM diagnosis codes were used to identify patients receiving treatment for substance abuse (N = 313,886). PRINCIPAL FINDINGS: The case mix model explains 36 percent of the observed facility level variation in readmission. Over half of the VAMCs had numbers of readmissions that were significantly different than expected. There were also noticeable differences between the rankings based on actual and case mix-adjusted readmissions. CONCLUSIONS: Secondary data can be used to build a reasonably stable case mix model for substance abuse treatment that will identify meaningful variation across facilities. Further, case mix has a large effect on facility level readmission rates for substance abuse treatment. Uncontrolled facility comparisons can be misleading. Case mix models are potentially useful for quality assurance efforts.

Adult↗
PubMedDate not supplied

Statistical models of outcome in malpractice lawsuits involving death or neurologically impaired infants.

The objective was to determine whether factors could be identified in medical and legal records that are associated with the successful defense of obstetrical malpractice cases involving the death or neurological impairment of infants. Obstetrical claims (169) closed by PROMUTUAL between January 1, 1990, and December 31, 1994, were retrospectively abstracted and analyzed to identify associations between medical and legal factors, and the medicolegal outcome. Multivariable analysis identifies that the use of pitocin, diagnosis of asphyxia, a delay in delivery, and the use of multiple defense expert witnesses decreased the chances of a successful defense. Two statistical models explaining indemnity payment were developed. The first, based on medical outcome, showed an increased indemnity payment when a case involved major neurological deficits, diagnosis of asphyxia, newborn seizures, later year of delivery, and participation of a particular defense firm. Perinatal or childhood death and the use of pitocin were indicators of a decrease in payment. The second model was based on long-term care requirements. In this model, indicators of increased indemnity payment were: nonreassuring intrapartum fetal heart rate tracing, later year of delivery, intensity of long-term care required, and participation of a particular defense law firm. Perinatal or childhood death, the use of pitocin, and settlement date increasingly removed from the occurrence date were the determinants of decreased payments in this model. Finally, the presence of major neurological deficits, the prolongation of a case, and the involvement of multiple law firms and defense witnesses increased the expense charged to and paid by the insurance company. Using the medical, legal, and financial data relevant to 169 obstetrical cases closed by one malpractice insurance carrier between 1990 and 1994, statistical models with potential predictive values for future malpractice claims involving neurologically impaired infants were constructed. These models may help determine in advance the chance a future case has for successful defense and the likely amount of expense and indemnity dollars that will be paid out to settle and defend it.

Adolescent↗
PubMed1981

Toward understanding elders' health service utilization.

Providing appropriate health services to the elderly is emerging as one of the major challenges of this decade. Using the theoretical framework developed by Andersen and Aday, this study attempts to improve our understanding of those factors which inhibit or facilitate elders' use of health services. The data come from a 1974 statewide random probability sample of 1,625 noninstitutionalized elders 65 years of age or older living in Massachusetts. Regression analysis is used to study the effects of predisposing, enabling, and need characteristics on the use of five health services: hospitals, physicians, dentists, home care, and ambulatory care. The model explains from 5% to 27% of the variance in health service utilization. Need characteristics, in general, account for most of the explained variance.

Aged↗
PubMed1994

How muscle may contract.

A new molecular model is proposed for muscle contraction, that involves the electrical charging of the long (C-terminal) alpha-helical part of the head of the myosin molecule (S1) while the head is attached to actin; as it charges the alpha-helical part moves in the radial electric field between the filaments. The alpha-helical part snaps back when the myosin molecule is discharged electrically, at the moment that ATP binds to the active enzymatic site. This snap-back model explains several puzzling phenomena in contractility, as well as providing a physical explanation for the origin of an impulsive force that drives muscle contraction.

Actins↗