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PubMed1999

Evaluation of orthodontists' perception of treatment need and the peer assessment rating (PAR) index.

This paper examines the relationship between orthodontists' subjective assessment of treatment need and objective measurements obtained during standardized intra- and extraoral examinations. Logistic regression modeling was used to develop predictive models of treatment need. Data were obtained from 1155 eighth-grade students by four orthodontists who used standardized examination forms to assess demographics, trauma, skeletal relationships, morphologic malocclusion traits, and mandibular function. At the conclusion of the examination, the orthodontist rated the subjective treatment need as none, elective, recommended, soon, or immediate. For some analyses, the categories were collapsed to represent no need and need. The peer assessment rating (PAR) index (American validated version) was computed from the clinical exam findings and scoring of dental models; PAR scores were used to document malocclusion severity and treatment difficulty. Spearman rank correlation coefficients quantified the relationship between PAR scores and need categories. Logistic regression analysis modeled treatment need using components of the PAR index as well as other variables. The components of these models, as well as sensitivity and specificity, were compared with malocclusion severity/treatment difficulty scores obtained from malocclusion assessments using the PAR index. The five subjective treatment need categories and the PAR index scores were significantly correlated (rho = 0.62, p<0.001). Significant differences were detected between the need and no need groups for all PAR components (p<0.001). PAR index scores and predicted probabilities from logistic regression models performed equally well for classification purposes (no need, need). The data suggest that the PAR index is highly correlated with orthodontists' subjective assessment of treatment need when that assessment is made in the absence of financial considerations and patient desires.

Adolescent↗

PubMed2005

Assessing genetically modified crops to minimize the risk of increased food allergy: a review.

The first genetically modified (GM) crops approved for food use (tomato and soybean) were evaluated for safety by the United States Food and Drug Administration prior to commercial production. Among other factors, those products and all additional GM crops that have been grown commercially have been evaluated for potential increases in allergenic properties using methods that are consistent with the current understanding of food allergens and knowledge regarding the prediction of allergenic activity. Although there have been refinements, the key aspects of the evaluation have not changed. The allergenic properties of the gene donor and the host (recipient) organisms are considered in determining the appropriate testing strategy. The amino acid sequence of the encoded protein is compared to all known allergens to determine whether the protein is a known allergen or is sufficiently similar to any known allergen to indicate an increased probability of allergic cross-reactivity. Stability of the protein in the presence of acid with the stomach protease pepsin is tested as a risk factor for food allergenicity. In vitro or in vivo human IgE binding are tested when appropriate, if the gene donor is an allergen or the sequence of the protein is similar to an allergen. Serum donors and skin test subjects are selected based on their proven allergic responses to the gene donor or to material containing the allergen that was matched in sequence. While some scientists and regulators have suggested using animal models, performing broadly targeted serum IgE testing or extensive pre- or post-market clinical tests, current evidence does not support these tests as being predictive or practical. Based on the evidence to date, the current assessment process has worked well to prevent the unintended introduction of allergens in commercial GM crops.

Animals↗

PubMed2006

Flashing liquid jets and two-phase droplet dispersion I. Experiments for derivation of droplet atomisation correlations.

The large-scale release of a liquid contained at upstream conditions above its local atmospheric boiling point is a scenario often given consideration in process industry risk analysis. Current-hazard quantification software often employs simplistic equilibrium two-phase approaches. Scaled water experiments have been carried out measuring droplet velocity and droplet size distributions for a range of exit orifice aspect ratios (L/d) and conditions representing low to high superheat. 2D Phase-Doppler Anemometry has been utilised to characterise droplet kinematics and spray quality. Droplet size correlations have been developed for non-flashing, the transition between non-flashing and flashing, and fully flashing jets. Using high-speed shadowography, transition between regimes is defined in terms of criteria identified in the external flow structure. An overview companion paper provides a wider overview of the problem and reports implementation of these correlations into consequence models and subsequent validation. The fluid utilised throughout is water, hence droplet correlations are developed in non-dimensional form to allow extrapolation to other fluids through similarity scaling, although verification of model performance for other fluids is required in future studies. Data is reduced via non-dimensionalisation in terms of the Weber number and Jakob number, essentially representing the fluid mechanics and thermodynamics of the system, respectively. A droplet-size distribution correlation has also been developed, conveniently presented as a volume undersize distribution based on the Rosin-Rammler distribution. Separate correlations are provided for sub-cooled mechanical break-up and fully flashing jets. This form of correlation facilitates rapid estimates of likely mass rainout quantities, as well as full distribution information for more rigorous two-phase thermodynamic modelling in the future.

Aerosol Propellants↗

PubMedDate not supplied

Industrial odorants: the relationship between modeled exposure concentrations and annoyance.

In a series of epidemiologic studies, the relationship between objective exposure to odorant concentrations emitted by several industrial plants was investigated, as was the relationship between odor annoyance and subjective health complaints. Exposure was determined with a dispersion model of odorants, in which meteorological data and industrial emissions were used as input. Long-term averaged exposure was related to odor annoyance measured with a questionnaire. In addition, the influence of several other factors (demographic variables and variables emanating from the coping theory) on odor annoyance was studied. Among others, it appears that the dispersion model performs moderately well in predicting annoyance (correlations between odorant concentrations and odor annoyance were about 0.35). The extent to which people regard mal-odor as a threat to their health is a relatively strong predictor of annoyance. Moreover, the effects of long-term low exposure are similar to the effects of temporary high exposure.

Adaptation, Psychological↗

PubMed1994

A comparison of normal and nonnormal mixed models for number of lambs born in Norwegian sheep.

A comparison of linear (LM), threshold (TM), and Poisson (PM) mixed models for genetic analysis of number of lambs born (NLB) from 1-yr-old ewes was conducted using 37,718 and 18,633 records of two Norwegian breeds, Dala and Spaelsau, respectively. Models fitted included flock-year as a fixed effect and the random effect of sire. In the Poisson model, the residual variation was assumed to be Poisson, whereas it was normal in LM and multinomial in TM. The models were compared with respect to goodness of fit, predictive ability, and ranking of sires. Goodness of fit and predictive ability were assessed via the mean squared error and the correlation between observed NLB and fitted (predicted) values. Predictive ability was evaluated by estimating effects of sire and flock-year using a random half of the data and then using these estimates to predict records on the other half of the data. The heritability of NLB for Dala was estimated to be .20, .39, and .08 with LM, TM, and PM, respectively. For Spaelsau, corresponding estimates were .12, .26, and .00, respectively. In the PM, problems of low or zero estimates of sire variances were encountered. Hence, an alternative sire variance (PM-L) was approximated from the heritability estimated on the outward scale by REML. All models performed similarly with respect to goodness of fit, predictive ability, and ranking of sires. The TM was very slightly better for both breeds, but the PM and PM-L seemed clearly poorer than TM and LM. An approximate test rejected the hypothesis that the conditional distribution of NLB was Poisson.

Animals↗

PubMed1997

Health status prediction in critically ill children: a pilot study introducing Standardized Health Ratios.

Performance of intensive care is usually quantified by means of standardized mortality rates, where standardization is directed towards the severity of illness on admission. However, as more critically ill patients survive, functional outcome and quality of life of these patients becomes more important. In a prospective study in a 10-bed tertiary paediatric intensive care unit (ICU), admission and follow-up health status were collected for 209 surviving patients. For this cohort of patients, health status 1 year after admission was also predicted, using the quantified health-utility-index (HUI), as a value between 0 and 1. For this purpose, two alternative multiple regression models were constructed. The most important predictors of 1-year health status were the level of sensation, mobility and cognition on admission to which self-care, systolic blood pressure, oxygen, Glascow Coma Scale, glucose and age may be added. The two alternative predictive models performed equally well (R2 = 0.83 and 0.84 respectively), indicating that health status could be predicted to a significant degree. The concept of relating expected future health status (based on base-line health status), with actual (observed) health status is denoted with the Standardized Health Ratio (SHR). In combination with the Standardized Mortality Ratios (SMR), such a ratio may become a new comprehensive indicator of performance in intensive care medicine.

Adolescent↗

PubMed2005

Modelling the long-term behaviour of radiocaesium and radiostrontium in two Italian lakes.

The present paper describes the application of a state-of-the-art model to two lakes in central Italy (Trasimeno and Monterosi) for the assessment of migration parameters of (137)Cs and (90)Sr (migration velocity to sediment, transfer rates from sediment to water and to bottom sediment). Applications of a compartment model and a model based on the diffusion equation to predict the behaviour of pollutants in water and through bottom sediment are presented and discussed. The application of the diffusion equation shows some difficulties of a general nature and typical of such a modelling approach. Moreover, there is no evidence of significant improvements of the model performances when the diffusion equation is applied. Very low levels of sedimentation rate of suspended matter in Lake Monterosi were evaluated by the quantitative assessment of radiocaesium migrating to bottom sediment. This suggests that, in this lake, the removal of radionuclide from the water column is mainly due to the turbulent mixing of bottom sediment causing radionuclide burial.

Cesium Radioisotopes↗

PubMed2001

Evaluation of methods for prediction of bone mineral density by clinical and biochemical variables in perimenopausal women.

OBJECTIVES: to predict spinal and femoral bone mineral density (BMD) in perimenopausal women from simple clinical and biochemical variables. METHODS: 2016 women 3-24 months past last menstrual bleeding. Mean age 50.1+/-2.8 years. Age, height, weight, number of full term pregnancies, weekly hours of physical activity, sunbathing habits, use of sun bed, daily intake of calcium and vitamin D, smoking habits, consumption of alcohol, coffee, and tea, history of forearm or femoral neck fractures among the parents, serum osteocalcin (S-OC), serum bone specific isoenzyme of alkaline phosphatase (BSAP), and urine hydroxyproline/creatinine ratio (U-OHP) were used as predictors in three different mathematical models. Lumbar spine (L2-L4) and femoral neck BMD were measured by DEXA. Three mathematical models (multiple regression, logistic regression, and discriminant analysis) were applied. RESULTS: the multiple regression explained 19-21% of the total variation, and the logistic regression and discriminant function had a sensitivity between 53 and 67% with specificity ranging from 67 to 80%. Age, S-OC, serum bone specific alkaline phosphatase, and a maternal history of forearm or femoral neck fractures seemed to be reproducible risk factors for low bone mineral density irrespective of the mathematical model applied. When applied to a separate population, the models performed poorly. CONCLUSIONS: Simple clinical and biochemical variables are not useful to predict spinal and femoral BMD in the individual perimenopausal woman.

Alkaline Phosphatase↗

PubMed1998

Allelic association under map error and recombinational heterogeneity: a tale of two sites.

Recombination acts on the genetic map, not on the physical map. On the other hand, the physical map is usually more accurate. Choice of the genetic or physical map for positional cloning by allelic association depends on the goodness of fit of data to each map under an established model. Huntington disease illustrates the usual case in which the greater reliability of physical data outweighs recombinational heterogeneity. Hemochromatosis represents an exceptional case in which unrecognized recombinational heterogeneity retarded positional cloning for a decade. The Malecot model performs well for major genes, but no approach assuming either equilibrium or disequilibrium has been validated for oligogenes contributing to common disease. In this case of greatest interest, the power of allelic association relative to linkage is less clear than for major genes.

Alleles↗

PubMed1994

A simulation model of clustered breast microcalcifications.

A simulation model of clustered microcalcifications superimposed on normal mammographic backgrounds has been developed and evaluated. A cluster is described according to its size, the number of microcalcifications it contains, and their density. A microcalcification is defined on the basis of its size, shape, location within the cluster, its contrast, and the distribution of the gray-level values between pixels that belong to it. Gray-level parameters are dependent on the surrounding tissue, which is also slightly modified. The main dependencies between the parameters are taken into account. All the parameters are randomly sampled using distribution laws determined from the statistical analysis of 408 real clusters containing a total of 8611 microcalcifications. Some statistical characteristics depend on the structural mammographic pattern on which the cluster is superimposed. The evaluation of the simulation model, performed by two radiologists on a test set of 100 real and simulated clusters, did not reveal any statistically significant difference between the simulated clusters and the real ones. This method provides clusters of microcalcifications with well-defined characteristics and can be used to evaluate the accuracy of computerized detection methods.

Biophysical Phenomena↗

PubMed2006

Probabilistic biokinetic modelling of radiocaesium uptake in Arctic seal species: verification of modelled data with empirical observations.

The necessity to provide information about radionuclide concentrations in Arctic marine species has been heightened in recent years due to a number of accidents in Arctic regions involving nuclear vessels and the presence of a large number of potential radioactive contamination sources. The provision for such information is largely dependent on the use of radionuclide uptake and transfer models. The uptake of radionuclides in Arctic seal species in this study has been modelled using a probabilistic biokinetic approach. In this paper, model results are compared with empirical data from relevant samples taken within the Arctic region. Results indicate that the model performs well when estimating concentrations of (137)Cs in two seal species for both median values and reproduction of the distribution of data values, but not as well for a third seal species. Likely factors affecting the results are the probability density functions used for the input parameters.

Animals↗

PubMed2026

Toward AI Virtual Cells for Hepatology: Representation, Generation, Dynamics, and Intervention in Single-Cell Models.

``Single-cell and spatial atlases describe the healthy and diseased liver at high resolution, including lobular hepatocyte zonation, fibrotic macrophage-stellate niches, cholangiocyte reactions, immune remodeling, and hepatocellular carcinoma ecosystems. These maps show where cell states occur but do not, by themselves, predict whether liver injury will progress or how the liver will respond to an untested drug, toxicant, or genetic perturbation. In this review, we organize current approaches toward an AI Virtual Cell (AIVC) for the liver into three complementary modeling routes. Generative models represent cell states, dynamics and transport models infer state transitions, and pretrained or foundation models test whether learned representations transfer across donors, etiologies, disease stages, and platforms. Perturbation-response prediction serves as a cross-cutting assessment of whether these layers can predict responses to untested genetic, chemical, inflammatory, or metabolic interventions. Available evidence can be categorized as direct liver validation, liver-included benchmarks, general single-cell evidence, and conceptual applications. Published models demonstrate individual components, including atlas integration, inferred trajectories, transferable representations, and retrospective response programs. However, these models do not constitute a prospectively validated liver simulator. At minimum, evaluation should include donor-, etiology-, stage-, platform-, and perturbation-level hold-outs. Model performance should be reported using response direction, recovery of differentially expressed genes and rare states, and calibrated uncertainty. Claims about tissue- or function-level prediction additionally require independent spatial, histologic, metabolic, and functional readouts. Near-term use should prioritize experiment selection and hypothesis generation, whereas clinical decision support remains a longer-term objective.

AI Virtual Cell↗

PubMed2005

Performance of prognostic models in critically ill cancer patients - a review.

INTRODUCTION: Prognostic models, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II or III, the Simplified Acute Physiology Score (SAPS) II, and the Mortality Probability Models (MPM) II were developed to quantify the severity of illness and the likelihood of hospital survival for a general intensive care unit (ICU) population. Little is known about the performance of these models in specific populations, such as patients with cancer. Recently, specific prognostic models have been developed to predict mortality for cancer patients who are admitted to the ICU. The present analysis reviews the performance of general prognostic models and specific models for cancer patients to predict in-hospital mortality after ICU admission. METHODS: Studies were identified by searching the Medline databases from 1994 to 2004. We included studies evaluating the performance of mortality prediction models in critically ill cancer patients. RESULTS: Ten studies were identified that evaluated prognostic models in cancer patients. Discrimination between survivors and non-survivors was fair to good, but calibration was insufficient in most studies. General prognostic models uniformly underestimate the likelihood of hospital mortality in oncological patients. Two versions of a specific oncological scoring systems (Intensive Care Mortality Model (ICMM)) were evaluated in five studies and showed better discrimination and calibration than the general prognostic models. CONCLUSION: General prognostic models generally underestimate the risk of mortality in critically ill cancer patients. Both general prognostic models and specific oncology models may reliably identify subgroups of patients with a very high risk of mortality.

APACHE↗

PubMed2001

Model-free linkage analysis: performance under real-world conditions.

The simulated data of the Genetic Analysis Workshop 12 problem set affords an ideal environment for testing real-world performance of model-free linkage analysis methods. To this end, we applied three different methods of model-free linkage analysis: mod scores [Hodge and Elston, Genet Epidemiol 11:329-42, 1994], maximized maximum lod score (MMLS) [Greenberg et al., Am J Hum Genet 63:870-9, 1998], and nonparametric linkage (NPL) scores [Whittemore and Halpern, Biometrics 50:118-27, 1994], as well as standard parametric linkage analysis to the detection of major gene 6 (MG6) using only the qualitative disease status data. Our results indicate that both mod scores and NPL scores perform well, even in the presence of an extremely complicated disease model. MMLS analysis did not perform well, except at the disease locus itself.

Chromosome Mapping↗

PubMed1995

The prevention of mechanical birth trauma by means of computer aided simulation of delivery by means of nuclear magnetic resonance imaging and finite element analysis.

Anatomic disproportion gains an increasing interest in obstetrics. Imaging procedures (radiologic pelvimetry, computed or magnetic resonance imaging (MRI) fail to reflect the dynamics of delivery including deformations of the birth channel as well as of fetal structures. To validate findings of imaging procedures in this respect a method has been developed to perform a dynamic, biomechanical postprocessing of the static informations obtained from MRI. Using an especially developed software MRI pixel matrices of maternal pelvis and fetal head were color-codef1p4d--according to the principle of same density--line data were created. After sectional attribution of the resulting polygones a three-dimensional mesh of so called Finite elements (FE) was created, which then can be used for deformation analysis. Fetal head was then moved through the birth channel by means of computed simulation. This allows not only ongoing deformations to be visualized but also resulting forces to be calculated for at any time of the delivery process for any point of the anatomical model. Performing these simulations assuming various anatomic and physiologic conditions an obstetrical-biomechanical data basis could be obtained, that was implemented in a PC-based expert system. This allows interpretation of pelvimetric data with regard to birth dynamics.

Biomechanical Phenomena↗

PubMed2005

Dynamic coordinate data for describing muscle-tendon paths: a mathematical approach.

When modelling the musculoskeletal system over a range of joint angles the use of fixed points to describe muscle-tendon paths has inherent limitations. These result in fewer deflection points and the use of effective insertions to accommodate both relative marker movement and avoid muscle paths contacting bony structures. Model performance is dependent on the joint angle relative to the anatomical position where the muscle-tendon paths were defined. The present study proposes a scheme for the implementation of dynamic coordinates for describing muscle-tendon paths. For each muscle-tendon element a plane is defined in which the muscle-tendon complex acts when crossing a given joint. The muscle-tendon plane is dependent on 3D segment orientations and describes one degree of freedom, while the remaining two degrees of freedom are described by polar coordinates and locate the dynamic point in the muscle-tendon plane. The dynamic approach is implemented on four muscles of the lower limb in modelled and simulated joint movements and offers a significant improvement on previous approaches based on fixed deflection points. The scheme accommodates compound 3D rotations about joint axes, is not computationally difficult or require large data sets, and does not impose limitations on the number of points that may be defined along a muscle-tendon path.

Biomechanical Phenomena↗

PubMed1987

Models of synchronized hippocampal bursts in the presence of inhibition. I. Single population events.

1. We constructed model networks with 520 or 1,020 cells intended to represent the CA3 region of the hippocampus. Model neurons were simulated in enough detail to reproduce intrinsic bursting and the electrotonic flow of currents along dendritic cables. Neurons exerted either excitatory or inhibitory postsynaptic actions on other cells. The network models were simulated with different levels of excitatory and inhibitory synaptic strengths in order to study epileptic and other interesting collective behaviors in the system. 2. Excitatory synapses between neurons in the network were powerful enough so that burst firing in a presynaptic neuron would evoke bursting in its connected cells. Since orthodromic or antidromic stimulation evokes both a fast and a slow phase of inhibition, two types of inhibitory cells were simulated. The properties of these inhibitory cells were modeled to resemble those of two types of inhibitory cells characterized by dual intracellular recordings in the slice preparation. 3. With fast inhibition totally blocked, a stimulus to a single cell lead to a synchronized population burst. Thus the principles of our epileptic synchronization model, developed earlier, apply even when slow inhibitory postsynaptic potentials (IPSPs) are present, as apparently occurs in the epileptic hippocampal slice. The model performs in this way because bursting can propagate through several generations in the network before slow inhibition builds up enough to block burst propagation. This can occur, however, only if connectivity is sufficiently large. With very low connection densities, slow IPSPs will prevent the development of full synchronization. 4. We performed multiple simulations in which the fast inhibitory conductance strength was kept fixed at various levels while the strength of the excitatory synapses was varied. In each simulation, we stimulated either one or four cells. For each level of inhibition, the peak number of cells bursting depended sensitively on excitatory synaptic strength, showing a sudden increase as this strength reached a critical level. The critical excitation, which depended on the level of inhibition, corresponded to the level at which bursting can propagate from cell to cell at the particular level of inhibition. 5. We performed an analogous series of simulations in which the strength of excitatory synapses was held constant while the strength of fast inhibitory synapses was varied, stimulating a single neuron in each case. These simulations correspond to experiments that have been done in the hippocampal slice as low doses of picrotoxin are washed into a slice, gradually abolishing fast inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1996

Intermittency route to chaos in a biochemical system.

The numerical analysis of a glycolytic model performed through the construction of a system of three differential-delay equations reveals a phenomenon of intermittency route to chaos. In our biochemical system, the consideration of delay time variations under constant input flux as well as frequency variations of the periodic substrate input flux allows us, in both cases, to observe a type of transition to chaos different from the 'Feigenbaum route'.

Biochemical Phenomena↗