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At least 1,243 records · Page 69Linked to original sources
PubMed1997

A model with separate hepato-portal compartment ("first-pass" model): fitting to plasma concentration-time profiles in humans.

PURPOSE: To demonstrate the value of "first-pass" pharmacokinetic models (FPMs) in which the hepato-portal (HP) system is kinetically separated from the central compartment in fitting pharmacokinetic data obtained after intravenous (IV) and oral administration. METHODS: Plasma concentration-time profiles of an investigational drug obtained in six healthy subjects each received 4 mg as an intravenous (IV) bolus dose and 10 mg as an oral solution served as a real data example. The common three- and four-compartment models with the first-order absorption and lag time (3CM and 4CM, respectively) in which HP system is assumed to be part of the central compartment were used as alternative models. We tested also: (i) the sensitivity of the output of FPM to variations in its parameters assuming IV and oral administration; (ii) practical estimability of the FPM parameters by fitting it to 20 simulated noisy data sets; (iii) distinguishability of FPM, 3CM and 4CM by fitting them to the simulated data sets. RESULTS: FPM was shown to give the best fit as compared to 3CM or 4CM in 5 subjects of 6. The sensitivity of FPM was sufficient for the sake of parameter estimation. The "individual" means of parameter estimates obtained after fitting simulated data did not differ significantly from the preselected values. The variance in "individual" estimates was dependent on the sampling frequency. FPM was demonstrated to be distinguishable among relevant models. CONCLUSIONS: FPM is preferable as compared to standard compartmental models for drugs extensively taken up by the intestine and/or the liver, and may have a broad spectrum of applications.

Administration, Oral↗
PubMed2004

Service quality as measured by service fit and mortality among public mental health system service recipients.

Service fit, defined as consistency between mental health services judged needed and services received was measured for a random sample of service recipients in a public mental health system (N = 6588). A variant of small area analysis was used to measure the relationship between catchment area mortality rates from natural causes, suicide, and medicolegal causes and area fit scores for a variety of services. We tested the theory-based hypothesis that service fit would predict interarea variations in mortality better than simple measures of amount of service prescribed and received. We also tested the hypothesis that, controlling for relevant demographic and clinical factors, fit would be protective for mortality from all causes. Findings supported the first hypothesis. With respect to the second, service fit for only certain services was protective. Housing and clubhouses services were particularly protective, suggesting the importance of services providing social support.

Adult↗
PubMed2002

A high exercise load is linked to pathological weight control behavior and eating disorders in female fitness instructors.

Demographic data, exercise habits, weight control behavior, attitudes towards body shape, eating disorder (ED) experience, and menstrual regularity among female fitness instructors were descriptively assessed. A 60-item questionnaire was sent to 295 female fitness instructors at eight fitness centers. Responders (57%) reported a mean weekly exercise load of 5.5 h week(-1) (SD 2.6), which indicates frequent training, however, less than that of athletes. Overall, 35% reported ED experience (DSM-IV criteria), with an onset at 15-17 years of age. The problems had lasted 5-7 years, and 20% of the entire group reported recovery, however, 11% still had EDs. For the entire group, it was found that a high weekly exercise load was linked to a pathological weight control behavior. Fitness instructors with an active ED exercised more than instructors who never had an ED or who had a past ED. Menstrual irregularity was more common among instructors who did not use contraceptives (14%), compared to those who did (5%). As ED experience and pathological weight control behavior were common in the studied group, the importance of guidelines regarding communication from female fitness instructors about healthy training habits to regular exercisers is discussed in the article.

Adolescent↗
PubMed1992

Selectivity, scope, and simplicity of models: a lesson from fitting judgments of perceived depth.

When comparing psychological models a researcher should assess their relative selectivity, scope, and simplicity. The third of these considerations can be measured by the models' parameter counts or equation length, the second by their ability to fit random data, and the first by their differential ability to fit patterned data over random data. These conclusions are based on exploration of integration models reflecting depth judgments. Replication of Massaro's (1988a) results revealed an additive model (Bruno & Cutting, 1988), and Massaro's fuzzy-logical model of perception (FLMP) fit data equally well, but further exploration showed that the FLMP fit random data better. The FLMP's successes may reflect not its sensitivity in capturing psychological process but its scope in fitting any data and its complexity as measured by equation length.

Adult↗
PubMed2003

Potential problems with "well fitting" models.

The assessment of model fit is a more complex and indeterminate process than is commonly acknowledged by researchers who use structural equation modeling (SEM) techniques. Even models that are well fitting according to commonly used statistical tests and descriptive fit indices can have significant problems and ambiguities. The authors discuss 7 potential difficulties that can arise and that should temper researchers' conclusions: equivalent models, nonequivalent but well-fitting alternative models, omitted variables, problematic lower-order model components, the failure to parse composite models into meaningful partitions (e.g., measurement vs. structural), inattention to the multiple factors that affect the sensitivity of measures of fit to model misspecifications, and reliance on specification searches. In addition to providing examples of each of these problems, the authors offer recommendations for psychopathologists who conduct SEM analyses.

Analysis of Variance↗
PubMed1993

Job demands and worker health: three-dimensional reexamination of the relationship between person-environment fit and strain.

The most influential study of the person-environment (P-E) fit approach to stress was conducted by J. R. P. French, R. D. Caplan, and R. V. Harrison (1982). Unfortunately, this study operationalized fit using various transformations of difference scores, thereby introducing numerous substantive and methodological problems. In the present study, the authors reanalyze data from French et al., using a procedure described by J. R. Edwards (in press) that avoids problems with difference scores and captures the underlying three-dimensional relationship between E, P, and strain. Results resolve ambiguities in the French et al. findings and identify relationships between E, P, and strain that, although consistent with P-E fit theory, cannot be adequately represented by fit measures such as those used by French et al. Implications for P-E fit research are discussed.

Adaptation, Psychological↗
PubMed2002

Structural contingency theory and individual differences: examination of external and internal person-team fit.

This article develops and tests a structurally based, integrated theory of person-team fit. The theory developed is an extension of structural contingency theory and considers issues of external fit simultaneously with its examination of internal fit at the team level. Results from 80 teams working on an interdependent team task indicate that divisional structures demand high levels of cognitive ability on the part of teammembers. However, the advantages of high cognitive ability in divisional structures are neutralized when there is poor external fit between the structure and the environment. Instead, emotional stability becomes a critical factor among teammembers when a divisional structure is out of alignment with its environment. Individual differences seem to play little or no role in functional structures, regardless of the degree of external fit.

Cooperative Behavior↗
PubMed2004

Toward an understanding of the relationships among organizational change, individual differences, and changes in person-environment fit: a cross-level study.

Organizational behavior literature has not typically viewed person-environment (P-E) fit as an outcome of change. Whereas the study of antecedents to employees' fit with their work environment has largely been restricted to the selection and socialization of newcomers, this study examines individuals' perceptions of changes in P-E fit in relation to organizational changes occurring in 34 different organizational work units. Results suggest that the relationships between organizational change and perceived changes in fit are best understood as interactions between the characteristics of the change process, the extent of change, and individual differences. Both age and mastery orientation related to perceived changes in P-E fit through interactions with aspects of the change process.

Adult↗
PubMed2003

Transfer of value from fit.

People experience regulatory fit when they pursue a goal in a manner that sustains their regulatory orientation (E. T. Higgins, 2000). Five studies tested whether the value experienced from regulatory fit can transfer to a subsequent evaluation of an object. In Studies 1 and 2, participants gave the same coffee mug a higher price if they had chosen it with a strategy that fit their orientation (eager strategy/promotion; vigilant strategy/prevention) than a strategy that did not fit. Studies 3-5 investigated possible mechanisms underlying this effect. Value transfer was independent of positive mood, perceived effectiveness (instrumentality), and perceived efficiency (ease), and occurred for an object that w as independent of the fit process itself. The findings supported a value confusion account of transfer.

Decision Making↗
PubMed2004

Regulatory fit and persuasion: transfer from "Feeling Right.".

The authors propose that when a message recipient "feels right" from regulatory fit (E. T. Higgins, 2000), this subjective experience transfers to the persuasion context and serves as information for relevant evaluations, including perceived message persuasiveness and opinions of the topic. Fit was induced either by strategic framing of message arguments in a way that fit/did not fit with the recipient's regulatory state or by a source unrelated to the message itself. Across 4 studies, regulatory fit enhanced perceived persuasiveness and opinion ratings. These effects were eliminated when the correct source of feeling right was made salient before message exposure, supporting the misattribution account. These effects reversed when message-related thoughts were negative, supporting the claim that fit provides information about the "rightness" of one's (positive or negative) evaluations.

Adult↗
PubMed2006

Regulatory fit as input for stop rules.

Three experiments show that the motivational effects of regulatory fit (consistency between regulatory state and strategic means) are context dependent. With no explicit decision rule about when to stop (Experiment 1) or an explicit enjoyment stop rule (Experiments 2 and 3), participants exerted more effort on tasks when experiencing regulatory fit than when experiencing regulatory nonfit. With an explicit sufficiency stop rule (Experiments 2 and 3), participants exerted less effort when experiencing regulatory fit than when experiencing regulatory nonfit. The interactive effect of regulatory fit and stop rules can be explained by misattribution of rightness feelings from regulatory fit; the effect was eliminated by drawing participants' attention to an earlier event as a source of rightness feelings (Experiments 1 and 3).

Adult↗
PubMed2003

On specifying the null model for incremental fit indices in structural equation modeling.

In structural equation modeling, incremental fit indices are based on the comparison of the fit of a substantive model to that of a null model. The standard null model yields unconstrained estimates of the variance (and mean, if included) of each manifest variable. For many models, however, the standard null model is an improper comparison model. In these cases, incremental fit index values reported automatically by structural modeling software have no interpretation and should be disregarded. The authors explain how to formulate an acceptable, modified null model, predict changes in fit index values accompanying its use, provide examples illustrating effects on fit index values when using such a model, and discuss implications for theory and practice of structural equation modeling.

Data Interpretation, Statistical↗
PubMed1992

The genomic mutation rate for fitness in Drosophila.

The mutation rate per genome for local affecting fitness is crucial in theories of the evolution of sex and recombination and of outbreeding mechanisms. Mutational variation in fitness may also be important in the evolution of mate choice in animals. No information is available on the rate at which spontaneous mutations with small effects on fitness arise, although viability (probability of survival to adulthood) has been studied in Drosophila melanogaster. These experiments involved the accumulation of spontaneous mutations in the virtual absence of natural selection, in a set of independently maintained lines with a common origin. The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation (U) and the average homozygous effect of a new mutation of minor effect(s). For the second chromosome of D. melanogaster, the value of U is at least 0.17 (ref. 7), and (1-h)s is less than 0.02, where hs is the average decline in fitness of heterozygotes. As the second chromosome is about 40% of the genome, these data indicate a mutation rate per haploid genome of at least 0.42 for viability. Here we present similar data on the effects of homozygous spontaneous mutations on a measure of fitness in D. melanogaster.

Animals↗
PubMed1981

The estimation of epistasis in components of fitness in experimental populations of drosophila melanogaster II. Assessment of meiotic drive, viability, fecundity and sexual selection.

An analysis of fitness components was performed on laboratory populations of Drosophila melanogaster bearing Curly and Plum marked second chromosome inversions with two genetic backgrounds. Selective differences between Curly, Plum, Curly-Plum, and wild phenotypes were partitioned into meiotic drive, viability, fecundity and mating success. Although no significant meiotic drive was detected, there were significant differences between genotypes in the other three components. Interlocus interactions in fertility and sexual selection components were measured, and statistics to quantify epistasis at these levels of fitness were devised. Significant fitness interactions between genes on the Curly and Plum inversions in viability, fecundity, and sexual selection were found. These results were qualitatively consistent with the maximum likelihood fitness estimates found previously. The expected allele frequency trajectories computed from the estimated components adequately fitted the observed selection trajectories.

Animals↗
PubMed2004

Fitness benefits of prolonged post-reproductive lifespan in women.

Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction.

Adult↗
PubMed2006

Future fitness and helping in social queues.

Helpers in primitively eusocial and cooperatively breeding animal societies forfeit their own reproduction to rear the offspring of a queen or breeding pair, but may eventually attain breeding status themselves. Kin selection provides a widely accepted theoretical framework for understanding these societies, but differences in genetic relatedness do not explain a universal societal feature: the huge variation between individuals in helping effort. An alternative explanation for this variation lies in a fundamental trade-off faced by helpers: by working harder, they increase the indirect component of their fitness, but simultaneously decrease their own future survival and fecundity. Here, we show that individuals work less hard when they stand to lose more future fitness through working. We experimentally manipulated two components of future fitness in social queues of hover wasps (Stenogastrinae): a helper's chance of inheriting an egg-laying position, and the workforce available to rear her offspring should she inherit. After each manipulation, helpers increased or decreased their effort as appropriate to the change in expected future fitness that they experienced. Although helping provides significant indirect fitness benefits for hover wasps, our study shows that variation in the costs associated with helping is the major determinant of helping effort.

Animals↗
PubMed2006

Distribution of fitness effects among beneficial mutations before selection in experimental populations of bacteria.

The extent to which a population diverges from its ancestor through adaptive evolution depends on variation supplied by novel beneficial mutations. Extending earlier work, recent theory makes two predictions that seem to be robust to biological details: the distribution of fitness effects among beneficial mutations before selection should be (i) exponential and (ii) invariant, meaning it is always exponential regardless of the fitness rank of the wild-type allele. Here we test these predictions by assaying the fitness of 665 independently derived single-step mutations in the bacterium Pseudomonas fluorescens across a range of environments. We show that the distribution of fitness effects among beneficial mutations is indistinguishable from an exponential despite marked variation in the fitness rank of the wild type across environments. These results suggest that the initial step in adaptive evolution--the production of novel beneficial mutants from which selection sorts--is very general, being characterized by an approximately exponential distribution with many mutations of small effect and few of large effect. We also document substantial variation in the pleiotropic costs of antibiotic resistance, a result that may have implications for strategies aimed at eliminating resistant pathogens in animal and human populations.

Biological Evolution↗
PubMed2024

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

Female↗