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Comparing the ex vivo fitness of CCR5-tropic human immunodeficiency virus type 1 isolates of subtypes B and C.

Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4(+) T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.

Cells, Cultured↗

Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry.

The ability of one primary human immunodeficiency virus type 1 (HIV-1) isolate to outcompete another in primary CD4+ human lymphoid cells appears to be mediated by the efficiency of host cell entry. This study was designed to test the role of entry on fitness of wild-type HIV-1 isolates (e.g., replicative capacity) and to examine the mechanism(s) involved in differential entry efficiency. The gp120 coding regions of two diverse HIV-1 isolates (the more-fit subtype B strain, B5-91US056, and less-fit C strain, C5-97ZA003) were cloned into a neutral HIV-1 backbone by using a recently described yeast cloning technique. The fitness of the primary B5 HIV-1 isolates and its env gene cloned into the NL4-3 laboratory strain had similar fitness, and both were more fit than the C5 primary isolate and its env/NL4-3 chimeric counterpart. Increased fitness of the B5 over C5 virus was mediated by the gp120 coding region of the env gene. An increase in binding/fusion, as well as decreased sensitivity to entry inhibitors (PSC-RANTES and T-20), was observed in cell fusion assays mediated by B5 gp120 compared to C5 gp120. Competitive binding assays using a novel whole virus-cell system indicate that the primary or chimeric B5 had a higher avidity for CD4/CCR5 on host cells than the C5 counterpart. This increased avidity of an HIV-1 isolate for its cell receptors may be a significant factor influencing overall replicative capacity or fitness.

Base Sequence↗

Modeling and estimation of replication fitness of human immunodeficiency virus type 1 in vitro experiments by using a growth competition assay.

Growth competition assays have been developed to quantify the relative fitnesses of human immunodeficiency virus (HIV-1) mutants. In this article we develop mathematical models to describe viral/cellular dynamic interactions in the assay experiment, from which new competitive fitness indices or parameters are defined. These indices include the log fitness ratio (LFR), the log relative fitness (LRF), and the production rate ratio (PRR). From the population genetics perspective, we clarify the confusion and correct the inconsistency in the definition of relative fitness in the literature of HIV-1 viral fitness. The LFR and LRF are easier to estimate from the experimental data than the PRR, which was misleadingly defined as the relative fitness in recent HIV-1 research literature. Calculation and estimation methods based on two data points and multiple data points were proposed and were carefully studied. In particular, we suggest using both standard linear regression (method of least squares) and a measurement error model approach for more-accurate estimates of competitive fitness parameters from multiple data points. The developed methodologies are generally applicable to any growth competition assays. A user-friendly computational tool also has been developed and is publicly available on the World Wide Web at http://www.urmc.rochester.edu/bstools/vfitness/virusfitness.htm.

HIV-1↗

Fit of bicycle safety helmets and risk of head injuries in children.

BACKGROUND: Although bicycle helmets are effective in preventing head and brain injury, some helmeted individuals nevertheless sustain head injury. One of the possible reasons may be poor fit of the helmet on the head. This study was undertaken to examine the relationship between helmet fit and risk of injury. METHODS: 1718 individuals who were helmeted riders in a crash were queried on helmet fit and position. A sample of 28 children 2-14 years of age who sustained a head injury while wearing a bicycle helmet and 98 helmeted individuals of the same age treated in the same hospital emergency departments for injuries other than to the head, underwent anthropometric measurements of helmet fit. Measurements were made of the child's head, the helmet, and on a cast made of the child's head. RESULTS: Individuals whose helmets were reported to fit poorly had a 1.96-fold increased risk of head injury compared with those whose helmets fit well. Children with head injuries had helmets which were significantly wider than their heads compared with children without head injuries. Helmet fit was poorer among males and among younger children. CONCLUSIONS: Poor fit of helmets may be associated with an increased risk of head injury in children, especially in males. Helmets may not be designed to provide optimal protection.

Adolescent↗

Attenuation performance of four hearing protectors under dynamic movement and different user fitting conditions.

An experiment was conducted to determine the effects of movement activities and alternative fitting procedures on protection levels afforded by four hearing protection devices (HPDs). Psychophysical attenuation measurements at nine one-third-octave bands from 125 to 8000 Hz were obtained prior to, during, and following a 2-hr wearing stint that included periods of either highly kinematic but controlled work activity or vigorous temporomandibular movement. The 40 subjects, who were nonusers of HPDs, initially fit the protectors according to either the instructions on the package (i.e., subject fit) or after receiving interactive training on proper fit (i.e., trained fit). Thereafter no further protector adjustments were allowed during the wearing period. The subject-fit condition resulted in significantly lower protection levels, from 4 to 14 dB, at 1000 Hz and below for a premolded polymer earplug, a user-molded foam earplug, and a double protector consisting of a muff over the foam plug. The muff alone was significantly more resilient to fitting effects on attenuation than were the plugs. Movement activity caused up to a 6-dB significant reduction in frequency-specific attenuation over time for the premolded plug, muff, and muff-plug combination. The compliant foam earplug was largely resistant to either type of movement effect but did benefit more than the other devices from use of the trained-fit procedure. Implications of the results for hearing protector testing protocol, device selection, and user training are discussed.

Adult↗

Femoral press-fit fixation of the hamstring tendons for anterior cruciate ligament reconstruction.

BACKGROUND: Press-fit fixation of patellar tendon-bone anterior cruciate ligament autografts is an interesting technique because no hardware is necessary. For hamstring tendon grafts, no biomechanical data exist of a press-fit procedure. HYPOTHESIS: Press-fit femoral fixation of hamstring tendons is mechanically equivalent to press-fit patellar tendon-bone fixation. STUDY DESIGN: Controlled laboratory study. METHODS: Patellar and hamstring tendons of 30 human cadavers (age, 53.8 +/- 18.0 years) were used. An outside-in press-fit fixation with a knot in the semitendinosus and gracilis tendons and an inside-out and outside-in fixation with the tendons wrapped around a bone block were compared with patellar tendon-bone press-fit fixation in 30 ovine femora. Constructs were cyclically strained and then loaded until failure. Maximum load to failure, stiffness, and elongation during failure testing and cyclical loading were investigated. RESULTS: The maximum load to failure was 561 +/- 309 N for the patellar tendon, 599 +/- 234 N for the semitendinosus/gracilis tendons knot construct, 678 +/- 231 for the semitendinosus/gracilis tendons bone construct inserted outside in, and 339 +/- 236 for the semitendinosus/gracilis tendons bone construct inserted inside out (inferior to the others; analysis of variance, Dunn test, P < .01). Stiffness of the constructs averaged 134 +/- 32 N/mm for the patellar tendon, 124 +/- 21 N/mm for the knot construct, 118 +/- 27 N/mm for the outside-in fixation, and 117 +/- 23 N/mm for inside-out fixation. Elongation during initial cyclical loading was 0.7 +/- 0.6 mm for the patellar tendon, 1.6 +/- 0.5 mm for the knot construct, 1.9 +/- 1.2 mm for the outside-in fixation, and 1.9 +/- 0.9 mm for the inside-out fixation (significantly larger for all semitendinosus/gracilis tendon techniques, P < .05). CONCLUSIONS: Failure loads for the semitendinosus/gracilis tendons bone construct inserted outside in and the semitendinosus/ gracilis tendons knot construct were within the confidence interval of the patellar tendon press-fit fixation. All semitendinosus/ gracilis tendon graft techniques exhibited larger elongation during initial cyclical loading than the patellar tendon graft. There was no difference in stiffness between all techniques. CLINICAL RELEVANCE: Two of the 3 hamstring press-fit fixation techniques showed loads to failure similar to the patellar tendon fixation. Preconditioning of the constructs is critical. These results must be interpreted with care because of high standard deviations.

Adolescent↗

Inclusive fitness, altruism and family adaptation.

An integrative model of family functioning is put forward using a sociobiological framework. Three key sociobiological concepts that have a relevance to family interaction are inclusive fitness, altruism, and a struggle for status. The term 'inclusive fitness' encompasses the parents' own fitness and that of their kith and kin. Altruism refers to how parents promote the survival of their progeny and extended family. The struggle for status refers to a struggle for power and prestige. According to the author's hypothesis 'inclusive fitness' exerts its influence through the struggle for status which in turn influences the degree of altruism and the level of 'family adaptation'. The parents' level of inclusive fitness largely determines the level of family adaptation which in turn influences the growth and individuation of the next generation. A common negative outcome of failure in the struggle for status and power is a displacement of the struggle for power into a family context. Failure in a struggle for status between peer group members would in a pretechnological society probably have reflected a relative lack of fitness. Failure in the struggle for status is likely to generate maladaptive cycles in the family which will lower the inclusive fitness of the parents. A concept of ideal family functioning is derived from sociobiology and specifically related to a high inclusive fitness in the parents. The author argues that sociobiological concepts can contribute to the development of an integrative theory of family behaviour. The clinical implications of this model are explored.

Adaptation, Psychological↗

Algorithm for multi-curve-fitting with shared parameters and a possible application in evoked compound action potential measurements.

BACKGROUND: Experimental results are commonly fitted by determining parameter values of suitable mathematical expressions. In case a relation exists between different data sets, the accuracy of the parameters obtained can be increased by incorporating this relationship in the fitting process instead of fitting the recordings separately. METHODS: An algorithm to fit multiple measured curves simultaneously was developed. The method accounts for parameters that are shared by some curves. It can be applied to either linear or nonlinear equations. Simulated noisy "measurement results" were created to compare the introduced method to the "straight forward" way of fitting the curves separately. RESULTS: The analysis of the simulated measurements confirm, that the introduced method yields more accurate parameters compared to the ones gained by fitting the measurements separately. Therefore it needs more computer time. As an example, the new fitting algorithm is applied to the measurements of the evoked compound action potentials (ECAP) of the auditory nerve: This leads to promising ideas to reduce artefacts generated by the measuring process. CONCLUSION: The introduced fitting algorithm uses the relationship between multiple measurement results to increase the accuracy of the parameters. Its application in the field of ECAP measurements is promising and should be further investigated.

Action Potentials↗

Correlation between quantitative fit factors and workplace protection factors measured in actual workplace environments at a steel foundry.

Past studies have found little or no correlation between workplace protection factors (WPFs) and quantitative fit factors (FFs). This study investigated the effect of good- and poor-fitting half-facepiece, air-purifying respirators on protection in actual workplace environments at a steel foundry and the correlation between WPFs and FFs. Fifteen burners and welders, who wore respirators voluntarily, and chippers participated in this study. Each subject was fit-tested with two respirator models each with three sizes, for a total of six fit-tests. Models and sizes were assigned this way to provide a wide range of FFs among study participants. Each worker donned the respirator twice per day (at the beginning of the shift and following the lunch break) for 2 days. Quantitative FFs were first obtained for each donning using the PortaCount Plus trade mark in a separate room. Without redonning the respirators, workers performed normal work for 1 to 2 hours, and WPFs were measured by collecting ambient and in-facepiece samples simultaneously. A second fit-test was conducted without disturbing the respirator. FFs were obtained by averaging the results from the first and second fit-tests. The resulting FFs had a geometric mean (GM) of 400 (range=10-6010) and a geometric standard deviation (GSD) of 6.1. Of the 55 valid donnings, 43 were good fitting (FFs> or =100) and 12 were poor fitting (FFs<100). The WPFs had a GM of 920 (range=13-230,000) and a GSD of 17.8. The WPFs were found to be significantly correlated with the FFs (R(2)=.55 and p-value=.0001). Therefore, FF was shown to be a meaningful indicator of respirator performance in actual workplace environments.

Adult↗

Computationally efficient curve-fitting procedure for large two-dimensional experimental infrared spectroscopic arrays using the Pearson VII model.

Extraction of quantitative information from large sets of sequential time-series spectra (two-dimensional, 2D, data) using a curve-fitting procedure is investigated. The difference between any experimental spectrum and any curve-fitted spectrum is constructed in a least-squares manner and the Pearson VII model is selected as the general band-shape function for the infrared absorbance spectra. The starting point for the curve-fitting procedure is a 2D peak map. Next, an interior spectrum from the 2D array is chosen, initial guesses of the band parameters are provided by an initialization scheme, and curve fitting is performed. Once optimal values of the Pearson VII model band parameters are obtained from the starting spectrum in the 2D array, these are then used as reasonable and judicious initial guesses for subsequent curve fitting of the neighboring spectra in the time series. This increases computational efficiency enormously. By adjusting the band center positions for moving bands, and re-optimizing each subsequent curve-fitting calculation to account for changing band shapes, the entire 2D array is rapidly and efficiently modeled. A 2D experimental spectroscopic time-series array from a homogeneous rhodium-catalyzed hydroformylation reaction was successfully curve fitted in this manner. The procedure holds considerable promise for the curve fitting of massive time-series spectroscopic data, such as that arising from on-line process monitoring of expensive value-added specialty chemical and pharmaceutical syntheses.

Algorithms↗

Fitness costs of mutations affecting the systemic acquired resistance pathway in Arabidopsis thaliana.

This study investigated the fitness effects of four mutations (npr1, cpr1, cpr5, and cpr6) and two transgenic genotypes (NPR1-L and NPR1-H) affecting different points of the systemic acquired resistance (SAR) signaling pathway associated with pathogen defense in Arabidopsis thaliana. The npr1 mutation, which resulted in a failure to express SAR, had no effect on fitness under growth chamber conditions, but decreased fitness in the field. The expression of NPR1 positively correlated with the fitness in the field. Constitutive activation of SAR by cpr1, cpr5, and cpr6 generally decreased fitness in the field and under two nutrient levels in two growth chamber conditions. At low-nutrient levels, fitness differences between wild type and the constitutive mutants were unchanged or reduced (especially in cpr5). The reduced fitness of the constitutive mutants suggests that this pathway is costly, with the precise fitness consequences highly dependent on the environmental context.

Arabidopsis↗

Genetic variation for total fitness in Drosophila melanogaster: complex yet replicable patterns.

The extent of genetic variation in fitness is a crucial issue in evolutionary biology and yet remains largely unresolved. In Drosophila melanogaster, we have devised a method that allows the net effects on fitness of heterozygous wild-type chromosomes to be measured, by competing them against two different "balancer" chromosomes. We have applied the method to a large sample of 40 wild-type third chromosomes and have measured fitnesses of nonlethal chromosomes as well as chromosomes bearing recessive lethals. The measurements were made in the environment to which the population was adapted and did not involve inbreeding. The results show an extraordinary similarity in the behavior of replicates of the same chromosome, indicating consistent genetic effects on total fitness. Some invading chromosomes increased rapidly and some slowly, and some rose to appreciable frequency after several months, but then declined again: in every case, the same pattern was seen in each replicate. We estimated relative fitnesses, rates of change of fitness, and relative viabilities, for each chromosome. There were significant fluctuations around the fitted model, which were also highly replicable. Wild-type chromosomes varied substantially in their effects on heterozygous fitness, and these effects vary through time, most likely as a result of genotype x environment interactions.

Animals↗

Bicycle helmet assessment during well visits reveals severe shortcomings in condition and fit.

BACKGROUND: Improper bicycle helmet fit increases the risk of head injury. Information on the rate of proper use of bicycle helmets is lacking. Promotion of helmet use is recommended at well-child and adolescent visits. Actual helmet assessment during such visits has not been reported. OBJECTIVES: The primary goal of this study is to measure the proportion of children whose helmets are in proper condition and can be made to fit properly by the child and/or parent. The secondary goal is to begin to assess the value and practicality of helmet inspection during well-child and adolescent visits. METHODS: The study took place at a private pediatric office in Falmouth, Massachusetts, from June 1 through August 31, 2001. Eligible children and adolescents were those aged 4 to 18 years presenting for well examination, along with siblings present at the visit. Eligible families completed a questionnaire, then had a timed attempt to fit a helmet, followed by an assessment of helmet fit and condition against a predetermined standard. RESULTS: Eighty-four percent (395/473) of eligible families participated. A total of 479 participants were assessed. Eighty-eight percent of participants (419/478) owned a helmet. Reported helmet use "always" or "almost always" was 73% for bicycling (317/434), 69% for in-line skating (193/279), 58% for scootering (179/310), and 50% for skateboarding (79/158). Compared with younger children, teenagers were less likely to wear helmets for all activities. Complete pass rate for every aspect of condition and fit was 4% (20/478, 95% confidence interval: 3-6). The pass rate when the parent alone fit the helmet was 0% (0/52). Three individual aspects of fit were most problematic: 1) helmet 'resting position' too high on the forehead (pass rate 249/479; 52%), 2) improper strap position (pass rate 157/476; 33%), and 3) excessive movement of the helmet from front to back of the head (pass rate 247/479; 52%). Mean time for questionnaire completion was 4 (standard deviation: +/-1) minutes, and 7 (standard deviation: +/-3) minutes for helmet assessment. CONCLUSIONS: Ninety-six percent of children and adolescents wore helmets in inadequate condition and/or with inadequate fit. This occurred despite a high acceptance of helmet use by this population. Initial evidence suggests that helmet assessment during well visits may be practical and valuable.

Adolescent↗

Use and effectiveness of oral analgesia when fitting an intrauterine device.

OBJECTIVE: To explore (a). if analgesia taken before an intrauterine device (IUD) fitting actually lessens the discomfort of the fitting and (b). whether there is a relationship between anxiety and choosing to take pain relief before an IUD fitting. POPULATION: Women having an IUD fitted in participating clinics in Leeds between 1 April and 31 July 2001. METHOD: Advice was given to women who were having an IUD fitted to take analgesia before they came to the clinic if they wished. The women completed a questionnaire at the time of fitting to record anticipated discomfort, actual discomfort and the use of analgesia before the fitting. A second questionnaire was sent to women 6 months later. RESPONSE: A total of 109 women completed the first questionnaire and 54 completed the second questionnaire. FINDINGS AND DISCUSSION: Women who were more anxious and who anticipated that the procedure would be painful, even if it was not as bad as expected at the time of the fitting, will recall that it was a painful experience. Those who chose to take painkillers before the procedure may identify this group of women. Higher anxiety levels may contribute to the perceived discomfort.

Adult↗

Exponential hyperbolic sine function fitting of heart rate response to constant load exercise.

We attempted to fit heart rate (HR) changes induced by constant exercise loads of different intensities to an exponential hyperbolic sine curve by the least-squares method, and we compared the results with the fitting of the changes to exponential curves. Seven healthy male volunteers performed three different intensities of constant-load exercise on a bicycle ergometer. The exponential hyperbolic sine function adequately fitted the HR responses induced by all three different intensities of loads: low (30 W: correlation coefficient, r = 0.68 +/- 0.13, mean +/- SD), moderate (75 W: r = 0.93 +/- 0.07) and high (125 W: r = 0.97 +/- 0.02). The first-order exponential curve fitted only the moderate load response. Although the second-order exponential equation fitted the HR response for both the moderate and high loads, the equation did not fit the low-load response (r = 0.43 +/- 0.26). In low-load exercise, the sum of the power of the residuals for the exponential hyperbolic sine curve fitting was significantly smaller than that for the first- or second-order exponential curve fitting. In conclusion, the exponential hyperbolic sine function is useful for quantitative analyses of the HR response to exercise loads of various intensities.

Adult↗

A comparison of trial shoe and shell shoe fitting techniques.

In Europe, bespoke orthopaedic shoes are usually sent for a trial fitting in order to check the fit and indicate any modifications required before final finishing. The use of shell shoes at the fit assessment stage, rather than the traditional alternative of partially or fully finished shoes, can offer service advantages, and is widely used for example in the Netherlands. However the comparability of shell fit assessment with the traditional method of trial shoe fit assessment has not been evaluated, either to assess its sensitivity or to elucidate any difference in assessment technique required of the orthotist. In this work, the results of fit assessments by both methods are compared. The trial involved a group of normal subjects wearing high street shoes of styles similar to those used for orthopaedic footwear. The results indicate that the shell fit assessments were in the main comparable to those for trial shoe fit. The only consistent area of deviation noted, in the heel at the topline, is attributable to a construction factor in shoe making. Apart from this area, the orthotist need not adjust his technique to make use of the shell method.

Anthropometry↗

PHARMFIT--a nonlinear fitting program for pharmacology.

A new program is presented for nonlinear fitting of data from pharmacological and chronobiological investigations. It contains functions for calculating data from ligand-binding studies and competition experiments, for the analysis of dose-response curves, for pharmacokinetic calculations, and for cosine analysis of harmonic and overlapping rhythms. In addition, it is possible to implement general equations by the user. The program allows data exchange with most spreadsheet, database, and graphics presentation programs, and accepts data from two widely used ambulatory 24-h blood-pressure monitoring systems. The fitting procedure uses the Marquardt-Levenberg algorithm. It calculates the weighted or the unweighted fit together with a great variety of statistics for estimation of goodness of fit. A graphics module permits graphical presentation of the fitted curve. Moreover, fitting of data to different models can be compared for the most likely fit and model discrimination statistics for improvement of further experiments are provided. To demonstrate the chronobiological application of the fitting program PHARMFIT, the analysis of telemetric heart rate data from rats is presented.

Binding Sites↗

How to fit a response time distribution.

Among the most valuable tools in behavioral science is statistically fitting mathematical models of cognition to data--response time distributions, in particular. However, techniques for fitting distributions very widely, and little is known about the efficacy of different techniques. In this article, we assess several fitting techniques by simulating six widely cited models of response time and using the fitting procedures to recover model parameters. The techniques include the maximization of likelihood and least squares fits of the theoretical distributions to different empirical estimates of the simulated distributions. A running example is used to illustrate the different estimation and fitting procedures. The simulation studies reveal that empirical density estimates are biased even for very large sample sizes. Some fitting techniques yield more accurate and less variable parameter estimates than do others. Methods that involve least squares fits to density estimates generally yield very poor parameter estimates.

Chi-Square Distribution↗