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PubMed1997

The pathophysiology of giant SEPs in cortical myoclonus: a scalp topography and dipolar source modelling study.

Somatosensory evoked potential (SEP) recordings in patients suffering from cortical myoclonus (CM) are characterised by evidence of abnormally enhanced scalp components. Our aim was to verify whether enhanced activity in giant SEPs arises from the same generators as in healthy subjects. We used the brain electrical source analysis (BESA) to compare scalp SEP generators of healthy subjects to those calculated in 3 patients with CM of varying causes. Firstly, we built a 4-dipole model explaining scalp distribution of early SEPs in normal subjects and then applied it to traces recorded from CM patients. Our model, issued from the right median nerve grand average and applied also to recordings from single individuals, included a dipole at the base of the skull and three other perirolandic dipoles. The first of the latter dipoles was tangentially oriented and was active at the same latencies as the N20/P20 potentials and, with opposite polarity, the P24/ N24 responses; the second dipole explained the central P22 distribution and the third had a peak of activity corresponding to the N30 component. When we applied our 4-dipole model to CM recordings, the first perirolandic dipole had a third peak of activity in all patients at the same latency as a parietal negativity and a frontal positivity, both following giant P24/N24 components; on the other hand, in one patient the second perirolandic dipole showed a later activation corresponding to a high central negativity, following a giant P22 response. We suggest that only the initial giant SEPs correspond to physiological potentials evoked in healthy subjects. The occurrence of late giant SEPs could be explained by hyperpolarization, following the postsynaptic excitatory potentials responsible for the early giant components.

Adult↗

PubMed2004

Derivation of preliminary three-dimensional pharmacophoric maps for chemically diverse intravenous general anaesthetics.

BACKGROUND: The molecular basis of i.v. general anaesthetic activity was investigated using comparative molecular field analysis (CoMFA). METHODS: The free plasma concentrations that abolish movement to a noxious stimulus for 14 structurally diverse i.v. anaesthetics were obtained from the literature. The compounds were randomly divided into a training set (n=10) to derive the activity model, and a separate test set (n=4) used to assess its predictive capability. The anaesthetic structures were aligned so as to maximize their similarities in molecular shape and electrostatic potential to conformers of the most active agent in the group, eltanolone. The conformers and alignments that showed the maximum similarity (calculated using combined Carbo indices) were retained, and used to derive the CoMFA models. RESULTS: The final model explained 94.0% of the variance in the observed activities of the training set (n=10, P<0.0001) and was a good predictor of test set activity (n=4, r(2)=0.799). In contrast, a model based on non-polar solubility (LogP) explained only 78.3% of the variance in the observed activities of the training set (n=10, P=0.0007) and was a poor predictor for the test set (n=4, r(2)=0.272). Further analysis of the CoMFA results identified the spatial distribution of key areas where steric and electrostatic interactions are important in determining the activity of the 14 anaesthetics considered. CONCLUSIONS: A single activity model can be formulated for i.v. general anaesthetics and preliminary pharmacophoric maps derived, which describe the molecular basis of their in vivo potency.

Anesthetics, Intravenous↗

PubMedDate not supplied

Allometric scaling of strength in an independently living population age 55-86 years.

Most physiological functions vary allometrically with body size; however, few investigators have examined the relationship between strength and body size with allometric scaling. Thus, we hypothesized that allometric analysis would reveal that both the amount and quality of muscle are significant determinants of strength in the elderly. Allometric analyses were used to determine the influence of limb cross-sectional area (CSA), physical activity, demispan (distance between index-middle finger web and the sternal notch), leg length, and sex on grip and plantar flexor strength in men (n = 188) and women (n = 205) age 55-86 years. Physical activity was measured using a self-reporting questionnaire (Taylor et al. [1978] J Chron Dis 31:741-755). Forearm and leg CSA was estimated from anthropometry. There was an age-related decline in grip strength, independent of forearm CSA, demispan, and sex, equal to approximately 12% per decade, whereas plantar flexor strength adjusted for leg CSA, physical activity, and sex was reduced at a rate of approximately 15% per decade. The allometric models explained 71.4% (r = 0.845) and 38.8% (r = 0.623) of the variance in grip and plantar flexor strength, respectively. Model parameters were identified using multiple linear regression (P < 0.05). Thus, grip strength = forearm CSA(0.435). demispan(0.161). exp(3.905 - 0.012 age + 0.413 sex) and plantar flexor strength = leg CSA(0.223). physical activity (0.115). exp(5.867 - 0.015 age + 0.366 sex). These findings indicate that age-related reductions in muscle CSA do not fully account for strength declines with age. Physical activity is also important and partially explains these reductions.

Activities of Daily Living↗

PubMed1999

Sympathetic activation in heart failure and its treatment with beta-blockade.

Multiple models explaining the pathogenesis of heart failure have been put forth during the past 5 decades. These models were modified as clinical evidence supported or refuted their assumptions. During the past 2 decades, heart failure models emphasized the importance of neurohormonal systems in heart failure progression. The positive impact that angiotensin-converting enzyme inhibitors have had on mortality from heart failure has bolstered the neurohormonal theory. Attention recently has turned to the sympathetic nervous system and its potential deleterious effects on the cardiovascular system in heart failure. The sympathetic nervous system can negatively impact the cardiovascular system in heart failure in several ways, including down-regulating beta1-receptors, exerting direct toxic effects on the myocardium, and contributing to myocardial remodeling and life-threatening arrhythmias. Beta-adrenergic blockers have shown promise for reducing morbidity and mortality in heart failure, but definitive reductions in mortality remain to be shown by future investigations.

Adrenergic beta-Antagonists↗

PubMed1992

Interpretation of the X-ray diffraction pattern from relaxed skeletal muscle and modelling of the thick filament structure.

The first part of this paper is devoted to the model-building studies of our high resolution meridional X-ray diffraction patterns (in the region from 1/500 to 1/50 A-1) obtained from relaxed frog muscle. A one-dimensional model of thick filament was proposed which basically consists of two symmetrical arrays of 50 crossbridge crown projections. In the proximate and central zones of the filament the crossbridge crowns are regularly shifted with a 429 A period and appear as triplets with a 130 A distance between crowns, while the crowns in the distal parts of filament are regularly ordered with a 143 A repeat. The centre-to-centre distance between regions with crossbridge perturbations is 7050 A. The length of each crown projection is about 125 A. The model includes also (1) C-protein component represented in each half of the filament by seven stripes of about 350 A long and located 429 A apart, (2) a uniform density of filament backbone of about 1.5 micron length, and (3) 13 high density stripes in a central zone located with 223 A period. The final model explains very well the positions and intensities of the main meridional reflections. A three-dimensional model of crossbridge configuration is described in the second part of the work. The model was constructed by using the intensity profiles of the first six myosin layer lines of the X-ray pattern from stretched muscle and taking into account the crossbridge perturbations and the axial size of crossbridge crown obtained from the one-dimensional studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

PubMed1992

A mechanistic model for morphogenesis and regeneration of limbs and imaginal discs.

When an amphibian limb, cockroach leg or Drosophila imaginal disc is subjected to a surgical operation, it is capable of regenerating or duplicating certain parts. Although the structure of the regenerated tissue varies depending on the location and mass of the amputated or transplanted part, it can be predicted from a set of formal rules, called the polar coordinate model [French et al., (1976) Science 193, 969-983; Bryant et al., (1981) Science 212, 993-1002]. In the polar coordinate model, it is assumed (and experimentally proven) that the juxtaposition of normally non-adjacent cells stimulates cell proliferation locally, which implies that the underlying mechanism which gives positional values to each cell, is also responsible for the control of cell growth. Because locally activated proliferation alters the shape and size of the developmental field, the question of how to control the cell growth is the central problem in the regeneration of the limbs and imaginal discs. In this paper, I propose a possible underlying mechanism for the 'polar coordinate rules', and show how this mechanistic model explains the experimental results using computer simulation. The proposed mechanism is an extension of Turing's model (1952). In addition to the reaction-diffusion of the molecules, cell proliferation is taken into consideration. With appropriate initial conditions, the computer simulation shows that a small mass of cells grows up to form a mature limb, and that the mature limb is able to respond to surgical operations as predicted by the polar coordinate model.

Amphibians↗

PubMed2005

Estimating ground-level PM2.5 in the eastern United States using satellite remote sensing.

An empirical model based on the regression between daily PM2.5 (particles with aerodynamic diameters of less than 2.5 microm) concentrations and aerosol optical thickness (AOT) measurements from the multiangle imaging spectroradiometer (MISR) was developed and tested using data from the eastern United States during the period of 2001. Overall, the empirical model explained 48% of the variability in PM2.5 concentrations. The root-mean-square error of the model was 6.2 microg/m3 with a corresponding average PM2.5 concentration of 13.8 microg/m3. When PM2.5 concentrations greater than 40 microg/m3 were removed, model results were shown to be unbiased estimators of observations. Several factors, such as planetary boundary layer height, relative humidity, season, and other geographical attributes of monitoring sites, were found to influence the association between PM2.5 and AOT. The findings of this study illustrate the strong potential of satellite remote sensing in regional ambient air quality monitoring as an extension to ground networks. With the continual advancement of remote sensing technology and global data assimilation systems, AOT measurements derived from satellite remote sensors may provide a cost-effective approach as a supplemental source of information for determining ground-level particle concentrations.

Air Movements↗

PubMedDate not supplied

Maternal morbidity in rural upper Egypt: levels, determinants, and care seeking.

Although maternal morbidity constitutes a serious public health problem in Egypt, it has remained a neglected area for public health research. In this study we used a synthetic design combining quantitative and qualitative methods to determine the level of maternal morbidity as reported by mothers in rural Upper Egypt and to identify patterns and determinants of care seeking for perceived morbidity in pregnancy, childbirth, and the postpartum period. The reported incidence of danger symptoms indicated that maternal morbidity is a serious problem in Egypt and, therefore, warranted community-based interventions. The study suggested a model explaining the criteria women used to judge whether and from where they would seek care. The model incorporates three cognitive components related to the perceived frequency, and seriousness of the problem and the degree of personal responsibility for the problem. Utilization of care was shown to be low and significantly associated with poverty and husband illiteracy. Likewise, most deliveries were not attended by a trained health care workers, and these unattended deliveries were shown to be associated with nonutilization of antenatal care, illiteracy, nonownership of cattle, and inaccessibility to potable water.

Adult↗

PubMed2005

Modeling genome evolution with a diffusion approximation of a birth-and-death process.

MOTIVATION: In our previous studies, we developed discrete-space birth, death and innovation models (BDIMs) of genome evolution. These models explain the origin of the characteristic Pareto distribution of paralogous gene family sizes in genomes, and model parameters that provide for the evolution of these distributions within a realistic time frame have been identified. However, extracting the temporal dynamics of genome evolution from discrete-space BDIM was not technically feasible. We were interested in obtaining dynamic portraits of the genome evolution process by developing a diffusion approximation of BDIM. RESULTS: The diffusion version of BDIM belongs to a class of continuous-state models whose dynamics is described by the Fokker-Plank equation and the stationary solution could be any specified Pareto function. The diffusion models have time-dependent solutions of a special kind, namely, generalized self-similar solutions, which describe the transition from one stationary distribution of the system to another; this provides for the possibility of examining the temporal dynamics of genome evolution. Analysis of the generalized self-similar solutions of the diffusion BDIM reveals a biphasic curve of genome growth in which the initial, relatively short, self-accelerating phase is followed by a prolonged phase of slow deceleration. This evolutionary dynamics was observed both when genome growth started from zero and proceeded via innovation (a potential model of primordial evolution), and when evolution proceeded from one stationary state to another. In biological terms, this regime of evolution can be tentatively interpreted as a punctuated-equilibrium-like phenomenon whereby evolutionary transitions are accompanied by rapid gene amplification and innovation, followed by slow relaxation to a new stationary state.

Algorithms↗

PubMed2005

Altering state policy: interest group effectiveness among state-level advocacy groups.

Because social policy making continues to devolve to the state level, social workers should understand how advocacy and policy making occur at that level. Interest groups active in the human services arena were surveyed and data were used to test a model of interest group effectiveness in four states. The independent variables were amount of resources invested, strategy used, relationships with key actors, use of coalitions, and policy positions taken. Results indicate that the model explains low to middling amounts of the variation in group effectiveness. Results also show that the model fits different states to different degrees, indicating that social workers need to approach advocacy in different ways to achieve maximum effectiveness in altering state policy. Implications for altering state policy are provided.

Consumer Advocacy↗

PubMed1991

An evaluation of the Johnson Behavioural System Model of Nursing.

In this paper the authors evaluate the Johnson Behavioural System Model of Nursing by applying the assessment criteria described in an earlier paper. Data for the evaluation were collected by one of the authors (W.R.) at the UCLA Neuropsychiatric Institute and Hospital, and the UCLA School of Nursing, Los Angeles. The major focus of this paper relates to how nurses at the above facilities apply the Johnson Behavioural System Model of Nursing and how that relates to the questions posed in a previous paper which should be asked by clinicians when assessing the relevance of a model to clinical nursing practice: namely, (a) to what extent does the model assist with the identification of the range of human responses to actual or potential health problems? (b) How does the model enable a nursing diagnosis to be made, and what is the basis of that diagnosis? (c) Does the model explain why individuals respond to health problems in the way that they do? (d) Does the model inform clinicians of the nursing interventions required to enable the client to move towards optimum health? (e) Does the model help to provide an understanding of the desired outcome of nursing intervention?

Adolescent↗

PubMed2000

Prediction of the mediastinal drainage after coronary artery bypass surgery.

Using multiple correlation and linear regression approaches, we investigated the association between the amount of mediastinal drainage for the first 24 postoperative hours and clinical variables as well as multiple haematological tests performed at three time points: before anaesthesia induction, 10 minutes after protamine administration and just after skin closure, on 46 patients undergoing primary coronary artery bypass grafting. Three models from the three times were then developed to predict mediastinal drainage. The number of internal mammary grafts, the total number of grafts and plasma fibrinogen concentration were useful predictors of mediastinal drainage at all three times. The platelet count taken only after skin closure was found to provide additional predictive information. Each regression model explained approximately 60% of the variation in postoperative mediastinal drainage. The information obtained from these predictive models is useful in defining high-risk populations.

Aged↗

PubMed2004

Derivation of preliminary three-dimensional pharmacophores for nonhalogenated volatile anesthetics.

We investigated the molecular basis for the immobilizing activity of nonhalogenated volatile anesthetics by using comparative molecular field analysis (CoMFA). In vivo potency data (expressed as minimum alveolar anesthetic concentrations) for 38 structurally diverse drugs were obtained from the literature. The anesthetics were randomly divided into a training-set (n = 28) used to formulate the activity models and a test-set (n = 10) used to independently assess the models' predictive power. The anesthetic structures were aligned to maximize their similarity in molecular shape and electrostatic potential to conformers of the most active drug in the group: hexanol. The individual conformers and alignments with maximum similarity (calculated with combined Carbo indices) were retained and used to derive the CoMFA activity models. The final CoMFA model explained 95.5% of the variance in the observed activities of the training-set anesthetics. The model had good predictive capability for both the training-set drugs (cross-validated r(2) = 0.824) and the randomly excluded test-set anesthetics (r(2) = 0.921). Pharmacophoric maps were derived by identifying the spatial distribution of key areas in which steric and electrostatic interactions are important in determining the immobilizing activity of the anesthetics considered.

Anesthetics, Inhalation↗

PubMed2000

Menarche, sexual practices, and pregnancy: model testing.

Rates of adolescent pregnancy and childbearing, while in slight decline in the United States since 1992, remain high enough to warrant significant national concern. Birth rates, however, remain particularly high for minority adolescents. One hundred fifty-two records of African American and Latina adolescents receiving prenatal care from nurse midwives at an inner city university clinic were reviewed to partially test a developmental maturity model of pregnancy using logistic regression. The relationships between age at menarche to sexual practices and age at first pregnancy were examined. Mean age of the sample was 16.5 years, mean age at menarche was 12.2 years, at first coitus was 14.6 years, and at first pregnancy was 15.6 years. Thirty percent of the girls were experiencing second pregnancies. Birth control use by the adolescents was inconsistent, with only 20 percent using birth control at first coitus. Multiple regression analyses produced a model explaining 50 percent of the variance in age at first pregnancy. The predictor variables in the model were age at first coitus, age at menarche, race/ethnicity, and use of birth control at first coitus. Further analyses indicate that for childbearing adolescents, age at first coitus is a classic intervening variable between age at menarche and age at first pregnancy. Early physiologic maturers appear to lack the psychological and cognitive maturity required to cope with their emerging sexuality resulting in early unprotected coitus and pregnancy. Findings provide guidance to healthcare providers for the development of interventions to prevent unplanned pregnancies.

Adaptation, Psychological↗

PubMed1998

C1 inhibitor gene sequence facilitates frameshift mutations.

Mutations disrupting the function or production of C1 inhibitor cause the disease hereditary angioneurotic edema. Patient mutations identified an imperfect inverted repeat sequence that was postulated to play a mechanistic role in the mutations. To test this hypothesis, the inverted repeat was cloned into the chloramphenicol acetyltransferase gene in pBR325 and its mutation rate was studied in four bacterial strains. These strains were selected to assay the effects of recombination and superhelical tension on mutation frequency. Mutations that revert bacteria to chloramphenicol resistance (Cmr) were scored. Both pairs of isogenic strains had reversion frequencies of approximately 10(-8). These rare reversion events in bacteria were most often a frameshift that involved the imperfect inverted repeat with a deletion or a tandem duplication, an event very similar to the human mutations. Increased DNA superhelical tension, which would be expected to enhance cruciform extrusion, did not accentuate mutagenesis. This finding suggests that the imperfect inverted repeat may form a stem-loop structure in the single-stranded DNA created by the duplex DNA melting prior to replication. Models explaining the slippage can be drawn using the lagging strand of the replication fork. In this model, the formation of a stem-loop structure is responsible for bringing the end of the deletion or duplication into close proximity.

Angioedema↗

PubMed1993

Nursing home queues and home health users.

Home health market growth suggests the need for models explaining home health utilization. We have previously explained state-level Medicare home health visits with reference to nursing home markets. Here we introduce a model whereby state-level Medicare home health use is a function of nursing home queues and other demand and supply factors. Medicare home health users per state population is negatively related to nursing home bed stock, positively to Medicaid eligibility levels and to Medicaid nursing home recipients per population, as well as to various other demand and supply measures. This explanation of home health users explains previously-reported findings for home health visits. The findings support the argument that home health use is explained by factors affecting lengths of nursing home queues.

Health Services Needs and Demand↗

PubMed2000

Toggles and oscillators: new genetic circuit designs.

Two recent papers report the de novo design of a functioning biological circuit using well-characterized genetic elements.(1,2) Gardner et al. designed and constructed a genetic toggle switch while Elowitz and Leibler built an oscillating genetic circuit. Both circuits were designed with the aid of mathematical models. These papers demonstrate progress towards the unification of theory and experiment in the study of genetic circuits. Comparison of the predicted and observed behavior of the circuits, however, shows that the models explain only some of the circuits' properties. Further study of the observed behaviors not predicted by the model would lead to new insight into the properties of genetic networks. BioEssays 22:507-509, 2000.

Mathematics↗

PubMed1997

Modeling obesity using abductive networks.

This paper investigates the use of abductive-network machine learning for modeling and predicting outcome parameters in terms of input parameters in medical survey data. Here we consider modeling obesity as represented by the waist-to-hip ratio (WHR) risk factor to investigate the influence of various parameters. The same approach would be useful in predicting values of clinical parameters that are difficult or expensive to measure from others that are more readily available. The AIM abductive network machine learning tool was used to model the WHR from 13 other health parameters. Survey data were collected for a randomly selected sample of 1100 persons aged 20 yr and over attending nine primary health care centers at Al-Khobar, Saudi Arabia. Models were synthesized by training on a randomly selected set of 800 cases, using both continuous and categorical representations of the parameters, and evaluated by predicting the WHR value for the remaining 300 cases. Models for WHR as a continuous variable predict the actual values within an error of 7.5% at the 90% confidence limits. Categorical models predict the correct logical value of WHR with an error in only 2 of the 300 evaluation cases. Analytical relationships derived from simple categorical models explain global observations on the total survey population to an accuracy as high as 99%. Simple continuous models represented as analytical functions highlight global relationships and trends. Results confirm the strong correlation between WHR and diastolic blood pressure, cholesterol level, and family history of obesity. Compared to other statistical and neural network approaches, AIM abductive networks provide faster and more automated model synthesis. A review is given of other areas where the proposed modeling approach can be useful in clinical practice.

Adult↗