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PubMed1991

A comparison of static and dynamic characteristics between rectus eye muscle and linear muscle model predictions.

The characteristics of a muscle model are analyzed using rectus eye muscle parameter values and compared to rectus eye muscle data. The muscle is modeled as a viscoelastic parallel combination connected to a parallel combination of active state tension generator, viscosity element, and length tension elastic element. Each of the elements is linear and their existence is supported with physiological evidence. The static and dynamic properties of the muscle model are compared to rectus eye muscle data. The length-tension characteristics of the model are in good agreement with the data within the operating region of the muscle. With the muscle model incorporated into a lever system to match the isotonic experiment paradigm, simulation results for this linear system yield a nonlinear force-velocity curve. Moreover, the family of force-velocity curves generated with different stimulus rates reported in the literature match the predictions of the model without parametric changes. The results of this paper are important in studies involving the oculomotor plant and oculomotor neural networks. Additionally, these results may be applicable to other muscles.

Isometric Contraction↗
PubMed1986

Predictive model for prognosis in advanced diffuse histiocytic lymphoma.

The purpose of this study was to examine the validity of a predictive model for response to treatment and survival in advanced diffuse histiocytic lymphoma. One hundred twenty-seven consecutive patients with Ann Arbor stage II-IV diffuse histiocytic lymphoma, who completed treatment between 1974 and 1984 in one of four different Memorial Hospital combination chemotherapy protocols, were reviewed. The median follow-up time was 66.9 months for survivors (range, 21-153.1 months). Factors studied included: age; sex; Ann Arbor stage; prior therapy; B symptoms; serum lactic dehydrogenase (LDH); sites of initial disease; and tumor bulk. LDH was grouped accordingly (units/liter): low, less than 225; medium, 225-500; high, greater than 500. Each patient was assigned an overall level of site involvement (LSI) from the following mutually exclusive groups: group I, peripheral lymph node (PLN) (including +/- Waldeyer ring involvement, +/- spleen); group II, extranodal disease (EN) +/- PLN; group III, retroperitoneal lymph node (RLN) +/- PLN; group IV, bulky mediastinal disease (MED) +/- any other disease; group V, EN with RLN +/- PLN. The Ann Arbor staging system failed to dissect patient groups differing significantly in their prognosis. Serum LDH, LSI, and age were the only factors important for predicting response and survival after multivariate logistic regression and a parametric Weibull survival analysis. Using three levels of serum LDH and correlating them with the different LSI, four tentative "stages" differing significantly in their survival at 48 months were defined: stage I, low LDH, any LSI (80% alive); stage II, medium LDH, PLN, and/or EN (50% alive); stage III, high LDH, PLN, and/or EN or medium LDH, RLN +/- PLN +/- EN, and/or MED (35% alive); stage IV, high LDH, RLN +/- PLN +/- EN, and/or MED (15% alive). Identification of prognostic stages on the basis of LDH level and LSI will allow more accurate comparison of clinical trials for patients with advanced diffuse histiocytic lymphoma.

Adult↗
PubMed1990

The development of a model for predicting infants at high risk of sudden infant death syndrome in Tasmania.

A statutory 'Notification of Birth' form, containing obstetric and perinatal information, has been routinely collected for Tasmanian deliveries since 1974. For the period 1980 to 1984, birth notification data was collected for over 99% of Tasmanian deliveries. This data was examined for the 130 cases of sudden infant death syndrome (SIDS) that occurred from 1980 to 1984 and for 610 controls. It was then used to construct an at-birth scoring system to predict infants at higher risk of SIDS in the postneonatal period. A predictive model of the relative risk of SIDS was developed by fitting a binomial/logistic generalised linear model to the binary 1980-1984 case control data with birth variables used as predictors. The final predictive model contained five variables (maternal age, infant sex, birth weight, month of birth and feeding practice) and had a sensitivity of 62% and specificity of 73%. The model was then tested on independent birth cohorts from 1985 and 1986 and found to have a sensitivity of 47% and specificity of 77%. The risk of SIDS in the group of infants classified as high risk was 7.9 per 1000 live births and in the group at low risk it was 2.5 per 1000 live births. In addition, the model predicted 74% of neonatal deaths occurring during these 2 years. This compares well with other predictive models developed elsewhere. The predictive model will be used to identify infants at high risk for SIDS in a prospective cohort study.

Cohort Studies↗
PubMed1990

A predictive model for vapor concentration in a nose-only inhalation chamber.

A unique nose-only inhalation chamber was designed and constructed to deliver uniform concentrations of gas, vapor, and aerosol contaminants to mice. This research investigated the fluid dynamics of a vaporous contaminant in the vertical flow chamber. The vapor was introduced by allowing the liquid phase of the contaminant to evaporate freely into the chamber interior. A contaminant mass transfer model was developed to predict concentrations generated by the system. The mathematical model of the system used clean airflow, liquid surface area, thickness of the stagnant air layer covering the liquid, system pressure, contaminant diffusion coefficient, and contaminant vapor pressure to compute the vapor concentration delivered to exposure ports. The equation was verified by placing various containers of methyl isobutyl ketone in the chamber and determining with a photospectrometer the resulting equilibrium concentrations. Vapor pressure, diffusion coefficient, and system pressure were held constant while airflow, surface area, and stagnant air layer thickness were varied systematically within the chamber. The resulting empirical data points were compared to the curves predicted by the theoretical model. Empirical concentrations fell within 0 to 48% of the theoretical values, showing that the equation can be used to choose values for airflow, surface area, and stagnant air layer thickness that will result in chamber concentrations in close proximity to the target concentration. If an exact concentration is essential, parameters may be individually adjusted to converge on the target concentration.

Animals↗
PubMed1989

A psychosociomedical prediction model of response to treatment by chronically disabled workers with low-back pain.

There has been much interest in identifying variables that can predict which individuals are susceptible to developing chronic low-back pain. There currently are a number of studies that are evaluating primary predictors (which uninjured workers are likely to develop chronic low-back pain) and secondary predictors (which workers with acute episodes will develop chronic pain). The present study reports the first results from a large-scale investigation of tertiary predictors. Specifically, it addresses the issue of what psychosociomedical variables are predictive of success/failure in response to a comprehensive Functional Restoration treatment program by workers who are chronically disabled with low-back pain. Three stages were involved in the development of this prediction model. First, a group of treatment and research professionals who had extensive experience in the area of chronic low-back pain identified an array of 42 variables, from a larger pool of quantified physical, psychosocial, and medical parameters rated to be important with this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

A simplified in vitro classification for prognosis in adult acute leukemia: the application of in vitro results in remission-predictive models.

Previous classification in vitro of adult acute leukemia incorporating morphology has been complex and difficult to understand. We have devised a simplified classification based solely on leuekemic proliferation in vitro. Seventy-six patients with adult acute leukemia previously untreated were included in this study and received identical chemotherapy. Three groups were recognized. The complete remission rate was 76% in the 21 patients with no leukemic growth in vitro (Group 1), 75% in 36 patients with leukemic cell growth but aggregates of 20 cells or less (Group 2), and only 21% in the 15 patients with aggregates of greater than 20 (Group 3). There was a highly significant difference in complete remission rates between Group 3 and the other two groups (p less than 0.001). Linear logistic regression analysis demonstrated the independence of the growth in vitro from other prognostic variables. A predictive model utilizing the in vitro result more accurately predicted for remission, both retrospectively and prospectively, than a model constructed with presently known prognostic parameters. The cause of death in failures suggested that this system detects resistance to the chemotherapy.

Acute Disease↗
PubMed1990

The health belief model: predicting compliance and dropout in cardiac rehabilitation.

We investigated the health belief model and the health locus of control constructs as predictors of group membership (compliers or dropouts) with cardiac rehabilitation and whether they added predictive utility to routinely assessed patient demographics and health behaviors. Questionnaires were completed on entry into the study by 120 patients with coronary artery disease, and by the end of the 6 month program there were 58 compliers and 62 dropouts. Discriminant function analyses were carried out to determine prediction of group membership. The health belief model predicted group membership 64.6% of the time, explaining 5.2% of the variance. Demographics, health behaviors, and health belief model factors accounted for 21.1% of the variance between compliers and total dropouts with group membership correctly predicted 74.4% of the time; avoidable and unavoidable dropout was correctly predicted 84.2% of the time with 56.9% of the variance explained. Health locus of control did not distinguish between compliers and dropouts. The addition of the health belief model provided additional information about compliance with cardiac rehabilitation beyond that explained by demographic and health behavior variables alone, particularly when predicting avoidable/unavoidable dropout.

Attitude to Health↗
PubMed1991

Drug resistance-reversal strategies: comparison of experimental data with model predictions.

We previously developed a mathematical model to describe the emergence and dynamic growth of a drug-resistant subpopulation in a tumor. In the present study, our objective was to test the model's ability to mimic two strategies for reversal of drug resistance. We present data from one in vitro cell proliferation assay with drug-resistant LS174T human colon carcinoma variants and one in vivo assay of survival after treatment of female (C57BL/6 x DBA/2)F1 mice inoculated with doxorubicin-resistant P388/ADR leukemia cells. The in vitro assay examined the effects of inhibiting the biosynthesis of glutathione in cells resistant to alkylating agents or cisplatin. The in vivo assay compared the effects on cell survival of low-level continuous infusion versus high-intensity bolus dosing, with or without coadministration of the drug efflux pump blocker verapamil. Results in vitro and in vivo were comparable for qualitative accuracy and predictability to results with the model. Both the in vitro study and the model showed that, for resistant cells with high levels of glutathione, short-term cell survival was dose dependent and that even high doses of drug did not eliminate all of these cells. Addition of an inhibitor of glutathione biosynthesis did, however, augment elimination of the resistant cells. Resistant cells with low levels of glutathione could be eliminated with high drug doses or coadministration of drug and a glutathione synthesis inhibitor. In vivo, coadministration of doxorubicin with verapamil increased animal survival when either continuous infusion or bolus dosing regimens were used. The effectiveness of the blocker is crucial; when a partially (50%) effective blocker is used, continuous infusion achieves better elimination of resistant cells, but a completely (100%) effective blocker is efficacious in both dosing scenarios. Careful interpretation of these findings is necessary because the pharmacokinetics of drug in the small populations of cells in the model are not easily extrapolated to those in large tumors. This model may be useful in determining resistance mechanisms, their levels of effectiveness, and concentrations of compounds required at target sites to overcome them.

Animals↗
PubMed1990

Return to work after stroke: development of a predictive model.

Seventy-nine stroke patients who underwent a vocationally oriented, comprehensive, inpatient stroke rehabilitation program were followed up to evaluate their return to work. At follow-up, 49% had returned to work a mean of 3.1 months after rehabilitation discharge. Factors associated with success and with failure of vocational rehabilitation were then identified, and a predictive model was developed. There were positive associations between return to work and Barthel Index on admission (p = 0.0002) and discharge (p = 0.0015). Negative associations were found between return to work and aphasia (p = 0.0009), rehabilitation length of stay (p less than 0.0001), and prior alcohol consumption (p = 0.03). A step-wise multiple regression model explained 42% of the variance in return to work. Those most likely to return to work were not aphasic; they had shorter rehabilitation lengths of stay and higher Barthel Index scores on discharge; and they were lighter consumers of alcoholic beverages before their strokes. In conclusion, a set of factors predictive of return to work in younger stroke patients was identified, including, most notably, a strong negative association with aphasia and an intriguing negative association with prior alcohol consumption.

Adult↗
PubMed1990

Crystal structure of a protein-toxin alpha 1-purothionin at 2.5A and a comparison with predicted models.

Alpha 1-Purothionin (alpha 1-P), a wheatgerm protein and lytic toxin, has a secondary and tertiary structure similar to that of crambin as revealed by CD and NMR studies. alpha 1-P crystallizes in the tetragonal space group 1422 with unit cell dimensions: a = b = 53.59 and c = 69.79 A. X-ray diffraction data have been measured to 2.5 A Bragg spacing. The crystal structure has been determined by molecular replacement methods, using an energy-minimized alpha 1-P model structure derived from crambin (Whitlow and Teeter: Journal of Biomolecular Structure and Dynamics 2:831-848, 1985, Journal of the American Chemical Society 108:7163-7172, 1986). The energy-minimized model gives a slightly cleaner rotation solution and better refinement against the x-ray data than do the crambin or unminimized alpha 1-P structures. The final crystallographic residual with the data in the 10-2.5 A resolution range is 0.216. The refined alpha 1-P structure has a backbone rms difference of 0.74 A from crambin and 0.55 A from the energy-minimized alpha 1-P model. A low resolution NMR model of alpha 1-P calculated from metric matrix distance geometry and restrained molecular dynamics differs from crambin's backbone by 2.3 A rms deviation (Clore et al.: EMBO Journal 5:2729-2735, 1986). Backbone dihedral angles for our predicted model differ from the refined alpha 1-P structure in only one region (at a turn where there is a deletion relative to crambin). The NMR model had differences in four regions.

Antimicrobial Cationic Peptides↗
PubMed1992

A predictive model for the clinical response to low dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia.

The response to treatment with low-dose ara-C was studied in 102 consecutive patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo-Pelger morphology and > or = 2 chromosomal aberrations. Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38.6% of the patients, with a response rate of > 50%, an intermediate group, 32.7% of the patients, with a response rate of 24%, and an unfavourable group, 28.7% of the patients, with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two-thirds of patients with MDS and MDS-AML by identifying patients who should not be treated with low-dose ara-C as well as patients with a relatively high probability of response.

Aged↗
PubMed2026

Personalized functional topography-based multisite brain age prediction modeling reveals divergent neurodevelopment in major depression.

Major depressive disorder (MDD) is associated with widespread alterations in functional brain networks across the lifespan. However, heterogeneity in atypical brain development among patients with MDD remains largely uncharacterized. Using a multisite resting-state functional MRI dataset consisting of 1,105 MDD patients and 1,065 healthy controls, we constructed a harmonized multicenter brain age prediction model based on individualized functional topography and identified two patient subgroups with positive or negative brain age gaps (BAGs). In patients with a positive BAG (BAG+), expansion of the salience network (SAL) into the dorsolateral prefrontal and ventrolateral prefrontal cortices, in addition to contraction of the sensorimotor and dorsal attention networks (DAN), contributes to accelerated brain aging. Conversely, in the negative BAG (BAG-) group, SAL expansion into the orbitofrontal cortex (OFC) and contraction of the visual and sensorimotor networks (SMN) were linked to delayed brain development. These subgroups also exhibited distinct neurodevelopmental trajectories. Clinically, BAG+ patients showed stronger associations between higher-order network topography and mood symptoms, whereas BAG- patients exhibited links between visual/default mode network topography and insomnia. At the molecular level, both groups showed enrichment of genes related to synaptic signaling but displayed distinct expression patterns and divergent expression trajectories in key neurodevelopmental gene sets. Notably, antidepressant treatment modulated the brain in ways that were specific to each subgroup. These findings reveal heterogeneous neurodevelopmental profiles in MDD with distinct biological and clinical signatures, offering insights into personalized precision medicine for this disorder.

Humans↗
PubMed1986

Multivariate prediction model of kidney transplant success rates.

An excellent correlation of predicted and observed cadaver kidney graft survival rates was obtained using a nine-factor computer model. A total of 924 recipients for whom a greater than 80% 1-year survival rate was predicted had an observed rate of 84.6%, whereas 179 recipients with a predicted 1-year success rate of less than 40% had an observed rate of 38.2%. Our model gives improved results as compared with previously published methods. We anticipate that the model's predictive power can be further refined, and that patient selection and organ sharing will benefit from the application of sophisticated computer models for the prediction of transplant success.

Analysis of Variance↗
PubMed1991

Pharmacokinetics of acetaminophen, antipyrine, and salicylic acid in the lactating and nursing rabbit, with model predictions of milk to serum concentration ratios and neonatal dose.

The rabbit was utilized for examining the pharmacokinetics of three compounds (acetaminophen, AC; antipyrine, AN; and salicylic acid, SA) in nursing adults and their suckling offspring and for assessing the ability of a diffusional model to predict milk to serum drug concentration ratios (M/S) from in vitro experiments. AC, AN, and SA serum concentration time profiles declined monoexponentially for both adults and their pups. The mean systemic clearance (Cls) for AC in the adults and pups was 16.1 and 13.7 ml/min/kg, respectively. The mean half-lives of AC (t1/2) were 25.5 and 33.3 min in the adult and pup groups, respectively. AN declined in parallel for adult rabbits and an older group of suckling pups (23-25 days old). In a younger group of pups (18-21 days old) it declined with a longer t1/2 (97.5, 95.1, and 347.6 min in the adults, older pups, and younger pups, respectively). The mean AN Cls in the adults, the older pups, and the younger pups was 5.34, 6.30, and 1.91 ml/min/kg, respectively. The time course of SA was prolonged in the suckling pups (t1/2 of 633 min in the pups vs 78.7 min in the adult). The mean Cls values in the adults and the pups were 1.05 and 0.27 ml/min/kg, respectively. The mean systemic clearance of unbound drug (Clu) for SA was 11.2 ml/min/kg in the adults and 0.92 ml/min/kg in the pups. The serum protein binding of AC and AN was limited, whereas the mean free fraction for SA was 9.7% in adult serum and 32.5% in pup serum. AC and AN in milk paralleled serum drug profiles; a time lag was noted for milk SA. M/S ratios were determined in vivo (M/Sobs; AN = 0.885, AC = 0.580, and SA = 0.125) using area under the milk and serum concentration time profiles. Predicted M/S values (M/Spred; AN = 0.779, AC = 0.578, and SA = 0.085) were calculated from in vitro measurements of the unbound fractions of drug in skim milk and serum, the skim to whole milk drug concentration ratio, milk and serum pH, and the pKa of the model compound. Mean values for M/Sobs were highly correlated with M/Spred values (r2 = 0.976) when the present data were combined with previous data for propranolol, phenobarbital, phenytoin, and diazepam (Fleishaker, J.C., and McNamara, P.J., J. Pharmacol. Exp. Ther. 244, 919, 1988). These results support the usefulness of the diffusional model for predicting M/S in vivo, provided that the distributional process is governed by passive diffusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗
PubMed1990

Evaluation of a spectrum target prediction model in speech perception.

A model of a spectrum target prediction mechanism is proposed and evaluated by comparing predicted values with results of psychoacoustic experiments. When the trajectory of the cepstrally smoothed LPC spectrum is approximated by a second-order critically damped system, the proposed model can estimate target values using short-period spectrum sequences (50 ms) without being given the onset positions of the spectral transition. Additionally, this model decreases the length of transitional sounds and recovers vowel characteristics neutralized by coarticulation. Moreover, this model compensates for the transitions of syllables and extracts stable characteristics from syllable transitions. This model is applicable to coarticulation recovery in speech signal processing.

Humans↗
PubMed2026

Dissecting genetic variance structure and evaluating genomic prediction models for single-cross hybrids derived from Stiff Stalk and Non-Stiff Stalk maize heterotic groups.

The early 20th-century discovery of heterosis and the establishment of heterotic groups transformed maize (Zea mays L.) into a keystone of global agriculture. However, maize breeding faces two significant challenges: the gradual decline of general combining ability (GCA) variance within heterotic groups and the impracticality of testing all possible single crosses in the early stages of a breeding program. Here, we developed genomic best linear unbiased prediction (GBLUP)-based multikernel models, using additive and two alternative nonadditive genomic relationship matrices, to estimate the variance components associated with the general combining ability of Stiff Stalk (SS) and Non-Stiff Stalk (NSS) heterotic groups and the specific combining ability arising from their crosses. We further applied these models to predict the performance of untested single-cross combinations under varying levels of parental information. We showed that the SS and NSS groups retained significant GCA variance across traits in both early- and late-maturity groups. The SS group, in contrast, exhibited no detectable GCA variance in grain yield for the intermediate-flowering subset of hybrids, highlighting a limitation for future genetic improvement. Furthermore, our results showed that GBLUP-based multikernel models effectively identified superior hybrids when parental information was available. In the absence of this information, however, these models underperformed compared to covariance-based approaches. Both nonadditive matrices yielded similar results, indicating that they capture comparable genetic relationship patterns despite their distinct formulations. Overall, this study sheds light on the future use of US maize commercial germplasm and demonstrates how GBLUP-based multikernel models can improve the efficiency of hybrid breeding programs.

Zea mays↗