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PubMed1992

Family therapy in the treatment of adolescents.

A family with an adolescent must transform itself from a predominantly nurturant unit to one that can tolerate and encourage the adolescent's need to separate. When an adolescent presents with symptoms that disrupt the developmental process, the clinician who is familiar with several models of family therapy is better able to select a therapeutic and cost-effective intervention. For family assessments, the authors recommend a biopsychosocial approach, which has replaced the outdated view that families cause psychiatric problems and which acknowledges the family as a potential source of healing. The authors describe several models of family therapy--Satir's communication model, the structural model of Minuchin, Bowen's cross-generational model, and psycho-education--and examine features of these approaches useful for working with adolescents. Illustrative vignettes and some guiding principles for matching model and problem are offered.

Adolescent↗

PubMed1989

The clinical and renal biopsy predictors of long-term outcome in lupus nephritis: a study of 87 patients and review of the literature.

The prognostic markers in 87 consecutive patients with lupus nephritis who underwent renal biopsy are reported for five clinically relevant long-term outcomes--renal insufficiency, renal failure, death due to renal systemic lupus erythematosus, death due to non-renal SLE and death due to SLE, both renal and non-renal. We have demonstrated that a number of previously neglected or rarely studied predictors were important prognostic markers. These included the duration of renal disease before biopsy, overall severity of SLE, as well as the presence of vasculitis, hypertension or a comorbid ailment. Furthermore, the study confirms the predictive importance of serum creatinine, 24-h urinary excretion of protein, C3, and of the activity and chronicity indices on biopsy. However, overall a simple measure of tubulointerstitial disease was the best predictor obtained from biopsy. Prognostic models based on clinical data alone were developed for each of the five outcomes. The models amplify our clinical understanding of lupus nephritis. Markers of renal severity were most important in predicting renal outcomes such as renal insufficiency and renal failure. Prognostic factors less directly related to renal disease (comorbidity and vasculitis) were important predictors of fatality. A marker of immunologic disease activity (C3) was a valuable predictor for many of the outcomes. Thus markers of disease severity reflecting organ damage due to SLE and other comorbid conditions could be combined with markers of immunologic activity to predict a variety of outcomes of relevance to a clinician. When biopsy data obtained by light or electron microscopy were evaluated for their ability to add new predictive information to the clinical models, only a limited value for biopsy was noted. It is likely that this reflected the close correlational relationships between clinical and biopsy variables, the strong clinical models generated, and the inclusion in the clinical models of the previously neglected clinical variables, duration of renal disease before biopsy and the presence of vasculitis or comorbid disease.

Adolescent↗

PubMed1994

Nonword pronunciation and models of word recognition.

Nonword pronunciation is a form of generalization behavior that has been at the center of debates about models of word recognition, the role of rules in explaining behavior, and the adequacy of the parallel distributed processing approach. An experiment yielded data concerning the pronunciation of a large corpus of nonwords. The data were then used to assess 2 models of naming: a model developed by D. C. Plaut and J. L. McClelland (1993), which is similar to the one described by M. S. Seidenberg and J. L. McClelland (1989) but uses improved orthographic and phonological representations, and the grapheme-phoneme correspondence rules of M. Coltheart, B. Curtis, P. Atkins, and M. Haller's (1993) dual-route model. Both models generate plausible nonword pronunciations and match subjects' responses accurately. The dual-route model does so by using rules that generate correct output for most words but mispronounce a significant number of exceptions. The parallel distributed processing model does so by finding a set of weights that allow it to generate correct output for both "rule-governed" items and exceptions. Some ways in which the two approaches differ and other issues facing them are also discussed.

Humans↗

PubMed1989

Expression of N-acetylglucosaminyltransferase III in hepatic nodules generated by different models of rat liver carcinogenesis.

Our earlier studies revealed that N-acetylglucosaminyltransferase III (GnTase III), which catalyzes the insertion of a bisecting N-acetylglucosamine (bi-Gn) in the complex-type N-linked glycans of cellular glycoproteins, is present in hepatic nodules promoted by the orotic acid model. Neither the bi-Gn residues nor the activity of GnTase III is detectable in normal livers and in the surrounding non-nodular liver of the rat. The present study was designed to find out whether an expression of activity of GnTase III is a phenotypic property characteristic of hepatic nodules or simply unique to nodules produced by the orotic acid model. Fischer male 344 rats were initiated with two different carcinogens namely 1,2-dimethyl-hydrazine or diethylnitrosamine and promoted by other models such as the resistant hepatocyte model and the choline deficient diet model, in addition to the orotic acid model. The hepatic nodules generated by these three different models and hepatocellular carcinomas exhibited significant levels of activity of GnTase III while non-nodular surrounding liver, regenerating liver after 2/3 partial hepatectomy or livers of age and sex matched control rats, had no detectable activity. The detection of the activity of GnTase III in nodules and in cancer is in agreement with the presence of bi-Gn residues reported in gamma-glutamyltranspeptidase of cancer tissues of rats. These results are consistent with the conclusion that the expression of GnTase III is activated during hepatocarcinogenesis and is not related to any particular initiator or promoter.

Animals↗

PubMed1980

A computer model for the 30S ribosome subunit.

We describe a computer-generated model for the locations of the 21 proteins of the 30S subunit of the E. coli ribosome. The model uses a new method of incorporating experimental measurements based on a mathematical technique called distance geometry. In this paper, we use data from two sources: immunoelectron microscopy and neutron-scattering studies. The data are generally self-consistent and lead to a set of relatively well-defined structures in which individual protein coordinates differ by approximately 20 A from one structure to another. Two important features of this calculation are the use of extended proteins rather than just the centers of mass, and the ability to confine the protein locations within an arbitrary boundary surface so that only solutions with an approximate 30S "shape" are permitted.

Computers↗

PubMed1991

Computer modeling 16 S ribosomal RNA.

A three-dimensional structure for 16 S RNA has been produced with a computer protocol that is not dependent on human intervention. This protocol improves upon traditional modeling techniques by using distance geometry to fold the molecule in an objective and reproducible fashion. The method is based on the secondary structure of RNA and treats the molecule as a set of double-stranded helices that are linked by flexible single-strands of variable length. Data derived from chemical cross-linking studies of 16 S RNA and tertiary phylogenetic relationships provide the constraints used to fold the molecule into a compact three-dimensional form. Possibly subjective evaluation of the input data are transformed into verifiable quantitative parameters. Relationships based on general locations within the 30 S subunit or on protein-RNA interactions have been specifically excluded. The resolution of the model exceeds that of electron micrographs and approaches that obtained in preliminary X-ray crystal structures. The model size of 245 x 190 x 140 A is compatible with that of the 30 S subunit as determined by electron microscopy. The volume of the model is 1.87 x 10(6) A which is similar to that of the small subunit in a preliminary X-ray crystal structure. The radius of gyration of the model structure of 76 A is intermediate to that seen for partially denatured and fully folded 16 S RNA. Computer graphics are used to display the results in a manner that maximizes the opportunities for human visual interpretation of the models. A format for displaying the structures has been developed that will make it possible for researchers who have not devoted themselves to ribosomal modeling to comprehend and make use of the information that the models embody. On this basis the computer-generated models are compared with models developed by other researchers and with structural data not included in the folding parameter data set.

Base Sequence↗

PubMed1993

A linear time-varying model of force generation in skeletal muscle.

A model of isometric force production by skeletal muscle was developed in which the response to each stimulus in a train was described by a critically damped, linear second-order system. The parameters describing the system were constrained to be constant within an interstimulus interval, but were allowed to vary between interstimulus intervals. The ability of this model to match experimental data, and the time variation in the parameters (low-frequency gain and natural frequency) required to do so were examined in soleus and plantaris muscles of the cat stimulated by synchronous whole-nerve stimulation. The model produced good fits across firing rates from twitch to tetanus for slow and fast muscle, rested and fatigued muscle, and maximal submaximal stimulation. Both gain and natural frequency generally varied smoothly and predictably under all conditions. Gain increased at intermediate stimulation rates and in potentiated muscle, and decreased with fatigue and submaximal stimulation. Natural frequency was higher in fast muscle, and decreased with stimulation rate and fatigue. This modeling approach may provide a useful alternative to current models of skeletal muscle force, as its implementation is simple and it can describe force under conditions (fatigue, potentiation) where the muscle dynamics change with time.

Animals↗

PubMed1987

A model of handwriting.

The research reported here is concerned with hand trajectory planning for the class of movements involved in handwriting. Previous studies show that the kinematics of human two-joint arm movements in the horizontal plane can be described by a model which is based on dynamic minimization of the square of the third derivative of hand position (jerk), integrated over the entire movement. We extend this approach to both the analysis and the synthesis of the trajectories occurring in the generation of handwritten characters. Several basic strokes are identified and possible stroke concatenation rules are suggested. Given a concise symbolic representation of a stroke shape, a simple algorithm computes the complete kinematic specification of the corresponding trajectory. A handwriting generation model based on a kinematics from shape principle and on dynamic optimization is formulated and tested. Good qualitative and quantitative agreement was found between subject recordings and trajectories generated by the model. The simple symbolic representation of hand motion suggested here may permit the central nervous system to learn, store and modify motor action plans for writing in an efficient manner.

Cybernetics↗

PubMed1992

A theoretical framework for the immunoepidemiology of helminth infection.

Field studies of parasitic helminths in endemically infected human communities have provided quantitative information on the relationships between parasite burdens, immune responses and age. There are considerable difficulties in the interpretation of these immunoepidemiological data due to the complexities of the biological processes generating the observed patterns. In this paper simple mathematical models are used to explore the expected patterns of variation with host age in parasite burdens, the aggregation of parasites among hosts, levels of immune response, and the correlation between parasite burdens and immune responses. These relationships reflect rates of infection, rates of parasite mortality, the strength of the immune response, and the duration of immunological memory. The models generate some complex and counterintuitive patterns. The analysis suggests that some of these patterns might serve to (i) distinguish effects due to acquired immunity from effects due to age-dependent exposure, (ii) identify potentially protective immune responses, and (iii) identify the parasite stages important in the development of acquired immunity. The results imply that previous analyses of immunoepidemiological data may have been overly simplistic and, especially, that patterns believed to be inconsistent with protective immunity may have been incorrectly interpreted.

Adolescent↗

PubMed1991

Time required for gene frequency change in a deterministic model of gene-culture coevolution, with special reference to the lactose absorption problem.

The time required for gene frequency change under natural selection in a deterministic model of gene-culture coevolution is investigated. A discrete generations model is formulated, and its continuous time approximation is derived. In passing to the continuous time limit, it is assumed that the frequency of the culturally transmitted trait does not change under oblique (between generations) transmission. The system of ordinary differential equations thus obtained are solved, and the dependence on the parameters of horizontal (within generations) transmission and natural selection is examined. The time required is found to be substantially longer when the determination of a phenotypic difference subject to natural selection is partly cultural rather than completely genetic. The predictions are relevant to the possibility of the coevolution of lactose absorbers and milk drinkers in some human populations. Alternative hypotheses are briefly discussed in the light of the theoretical results.

Biological Evolution↗

PubMed1983

A model of dynamic vagus-sinoatrial node interactions.

Computer simulations of dynamic vagus-sinoatrial (SA) node interactions were performed using an empirical model. The phasic effects of single vagal trains on pacemaker cycle length obtained experimentally in isolated preparations were summarized in phase response curves (PRCs). These PRCs were used to stimulate the interactions of the sinoatrial pacemaker with single or with repetitive vagal input. For single stimuli, the triphasic inhibitory curve describing the time course of a brief vagal burst (G. Brown and J. Eccles. J. Physiol. London 82: 211-241, 1934; and J. Jalife and G. K. Moe. Circ. Res. 45: 595-607, 1979) was used to predict the PRC at any given spontaneous pacemaker cycle length. In simulations of repetitive vagal input the model predicted the entrainment of the pacemaker. The patterns of interaction were dependent on the shape and amplitude of the PRC as well as on the relationship between the spontaneous pacemaker period and the vagal cycle length. At certain vagal frequencies, stable entrainment of the pacemaker occurred, and the entrained pacemaker period held harmonic relations to the vagal input (i.e., 1:1, 2:1, and so on). At other frequencies, zones of instability were found in which arrhythmic patterns developed. These predictions of the model matched the experimental results very closely. Under some conditions, during simulations with fixed sinovagus coupling intervals, the model generated patterns of sinus activity similar to those occurring experimentally or in patients with apparent sinoatrial block. The model was also capable of generating patterns similar to those obtained in cases of isorhythmic atrioventricular dissociation. The study of these interactions may have important bearing on the understanding of the dynamic control of heart rate by the parasympathetic nervous system and may be used to explain certain cardiac dysrhythmias.

Animals↗

PubMed1991

Computer modelling of Tetrahymena axonemes at macromolecular resolution. Interpretation of electron micrographs.

A computer-generated model of the structural arrangement of the complete 9+2 ciliary axoneme of Tetrahymena at macromolecular resolution (4 nm) is presented. The model reconciles detailed information about subcomponents from negative-stained, thin-section and freeze-fracture electron micrographs, integrating the images into a consistent three-dimensional picture. This illuminates problems such as the requirement for compaction of dynein to form the arm, difficulties in visualization of the circumferential links, construction of the central sheath, and the comparative periodicities of the inner and outer arms. The model is pragmatic in that it is flexible and easily changed, as new information becomes available. It is also useful in the development of dynamic concepts, such as a spatial description of the dynein cross-bridge cycle, which is illustrated, or relationships between adjacent doublets during sliding and bending.

Animals↗

PubMed1992

Experimental tests of a superposition hypothesis to explain the relationship between the vestibuloocular reflex and smooth pursuit during horizontal combined eye-head tracking in humans.

1. We used a modeling approach to test the hypothesis that, in humans, the smooth pursuit (SP) system provides the primary signal for cancelling the vestibuloocular reflex (VOR) during combined eye-head tracking (CEHT) of a target moving smoothly in the horizontal plane. Separate models for SP and the VOR were developed. The optimal values of parameters of the two models were calculated using measured responses of four subjects to trials of SP and the visually enhanced VOR. After optimal parameter values were specified, each model generated waveforms that accurately reflected the subjects' responses to SP and vestibular stimuli. The models were then combined into a CEHT model wherein the final eye movement command signal was generated as the linear summation of the signals from the SP and VOR pathways. 2. The SP-VOR superposition hypothesis was tested using two types of CEHT stimuli, both of which involved passive rotation of subjects in a vestibular chair. The first stimulus consisted of a "chair brake" or sudden stop of the subject's head during CEHT; the visual target continued to move. The second stimulus consisted of a sudden change from the visually enhanced VOR to CEHT ("delayed target onset" paradigm); as the vestibular chair rotated past the angular position of the stationary visual stimulus, the latter started to move in synchrony with the chair. Data collected during experiments that employed these stimuli were compared quantitatively with predictions made by the CEHT model. 3. During CEHT, when the chair was suddenly and unexpectedly stopped, the eye promptly began to move in the orbit to track the moving target. Initially, gaze velocity did not completely match target velocity, however; this finally occurred approximately 100 ms after the brake onset. The model did predict the prompt onset of eye-in-orbit motion after the brake, but it did not predict that gaze velocity would initially be only approximately 70% of target velocity. One possible explanation for this discrepancy is that VOR gain can be dynamically modulated and, during sustained CEHT, it may assume a lower value. Consequently, during CEHT, a smaller-amplitude SP signal would be needed to cancel the lower-gain VOR. This reduction of the SP signal could account for the attenuated tracking response observed immediately after the brake. We found evidence for the dynamic modulation of VOR gain by noting differences in responses to the onset and offset of head rotation in trials of the visually enhanced VOR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Applied muscle modelling: implementation of muscle-specific models.

Recent work in musculoskeletal modelling has seen the use of models which represent individual muscles in the human system. This paper presents a model of forearm supination in which models generate specific muscular forces to produce external supinator torque. The model output is compared to measured external torque for isometric and dynamic loading conditions. These data are used to construct isometric torque-angle and torque-angular velocity graphs for both model and experimental output. The discussion focuses on specific topics regarding implementation of muscle models in applied situations. These topics are demonstrated by observing the effect of parameter alteration on model output.

Computer Simulation↗

PubMed1987

Extracellular currents and potentials of the active myelinated nerve fiber.

This paper is concerned with the accurate and rapid calculation of extracellular potentials and currents from an active myelinated nerve fiber in a volume conductor, under conditions of normal and abnormal conduction. The neuroelectric source for the problem is characterized mathematically by using a modified version of the distributed parameter model of L. Goldman and J. S. Albus (1968, Biophys. J., 8:596-607) for the myelinated nerve fiber. Solution of the partial differential equation associated with the model provides a waveform for the spatial distribution of the transmembrane potential V(z). This model-generated waveform is then used as input to a second model that is based on the principles of electromagnetic field theory, and allows one to calculate easily the spatial distribution for the potential everywhere in the surrounding volume conductor for the nerve fiber. In addition, the field theoretic model may be used to calculate the total longitudinal current in the extracellular medium (I0L(z)) and the transmembrane current per unit length (im(z)); both of these quantities are defined in connection with the well-known core conductor model and associated cable equations in electrophysiology. These potential and current quantities may also be calculated as functions of time and as such, are useful in interpreting measured I0L(t) and im(t) data waveforms. An analysis of the accuracy of conventionally used measurement techniques to determine I0L(t) and im(t) is performed, particularly with regard to the effect of electrode separation distance and size of the volume conductor on these measurements. Also, a simulation of paranodal demyelination at a single node of Ranvier is made and its effects on potential and current waveforms as well as on the conduction process are determined. In particular, our field theoretic model is used to predict the temporal waveshape of the field potentials from the active, non-uniformly conducting nerve fiber in a finite volume conductor.

Mathematics↗

PubMed2026

GENKI: A generative framework for scalable and robust metabolic kinetic modeling.

GENKI (Generative ENsemble KPI-Informed) is a variational autoencoder-based framework for large-scale kinetic modeling of metabolism. Developed for metabolic engineering applications, GENKI is designed to improve the recovery of kinetically feasible models that reproduce experimentally observed phenotypes under genetic and environmental perturbations. The framework is trained on feasible kinetic model ensembles and uses phenotype-based key performance indicators (KPIs), derived from multi-omics and bioprocess data, to label and enrich models according to their agreement with mutant and condition-specific observations. This enables targeted generation of biologically relevant parameter sets with improved predictive performance. Crucially, GENKI recovers kinetic parameter sets that jointly reproduce wild-type and multiple perturbed physiologies within a single model. We apply GENKI to large-scale kinetic models of Escherichia coli and Saccharomyces cerevisiae under enzyme perturbations and oxygen shifts. In both systems, GENKI enriches kinetic ensembles with models that more accurately reproduce experimentally observed physiologies across multiple perturbations and conditions. GENKI therefore provides a practical framework for perturbation-aware kinetic model refinement within iterative Design-Build-Test-Learn workflows.

DBTL↗

PubMed1992

Cross-validation performance of mortality prediction models.

Mortality prediction models hold substantial promise as tools for patient management, quality assessment, and, perhaps, health care resource allocation planning. Yet relatively little is known about the predictive validity of these models. We report here a comparison of the cross-validation performance of seven statistical models of patient mortality: (1) ordinary-least-squares (OLS) regression predicting 0/1 death status six months after admission; (2) logistic regression; (3) Cox regression; (4-6) three unit-weight models derived from the logistic regression, and (7) a recursive partitioning classification technique (CART). We calculated the following performance statistics for each model in both a learning and test sample of patients, all of whom were drawn from a nationally representative sample of 2558 Medicare patients with acute myocardial infarction: overall accuracy in predicting six-month mortality, sensitivity and specificity rates, positive and negative predictive values, and per cent improvement in accuracy rates and error rates over model-free predictions (i.e., predictions that make no use of available independent variables). We developed ROC curves based on logistic regression, the best unit-weight model, the single best predictor variable, and a series of CART models generated by varying the misclassification cost specifications. In our sample, the models reduced model-free error rates at the patient level by 8-22 per cent in the test sample. We found that the performance of the logistic regression models was marginally superior to that of other models. The areas under the ROC curves for the best models ranged from 0.61 to 0.63. Overall predictive accuracy for the best models may be adequate to support activities such as quality assessment that involve aggregating over large groups of patients, but the extent to which these models may be appropriately applied to patient-level resource allocation planning is less clear.

Discriminant Analysis↗

PubMed1989

The perception of moving plaids reveals two motion-processing stages.

When viewed through a small aperture, the perceived motion exhibited by a long moving line or grating is ambiguous. This situation prevails because even a perfect machine could only detect motion perpendicular to a moving contour, so motion parallel to a contour is undetectable. The human visual system views the world through an aperture array--the neural receptive fields. Therefore a moving object is viewed through many small apertures and the motion within many of those apertures is ambiguous. This ambiguity may be resolved by monitoring the motion of a distinctive feature, such as a line-end or corner, and attributing to the larger object the motion of the feature. Alternatively, Adelson and Movshon have suggested that moving images are processed in two stages, that is, they are first decomposed into one-dimensional components which are later recombined to generate perceived object motion. For a moving plaid, defined as the sum of two drifting gratings, these alternative models generate different predictions concerning the resolution of the plaid's motion ambiguity. A feature monitor would respond to the motion of the intersections between gratings, whereas the two-stage motion processor would first decompose the plaid into its constituent gratings and subsequently recombine them to generate the perception of a moving plaid. Using speed discrimination to distinguish between the two models, I find that discrimination thresholds reflect the speed of a plaid's component gratings, rather than the speed of the plaid itself. This result supports the two-stage model. Although speed discrimination is limited by component processing, observers cannot directly access component speed. The only perceptually accessible velocity signal is generated by the second-stage pattern processing.

Humans↗