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PubMed2004

Supplementary motor area provides an efferent signal for sensory suppression.

Voluntary actions produce suppression of neural activity in sensory areas, and reduced levels of conscious sensation. Recent computational models of motor control have linked sensory suppression to motor prediction: an efferent signal from motor areas may cancel the sensory reafferences predicted as a consequence of movement. Direct evidence for the efferent mechanism in sensory suppression has been lacking. We investigated the perceived size of finger-muscle twitches (MEPs) evoked by TMS in eight normal subjects. Subjects freely chose on each trial whether to make or withhold a voluntary flexion of the right index finger, in synchrony with an instructional stimulus. A test MEP occurred at the instructed time of action. The subject then relaxed and a second reference MEP occurred a few seconds later. Subjects judged which of the two MEPs was larger. Subjects perceived the first test MEP to be smaller in trials where they made voluntary actions than on trials where they did not, demonstrating sensory suppression. On randomly selected trials, a conditioning prepulse was delivered over the supplementary motor area (SMA) 10 ms before the pulse producing the test MEP. The SMA prepulse reduced and almost abolished the sensory suppression effect in voluntary action trials. We suggest the SMA may provide an efferent signal which is used by other brain areas to modulate somatosensory activity during self-generated movement.

Adult↗

PubMed1996

Kinetics of cortical bone demineralization: controlled demineralization--a new method for modifying cortical bone allografts.

We investigated the kinetics of hydrochloric acid demineralization of human cortical bone with the objective of developing a method of controlled demineralization for structural bone allografts. It is known that the demineralization of cortical bone is a diffusion rate limited process with a sharp advancing reaction front. The demineralization kinetics of human cortical bone, described as the advance of the reaction front versus immersion time, were determined by measuring extraction of bone mineral in both planar and cylindrical geometries. Mathematical models based on diffusional mass transfer were developed to predict this process. The experimental data fit well with the behavior predicted by the model. The model for planar geometry is applicable to controlled demineralization of cortical bone allografts of irregular shapes such as cortical struts. The model for cylindrical geometry is appropriate when curved surfaces are involved such as in diaphyseal bone allografts. This method of demineralization has direct application to clinical modification of cortical bone allografts to potentially enhance their osteoinductive properties.

Adult↗

PubMed1988

Cell cycle models and mother-daughter correlation.

Among the different experimental features that are usually used to measure the variability of cell cycle duration (Tc), the mother-daughter correlation is a special case since apparently contradictory results have been reported from different experimental systems. Indeed, positive, null and negative experimental values have been found, raising problems in cell cycle modeling in as much as one would like a general, unified view of the control of the cell cycle. Such views are provided by mathematical models. We present a method to derive the value(s) of the correlation between mother and daughter Tcs predicted from any such model, provided Tc can be analytically expressed. An exact calculation is proposed for the case when Tc can be expressed as a linear combination of the parameters involved. Otherwise, using Taylor series expansion, an approximate expression for the correlation can be derived. In both cases, the predicted values can be compared with experimental ones. The proposed method is illustrated using the Growth Controlled model of Koch (1980, Nature 286: 80) and the Continuum model of Cooper (1982, J. theor. Biol. 94: 783). Whereas Koch's model leads to inflexible negative values of the correlation between mother and daughter Tcs, our results demonstrate that differences in the mean duration of the G1 phase may account for differences in the sign of this correlation in Cooper's model. Furthermore, the proposed method can also be applied to other correlations such as the correlation between sibling cell Tcs.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Cycle↗

PubMed2000

Particulate matter modeling in the Los Angeles basin using SAQM-AERO.

The SARMAP air quality model, enhanced with aerosol modeling capability, and its associated components were developed to understand causes of ozone (O3) and particulate matter exceedances in the San Joaquin Valley of California. In order for this modeling system to gain increasing acceptance and use in guiding air quality management, it is important to assess how transportable this modeling system is across geographic domains. We describe the first application of the modeling system outside the "home" domain for which it was developed and evaluated. We have chosen the August 27-28, 1987, intensive monitoring period of the Southern California Air Quality Study to evaluate the performance of the modeling system and to assess its sensitivity to emission control options. The predicted surface concentrations of O3 and other gas-phase species were spatially and temporally correlated with measured data. The fractional normalized absolute error was 0.32 to 0.36 for O3, and somewhat larger for other species. The fractional normalized bias for O3 on August 27 and 28, 1987, was 0.02 to 0.04. The simulated PM2.5 mass and constituent species concentrations reproduced the magnitude and variability of the observed daytime concentrations at most locations; however, nighttime PM2.5 concentrations were overpredicted by the model. The model's response to emission control options was consistent with other models of the same genre.

Air Pollutants↗

PubMed2002

Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy.

PURPOSE: We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. MATERIALS AND METHODS: We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS: On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). CONCLUSIONS: Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.

Humans↗

PubMedDate not supplied

Self-efficacy and self-reported functional status in coronary heart disease: a six-month prospective study.

OBJECTIVE: We examine prospectively the role of specific forms of self-efficacy in the physical and role function for patients with coronary heart disease after controlling for the effects of anxiety and depression. METHODS: A 6-month prospective cohort study was conducted after cardiac catheterization of 198 HMO members, demonstrating clinically significant coronary disease. Coronary disease severity was assessed through cardiac catheterization; physical function, role function, anxiety, depression, and self-efficacy were assessed through questionnaires. RESULTS: The Cardiac Self-Efficacy Scale had two factors (maintain function and control symptoms) with high internal consistency and good convergent and discriminant validity. In multiple regression models, the self-efficacy scales significantly predicted physical function, social function, and family function after controlling for baseline function, baseline anxiety, and other significant correlates. CONCLUSIONS: Self-efficacy to maintain function and to control symptoms helps predict the physical function and role function, after accounting for coronary disease severity, anxiety, and depression in patients with clinically significant coronary disease. Interventions to improve self-efficacy may have a broader applicability in the heart disease population than previously appreciated.

Activities of Daily Living↗

PubMed1999

Influence of surgical plugging on horizontal semicircular canal mechanics and afferent response dynamics.

Mechanical occlusion of one or more of the semicircular canals is a surgical procedure performed clinically to treat certain vestibular disorders and used experimentally to assess individual contributions of separate canals and/or otoliths to vestibular neural pathways. The present experiments were designed to determine if semicircular canal afferent nerve modulation to angular head acceleration is blocked by occlusion of the endolymphatic duct, and if not, what mechanism(s) might account for a persistent afferent response. The perilymphatic space was opened to gain acute access to the horizontal canal (HC) in the oyster toadfish, Opsanus tau. Firing rate responses of HC afferents to sinusoidal whole-body rotation were recorded in the unoccluded control condition, during the process of duct occlusion, and in the plugged condition. The results show that complete occlusion of the duct did not block horizontal canal sensitivity; individual afferents often exhibited a robust firing rate modulation in response to whole-body rotation in the plugged condition. At high stimulus frequencies (about >8 Hz) the average sensitivity (afferent gain; spikes/s per degrees /s of head velocity) in the plugged condition was nearly equal to that observed for unoccluded controls in the same animals. At low stimulus frequencies (about <0.1 Hz), the average sensitivity in the plugged condition was attenuated by more than two orders of magnitude relative to unoccluded controls. The peak afferent firing rate for sinusoidal stimuli was phase advanced approximately 90 degrees in plugged canals relative to their control counterparts for stimulus frequencies approximately 0.1-2 Hz. Data indicate that afferents normally sensitive to angular velocity in the control condition became sensitive to angular acceleration in the plugged condition, whereas afferents sensitive to angular acceleration in the control condition became sensitive to the derivative of acceleration or angular jerk in the plugged condition. At higher frequencies (>8 Hz), the phase of afferents in the plugged condition became nearly equal, on average, to that observed in controls. A three-dimensional biomechanical model of the HC was developed to interpret the residual response in the plugged condition. Labyrinthine fluids were modeled as incompressible and Newtonian; the membranous duct, osseous canal and temporal bone were modeled as visco-elastic materials. The predicted attenuation and phase shift in cupular responses were in close agreement with the observed changes in afferent response dynamics after canal plugging. The model attributes the response of plugged canals to labyrinthine fluid pressure gradients that lead to membranous duct deformation, a spatial redistribution of labyrinthine fluids and cupular displacement. Validity of the model was established through its ability to predict: the relationship between plugged canal responses and unoccluded controls (present study), the relationship between afferent responses recorded during mechanical indentation of the membranous duct and physiological head rotation, the magnitude and phase of endolymphatic pressure generated during HC duct indentation, and previous model results for cupular gain and phase in the rigid-duct case. The same model was adjusted to conform to the morphology of the squirrel monkey and of the human to investigate the possible influence of canal plugging in primates. Membranous duct stiffness and perilymphatic cavity stiffness were identified as the most salient model parameters. Simulations indicate that canal plugging may be the most effective in relatively small species having small labyrinths, stiff round windows, and stiff bony perilymphatic enclosures.

Afferent Pathways↗

PubMed2004

A computational tensegrity model predicts dynamic rheological behaviors in living cells.

Rheological properties of living cells play a key role in the control of cell shape, growth, movement, and contractility, yet little is known about how these properties are governed. Past approaches to understanding cell mechanics focused on the contributions of membranes, the viscous cytoplasm, and the individual filamentous biopolymers that are found within the cytoskeleton. In contrast, recent work has revealed that the dynamic mechanical behavior of cells depends on generic system properties, rather than on a single molecular property of the cell. In this paper, we show that a mathematical model of cell mechanics that depicts the intracellular cytoskeleton as a tensegrity structure composed of a prestressed network of interconnected microfilaments, microtubules, and intermediate filaments, and that has previously explained static cellular properties, also can predict fundamental dynamic behaviors of living cells.

Actin Cytoskeleton↗

PubMed2006

Prediction of obstructive sleep apnea in patients presenting to a tertiary care center.

The objective of this prospective observational clinical study is to derive and validate a diagnostic model for prediction of obstructive sleep apnea (OSA) in subjects presenting with non-sleep-related complaints in a tertiary care center in north India. We included 102 subjects (group I, range 31-70 years) presenting to the hospital with non-sleep-related complaints. None of the subjects had any significant comorbid illness such as respiratory or congestive cardiac failure. All subjects underwent detailed evaluation including polysomnography (PSG). Various parameters were compared between the cases (apnea-hypopnea index, AHI > or =15/h) and controls (AHI <15/h). Using multivariate logistic regression analysis, a diagnostic model for prediction of OSA was derived. Subsequently, using similar selection criteria, 104 subjects (group II, range 32-68 years) were included for validation of the newly derived diagnostic model. Body mass index [BMI; OR (95% CI), 1.14(1.1-1.2)], male gender 5.0(1.4-27.1), relative-reported snoring index (SI) 2.8(1.7-5.0), and choking index (ChI) 8.1(1.4-46.5) were significant, independent predictors of OSA. Diagnostic model was computed as score = [1.61 x (gender)] + [1.01 x (S1)] + [2.09 x (ChI)] + [0.1 x (BMI)] where, gender: 0 = female, 1 = male and SI, ChI, BMI are actual values. The diagnostic model had an area under the receiver operator characteristics curve of 89.6%. A cutoff of 4.3 for the score was associated with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.3, 68.5, 70.5, and 92.3%, respectively. Misclassification rate with the application of the diagnostic model on group II subjects was 13.5% (14/104). Sensitivity, specificity, PPV, and NPV of the model for predicting OSA in this group were 82, 90.7, 89.1, and 84.5%, respectively. BMI, male gender, SI, and ChI are independent predictors of OSA. Diagnostic model derived from these parameters is useful for predicting presence of OSA and screening subjects for PSG.

Adult↗

PubMed2006

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery.

The SELDI-TOF technique was used to profile serum proteins from Type 1 diabetes (T1D) patients and healthy autoantibody-negative (AbN) controls. Univariate and multivariate analyses were performed to identify putative biomarkers for T1D and to assess the reproducibility of the SELDI technique. We found 146 protein/peptide peaks (581 total peaks discovered) in human serum showing statistical differences in expression levels between T1D patients and controls, with 84% of these peaks showing technical replication. Because individual proteins did not offer great power for disease prediction, we used our model averaging approach that combines the information from multiple multivariate models to accurately classify T1D and control subjects (88.9% specificity and 90.0% sensitivity). Analyses of a test subset of the data showed less accuracy (82.8% specificity and 76.2% sensitivity), although the results are still positive. Unfortunately, no multivariate model could be replicated using the same samples. This first attempt of high throughput analyses of the human serum proteome in T1D patients suggests that model averaging is a viable method for developing biomarkers; however, the reproducibility of SELDI-TOF is currently not sufficient to be used for classification of complex diseases like T1D.

Adolescent↗

PubMed2004

Nutrient enrichment and food chains: can evolution buffer top-down control?

We show how evolutionary dynamics can alter the predictions of classical models of the effects of nutrient enrichment on food webs. We compare an ecological nutrient-plant-herbivore food-chain model without evolution with the same model, including herbivore evolution, plant evolution, or both. When only herbivores are allowed to evolve, the predictions are similar to those of the ecological model without evolution, i.e., plant biomass does not change with nutrient addition. When only plants evolve, nutrient enrichment leads to an increase in the biomass of all compartments. In contrast, when plants and herbivores are allowed to coevolve, although these two classical patterns are common, a wide variety of other responses is possible. The form of the trade-offs that constrain evolution of the two protagonists is then critical. This stresses the need for experimental data on phenotypic traits, their costs and their influence on the interactions between organisms and the rest of the community.

Adaptation, Biological↗

PubMed1985

Determinants of CO2 generation and maintenance in the renal cortex: role of metabolic CO2 production and diffusive CO2 transfer.

We have developed a mathematical model utilizing steady-state mass balance considerations in a compartmental analysis of bicarbonate reabsorption in the superficial proximal tubule and associated vasculature in order to describe quantitatively the determinants of the elevated PCO2 in the renal cortex. This analysis demonstrated for the first time that diffusive transfer of CO2 between vascular segments coupled with metabolic CO2 production could account for the PCO2 measured experimentally. In the present study the predictive value of the model was extended by comparing model-predicted and measured values for PCO2 before and after administration of metabolic and transport inhibitors. In control conditions diffusive CO2 transfer (FCO2) in combination with accepted levels of metabolic CO2 production (MCO2) can account for an elevation in PCO2 to 60 mm Hg. During rotenone and DNP administration the model predicts values for PCO2 which approximate closely the value measured in vivo. In addition, the model demonstrates that the reduction in PCO2 after rotenone and increase in PCO2 after DNP can be accounted for by parallel changes in MCO2 alone as expected. In each case a significant contribution from FCO2 is necessary, however. Therefore, this study demonstrates close agreement in both the magnitude and direction of predicted and determined values in cortical PCO2 in a variety of experimental conditions, thus, supporting a dual role for the major determinants: metabolic CO2 production and diffusive vascular to vascular CO2 transfer.

Animals↗

PubMed1999

Cognitive processing of multidimensional stimuli in schizophrenia: formal modeling of judgment speed and content.

This article presents a formal, mathematical account of relations between response times on simple cognitive tasks and content of complex judgments involving multiple stimulus dimensions for people with schizophrenia. Changes in multidimensional judgments were viewed as the result of interference from increased stages of encoding with respect to the individual dimensions. Information on dimensional properties encoded earlier in a judgment trial was considered to be more susceptible to loss over the rest of the trial, because of a larger number of encoding stages applied to the remaining dimensional properties. Model predictions were tested with samples of paranoid and nonparanoid schizophrenic participants and controls. Unidimensional encoding speed was assessed by reaction times in an explicit similarity ratings task, and multidimensional judgment content was assessed by the relative importance of different stimulus dimensions to participants' ratings in an implicit similarity ratings task. Results support validity of the model.

Adult↗

PubMed2003

Simultaneous control of hand displacements and rotations in orientation-matching experiments.

In reach-to-grasp movements, the interaction between the hand changes in position and those in orientation is poorly understood. A theoretical approach previously proposed (Torres EB and Zipser D. J Neurophysiol 88: 1-13, 2002) assumes that motion strategies are resolved in space independently from the temporal dynamics of the motion and predicts the coarticulation of the hand transport and rotation along the path. The model implies that this simultaneous control is independent of variations in speed and initial posture and required matching orientation. This paper presents experimental data from human subjects that confirm the model's predictions in the context of realistic, unconstrained, orientation-matching motions. Speed independence is quantified in the similarity of the postural and endpoint position-orientation paths obtained under three different speeds. Significant differences in hand and joint kinematics are shown in response to changes in initial posture and target orientation. The robustness of coarticulation under all three experimental conditions supports the idea of an intermediate stage that resolves the geometry of the motion independent of its temporal dynamics.

Arm↗

PubMed2004

The safety, feasibility, and acceptability of patient-controlled sedation for colonoscopy: prospective study.

OBJECTIVE: To assess the safety, feasibility, and acceptability of patient-controlled sedation for elective day-case colonoscopy, and the factors predicting patients' unwillingness to use patient-controlled sedation for colonoscopy. DESIGN: Prospective, non-randomised study. SETTING: University-affiliated endoscopy centre, Hong Kong. PARTICIPANTS: Five hundred patients who underwent elective day-case colonoscopy were prospectively recruited from January 2001 to June 2002. INTERVENTION: Sedation for colonoscopy was a mixture of propofol and alfentanil, which was delivered by means of a patient-controlled syringe pump. Each bolus delivered 4.8 mg propofol and 12 microg alfentanil. No loading dose was used and the lockout time was set at zero. MAIN OUTCOME MEASURES: Cardiopulmonary complications, dose of patient-controlled sedation used, recovery time, satisfaction score, delayed side-effects, and the willingness to use the same sedation protocol for future colonoscopy. A multiple stepwise logistic regression model was used to assess which factors might predict unwillingness to use patient-controlled sedation for colonoscopy. RESULTS: The mean (standard deviation) age of patients was 53.0 (13.9) years. The mean dose of propofol consumed was 0.93 (0.69) mg/kg. Forty-three (8.6%) patients developed hypotension during the procedure. The mean satisfaction score was 7.2 (2.6). Sixteen (3.2%) patients developed delayed side-effects. The median (interquartile range) recovery time was 0 (0-5) minutes. Approximately 78% of patients were willing to use patient-controlled sedation for future colonoscopy if needed. Younger age (<50 years), female sex, a higher mean dose of sedatives used, a lower satisfaction score, and the presence of delayed side-effects were independent factors that were associated with patients' unwillingness to use patient-controlled sedation for colonoscopy. CONCLUSION: . The use of patient-controlled sedation for elective colonoscopy is safe, feasible, and acceptable to most patients.

Adolescent↗

PubMed1994

Predicting oxygenator clinical performance from laboratory in-vitro testing.

Knowledge and predictability of oxygenator performance is vital to safe and effective conduct of cardiopulmonary bypass. The determination of oxygenator performance in the laboratory, however, is carried out under a strict set of conditions established by the Association for the Advancement of Medical Instrumentation (AAMI). This performance data is of limited value in the clinical setting where the perfusionist generally operates outside this set of parameters. This study (1) reports the laboratory performance characteristics of a hollow fiber membrane oxygenator (Sorin Monolyth), (2) uses this data to develop a model to predict performance under a wide range of clinical conditions, (3) compares predicted performance with clinical data collected at two open heart centers, and (4) reviews the complexities of comparing laboratory and clinical performance. An in-vitro "oxygenator-deoxygenator" circuit was utilized to determine O2 and CO2 gas exchange, blood path pressure drop, and heat exchanger efficiency at a variety of blood and gas flows, under standard (AAMI) blood inlet conditions: [table: see text] This laboratory performance data was compared to hospital and computer modeling data. Simple numerical comparison and analysis of variance of regression coefficients over groups indicated that some clinical parameters of performance (oxygen transfer and coefficient of heat exchange) were not predicted with the laboratory data. It is concluded that the laboratory performance data determined under strict controlled conditions may be of limited value in predicting clinical performance unless modeled to allow for variances in operating conditions.

Analysis of Variance↗

PubMed1994

A prediction model for identifying alcohol withdrawal seizures.

A retrospective review of alcohol withdrawal seizures was performed at a private chemical-dependence treatment facility to help identify patients who were at high risk for having a seizure. Patients were identified by two means: controlled substance records were reviewed to determine patients having received intramuscular phenobarbital, and patient charts were reviewed for all patients with a discharge diagnosis of a seizure disorder. Two thousand and one patient records were reviewed; alcohol withdrawal seizure patients were identified. Twenty-eight randomly selected nonseizure patient records served as controls. The statistical test consisted of a discriminant function analysis. The data yielded a statistically significant predictive model for alcohol withdrawal seizures based on six interdependent patient variables which will be helpful in treating future patients undergoing alcohol withdrawal.

Adult↗

PubMed2006

Development of a pharmacokinetic/pharmacodynamic model for carvedilol to predict beta1-blockade in patients with congestive heart failure.

To determine whether the controlled-release (CR) formulation of carvedilol given once daily provides 24-hour beta1-receptor blockade similar to the currently marketed immediate-release (IR) formulation given twice daily, changes in exercise-induced heart rate after bicycle ergometry were measured. The pharmacokinetic (PK)/pharmacodynamic (PD) relation between S(-)-carvedilol concentration-the enantiomer with beta-blocking activity-and change in exercise-induced heart rate was defined in healthy subjects and was best described using a direct effect inhibitory E(max) model (with E(max) being the maximum effect). The population estimates for E(max) and concentration at 50% of the maximum effect (EC50) were 19.2 beats per minute (an approximately 13% maximum decrease in exercise-induced heart rate) and 7.7 ng/mL, respectively. The PK/PD model was used to predict PD effects in patients with mild-to-severe heart failure and in patients after myocardial infarction with left ventricular dysfunction who had received both the IR and CR formulations of carvedilol. In these patients, carvedilol CR had equivalent predicted overall PD (area under the effect curve) and trough (PD(min)) effects compared with carvedilol IR, indicating 24-hour beta-blocking coverage for the new CR formulation of carvedilol given once daily.

Administration, Oral↗