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PubMed1993

Volume and osmotic properties of human neutrophils.

Quantitative models describing the dynamics of human neutrophils in the microcirculation require accurate morphometric parameters such as volume and surface membrane area. Using both a micropipette technique and video light microscopy (LM) to measure the diameters of the spherical cells, we have accurately determined the volume of the human neutrophil. Our value, 299 +/- 32 microns 3, is in good agreement with our earlier results, but 55% larger than that reported by Schmid-Schönbein et al (Blood 56:866, 1980). However, the measurements of Schmid-Schönbein et al were based on the actual mass of the cells derived from transmission electron microscopic (TEM) images. The membrane surface area, at lysis, was calculated to be 2.6 times its initial projected area. After lysis, the cells do not reduce their size, indicative of the possibility of a F-actin network formation that would stiffen the structure. Further, we show that neutrophils behave as ideal osmometers when exposed to anisotonic solutions at 21 degrees C, as predicted by the Boyle-Van't Hoff relationship. The calculated Ponder's value, R, is 0.77, which corresponds to 77% of the cell volume being osmotically active under isotonic conditions. However, at 37 degrees C, the cells are able to regulate their volumes toward the original volumes after an osmotic stress.

Humans↗
PubMed1995

Dynamic patient data bases: the foundation of an integrated approach to outcome measures for the healthcare professionals.

In recent years there has been a tremendous need among healthcare professionals to assess the effectiveness, efficiency, and appropriateness of the patient care services being provided through criteria-based outcome and program evaluation. Although the need for a tool which could evaluate the effectiveness of patient care is widely recognized, such an undertaking has been severely limited due to the lack of any automated means to collect and analyze patient data on a routine, continuous basis within a clinical setting. We have developed and implemented at Mineral Springs Hospital, Banff, Alberta an integrated and automated hospital information system that not only continuously collects administrative, financial, and patient data, but also contains an intelligent component for automated outcome measure and program evaluation. The system collects various non-duplicated data elements from each routine work process within the facility on a continuous basis. Through the creation of a dynamic patient database, data is transformed into information--a powerful decision support tool. The system provides flexible user-defined reports in patient-specific resource utilization, direct and/or indirect specific financial costs, result reporting of each intervention, service provided and user-defined criteria-based outcome, and program evaluation. The system design incorporates expert rules, dynamic data entry forms, quantitative models, and user-defined access control. Using information derived from the dynamic common database, managers and front-line clinicians can easily evaluate and modify management decisions or careplans on a macro or micro level. An external review is planned to evaluate whether the system has helped the assessment of effectiveness, efficiency and appropriateness of healthcare services being provided at the hospital. The fundamental concept behind the system design is that the patient is the center of activity for data collection. The system provides the answers to the 5 W's (who, what, where, when, and why) together with intervention and service result reports. A dynamic common patient database is the center of the system and is accessible to all with proper authorization. Common data elements are collected from routine work flow without extra data entry and this information is subsequently shared. Data collection is a continuous process. We believe that every process is the outcome of another sub-process or event. The design of the dynamic patient database incorporates patient-specific costing and outcome evaluation, user-defined flexible data entry forms, user-defined access control, outcome evaluation rules and information semantic rules. Such a patient database would provide the flexibility needed to accommodate diverse methodologies to evaluate outcomes whether it they be medical, cost, access and/or other combination of measures. The system was developed on a PC-based Network technology, using FOXPRO (XBase) as the database development tool incorporating advanced technology such as distributed processing and fault tolerant computing. We chose PC-based technology because it is economical, having relatively low maintenance costs and requires no major dependency on vendors. The developed system produces patient-specific reports with many dimensions. The reports are user-defined. The system reports general data, CMG, RGN, LOS, Expected LOS, and other user-defined demographic data. Resource utilization, financial costs, and result reportings are produced together with rule-based outcome assessments of any type of measures, including, but not limited to, pre-set functional/health goals, user satisfaction, clinicianUs text or codified comments etc. It provides the framework for continually capturing data at a practical, work-flow level. The incorporation of a dynamic patient database as the driving forece of an integrated, rule-based administration, financial and patient data system will provdie the tools for healthcar

Databases, Factual↗
PubMed1995

A knowledge-based care protocol system for ICU.

There is a growing interest in using care maps in ICU. So far, the emphasis has been on developing the critical path, problem/outcome, and variance reporting for specific diagnoses. This paper presents a conceptual knowledge-based care protocol system design for the ICU. It is based on the manual care map currently in use for managing myocardial infarction in the ICU of the Sturgeon General Hospital in Alberta. The proposed design uses expert rules, object schemas, case-based reasoning, and quantitative models as sources of its knowledge. Also being developed is a decision model with explicit linkages for outcome-process-measure from the care map. The resulting system is intended as a bedside charting and decision-support tool for caregivers. Proposed usage includes charting by acknowledgment, generation of alerts, and critiques on variances/events recorded, recommendations for planned interventions, and comparison with historical cases. Currently, a prototype is being developed on a PC-based network with Visual Basic, Level-Expert Object, and xBase. A clinical trial is also planned to evaluate whether this knowledge-based care protocol can reduce the length of stay of patients with myocardial infarction in the ICU.

Alberta↗
PubMed1996

Rheological studies of creams. III. Effect of lipophilic phase on consistency.

The 3rd part of the serial analyses the correlation between the rheological characteristics of creams and the composition of the lipophilic phase. It is proved qualitatively by comparison of flow curves of systems with identical water content, and quantitatively by changes of initial, equilibrium and plastic viscosity, that the main factor in structure formation is the interboundary interaction of the hydrophilic and the lipophilic phase. This interaction can be characterised by determining wetting. A correlation between the contact angle of wetting between the hydrophilic and lipophilic phases (the quantitative model of the interboundary interaction) and the rheological parameters was identified. A logarithmic relationship was established between the contact angle of wetting and the yield value and structural viscosity.

Emulsions↗
PubMed1996

[Evaluation of multidrug resistance phenotype on medullary specimens from patients with acute leukemia by determination of nuclear efflux of tetrahydropyranyl-doxorubicin. Approach by confocal laser microspectrofluorometry].

Confocal microspectrofluorometry allows the analysis of fluorescent molecules such as anthracylines in isolated living cells. An optical microscope fitted with a phase-contrast 100 X water-immersion objective enables simultaneous observation of the sample, focusing of the laser beam on the selected cell fraction (nucleus) and collection of the fluorescence emitted from the sample. The resulting intranuclear spectra are interpreted according to a quantitative model of the fluorescence spectra of both free and DNA-bound anthracycline. The intranuclear drug concentration can thus be determined. This technique has been applied to blast cells collected in patients with acute leukemia. Leukemic cells are aspirated from bone marrow, separated by Ficoll sedimentation and resuspended in RPMI-1640 containing 10% fetal calf serum and 200 nM tetrahydropyranyl-doxorubicin (THP-DOX). After one hour, 20 cells are analyzed and the mean nuclear drug content is determined (C1). Cells are then resuspended in the same medium but without anthracycline for 3 hours and the mean intranuclear drug concentration is then also determined (C3). From C1 and C3 the retention rate (RR) is calculated. Firstly, the accuracy of the method was checked. In 4 AML patients, two different samples aspirated on the same day were divided into two portions. Thus, two measurements were made on each one (4 values per patient). Coefficients of variation were satisfactory (4, 6, 12, and 12%). Secondly, blast cells collected in patients with AML and ALL at diagnosis or in relapse were studied. P-glycoprotein (P-gp) and CD34 expression was also studied using respectively immunohistochemistry land flow cytometry. Results obtained from the first 21 patients showed that there was no correlation between RR and either P-gp or CD34 expression. This could result from the efflux of THP-DOX by other mechanisms and/or low sensitivity of the staining technique.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Vascular wound healing and neointima formation induced by perivascular electric injury in mice.

Vascular interventions for atherothrombotic disease frequently induce neointima formation, which can contribute to restenosis of blood vessels. As the molecular mechanisms of this process remain largely unknown, quantitative models of arterial injury in transgenic animals may be useful to study this process at the genetic level. Here, an injury model is proposed in which surgically exposed femoral arteries in mice were injured perivascularly via a single delivery of an electric current. Transmission electron microscopy, light microscopy, and immunohistochemistry revealed that electric injury destroyed all medial smooth muscle cells, denuded the injured segment of intact endothelium, and transiently induced platelet-rich mural thrombosis. A vascular wound-healing response resulted that was characterized by degradation of the mural thrombus, transient infiltration of the vessel wall by inflammatory cells, and progressive removal of the necrotic debris. Topographic analysis revealed repopulation of the media and accumulation in the neointima of smooth muscle cells originating from the uninjured borders and progressing into the necrotic center. Within 3 weeks after injury, a neointima of 0.026 +/- 0.003 mm2 (n = 7 arteries) was formed that contained a maximum of 12 +/- 1 layers of smooth muscle alpha-actin-immunoreactive cells. Evans blue staining in five electrically injured arteries revealed a denuded distance of 2.8 +/- 0.2 mm immediately after injury, which became progressively re-endothelialized from the uninjured borders to 2.2 +/- 0.08 mm (P = 0.013 vs freshly injured by analysis of variance), 0.8 +/- 0.22 mm (P < 0.001), and 0.005 +/- 0.003 mm (P < 0.001) within 2, 7, and 14 days after injury, respectively. Analysis of 5'-bromo-2'-deoxyuridine incorporation revealed that a maximum of 35 +/- 10% endothelial cells proliferated within 2 days after injury and that in the media and neointima, a maximum of, respectively, 12 +/- 2% and 18 +/- 3% smooth muscle cells proliferated within 2 weeks after injury. Thus, electric injury of arteries provides a model of vascular wound healing with arterial neointima formation and re-endothelialization that may be useful for the genetic analysis of its molecular mechanisms in transgenic mice.

Animals↗
PubMed1997

Information processing through the first year of life: a longitudinal study using the visual expectation paradigm.

This Monograph uses a developmental function approach to describe age-related change and individual differences in infant information processing during the first year of life. The Visual Expectation Paradigm (VExP) is used to measure speed of information processing, response variability, and expectancy formation. Eye-movement reaction times and anticipatory saccades were gathered from 13 infants assessed monthly from 2 to 9 months and then again at 12 months. Analysis of response patterns demonstrated the applicability of the paradigm throughout the age range studied. Converging operations strongly indicate that the traditional estimate of the minimum time required for infants to initiate a saccade to a peripheral stimulus may be as much as 100 milliseconds (ms) too long. Moreover, the newly estimated minimum of 133 ms does not appear to change during the 2-12-month period. Reanalysis of the present data and past research reveals that the new, shorter minimum reaction time is unlikely to affect findings based on mean reaction time. However, using the traditional minimum reaction time will inflate estimates of percentage anticipation, especially in infants older than 5 months. Group and individual growth curves are described through quantitative models of four variables: reaction time, standard deviation of reaction time, percentage anticipation, and anticipation latency. Developmental change in reaction time was best described by an asymptotic exponential function, and evidence for a local asymptote during infancy is presented. Variability in reaction time was found to decline with age, independent of mean reaction time, and was best described by a polynomial function with linear and quadratic terms. Anticipation showed little lawful change during any portion of the age span, but latency to anticipate declined linearly throughout the first year. Stability of individual differences was strong between consecutive assessments of mean reaction time. For nonconsecutive assessments, stability was found only for the 6-12-month period. Month-to-month stability was inconsistent for reaction-time variability and weak for both anticipation measures. Analyses of individual differences in growth curves were carried out using random regressions for the polynomial models. The only significant individual difference (in growth curves) was found for reaction-time variability. Parameter estimates from the exponential models for reaction time suggested two or three developmental patterns with different exponential trajectories. This finding indicates that the strong form of the exponential growth hypothesis, which states that processing speed develops at the same rate for all individuals, does not hold for the first year of life. In the concluding chapter, Grice's Variable Criterion Model (Grice, 1968) is used to integrate three key findings: regular age changes in mean reaction time and variability but no age change in the minimum reaction time. It is argued that the rate of growth of sensory-detection information is developmentally constant during much of the first year but that age changes occur in the level and spread of the distribution of response threshold values. The unique strengths of the paradigm are discussed, and future directions are suggested for further developing the paradigm itself and for using it as a tool to study broad issues in infant cognition.

Eye Movements↗
PubMed1997

[Information model of systemic organization of human mental functions: new approach to the problem of artificial intelligence].

The information model of systemic functions of the human brain reproduces important features of human intelligence: goal planning, prediction of needed results, behavior correction by feedback from the parameters of the results obtained and their comparison with the acceptor of action results. Human behavior imitation in the model is statistically proved by testing the model on a computer. An Adaptron apparatus based on the model quantitatively estimates the parameters of an important mechanism of the brain, namely human intuitive learning. With the Adaptron, the ade-dependent properties and some human intellectual dysfunctions are estimated, which reflect the mechanisms of prediction of future results, the building of memory traces in intuitive learning when the findings coincide with the planned results and the restructure of memory and respective behavior changes when the findings do not coincide with the planned ones.

Artificial Intelligence↗
PubMed1998

Defining affinity with the GABAA receptor.

At nicotinic and glutamatergic synapses, the duration of the postsynaptic response depends on the affinity of the receptor for transmitter (Colquhoun et al., 1977;Pan et al., 1993). Affinity is often thought to be determined by the ligand unbinding rate, whereas the binding rate is assumed to be diffusion-limited. In this view, the receptor selects for those ligands that form a stable complex on binding, but binding is uniformly fast and does not itself affect selectivity. We tested these assumptions for the GABAA receptor by dissecting the contributions of microscopic binding and unbinding kinetics for agonists of equal efficacy but of widely differing affinities. Agonist pulses applied to outside-out patches of cultured rat hippocampal neurons revealed that agonist unbinding rates could not account for affinity if diffusion-limited binding was assumed. However, direct measurement of the instantaneous competition between agonists and a competitive antagonist revealed that binding rates were orders of magnitude slower than expected for free diffusion, being more steeply correlated with affinity than were the unbinding rates. The deviation from diffusion-limited binding indicates that a ligand-specific energy barrier between the unbound and bound states determines GABAA receptor selectivity. This barrier and our kinetic observations can be quantitatively modeled by requiring the participation of movable elements within a flexible GABA binding site.

Animals↗
PubMed1985

Radiation brain damage induced by interstitial 125I sources: a canine model evaluated by quantitative computed tomography.

The canine brain is a good model of the human brain for studying radiation damage after megavoltage x-irradiation for brain tumors. We have further developed this model to study radiation damage induced by high activity interstitial 125I sources. Removable 125I sources were implanted in normal canine brains, and doses of 1,000 to 10,000 rads were delivered to a reference point at a 10-mm radius from the source; dose rates were 35 to 40 rads/hour at the reference point. Serial quantitative analysis of tissue damage (tissue density and contrast enhancement) was done using computed tomographic scanning up to 6 months after implantation and was compared to histopathological findings after the animals were killed. At doses greater than 19,000 rads (i.e., inside the reference point), frank coagulation necrosis was observed. Pronounced vessel-related changes, manifest as areas of contrast enhancement, corresponded to tissues receiving a minimum of 6,000 rads and a maximum of 19,000 rads. These results indicate that this model can be used in serial noninvasive studies to quantify the development of damage induced by interstitial irradiation and to provide dose-response information in individual animals.

Animals↗
PubMed1992

An experimental model for simultaneous quantitative analysis of pulmonary micro- and macrocirculation during unilateral hypoxia in vivo.

An experimental model was developed for quantitative analysis of pulmonary microcirculation using in vivo fluorescence videomicroscopy during unilateral hypoxia induced by one-lung ventilation (1 LV). In five white New Zealand rabbits, pulmonary arterioles on the surface of the right lung were visualized by means of intra-arterial injection of FITC-labeled erythrocytes and FITC-Dextran. During 1 LV of the left lung, the mean airway pressure in the right lung was kept at the level of two-lung ventilation (2 LV) by means of N2-CPAP. Arteriolar diameters as well as parameters of macrocirculation (AP, CVP, PAP, LAP, CO) and gas exchange (paO2, Qs/Qt) were measured simultaneously during 2 LV and 1 LV. FiO2 was kept constant at 1.0 during both experimental phases. Macrohemodynamic parameters during 1 LV did not differ from those measured during 2 LV. 1 LV induced a significant decrease in paO2 (213 +/- 105 versus 427 +/- 22 mm Hg, P < 0.05) and a significant increase in Qs/Qt (22 +/- 7 versus 13 +/- 2%, P < 0.05). During 2 LV (baseline), the pulmonary arteriolar diameters ranged from 15-120 microns. 1 LV resulted in a significant decrease of arteriolar diameters to 89.0 +/- 9.3% of baseline (P < 0.05). Relative changes in arteriolar diameters were similar for vessels with baseline diameters of 0-40, 40-60, and 60-120 microns (88.4 +/- 9.9%, 89.6 +/- 9.4%, and 88.4 +/- 8.7%, respectively). The present model is the first one allowing in-vivo investigation of HPV during 1 LV and 2 LV on the basis of simultaneous measurement of pulmonary arteriolar diameters and macrocirculatory parameters in vivo. Although PAP and PVR did not change significantly, a reduction of pulmonary arteriolar diameters was proven in response to alveolar hypoxia during 1 LV. We suggest the model to be useful in studying the physiological effects of HPV on macro- and microcirculation as well as investigating pathophysiological and pharmacological influences on HPV.

Animals↗
PubMed2003

The topomer search model: A simple, quantitative theory of two-state protein folding kinetics.

Most small, single-domain proteins fold with the uncomplicated, single-exponential kinetics expected for diffusion on a smooth energy landscape. Despite this energetic smoothness, the folding rates of these two-state proteins span a remarkable million-fold range. Here, we review the evidence in favor of a simple, mechanistic description, the topomer search model, which quantitatively accounts for the broad scope of observed two-state folding rates. The model, which stipulates that the search for those unfolded conformations with a grossly correct topology is the rate-limiting step in folding, fits observed rates with a correlation coefficient of approximately 0.9 using just two free parameters. The fitted values of these parameters, the pre-exponential attempt frequency and a measure of the difficulty of ordering an unfolded chain, are consistent with previously reported experimental constraints. These results suggest that the topomer search process may dominate the relative barrier heights of two-state protein-folding reactions.

Amino Acids↗
PubMed1976

A new culture model facilitating rapid quantitative testing of mitotic spindle inhibition in mammalian cells.

A new culture model, which facilitated both mass screening of potential anticancer drugs acting on microtubules and quantitative experiments with known "antitubulins," was found to have the following advantages: use of mammalian cells (either transformed or not), simplicity of the techniques (phase-contrast microscopy or simple microscopy after Giemsa staining), and ease with which it lent itself to quantification. The model was based on the uniform multimicronucleation response induced by antitubulins in MO cells. The specificity (towards antitubulins) of this response was ascertained by the use of many substances, including most of the known antitubulins and a number of nonrelated cytostatic or cytotoxic compounds. The uniformity of the response was established with the use of time-lapse observation of large numbers of cells and quantitative approaches. The results obtained in this model with the standard antitubulins (colchicine, vinblastine, vincristine) showed similar effects. The major difference between colchicine and the Vinca alkaloids was that colchicine was less reversible, which might be an indication of stronger intracellular binding. The Vinca alkaloids acted synergistically with colchicine when threshold subactive doses were combined, although it is known that they bind at a different site on tubulins. A number of substances that have been claimed or were suspected to interfere with microtubules were tested. The results showed that the following substances were indeed active with MO cells: colchicine, vinblastine, vincristine, podophyllotoxin, rotenone, griseofulvin, mercaptoethanol, benomyl, methyl benzimidazol-2-yl carbamate, and R 17934. Compounds that were inactive on these mammalian cells in culture included isopropyl carbanilate and melatonin, both of which have been shown to be active in other systems.

Antineoplastic Agents↗
PubMed2000

A population genetics model for multiple quantitative traits exhibiting pleiotropy and epistasis.

We study a population genetics model of an organism with a genome of L(tot)loci that determine the values of T quantitative traits. Each trait is controlled by a subset of L loci assigned randomly from the genome. There is an optimum value for each trait, and stabilizing selection acts on the phenotype as a whole to maintain actual trait values close to their optima. The model contains pleiotropic effects (loci can affect more than one trait) and epistasis in fitness. We use adaptive walk simulations to find high-fitness genotypes and to study the way these genotypes are distributed in sequence space. We then simulate the evolution of haploid and diploid populations on these fitness landscapes and show that the genotypes of populations are able to drift through sequence space despite stabilizing selection on the phenotype. We study the way the rate of drift and the extent of the accessible region of sequence space is affected by mutation rate, selection strength, population size, recombination rate, and the parameters L and T that control the landscape shape. There are three regimes of the model. If LT< >L(tot), there are many small peaks that can be spread over a wide region of sequence space. Compensatory neutral mutations are important in the population dynamics in this case.

Animals↗
PubMed1975

A model for the quantitative study of Arthus (immunologic) hypersensitivity in rats.

A model of reverse passive Arthus (RPA) reaction in the pleural cavity of rats is described. The time course of development of exudate and migration of cells has been examined. It has been found to be complement dependent and dominated by polymorphonuclear cells. The reaction reaches a peak around 6 hours after challenge. Cyclic AMP levels have been measured both intracellularly and extracellularly and have been found to persist at high levels after the waning of the reaction.

Animals↗
PubMedDate not supplied

Everted rat intestinal sacs: a new model for the quantitation of P-glycoprotein mediated-efflux of anticancer agents.

P-Glycoprotein (p-gp) situated in the epithelium of the gastrointestinal tract is a recognised barrier limiting oral absorption of antitumour agents. Here we describe the rat everted gut sac as a new in vitro model for quantitation of p-gp-mediated efflux of anti-cancer agents using [3H]vinblastine, [14C] doxorubicin and verapamil as reference compounds. Tissue and serosal uptake of [3H]vinblastine was linear over 90 min (0.031 +/- 0.001 and 0.003 +/- 0.001 ng/mg protein/h respectively). [14C]Doxorubicin tissue accumulation was significantly lower; 0.006 +/- 0.001 ng/mg protein/h (p < 0.05) whereas serosal transfer was significantly higher 0.017 +/- 0.001 ng/mg protein/h (p < 0.05) than [3H]vinblastine. Addition of verapamil (40 ng/mL) increased significantly both tissue accumulation of [3H] vinblastine and [14C]doxorubicin (to 0.060 +/- 0.024 and 0.034 +/- 0.012 ng/mg protein/h respectively) and serosal transfer (to 0.006 +/- 0.002 and 0.023 +/- 0.001 ng/mg protein/h) (p < 0.05 in all cases). The reproducibility of this in vitro model suggests that the rat everted gut sac is a useful screening tool for studying transport of p-gp substrates and potential p-gp modifiers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

A quantitative risk assessment model for Salmonella and whole chickens.

Existing data and predictive models were used to define the input settings of a previously developed but modified quantitative risk assessment model (QRAM) for Salmonella and whole chickens. The QRAM was constructed in an Excel spreadsheet and was simulated using @Risk. The retail-to-table pathway was modeled as a series of unit operations and associated pathogen events that included initial contamination at retail, growth during consumer transport, thermal inactivation during cooking, cross-contamination during serving, and dose response after consumption. Published data as well as predictive models for growth and thermal inactivation of Salmonella were used to establish input settings. Noncontaminated chickens were simulated so that the QRAM could predict changes in the incidence of Salmonella contamination. The incidence of Salmonella contamination changed from 30% at retail to 0.16% after cooking to 4% at consumption. Salmonella growth on chickens during consumer transport was the only pathogen event that did not impact the risk of salmonellosis. For the scenario simulated, the QRAM predicted 0.44 cases of salmonellosis per 100,000 consumers, which was consistent with recent epidemiological data that indicate a rate of 0.66-0.88 cases of salmonellosis per 100,000 consumers of chicken. Although the QRAM was in agreement with the epidemiological data, surrogate data and models were used, assumptions were made, and potentially important unit operations and pathogen events were not included because of data gaps and thus, further refinement of the QRAM is needed.

Animals↗
PubMed2000

The use of mixture models to perform quantitative tests for linkage disequilibrium, maternal effects, and parent-of-origin effects with incomplete subject-parent triads.

The transmission disequilibrium test and related methods require complete triads of genotyped cases plus both parents to test for linkage disequilibrium in the presence of population stratification. Based on the work of Weinberg (1999ab) and Schaid and Li (1997) with dichotomous outcomes, we discuss how additional tests for maternal or parent-of-origin effects can be performed and incomplete subject-parent triads can be used in situations where the outcome is a quantitative variable. This is achieved using a finite mixture model where class membership is known for complete triads and unknown for incomplete triads. Simulations were performed assuming different genetic models and various amounts of missing parental genotypes. Results showed that the tests resulted in accurate Type I errors, recovered much of the loss in information caused by missing genotypes, and yielded unbiased parameter estimates. Extensions of the model to nuclear families, multiple loci, and multiple outcome variables are briefly discussed.

Alleles↗

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