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PubMed1991

Strategies for developing a family support group.

Various interventions may be used by nurses to provide social support to critical care families. Nurses may support family members in one-to-one relationships, or by facilitating the development of supportive relationships in the group setting. The steps described here are fundamental in developing a support group for family members of adults hospitalized in a surgical ICU to meet their predetermined needs. The support needs of family members and the timing of a support group during the critical care phase must first be validated. Once this assessment is completed, the support group may be based on the educational model, mutual-peer support model, educational-mutual support model, or ventilation model. The group model selected will provide direction to the structure, membership, and leadership of the support group. Regardless of the model considered appropriate for the needs of the family population and setting, critical care nurses need to evaluate the impact of the support group on the psychologic health of the family. The four different group perspectives clearly illustrate the need for nurses to determine what types of support are needed or are most beneficial for families during various phases of illness. Perhaps family members benefit from sharing and camaraderie during the acute or critical care phase, whereas educational support groups are more effective in reviewing illness and treatment implications after the immediate threat of the illness has passed. Findings from these evaluation studies will assist nurses in shaping intervention strategies for critical care family members in clinical practice.

Anxiety↗
PubMed1994

Host factors affecting seroprevalence of bluetongue virus infections of cattle.

Results of testing of 19,731 samples from a serologic survey of cattle with bluetongue virus (BTV) infections in Australia were analyzed for association between age, species, or sex and test result. Bivariate analysis indicated that all 3 host factors were associated with test result. After adjusting for confounding caused by the location of each animal in the study (high, moderate, and low BTV prevalence regions), cattle > or = 4 years old had an odds ratio of 4.33 (95% confidence interval, 3.99, 4.71) for a positive test result, compared with that for cattle < 2 years old. Cattle 2 to 4 years had an odds ratio of 2.28 (2.14, 2.54), compared with cattle < 2 years old. Bos taurus cattle had an odds ratio of 1.76 (1.63, 2.05) of a positive test result, compared with crossbred cattle, and B indicus cattle had an odds ratio of 1.20 (1.09, 1.33), compared with crossbred cattle. Sexually intact (+) male cattle were found to have an odds ratio of 3.13 (2.66, 3.49) for a positive test result, compared with castrated male (-) cattle, and female cattle were found to have an odds ratio of 1.38 (1.29, 1.48), compared with male (-) cattle. Multivariate analysis of BTV testing results was performed, using stepwise logistic regression. The most parsimonious model selected included age, species, and sex factors, and first-order interaction terms between these factors. This model was only able to be fit to data from cattle restricted to the high (> 25%) BTV prevalence region. Odds ratio were found to increase with age for male (-) cattle of all species.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1996

Genomic incompatibilities in the hybrid zone between house mice in Denmark: evidence from steep and non-coincident chromosomal clines for Robertsonian fusions.

The pattern of chromosomal variation is investigated in house mice from the Danish hybrid zone between the translocation-prone Mus musculus domesticus and the chromosomally conservative M. m. musculus. The cytogenetic analysis confirmed the non-introgression of three pairs of Robertsonian (Rb) fusions from M. m. domesticus into the M. m. musculus genome. The geographic distribution of two of these Rb fusions was shown to follow staggered chromosomal clines which increased in steepness the closer they were to the centre of the hybrid zone as defined by allozymes. Analysis of alternate hypotheses suggests that chromosomal differentiation of the Danish domesticus occurred after contact was established with musculus. The staggering of the clines would reflect the order of arrival of the Rb fusions into the hybrid zone. Several models with different processes of underdominance of the chromosomal heterozygotes are discussed to account for the difference in width between clines. A selective model with increasing levels of genomic underdominance due to interaction with a progressively enriched musculus genome provides the best fit for the observed pattern. Selection against Rb fusions with little effect on the recombination of linked allozyme markers supports the view that no reduction in gene flow due to chromosomal heterozygosity is yet apparent through the hybrid zone and that only the centromeric segments of the Rb fusions are incompatible with the musculus genome.

Animals↗
PubMed1999

Estimating the genetic architecture of quantitative traits.

Understanding and estimating the structure and parameters associated with the genetic architecture of quantitative traits is a major research focus in quantitative genetics. With the availability of a well-saturated genetic map of molecular markers, it is possible to identify a major part of the structure of the genetic architecture of quantitative traits and to estimate the associated parameters. Multiple interval mapping, which was recently proposed for simultaneously mapping multiple quantitative trait loci (QTL), is well suited to the identification and estimation of the genetic architecture parameters, including the number, genomic positions, effects and interactions of significant QTL and their contribution to the genetic variance. With multiple traits and multiple environments involved in a QTL mapping experiment, pleiotropic effects and QTL by environment interactions can also be estimated. We review the method and discuss issues associated with multiple interval mapping, such as likelihood analysis, model selection, stopping rules and parameter estimation. The potential power and advantages of the method for mapping multiple QTL and estimating the genetic architecture are discussed. We also point out potential problems and difficulties in resolving the details of the genetic architecture as well as other areas that require further investigation. One application of the analysis is to improve genome-wide marker-assisted selection, particularly when the information about epistasis is used for selection with mating.

Algorithms↗
PubMed2000

Summarizing the goodness of fit of generalized linear models for longitudinal data.

This paper extends four goodness-of-fit measures of a generalized linear model (GLM) to random effects and marginal models for longitudinal data. The four measures are the proportional reduction in entropy measure, the proportional reduction in deviance measure, the concordance correlation coefficient and the concordance index. The extended measures satisfy the basic requirements for measures of association. Two examples illustrate their use in model selection.

Adolescent↗
PubMed2005

Antitumor activity of erlotinib in combination with capecitabine in human tumor xenograft models.

PURPOSE: To examine the antitumor activity and tolerability of a combination comprising erlotinib and capecitabine in human colorectal, breast and epidermal cancer xenograft models. Further aims of the study were to examine the effects of single-agent erlotinib therapy on tumor growth, and on thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) levels, (enzymes which activate and deactivate capecitabine, respectively) in tumor tissue. METHODS: BALB/c nu/nu mice bearing LoVo and HT-29 (colon cancer), A-431 (vulval cancer), and KPL-4 and MAXF401 (breast cancer) human tumors were treated with erlotinib 100 mg/kg/day and/or capecitabine 359 or 90 mg/kg/day, by oral administration once daily for 14 days. RESULTS: The maximum tolerated dose (MTD) of erlotinib, formulated in carboxymethylcelluose/Tween 80, was identified as 125 mg/kg/day. Erlotinib at a dose of 100 mg/kg/day achieved significant tumor-growth inhibition in the, LoVo, KPL-4, and A-431 models. Some inhibition of MAXF401 tumor growth was observed, but was not significant. In the HT-29 model, erlotinib showed less marked but statistically significant antitumor activity. On day 15, mean tumor-growth inhibition in HT-29, LoVo, KPL-4, MAXF401, and A-431 models was 46, 74, 71, 20, and 85%, respectively. Evaluation of erlotinib/capecitabine combination therapy, at sub-optimal doses, in the three erlotinib-sensitive tumor models LoVo, KPL-4 and A-431, demonstrated at least additive activity with the combination compared with the single agents. In the A-431 and LoVo models, the combination of agents had greater antitumor activity than the single agent capecitabine alone at the MTD. Erlotinib in combination with capecitabine was not associated with significantly increased toxicity compared with single-agent therapy. Erlotinib 100 mg/kg/day induced significant upregulation of TP and DPD in the LoVo model, a significant upregulation of TP in the HT-29, MAXF401 and A-431 models, but had no obvious effect on TP and DPD levels in the KPL-4 model. In the A-431 model, selective upregulation of TP by erlotinib 100 mg/kg resulted in an increased TP:DPD ratio. In the LoVo model, immunohistochemistry revealed marked upregulation of TP (but not DPD by erlotinib). CONCLUSIONS: Erlotinib inhibits tumor growth in a range of human tumor xenograft models, including breast and colorectal cancer (CRC). Erlotinib and capecitabine demonstrated at least additive activity in LoVo, KPL-4 and A-431 tumor models. The antitumor activity of the combination was greater than that of capecitabine alone at the MTD. Erlotinib treatment did affect the TP in the CRC tumor models as confirmed immunohistochemically. The findings of this study support clinical evaluation of erlotinib, both as a single agent and in combination with capecitabine, for the treatment of CRC and breast cancer.

Animals↗
PubMed2006

A general bilinear model to describe growth or decline time profiles.

Linear models are widely used because of their unrivaled simplicity, but they cannot be applied for data that have a turning-or rate-change-point, even if the data show good linearity sufficiently far from this point. To describe such bilinear-type data, a completely generalized version of a linearized biexponential model (LinBiExp) is proposed here to make possible smooth and fully parametrizable transitions between two linear segments while still maintaining a clear connection with the linear models. Applications and brief conclusions are presented for various time profiles of biological and medical interest including growth profiles, such as those of human stature, agricultural crops and fruits, multicellular tumor spheroids, single fission yeast cells, or even labor productivity, and decline profiles, such as age-effects on cognition in patients who develop dementia and lactation yields in dairy cattle. In all these cases, quantitative model selection criteria such as the Akaike and the Schwartz Bayesian information criteria indicated the superiority of the bilinear model compared to adequate less parametrized alternatives such as linear, parabolic, exponential, or classical growth (e.g., logistic, Gompertz, Weibull, and Richards) models. LinBiExp provides a versatile and useful five-parameter bilinear functional form that is convenient to implement, is suitable for full optimization, and uses intuitive and easily interpretable parameters.

Adolescent↗
PubMed2005

Song learning in birds: diversity and plasticity, opportunities and challenges.

A common trend in neuroscience is convergence on selected model systems. Underlying this approach is an often implicit assumption that mechanisms observed in one species are characteristic of all related species. Although the model system approach has been extremely productive, it might not account for all of the mechanistic differences between species that differ behaviourally. Using the neural system that regulates song learning in songbirds as an example, we demonstrate how integrating model system and comparative approaches can lead to a more complete picture of neural mechanisms, and can resolve issues raised by a focus on selected species.

Animals↗
PubMed2000

Lipari-Szabo mapping: A graphical approach to Lipari-Szabo analysis of NMR relaxation data using reduced spectral density mapping.

In this paper, we explore connections between the Lipari-Szabo formalism and reduced spectral density mapping, and show how spectral density estimates can be associated with Lipari-Szabo parameters via a simple geometric construction which we call Lipari-Szabo mapping. This relationship can be used to estimate Lipari-Szabo parameters from spectral density estimates without the need for nonlinear optimization, and to perform 'model selection' in a graphical manner. The Lipari-Szabo map also provides insight into the Lipari-Szabo model, and allows us to determine when a given set of experimental spectral densities are inconsistent with the Lipari-Szabo formalism. Practical applications of Lipari-Szabo mapping in conjunction with more traditional analysis methods are discussed.

Anisotropy↗
PubMed1994

Evidence for the partial dominance of viability genes contributing to inbreeding depression in Mimulus guttatus.

The relative importance of different modes of gene expression of viability genes contributing to inbreeding depression was investigated in the wild plant, Mimulus guttatus. Viability genes were identified by self-fertilizing 31 outbred plants, each heterozygous for three to nine unlinked allozyme markers, and analyzing segregation ratios of selfed progeny at maturity for deviations from 1:2:1 ratios. In this study, 24 linkages of viability genes to marker loci were detected. To infer the nature of gene action for these viability genes, a "model-free" graphical method was developed that examines the "space" of segregation ratios allowed by each of seven selection models (i.e., overdominance, complete recessivity, partial recessivity, additivity, partial dominance, complete dominance and underdominance). Using this method, we found that, of 24 linkages detected, 18 were consistent with either partial dominance, complete dominance or underdominance. Six were consistent with either partial recessivity, complete recessivity or overdominance. This finding indicates that, in these chromosomal segments identified by allozyme markers, partial dominance plays the predominant role in inbreeding depression. This is inconsistent with either the dominance or overdominance hypotheses proposed to account for inbreeding depression.

Crosses, Genetic↗
PubMed1994

Assessment and control of nonresponse bias in a survey of medicine use by the elderly.

Health services research based on survey data is subject to potentially serious selection bias because observations are typically available only for survey respondents. This study describes a method of assessing and controlling for selection bias in the context of a survey of prescription and over-the-counter drug use by the elderly. A random sample of 6,500 Pennsylvania Medicare enrollees was sent a questionnaire regarding medicine use, insurance coverage, and health status in 1990. Applying a two-stage, limited dependent variable selection model developed by Heckman to baseline Medicare enrollment and utilization data for both respondents (70%) and nonrespondents (30%) allowed us to detect and control for negative and significant nonresponse bias in estimates of prescription drug use. Purchase of over-the-counter medication was free of such bias. The report describes how the Heckman method can be applied in other cases where health services survey samples are generated from program or organizational files that contain person-level data on all members of the sample frame.

Age Factors↗
PubMedDate not supplied

Integrated pharmacokinetic and metabolic modeling of ipriflavone and metabolites after oral administration.

PURPOSE: Disposition of ipriflavone, an agent indicated for the treatment of osteoporosis, is highly variable after oral administration. Ipriflavone has five major metabolites (M1, M2, M3, M4, and M5). The metabolites M2 and M5 have activity and are major metabolic constituents in humans. Hence, it is important to characterize both ipriflavone and metabolites simultaneously. Our purpose was to develop an integrated pharmacokinetic/metabolic model that simultaneously predicts plasma concentrations of ipriflavone and metabolites after a single oral administration. METHOD: The model was based on the reported metabolic conversion of ipriflavone to M1, M3, and M4; subsequent conversion of M4 to M5; and conversion of both M1 and M3 to M2 in rats. The further conversion of M5 to M6 and M7 was ignored, as this conversion represents an insignificant portion of the total metabolite pool. The input function was described by a first-order constant. Each analyte required two-compartment disposition. The elimination/nonmetabolic constants for each analyte accounted for urinary elimination. Plasma concentration data from a pilot pharmacokinetic study in which 16 healthy male volunteers were administered 200 mg of an ipriflavone corn suspension were used to examine the predictability of this model. RESULTS: The coefficient of determination was 0.99, and model selection criterion was 3.7 for mean data fits supporting the goodness-of-fit and predictability of the model. The model also predicted negligible urinary recoveries for ipriflavone, M1, M3, and M4; M2 and M5 had high urinary recoveries. The metabolic conversion constant from M3 to M2 was negligible. Divergence from the proposed pathway may be attributed to the species differences in metabolism between humans and rats. CONCLUSIONS: Model predictions supported the improvement in bioavailability with corn-oil suspension compared to the conventional oral tablet. Future model applications may also help identify significant covariates (i.e., age, gender, and disease state) in proposed clinical trials.

Administration, Oral↗
PubMed2004

Application of oscillating potentials to the Shaker potassium channel.

Nonequilibrium response spectroscopy (NRS) has been proposed recently to complement standard electrophysiological techniques used to investigate ion channels. It involves application of rapidly oscillating potentials that drive the ion channel ensemble far from equilibrium. It is argued that new, so far undiscovered features of ion channel gating kinetics may become apparent under such nonequilibrium conditions. In this paper we explore the possibility of using regular, sinusoidal voltages with the NRS protocols to facilitate Markov model selection for ion channels. As a test case we consider the Shaker potassium channel for which various Markov models have been proposed recently. We concentrate on certain classes of such models and show that while some models might be virtually indistinguishable using standard methods, they show marked differences when driven with an oscillating voltage. Model currents are compared to experimental data obtained for the Shaker K+ channel expressed in mammalian cells (tsA 201).

Cell Line↗
PubMed2004

Frequency-dependent selection with dominance: a window onto the behavior of the mean fitness.

Selection in which fitnesses vary with the changing genetic composition of the population may facilitate the maintenance of genetic diversity in a wide range of organisms. Here, a detailed theoretical investigation is made of a frequency-dependent selection model, in which fitnesses are based on pairwise interactions between the two phenotypes at a diploid, diallelic, autosomal locus with complete dominance. The allele frequency dynamics are fully delimited analytically, along with all possible shapes of the mean fitness function in terms of where it increases or decreases as a function of the current allele frequency in the population. These results in turn allow possibly the first complete characterization of the dynamical behavior by the mean fitness through time under frequency-dependent selection. Here the mean fitness (i) monotonically increases, (ii) monotonically decreases, (iii) initially increases and then decreases, or (iv) initially decreases and then increases as equilibrium is approached. We analytically derive the exact initial and fitness conditions that produce each dynamic and how often each arises. Computer simulations with random initial conditions and fitnesses reveal that the potential decline in mean fitness is not negligible; on average a net decrease occurs 20% of the time and reduces the mean fitness by >17%.

Alleles↗
PubMed2001

Methods and models to evaluate shear-dependent and surface reactivity-dependent antithrombotic efficacy.

The purpose of the present communication is to evaluate the importance of blood flow and surface reactivity for measurement of antithrombotic drug activity or efficacy in selected model systems of thrombus formation. Such information is essential for proper evaluation of antithrombotic drug profiles. The continuous development of flow-dependent thrombosis models for in vitro (anticoagulated blood) and ex vivo (native blood) studies and their application in in vivo animal models from the early 1970s and onwards are briefly considered. Central to this process was the development of various types of perfusion chambers in which a thrombogenic surface is exposed to flowing blood. Such perfusion chambers have been inserted into arteriovenous (AV) shunts in baboon, pig, dog, and rabbit. These approaches have allowed reproducible testing of traditional and novel experimental antithrombotic drugs, and studies on novel drug strategies under well-defined shear conditions and surface reactivity. Shear-dependent antithrombotic efficacy in these models is observed with anticoagulants such as unfractionated heparin, low-molecular weight heparins, or selective inhibitors of thrombin, Factor Xa, or Factor VIIa. However, the degree of shear dependency depends on the nature of the thrombogenic surface, e.g., the inhibition is more pronounced on a tissue factor (TF)-rich surface than on a collagen-rich surface, particularly at venous or low arterial shear. Platelet antagonists such as the COX-1 inhibitor aspirin, inhibitors of thromboxane A2 (TxA2) synthetase, the TxA2 platelet receptor, and of von Willebrand factor (vWf) are shear dependent also, being more efficient at high arterial shear. In contrast, the platelet ADP antagonist clopidogrel, or antagonists to the active platelet membrane glycoprotein IIb-IIIa complex (GPIIb-IIIa) are shear independent. At extremely high arterial shear, which activates platelets and elicit aggregates of circulating platelets, aspirin looses its antithrombotic effect, whereas ADP and GPIIb-IIIa antagonists still interrupt thrombus formation. In general, results obtained with these models mimic and predict antithrombotic efficacy in man when comparison is possible. Information on antithrombotic efficacy in flow devices with various thrombogenic surfaces is now sufficiently available to suggest recommendations for experimental conditions, particularly with regard to blood flow and reactive surfaces.

Animals↗
PubMed1993

Space-based visual attention models and object selection: constraints, problems, and possible solutions.

One of the functions of visual attention is the selection of object information. This seems to be in line with an influential group of attentional models that assume that attentional selection is space based. These models assume that the selection of an object in vision is realized by selection of the location of that object. Whether this relatively simple idea of space-based attention and the corresponding, more elaborated space-based models are sufficient to handle selected constraints and problems of object selection is the main issue of this article. The first step toward an answer is to describe the common computational structure of space-based attentional models. Two model classes will be distinguished: capacity-limited models (e.g., Treisman, 1988; LaBerge & Brown, 1989) and models that do not assume a capacity limitation (e.g., Van der Heijden, 1992). Next, three kinds of task and data on object selection are introduced that are especially challenging for space-based models. The first type of data refers to experiments that require selection between overlapping objects. The second type of data concerns the influence of early perceptual grouping--a strong object-defining factor--on late response competition, and the third type consists of a selection task in which a high-level (semantic) attribute defines an object and controls selection. In all three cases, problems of space-based models are analyzed and possible solutions are sketched. Finally, a brief evaluative summary is given.

Attention↗
PubMed2004

Assessing response bias from missing quality of life data: the Heckman method.

BACKGROUND: The objective of this study was to demonstrate the use of the Heckman two-step method to assess and correct for bias due to missing health related quality of life (HRQL) surveys in a clinical study of acute coronary syndrome (ACS) patients. METHODS: We analyzed data from 2,733 veterans with a confirmed diagnosis of acute coronary syndromes (ACS), including either acute myocardial infarction or unstable angina. HRQL outcomes were assessed by the Short-Form 36 (SF-36) health status survey which was mailed to all patients who were alive 7 months following ACS discharge. We created multivariable models of 7-month post-ACS physical and mental health status using data only from the 1,660 survey respondents. Then, using the Heckman method, we modeled survey non-response and incorporated this into our initial models to assess and correct for potential bias. We used logistic and ordinary least squares regression to estimate the multivariable selection models. RESULTS: We found that our model of 7-month mental health status was biased due to survey non-response, while the model for physical health status was not. A history of alcohol or substance abuse was no longer significantly associated with mental health status after controlling for bias due to non-response. Furthermore, the magnitude of the parameter estimates for several of the other predictor variables in the MCS model changed after accounting for bias due to survey non-response. CONCLUSION: Recognition and correction of bias due to survey non-response changed the factors that we concluded were associated with HRQL seven months following hospital admission for ACS as well as the magnitude of some associations. We conclude that the Heckman two-step method may be a valuable tool in the assessment and correction of selection bias in clinical studies of HRQL.

Acute Disease↗
PubMed2004

Bayesian representation learning in the cortex regulated by acetylcholine.

A brain needs to detect an environmental change and to quickly learn internal representations necessary in a new environment. This paper presents a theoretical model of cortical representation learning that can adapt to dynamic environments, incorporating the results by previous studies on the functional role of acetylcholine (ACh). We adopt the probabilistic principal component analysis (PPCA) as a functional model of cortical representation learning, and present an on-line learning method for PPCA according to Bayesian inference, including a heuristic criterion for model selection. Our approach is examined in two types of simulations with synthesized and realistic data sets, in which our model is able to re-learn new representation bases after the environment changes. Our model implies the possibility that a higher-level recognition regulates the cortical ACh release in the lower-level, and that the ACh level alters the learning dynamics of a local circuit in order to continuously acquire appropriate representations in a dynamic environment.

Acetylcholine↗