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PubMed2003

Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss.

RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.

Animals↗
PubMed2000

Social enhancement of fitness in yellow-bellied marmots.

The yellow-bellied marmot (Marmota flaviventris) is a social, ground-dwelling squirrel that lives either individually or in kin groups of from two to five adult females. Philopatry and daughter recruitment lead to the formation and persistence of matrilines at habitat sites. By using 37 years of demographic data for 12 habitat sites, we could determine long-term trends in the effects of group size on two measures of fitness, survivorship and net reproductive rate, which otherwise are obscured by annual fluctuations in these measures. Both size and number of matrilines varied among sites and survivorship and net reproductive rate varied among sites and among matriline sizes. The role of social organization was explored further by examining the effect of matriline size, averaged over all years and sites, on fitness. For both survivorship and net reproductive rate the relationship with matriline size was curvilinear. Fitness increased with the increase in matriline size and then decreased in the largest groups. Decreased fitness in matrilines of four or five was associated with agonistic behavior, a large number of 2-year-old females in the social group, and reproductive suppression. There is no evidence that females acted to increase their fitness by increasing indirect fitness; i.e., by assisting relatives, but attempted to increase direct fitness. Direct fitness increased when mortality and fission of large matrilines reduced group size and the surviving females increased reproduction.

Animals↗
PubMed2002

Three-axis ellipsoidal fitting of videokeratoscopic height data after penetrating keratoplasty.

PURPOSE: After penetrating keratoplasty corneal topography tends to be irregular and the fitting of spectacle glasses or contact lenses may be difficult. The purpose of this study was to demonstrate a mathematical method for approximation of discrete corneal topography height data with an ellipsoid for better appreciation of the clinical outcome after PK. PATIENTS AND METHODS: In 50 eyes (30 keratoconus, 20 Fuchs' dystrophy) penetrating keratoplasty was performed using nonmechanical trephination with the excimer laser 193 nm. Main outcome measures were objective corneal astigmatism (regular keratometry, corneal topography (TMS-1)), subjective refraction and best-corrected visual acuity (VA) in a fixed postoperative gate 3 and 12 month postoperatively and after suture removal. An approximation algorithm was applied for fitting a general ellipsoidal surface (not rotationally symmetric) to raw corneal topography height data. A set of parameters (meridional power, axis and asphericity) were calculated. The root mean square error (RMS) was determined between raw topography power data and the ellipsoidal model surface within an apical distance of 3 mm. The cylinder of subjective refraction was correlated with the keratometric readings, the Simulated Keratometry (SimK) of the topography system and the respective parameters of the model surface. RESULTS: The amount of the SimK cylinder yielded higher values than keratometry and the ellipsoidal fit; subjective refraction yielded the lowest value at each follow-up interval. The ellipsoidal fit showed the best correlation to the refractive cylinder at all follow-up stages (p = 0.04 at 3, p = 0.01 at 12 months and p = 0.002 after suture removal). The axis of the best ellipsoidal fit showed a significant correlation with the axis of the refractive cylinder at all follow-up intervals (p = 0.02 at 3 months, p = 0.01 before suture removal and p = 0.002 after suture removal). The axis of the keratometric cylinder showed a mild correlation at all follow-up examinations (p = 0.05 at 3 months, p = 0.02 before suture removal and p = 0.04 after suture). The cylinder of the topographic modeling system, however, showed a significant correlation with the refractive cylinder axis only after suture removal (p = 0.04). The paracentral corneal power of SimK (45.9D at 3 months, 44.4D at 12 months and 43.0D after suture removal) exceeded the respective values of conventional keratometry (43.1D at 3 months, 42.9D at 12 months and 41.7D after suture removal) and the ellipsoidal fit (43.3D at 3 months, 43.0D at 12 months and 41.8D after suture removal). The corneal asphericity from the ellipsoidal fit reached an approximately spherical shape in radial direction (A = 1.0) in the initial time period after penetrating keratoplasty, remained stable before suture removal and decreased significantly (p = 0.02) to a final value of A = 0.86 indicating a (normal) prolate shape of the cornea. The approximation error between the raw corneal topography height data and the best ellipsoidal fit model surface was nearly unchanged before suture removal (1.8 +/- 0.7 microm at 3 months and 1.9 +/- 1.1 microm at 12 months, p = 0.30) and decreased significantly to the examination after suture removal (0.9 +/- 0.5 microm, p = 0.01). CONCLUSIONS: The approximation of corneal topography height data with an ellipsoidal model surface renders reconstruction of clinically relevant corneal topography parameters including corneal asphericity. Even in markedly irregular corneal surfaces, such as after PK, the correlation of amount/axis of refractive cylinder with the model surface parameters is more accurate than with respective SimK values of corneal topography analysis.

Adult↗
PubMed2004

Dimensional differences for evaluating the quality of footwear fit.

Very few standards exist for fitting products to people. Footwear is a noteworthy example. This study is an attempt to evaluate the quality of footwear fit using two-dimensional foot outlines. Twenty Hong Kong Chinese students participated in an experiment that involved three pairs of dress shoes and one pair of athletic shoes. The participants' feet were scanned using a commercial laser scanner, and each participant wore and rated the fit of each region of each shoe. The shoe lasts were also scanned and were used to match the foot scans with the last scans. The ANOVA showed significant (p < 0.05) differences among the four pairs of shoes for the overall, fore-foot and rear-foot fit ratings. There were no significant differences among shoes for mid-foot fit rating. These perceived differences were further analysed after matching the 2D outlines of both last and feet. The point-wise dimensional difference between foot and shoe outlines were computed and analysed after normalizing with foot perimeter. The dimensional difference (DD) plots along the foot perimeter showed that fore-foot fit was strongly correlated (R(2) > 0.8) with two of the minimums in the DD-plot while mid-foot fit was strongly correlated (R(2) > 0.9) with the dimensional difference around the arch region and a point on the lateral side of the foot. The DD-plots allow the designer to determine the critical locations that may affect footwear fit in addition to quantifying the nature of misfit so that design changes to shape and material may be possible.

Adult↗
PubMed2006

Steps counts among middle school students vary with aerobic fitness level.

The purpose of this study was to examine if steps/day taken by middle school students varied based on aerobic fitness classification. Middle school students (N = 223; 112 girls, 111 boys) were assigned to three aerobic fitness categories (HIGH, MOD, LOW) based on results of the FlTNESSGRAM PACER test. Four weekdays of pedometer monitoring determined activity levels (steps/day). Boys accumulated significantly more steps/day than girls, 11,589 +/- 3,270 and 10,232 +/- 2,517 steps/day, respectively; F(1,219) = 16.0, p < .001, eta2 = .055. There were no differences in steps/day between grades. HIGH fit participants accumulated significantly more steps/day, F(2, 217) = 12.2, p < .101, eta2 = .101, than moderately fit and low fit participants (approximately 1,491 and ; 2,867 steps/day, respectively). Middle school students who participated in sports in addition to physical education (PE) accumulated significantly more steps/day (approximately 980 steps/day) than those participating in PE only, F(1, 219) = 10.0, p < .01, eta2 = .044. Although the relationship between physical activity and aerobic fitness was moderate (0.35; p < .01), these data demonstrated significant differences in accumulated steps/day among youth of varying aerobic fitness levels. Whether improved fitness levels were the result of additional activity or the cause of it remains to be determined. Regardless, the fittest middle school students were also the most active and accumulated a significant amount of steps/day through organized extracurricular physical activities.

Adolescent↗
PubMed2004

Components of variance underlying fitness in a natural population of the great tit Parus major.

Traits that are closely associated with fitness tend to have lower heritabilities (h2) than those that are not. This has been interpreted as evidence that natural selection tends to deplete genetic variation more rapidly for traits more closely associated with fitness (a corollary of Fisher's fundamental theorem), but Price and Schluter (1991) suggested the pattern might be due to higher residual variance in traits more closely related to fitness. The relationship between 10 different traits for females, seven traits for males, and overall fitness (lifetime recruitment) was quantified for great tits (Parus major) studied in their natural environment of Wytham Wood, England, using data collected over 39 years. Heritabilities and the coefficients of additive genetic and residual variance (CVA and CVR, respectively) were estimated using an "animal model." For both males and females, a trait's correlation (r) with fitness was negatively related to its h2 but positively related to its CVR. The CVA was not related to the trait's correlation with fitness in either sex. This is the third study using directly measured fitness in a wild population to show the important role of residual variation in determining the pattern of lower heritabilities for traits more closely related to fitness.

Animals↗
PubMed2006

Age-specific fitness components and their temporal variation in the barn owl.

Theory predicts that temporal variability plays an important role in the evolution of life histories, but empirical studies evaluating this prediction are rare. In constant environments, fitness can be measured by the population growth rate lambda, and the sensitivity of lambda to changes in fitness components estimates selection on these traits. In variable environments, fitness is measured by the stochastic growth rate lambda(S), and stochastic sensitivities estimate selection pressure. Here we examine age-specific schedules for reproduction and survival in a barn owl population (Tyto alba). We estimated how temporal variability affected fitness and selection, accounting for sampling variance. Despite large sample sizes of old individuals, we found no strong evidence for senescence. The most variable fitness components were associated with reproduction. Survival was less variable. Stochastic simulations showed that the observed variation decreased fitness by about 30%, but the sensitivities of lambda and lambda(S) to changes in all fitness components were almost equal, suggesting that temporal variation had negligible effects on selection. We obtained these results despite high observed variability in the fitness components and relatively short generation time of the study organism, a situation in which temporal variability should be particularly important for natural selection and early senescence is expected.

Age Factors↗
PubMed2002

Airway resistance estimation by best fit analysis in very premature infants.

Plethysmographic measurement of airway resistance (R(aw)) has been determined by single-point analysis, usually at 50% of maximum inspiratory flow (MIF). Computer-assisted (best fit) analysis, however, allows R(aw) to be calculated by applying a regression line to any portion of the plethysmograph pressure-flow loop. We determined whether the results of best fit analysis using a computer program, sampling at 200 Hz, were influenced by the portion of the inspiratory loop analysed and if best fit or single-point analysis gave more reproducible results. Twenty infants of median gestational age 26 (range 24-28) weeks, were studied at a median age of 12 (12-14) months corrected for prematurity. R(aw) was calculated by best fit analysis between 0 and 33% MIF, 0 and 50% MIF and 0 and 67% MIF and single-point analysis at 50% of MIF. Similar mean R(aw) values were obtained by best fit analysis between 0 and 33% MIF (2.79 kPa/(l/s)) and 0 and 50% MIF (3.01 kPa/(l/s)) and single-point analysis at 50% MIF (2.86 kPa/(l/s)), but best fit analysis between 0 and 67% gave higher results (3.60 kPa/(l/s)), p < 0.0001. Within the linear portion of the inspiratory loop, the mean intrasubject coefficient of variation was lowest for best fit analysis between 0 and 50% MIF. Best fit computerized analysis between 0 and 50% MIF is recommended as the analysis of choice.

Airway Resistance↗
PubMed1982

Chromosome interactions in Drosophila melanogaster. II. Total fitness.

In a large experiment, using nearly 200 population cages, we have measured the fitness of Drosophila melanogaster homozygous (1) for the second chromosome, (2) for the third chromosome, and (3) for both chromosomes. Twenty-four second chromosomes and 24 third chromosomes sampled from a natural population were tested. The mean fitness of the homozygous flies is 0.081 +/- 0.014 for the second chromosome, 0.080 +/- 0.017 for the third chromosome, and 0.079 +/- 0.024 for both chromosomes simultaneously. Assuming that fitnesses are multiplicative (the additive fitness model makes no sense in the present case because of the large selection coefficients involved), the expected mean fitness of the homozygotes for both chromosomes is 0.0066; their observed fitness is more than ten times greater. Thus, it appears that synergistic interactions between loci are considerable; and that, consequently, the fitness function substantially departs from linearity. Two models are tentatively suggested for the fitness function: a "threshold" model and a "synergistic" model.--The experiments reported here confirm previous results showing that the concealed genetic load present in natural populations of Drosophila is sufficient to account for the selective maintenance of numerous polymorphisms (of the order of 1000).

Animals↗
PubMed2003

Rifampicin resistance and its fitness cost in Enterococcus faecium.

OBJECTIVES: The genetic basis of rifampicin resistance and the associated fitness cost in Enterococcus faecium were investigated. METHODS: Twelve spontaneous rifampicin-resistant E. faecium mutants were selected from four parent strains recently isolated from porcine faecal material. The DNA sequence of the complete rpoB gene from the parent strains and of nucleotides -189 to +1785 from the mutants was determined from PCR amplicons. The fitness of the mutants was assessed by determining growth rate, by direct growth competition and by the ability of some of the mutants to survive in the pig intestine. RESULTS: The rpoB genes of the parent strains diverged from each other by 1-10% and each encoded proteins that were 1208 amino acids in length. All mutants had a single amino acid substitution in the region implicated in rifampicin resistance in other organisms. Six mutants carried the substitution H489Y/Q, two mutants carried the substitution R492H, one mutant carried the substitution Q480H, two mutants carried the substitutions S494L and V224I, and one mutant carried the substitutions G485D and V224I. Per generation fitness costs of the mutants ranged from a gain of 2.5% to a cost of 10%. Mutants with the substitution H489Y/Q were the most fit, whereas the double mutants were the least fit. The mutant with the substitution H489Q was able to survive in the pig gut for 12 days. There was some correlation between the rifampicin MIC and fitness cost, with higher MICs being associated with higher fitness costs. CONCLUSIONS: Substitutions in RpoB are associated with rifampicin resistance in E. faecium. The fitness cost of resistance is variable and can sometimes be absent.

Amino Acid Substitution↗
PubMed2004

Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure.

OBJECTIVES: Despite a 97% reduction in clinical sulphonamide usage, the prevalence of sulphonamide resistance among Escherichia coli has remained constant in the UK. Genetic linkage of sulphonamide resistance to other resistances is thought important for this maintenance, but the finding also implies that sulphonamide resistance exerts little fitness cost. To test this hypothesis, we examined the fitness impact of four naturally occurring sul2-coding plasmids upon their hosts. METHODS: The fitness impact of the plasmids upon E. coli was determined by pairwise growth competition in a minimal medium. The DNA sequence of plasmid p9123 was obtained by primer walking and PCR. RESULTS: Three of the four sul2-coding plasmids studied imposed fitness costs on their hosts. The fourth plasmid, a 6.2 kb resistance element carrying sul2, strA and strB designated p9123, conferred a 4% fitness advantage upon its original clinical host and also on E. coli K12 JM109. The complete sequence of p9123 revealed eight open reading frames, including five of unknown function. There was no obvious gene to which the fitness advantage might be attributed. CONCLUSIONS: The novel finding that p9123 can improve host fitness may explain why this plasmid and its close relatives are so widespread among enteric bacteria. In addition to other factors such as co-selection of sulphonamide resistance by other agents, the fitness advantage conferred by plasmids such as p9123 may have contributed to the maintenance of sulphonamide resistance in the UK in the absence of clinical selection pressure. These data indicate that once antibiotic resistance has been established on mobile genetic elements, it may be difficult to eliminate.

Anti-Infective Agents↗
PubMed2004

Effect of cardiorespiratory fitness on mortality among hypertensive and normotensive women and men.

BACKGROUND: The effects of fitness on mortality either from cardiovascular disease (CVD) or from all causes, among hypertensive adults, are not fully understood, especially among women. The objective of this study was to examine the effect of fitness on all-cause and CVD mortality among hypertensive and normotensive women and men. METHODS: Using the Lipids Research Clinics Prevalence Study, we examined the relationship of fitness with mortality among 2712 women and 3000 men followed from 1972-1976 to 1998. Cardiorespiratory fitness was measured using a treadmill test. Sex-specific hazard ratios (HRs) were calculated from proportional hazard models of fitness predicting all-cause or CVD mortality, adjusted for age, education, race, smoking, alcohol, body mass index, and hyperlipidemic sampling strata. RESULTS: Comparing the lowest with the highest quintile of fitness, the adjusted all-cause mortality among hypertensive women was 1.7 (95% confidence interval = 0.9-3.2) and among normotensive women was 2.3 (1.5-3.7). Comparing the same quintiles of fitness, the adjusted all-cause mortality among hypertensive men was 2.0 (1.2-3.4), and among normotensive men it was 1.9 (1.3-2.7). Elevated risks were also observed for CVD mortality. CONCLUSION: Higher levels of fitness were associated with a lower risk of all-cause and CVD mortality among both hypertensive and normotensive women and men.

Adult↗
PubMed1989

Ability of the Lapicque and Blair strength-duration curves to fit experimentally obtained data from the dog heart.

The objective of this study was to determine the ability of the empirical Lapicque and theoretically derived Blair expressions for excitation to fit experimentally obtained threshold current values to evoke a ventricular extrasystole using rectangular-wave stimuli applied to the dog heart. The data points were fitted to both expressions and the ability of each to predict the measured values was determined. The Levenberg-Marquardt (L-M) algorithm was used to fit the Lapicque and Blair expressions. The Lapicque data were also fitted to the linear charge-duration expression of Weiss (W). It was found that the ratio of the predicted to measured current was slightly different from one 0.95 (L-M) and 1.06 (W) for the Lapicque and 0.92 (L-M) for the Blair expression. Thus, there appears to be little difference between the ability of the expressions to fit the same experimentally obtained data. The L-M Lapicque fit is best for the short durations range; the Weiss-Lapicque fit overestimates in the short duration range and underestimates near chronaxie. The L-M Blair fit is best for the short duration range and poor for the durations near the membrane time constant.

Algorithms↗
PubMed2000

A gender perspective on Person-Manager fit and managerial advancement.

This article presents two studies examining (1) the relationship between Person-Manager (P-M) fit and managerial advancement of women and men with, and without managerial aspirations and (2) the P-M fit as related to managerial and non-managerial women. The P-M fit was assessed by computing the congruence between participants' self-rated personality profile and the perceived personality profile of a manager. Sex (men show a higher P-M fit than women), gender (the higher the individual's masculine gender-role, the higher the P-M fit) and group (managers and managerial aspirants show a higher P-M fit than non-managerial aspirants and non-managers) hypotheses were tested. There was no support for the sex difference hypothesis. However, the group and gender hypotheses were confirmed showing that managers and managerial aspirants had a higher P-M fit than non-managers and non-aspirants. Further, analyses revealed that the higher the participants' masculinity scores, the higher the P-M fit. Implications of these findings are discussed in relation to the gendered image of the managerial role and adaptation theory.

Adult↗
PubMed2000

Phenotypic selection in hawkmoth-pollinated Platanthera bifolia: targets and fitness surfaces.

The present study explored phenotypic selection on phenological and morphological reproductive traits in hawkmoth-pollinated Platanthera bifolia (Orchidaceae), a Eurasian perennial herb displaying bisexual, long-spurred flowers. The work was carried out during three flowering seasons (1993-1995) in a Swedish population. Fitness was estimated as the number of pollinia removed (male fitness) and fruits produced (female fitness). Targets and patterns of selection were compared between years and sex functions by the use of multiple linear regression (including correlational selection estimates, i.e., of combination of traits), analysis of covariance, and projection pursuit regression (PPR). Results from the nonparametric surface-fitting-method PPR showed that selection was mostly linear, thus justifying the use of the parametric methods. In all study years, male and female fitness were highest in plants with many flowers. This reflects that flower number sets an upper limit to fitness and that a large influorescence attracts more pollinators. In 1994, the summer was dry and the average spur length of P. bifolia was shorter than in the other years. In this year, male and female fitness were positively related to spur length, apparently because the spur of short-spurred plants was somewhat too short relative to the tongue length of the local pollinator for optimal pollen export and import. Additionally, the dry weather in 1994 caused a tendency for correlational selection, which was not found in the other years of study. Among small individuals (apparently more sensitive to drought than large ones), early-flowering plants had higher male and female fitness. The results show that patterns of selection may vary both between years and between sex functions in perennial hermaphroditic plants. The present study is one of the first to consider correlational selection in plants, which probably is of common occurrence and deserves to be investigated more.

Animals↗
PubMed2003

Fitness costs of chemical defense in Plantago lanceolata L.: effects of nutrient and competition stress.

Fitness costs of defense are often invoked to explain the maintenance of genetic variation in levels of chemical defense compounds in natural plant populations. We investigated fitness costs of iridoid glycosides (IGs), terpenoid compounds that strongly deter generalist insect herbivores, in ribwort plantain (Plantago lanceolata L.) using lines that had been artificially selected for high and low leaf IG concentrations for four generations. Twelve maternal half-sib families from each selection line were grown in four environments, consisting of two nutrient and two competition treatments. We tested whether: (1) in the absence of herbivores and pathogens, plants from lines selected for high IG levels have a lower fitness than plants selected for low IG levels; and (2) costs of chemical defense increase with environmental stress. Vegetative biomass did not differ between selection lines, but plants selected for high IG levels produced fewer inflorescences and had a significantly lower reproductive dry weight than plants selected for low IG levels, indicating a fitness cost of IG production. Line-by-nutrient and line-by-competition interactions were not significant for any of the fitness-related traits. Hence, there was no evidence that fitness costs increased with environmental stress. Two factors may have contributed to the absence of higher costs under environmental stress. First, IGs are carbon-based chemicals. Under nutrient limitation, the relative carbon excess may result in the production of IGs without imposing a further constraint on growth and reproduction. Second, correlated responses to selection on IG levels indicate the existence of a positive genetic association between IG level and cotyledon size. At low nutrient level, a path analysis based on family means revealed that in the presence of competitors, the negative direct effect of a high IG level on aboveground plant dry weight was partly offset by a positive direct effect of the associated larger cotyledon size. This indicates that fitness costs of defense may be modulated by environment-specific fitness effects of genetically associated traits.

Adaptation, Physiological↗
PubMed2006

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: an in-vitro model.

Cementless total hip femoral components rely on press-fit for initial stability and bone healing and remodeling for secondary fixation. However, the determinants of satisfactory press-fit are not well understood. In previous studies, human cortical bone loaded circumferentially to simulate press-fit exhibited viscoelastic, or time dependent, behavior. The effect of bone viscoelastic behavior on the initial stability of press-fit stems is not known. Therefore, in the current study, push-out loads of cylindrical stems press-fit into reamed cadaver diaphyseal femoral specimens were measured immediately after assembly and 24 h with stem-bone diametral interference and stem surface treatment as independent variables. It was hypothesized that stem-bone interference would result in a viscoelastic response of bone that would decrease push-out load thereby impairing initial press-fit stability. Results showed that push-out load significantly decreased over a 24 h period due to bone viscoelasticity. It was also found that high and low push-out loads occurred at relatively small amounts of stem-bone interference, but a relationship between stem-bone interference and push-out load could not be determined due to variability among specimens. On the basis of this model, it was concluded that press-fit fixation can occur at relatively low levels of diametral interference and that stem-bone interference elicits viscoelastic response that reduces stem stability over time. From a clinical perspective, these results suggest that there could be large variations in initial press-fit fixation among patients.

Adult↗
PubMed2000

Estimating relative fitness in viral competition experiments.

The relative fitness of viral variants has previously been defined as the slope of the logarithmic ratio of the genotype or phenotype frequencies in time plots of pairwise competition experiments. Developing mathematical models for such experiments by employing the conventional coefficient of selection s, we demonstrate that this logarithmic ratio gives the fitness difference, rather than the relative fitness. This fitness difference remains proportional to the actual replication rate realized in the particular experimental setup and hence cannot be extrapolated to other situations. Conversely, the conventional relative fitness (1 + s) should be more generic. We develop an approach to compute the generic relative fitness in conventional competition experiments. This involves an estimation of the total viral replication during the experiment and requires an estimate of the average lifetime of productively infected cells. The novel approach is illustrated by estimating the relative fitness, i.e., the relative replication rate, of a set of zidovudine-resistant human immunodeficiency virus type 1 variants. A tool for calculating the relative fitness from observed changes in viral load and genotype (or phenotype) frequencies is publically available on the website at http://www-binf.bio.uu.nl/( approximately )rdb/fitness.html.

HIV-1↗