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Assessment of regional left ventricular wall stress after myocardial infarction by echocardiography-based structural analysis.

OBJECTIVES: The objective of this study was to determine the distribution of regional left ventricular (LV) wall stress after myocardial infarction (MI). BACKGROUND: After a large MI, structural changes occur in the heart that ultimately may lead to alterations in LV size and shape, a process generally referred to as ventricular remodeling. Regional variation in myocardial wall stress may be responsible for initiation of physiologic and cellular changes that result in myocardial hypertrophy, dilatation, and remodeling after MI. Simplified geometric analytic methods of estimating global LV wall stress cannot determine regional variation such as that occurring after MI. METHODS AND RESULTS: To assess regional LV wall stress after MI, we applied the finite element method to patient-specific end-systolic LV models generated from echocardiographic imaging. After validation by comparison with analytic solutions of LV wall stress in idealized ventricles, LV models were constructed from rotated orthogonal apical images from 13 normal volunteers, 16 patients with recent (<4 days) anterior MI, and 7 patients with recent infero-posterior MI. The mean Von Mises stress was calculated for the entire LV and for 5 separate regions of the LV. Von Mises LV wall stress was increased globally in patients with anterior MI (211 +/- 46 kdyne/cm2; P < .002) or infero-posterior MI (175 +/- 23 kdyne/cm2; P = .04) compared with normal patients (144 +/- 57 kdyne/cm2). Global wall stress correlated directly with ejection fraction (P < .0001) and inversely with wall motion index (P < .004) in patients with anterior MI. Wall stress in the apical regions was increased by a factor of 2.3 in patients with anterior MI (P < .0001), whereas other regions did not differ from normal patients. There were no individual regions that were significantly different from normal in patients with infero-posterior MI. CONCLUSIONS: Anterior MI is associated with an increase in apical end-systolic wall stress compared with normal and infero-posterior MI. This may be an important stimulus for LV remodeling after anterior MI.

Female

Conjoint recognition.

The process-dissociation model has stimulated important advances in the study of dual-process conceptions of memory. The authors review some limiting properties of that model and consider the degree of support for its parent theory (the recollection-familiarity distinction). A 2nd-generation model (conjoint recognition) is proposed that addresses these limitations and supplies additional capabilities, such as goodness-of-fit tests, the ability to measure dual processes for false-memory responses, and statistical procedures for testing within- and between-conditions hypotheses about its parameters. The conjoint-recognition model also implements an alternative theoretical interpretation (the identity-similarity distinction of fuzzy-trace theory). Worked applications to data are provided.

Adolescent

[A model for handling grievances in nursing services].

A model for management of grievances in a nursing service is described, in terms of the guidelines for model generation, based on a qualitative, exploratory, descriptive and theory generating research strategy and design. Potgieter's (1992) research served as the conceptual framework for the description of a model case. The statements derived from this description was used as basis for the description of the model. The central concepts were identified, defined and classified. The model was implemented in practice and was evaluated by means of a retrospective case study. Guidelines for the implementation of the model were consequently described and the model was positively evaluated by a panel of experts. The testing of hypothesis is recommended to validate the model.

Employee Grievances

Alloplastic cranial implants made from computed tomographic scan-generated casts.

The complexity of cranioplasty increases with increased defect size. It is difficult to produce a symmetric, accurate implant presurgically or at the time of surgery when the defect is greater than 50 cm2. The procedure is also more difficult to perform when the defect is located in the temporal, infratemporal, or frontal areas. A new procedure generates a three-dimensional cast of the skull through computed tomography and computer-aided design reformation. This article describes the process of model generation and the production of a preprocessed cranial implant. To date, six cranial implants have been made with this technique. The whole head models are accurate and help the neurosurgeon-prosthodontist team in the creation of a symmetric, anatomically correct restoration. It is the technique of choice for large implants or where the cranial bones are thin. It is not necessary to augment or alter the implant during surgery. The technique reduces surgical time, and postsurgical complications have been minimal.

Artificial Intelligence

Computer model of membrane current and intracellular Ca2+ flux in the isolated guinea pig ventricular myocyte.

This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K-adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca(2+)-ATPase, Ca(2+)-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].

Action Potentials

Non-isotopic method for quantitation of platelets and erythrocytes in experimental thrombi.

Experimental animal models of thrombosis have been established in several species to examine factors responsible for thrombotic disorders in man. One technical facet of all thrombosis models is the need to quantitate cell deposition on thrombogenic surfaces, and this is routinely accomplished with radioisotopic labeling of specific components. Data reported here demonstrate that formalin-fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and quantitation of platelets and erythrocytes incorporated within the clot. Recovery of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/- 1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was 94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release platelets and erythrocytes from string-bound thrombi generated in vivo with an arterio-venous shunt model in beagle dogs. Platelet recovery from these string clots after chymotrypsin hydrolysis was independently verified with a quantitative Western blot assay of platelet antigens. These data demonstrate that experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only eliminating the need for radioisotopes, but also permitting flow cytometric analysis of cells comprising the thrombus.

Animals

The power of iterated generalized least squares (GLS) method to detect direct relationships in the analysis of correlated quantitative traits.

We examined the power of the stepwise iterated generalized least squares (GLS) method by modeling the relationship between quantitative traits and other variables using the simulated data for Problem 2A. The comparison between the generating model provided by the workshop and the results of the stepwise iterated GLS model showed that this method could be used as a first step in identifying the underlying model for genetic data. The estimated covariance matrices also provide useful information about the genetic properties of the traits.

Computer Simulation

Intracardiac electrogram parameters, electrode surface area and pacer input impedance: their correlations.

Small surface area electrodes are accused of sensing defects which were related to alterations that they induce in the endocardiac electrograms. Since several factors affect the cardiac signal coming from electrode to sensing circuit, i.e. electrode surface area, electrode-tissue interface, pacemaker input impedance and sensing amplifier pass-band, Authors present their studies performed on 252 implanted electrodes of various type. Study was carried out by connecting in parallel to the recorder a variable resistor in order to simulate different pacer input impedances. The results showed a significant reduction in RS amplitude when recorder was paralleled with resistor values lower than 40 K. Slew rates showed a similar behaviours since RS steep tract did not change his duration with load, while total QRS duration is reduced. High speed analysis has shown that the RS segment is not linear in about 40% of cases: the main tract is used for calculations. The most significant attenuations and distortions of endocardial electrogram were observed with smallest electrodes and lowest resistances parallel connected: in these cases the sensing impedance at the electrode-tissue interface appears to be between 3 to 5 K ohms. The results suggest that the most of the alledged sensing faults experienced in the past were probably due to small tip electrodes connected to low input impedance generators or to impending failure situations. The AA. conclude that the main question does not concerne a true electrode inefficiency but a wrongly chosen pacemaker-electrode combination, i.e. small tip electrode connected with old generator models. To avoid the evaluation error, it would be instrumental that the pacemaker manufacturers would specify input characteristics of their generators. So, the implanting clinician becomes able to exactly evaluate the true signal arriving to the sensing circuit by connecting in parallel with the recorder input a resistor whose value approximates the input resistance of the generator to be implanted.

Cardiac Pacing, Artificial

Testing models of female reproductive migratory behaviour and population structure in the Caribbean hawksbill turtle, Eretmochelys imbricata, with mtDNA sequences.

Information on the reproductive behaviour and population structure of female hawksbill turtles, Eretmochelys imbricata, is necessary to define conservation priorities for this highly endangered species. Two hypotheses to explain female nest site choice, natal homing and social facilitation, were tested by analyzing mtDNA control region sequences of 103 individuals from seven nesting colonies in the Caribbean and western Atlantic. Under the social facilitation model, newly mature females follow older females to a nesting location, and subsequently use this site for future nesting. This model generates an expectation that female lineages will be homogenized among regional nesting colonies. Contrary to expectations of the social facilitation model, mtDNA lineages were highly structured among western Atlantic nesting colonies. These analyses identified at least 6 female breeding stocks in the Caribbean and western Atlantic and support a natal homing model for recruitment of breeding females. Reproductive populations are effectively isolated over ecological time scales, and recovery plans for this species should include protection at the level of individual nesting colonies.

Animals

Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.

Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that removes the expression of the small t antigen) to deliver consistently high levels of transgene expression to the transgenic mouse prostate. Seven male founders, their male offspring, and all the male offspring from two female founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of age, indicating that the incidence of transformation was 100%. Tumorigenesis in the LPB-Tag animals progressed in a manner similar to that observed in the human prostate. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, which continued to progress into hyperplasia involving the entire epithelium and then low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies indicated that most stromal cells stained positively for both androgen receptor and smooth muscle alpha-actin, suggesting that stromal overgrowth largely represented mesenchymal cells that had differentiated into smooth muscle cells. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. Tumor growth was regarded as androgen-dependent because tumors regressed in animals castrated at 11 weeks of age, and androgen treatment restored both epithelial/stromal cell ratio and tumor growth. Furthermore, small populations of prostatic epithelial cells in castrated animals continued to proliferate, suggesting the potential for androgen-independent growth. Although prostatic metastasis to other organs was not observed, local invasion was detected. In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation. Moreover, this model undergoes molecular changes similar to those found in human prostate including: (a) the multi-focal nature of tumorigenesis, (b) the progressive histopathologic changes from low- to high-grade dysplasia similar to human prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus, the LPB-Tag prostate tumor model will be useful for studying the sequential mechanisms underlying the development of multistep tumorigenesis.

Androgen-Binding Protein

Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.

Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that removes the expression of the small t antigen) to deliver consistently high levels of transgene expression to the transgenic mouse prostate. Seven male founders, their male offspring, and all the male offspring from two female founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of age, indicating that the incidence of transformation was 100%. Tumorigenesis in the LPB-Tag animals progressed in a manner similar to that observed in the human prostate. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, which continued to progress into hyperplasia involving the entire epithelium and then low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies indicated that most stromal cells stained positively for both androgen receptor and smooth muscle alpha-actin, suggesting that stromal overgrowth largely represented mesenchymal cells that had differentiated into smooth muscle cells. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. Tumor growth was regarded as androgen-dependent because tumors regressed in animals castrated at 11 weeks of age, and androgen treatment restored both epithelial/stromal cell ratio and tumor growth. Furthermore, small populations of prostatic epithelial cells in castrated animals continued to proliferate, suggesting the potential for androgen-independent growth. Although prostatic metastasis to other organs was not observed, local invasion was detected. In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation. Moreover, this model undergoes molecular changes similar to those found in human prostate including: (a) the multi-focal nature of tumorigenesis, (b) the progressive histopathologic changes from low- to high-grade dysplasia similar to human prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus, the LPB-Tag prostate tumor model will be useful for studying the sequential mechanisms underlying the development of multistep tumorigenesis.

Androgen-Binding Protein

PRISM-G: an interpretable privacy scoring framework for assessing risk in synthetic human genome data.

MOTIVATION: Synthetic genomic data promises broader data access, but unresolved privacy risks remain a major concern. Existing evaluations often rely on similarity-based metrics that measure proximity between real and synthetic genomes, overlooking additional mechanisms through which genomic information may leak. RESULTS: We introduce PRISM-G, a model-agnostic framework that quantifies privacy exposure in synthetic genomic data across three complementary components: proximity to real genomes in genetic-coordinate space, replay of familial or population-structure patterns, and trait-linked exposure through rare variants and membership-inference signals. These components are normalized and combined through a risk-averse aggregation into a single 0-100 PRISM-G score. By pairing PRISM-G with downstream utility metrics, the framework also enables analysis of privacy-utility trade-offs across generative models. We evaluated PRISM-G on synthetic cohorts generated by a generative adversarial network (GAN), a restricted Boltzmann machine (RBM), and a logic-based SAT solver (Genomator). Our results show that privacy vulnerabilities arise along different axes across models and marker densities, demonstrating that a single similarity-based metric is insufficient to characterize genomic privacy risk. AVAILABILITY AND IMPLEMENTATION: The source code of PRISM-G is available at https://github.com/alejocrojo09/prismg.

Humans

A molecular modeling analysis of the binding interactions between the okadaic acid class of natural product inhibitors and the Ser-Thr phosphatases, PP1 and PP2A.

We have proposed computer-generated models of the catalytic subunits of the serine-threonine protein phosphatases PP1 and PP2A complexed with their endogenous substrate phospho-DARPP-32, and several known naturally occurring inhibitors. This study is part of an overall effort to elucidate the signal transduction pathways in which PP1 and PP2A may play an important role.

Amino Acid Sequence

[Use of voxel-oriented femur models for stress analysis. Generation, calculation and validation of CT-based FEM models].

A means of interfacing computed tomography with the finite element method for the analysis of stress distribution in human femurs is described. With the aid of data transfer and image processing programs, three-dimensional voxel models of four macerated and a fresh-frozen cadaveric femur were generated from CT data sets. The underlying basic principle is direct generation of model elements from one or more adjacent CT-voxels, which are characterised by their coordinates and local absorption coefficients. A new algorithm was used for smoothing the edges of the model. All the models were analysed with respect to their stress distribution under different load situations, and the results were compared with the data of a parallel study utilizing the strain-gauge technique. Using the method of linear regression, a high correlation (coefficient of determination r2: 0.80-0.91) was found between the calculated and experimentally measured principal stresses at the surface of the bones.

Biomechanical Phenomena

Dynamics of membrane excitability determine interspike interval variability: a link between spike generation mechanisms and cortical spike train statistics.

We propose a biophysical mechanism for the high interspike interval variability observed in cortical spike trains. The key lies in the nonlinear dynamics of cortical spike generation, which are consistent with type I membranes where saddle-node dynamics underlie excitability (Rinzel & Ermentrout, 1989). We present a canonical model for type I membranes, the theta-neuron. The theta-neuron is a phase model whose dynamics reflect salient features of type I membranes. This model generates spike trains with coefficient of variation (CV) above 0.6 when brought to firing by noisy inputs. This happens because the timing of spikes for a type I excitable cell is exquisitely sensitive to the amplitude of the suprathreshold stimulus pulses. A noisy input current, giving random amplitude "kicks" to the cell, evokes highly irregular firing across a wide range of firing rates; an intrinsically oscillating cell gives regular spike trains. We corroborate the results with simulations of the Morris-Lecar (M-L) neural model with random synaptic inputs: type I M-L yields high CVs. When this model is modified to have type II dynamics (periodicity arises via a Hopf bifurcation), however, it gives regular spike trains (CV below 0.3). Our results suggest that the high CV values such as those observed in cortical spike trains are an intrinsic characteristic of type I membranes driven to firing by "random" inputs. In contrast, neural oscillators or neurons exhibiting type II excitability should produce regular spike trains.

Algorithms

Simulation studies of self-associating systems; discrimination between specific and isodesmic associations.

The possibilities of discriminating between definite and indefinite (isodesmic) modes of self-association are explored by fitting the different models to stimulated data, using non-linear least-squares curve-fitting to determine the fitting parameters for real and impostor models. It was found that over an extensive range of values for the equilibrium constant of a non-ideal isodesmic generating model, only a non-ideal monomer-dimer-tetramer-octamer was a successful impostor model. Some criteria for rejecting inappropriate models are discussed.

Binding Sites

Improving the quality of the NCQA (National Committee for Quality Assurance) Annual Member Health Care Survey Version 1.0.

The National Committee for Quality Assurance (NCQA) developed a standardized survey instrument in 1995 designed to measure enrollee satisfaction with the care and services received from health plans across the United States. After the survey was administered for a large number of health plans and thousands of responses were received, some areas for survey improvement have emerged. The objective of this research was to evaluate the NCQA Annual Member Health Care Survey Version 1.0 (the standard form) relative to an alternate survey form created in cooperation with the HMO Group, Maritz Marketing Research, Inc., and Healthcare Research Systems, Ltd. The alternate form of the NCQA survey was constructed to test several theories of measurement improvement via rewording of items, reordering of items, deletion of items, and addition of items. The most important findings of the research project are reported herein. Ten geographically dispersed member health maintenance organizations (HMOs) of The HMO Group took part in the project. A split-half design was used to test the standard and alternate survey forms concurrently. Surveys were administered by using the NCQA-recommended mail methodology of survey and cover letter, reminder card, and second survey. Assuming a 50% response rate, a target of 400 responses (200 for each survey form) per HMO was planned. The window for responding was allowed to remain open 4 weeks beyond the mailing of the second survey to achieve the desired response rate. A total of 4,056 responses were collected (2,022 for the standard form and 2,034 for the alternate form). It was found that the addition of "No Experience" and "No Opinion" response options to the majority of satisfaction items reduced the random error associated with informed responses and produced statistically significant higher correlations with the global satisfaction items relative to the standard form items. Only four of the eight Short Form 12 summary scales, General Health, Reported Health Transition, Mental Health, and Social Functioning, were useful for adjusting data (covariation). The entire set of comorbidities (chronic disease checklist) could be eliminated without losing significant data adjustment capability. The multiple linear regression models generated by using the global satisfaction items on the alternate form had higher adjusted R2 values than the standard-form models. The alternate-form item Overall Value correlated highly with cost items and general satisfaction item, making it a useful global satisfaction variable for predictive modeling.

Health Care Surveys

The steady expiratory pressure-flow relation in a model pulmonary bifurcation.

Experiments were conducted over a range of Reynolds numbers from 50 to 8000 to study the pressure-flow relationship for a single bifurcation in a multi-generation model during steady expiratory flow. Using the energy equation, the measured static pressure drop was decomposed into separate components due to fluid acceleration and viscous energy dissipation. The frictional pressure drop was found to closely approximate that for an equivalent length of curved tube with the same curvature ratio as in the model bifurcation. The sensitivity of these results to changes in airway cross-sectional shape, non-planar configuration, and flow regime (laminar-turbulent) was investigated. In separate experiments using dye visualization and hot-wire anemometry, a transition to turbulent flow was observed at Reynolds numbers between 1000 and 1500. Transition had very little effect on the pressure-flow relation.

Acceleration