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Alcohol-related problems and fitness to drive.

This paper analyses the alcohol consumption patterns in Spanish drivers, the incidence of alcohol-related problems and attempts to ascertain whether, in the end, drivers with alcohol-related problems are considered fit or unfit to drive. In accordance with Spanish and European Union legislation, driving licences cannot be issued or renewed to people suffering from alcohol-related problems. A medical, psychological and eyesight evaluation was performed to test the driving fitness of 8043 drivers attending 25 Medical Driving Test Centres on a national scale. Among other things, information was collected on the patterns of alcohol consumption, the AUDIT and CAGE tests, the incidence of alcohol-related problems (DSM-IV criteria for abuse, dependence and alcohol-induced disorder), as well as an evaluation of their fitness to drive. In all, 60.3% of drivers drink alcohol on a regular basis; 7.3% of drivers scored > or = 8 points in the AUDIT test, and 2% met criteria for DSM-IV alcohol abuse, dependence or induced disorder. Drivers with alcohol-related problems have been involved in traffic accidents (23.2%) and have infringed driving regulations (18.7%) more frequently (P < 0.0001) than those without alcohol-related problems. Of those with alcohol-related problems, 72.2% were considered fit to drive. The study reveals that alcohol consumption is common among drivers, that a significant number of drivers have alcohol-related problems, and that three in four of the latter were considered fit to drive.

Adult↗

The alternative fitness sets which preserve allele trajectories: a general treatment.

A general solution is presented of the problem of specifying all alternative, generally frequency-dependent, (absolute) fitness sets which give rise to the same allele frequency changes and population dynamics as a given fitness set. The one- and two-locus cases are analyzed in detail and the method is then extended to the n-locus case. It is shown that if biological constraints can be used to specify the mean fitness of the population and the relative fitnesses of the heterozygotes, then the allele frequency trajectories determine a unique fitness set.

Alleles↗

Dominance and overdominance of mildly deleterious induced mutations for fitness traits in Caenorhabditis elegans.

We estimated the average dominance coefficient of mildly deleterious mutations (h, the proportion by which mutations in the heterozygous state reduce fitness components relative to those in the homozygous state) in the nematode Caenorhabditis elegans. From 56 worm lines that carry mutations induced by the point mutagen ethyl methanesulfonate (EMS), we selected 19 lines that are relatively high in fitness and estimated the viabilities, productivities, and relative fitnesses of heterozygotes and homozygotes compared to the ancestral wild type. There was very little effect of homozygous or heterozygous mutations on egg-to-adult viability. For productivity and relative fitness, we found that the average dominance coefficient, h, was approximately 0.1, suggesting that mildly deleterious mutations are on average partially recessive. These estimates were not significantly different from zero (complete recessivity) but were significantly different from 0.5 (additivity). In addition, there was a significant amount of variation in h among lines, and analysis of average dominance coefficients of individual lines suggested that several lines showed overdominance for fitness. Further investigation of two of these lines partially confirmed this finding.

Animals↗

Effector genes of Xanthomonas axonopodis pv. vesicatoria promote transmission and enhance other fitness traits in the field.

Establishing durable disease resistance in agricultural crops, where much of the plant defense is provided through effector-R gene interactions, is complicated by the ability of pathogens to overcome R gene resistance by losing the corresponding effector gene. Many proposed methods to maintain disease resistance in the field depend on the idea that effector gene loss results in a fitness cost to the pathogen. In this article we test for fitness costs of effector gene function loss. We created directed knockouts of up to four effector genes from the bacterial plant pathogen Xanthomonas axonopodis pv. vesicatoria (Xav) and examined the effect of the loss of a functional gene product on several important fitness parameters in the field. These traits included transmission, lesion development, and epiphytic survival. We found that the products of all four effector genes had significant and often additive effects on fitness traits. Additional greenhouse tests revealed costs of effector gene loss on in planta growth and further showed that the effects on lesion development were separable from the effects on growth. Observable fitness effects of the three plasmid-borne effector genes were dependent upon the loss of functional avrBs2, indicating that complex functional interactions exist among effector genes with Xav.

Analysis of Variance↗

Heterozygous effects on fitness of EMS-treated chromosomes in Drosophila melanogaster.

The heterozygous effects on fitness of second chromosomes carrying mutants induced with different doses of EMS were ascertained by monitoring changes in chromosome frequencies over time. These changes were observed in populations in which the treated chromosomes, as well as untreated competitors, remained heterozygous in males generation after generation. This situation was achieved by using a translocation which links the second chromosome to the X chromosome; however, only untranslocated second chromosomes were mutagenized. Chromosomes were classified according to their effects on viability in homozygous condition. A preliminary homozygosis identified completely lethal chromosomes; secondary tests distinguished between drastic (viability index < 0.1) and nondrastic chromosomes. Chromosomes that were nondrastic after treatment were found to reduce the fitness of their heterozygous carriers by 3-5%. The data show that flies homozygous for these chromosomes were about 2.7% less viable per treatment with 1 mm EMS than flies homozygous for untreated chromosomes. By comparing the fitness-depressing effects of nondrastic EMS-induced mutants in heterozygous condition with the corresponding viability-depressing effects measured by Temin, it is apparent that the total fitness effects are several times larger than the viability effects alone. Completely lethal chromosomes derived from the most heavily treated material reduced fitness by 11% in heterozygous condition; approximately half of this reduction was due to the lethal mutations themselves.

Animals↗

Enhancement of motility by treating spermatozoa with an antioxidant solution (Sperm-Fit) following ejaculation.

Oxygen radical generation is known to be detrimental to sperm function, especially motility, through the lipid peroxidation of the membranes. Generation of reactive oxygen species can be induced by leukocyte contamination, sperm centrifugation and the presence of abnormal spermatozoa with excess residual cytoplasm. This study aims to evaluate the effect on sperm motility of incubation in an antioxidant-containing solution, during liquefaction and centrifugation. Thirty semen samples were each divided into two equal parts: one mixed with Tyrode's solution, the other with a salt solution containing antioxidants (Sperm-Fit; Ellios Bio-Media, Paris, France). All the procedures were identical in the two groups. The ratio of leukocytes to spermatozoa was significantly correlated with the motility after liquefaction and after a 24 h incubation in routine in-vitro fertilization (IVF) medium and with the number of motile spermatozoa recovered after Percoll preparation. Moreover, when this ratio was > or = 0.2, all motility parameters were lowered. Incubation with Sperm-Fit allowed a higher percentage of motility after Percoll preparation when the ratio was > or = 0.2 (48 +/- 5% versus 41 +/- 6% for Sperm-Fit and Tyrode's solution respectively; P < 0.05) and a greater number of motile spermatozoa recovered after Percoll preparation, whatever the ratio (3.2 +/- 1.0 x 10(6) versus 2.4 +/- 0.7 x 10(6) for Sperm-Fit and Tyrode's solution respectively when ratio > or = 0.2; 18.1 +/- 3.4 x 10(6) versus 14.4 +/- 2.9 x 10(6) for Sperm-Fit and Tyrode's solution respectively when ratio < 0.2; P < 0.05). These results show that incubation with antioxidants during liquefaction and centrifugation increases recovery of motile spermatozoa.

Antioxidants↗

Reduction of the fitness burden of quinolone resistance in Pseudomonas aeruginosa.

OBJECTIVES: Quinolone resistance in the opportunistic pathogen Pseudomonas aeruginosa is commonly caused by mutations that alter the target molecules DNA gyrase/topoisomerase IV, or cause activation of various efflux systems. We have analysed the effect of quinolone resistance caused by DNA gyrase/topoisomerase IV mutations on bacterial fitness. METHODS: Norfloxacin-resistant mutants were isolated and by DNA sequencing the mutations conferring resistance were identified. Mutant fitness was determined by measuring growth rates in vitro. Mutants with reduced growth rates were serially passaged to obtain growth-compensated mutants. The level of DNA supercoiling was determined by isolating plasmid DNA from the susceptible, resistant and compensated mutants and comparing the topoisomer distribution patterns by gel electrophoresis in the presence of chloroquine. RESULTS: Low-level resistance (4-48 mg/L) was caused by single mutations in gyrA or gyrB. Among these strains, three out of eight mutants showed lower fitness, whereas high-level resistant (>256 mg/L) mutants with double mutations in gyrA and parC, parE, nfxB or unknown genes all showed a reduced fitness. Slow-growing resistant mutants with a gyrA mutation had decreased DNA supercoiling. After serial passage in laboratory medium, mutant fitness was increased by compensatory mutation(s) that restored supercoiling to normal levels. The compensatory mutation(s) was not located in any of the genes (gyrAB, topA, parCE, hupB, fis, hupN, himAD or PA5348) that were expected to affect supercoiling. CONCLUSIONS: Our results show that 'no cost' and compensatory mutations are common in quinolone-resistant P. aeruginosa.

Anti-Infective Agents↗

Accumulation of transposable elements in the genome of Drosophila melanogaster is associated with a decrease in fitness.

Replicates of the two isogenic laboratory strains of Drosophila melanogaster, 2b and Harwich, contain different average transposable element (TE) copy numbers in the same genetic background. These lines were used to analyze the correlation between TE copy number and fitness. Assuming a weak deleterious effect of each TE insertion, a decrease in fitness is expected with an increase in genomic TE copy number. Higher rates of ectopic exchanges and, consequently, chromosomal rearrangements resulting in early embryonic death are also predicted from an increase in TE copy number. Therefore egg hatchability is expected to decrease as the genomic TE copy number increases. In 2b, where replicate lines have diverged up by 90 TE copies per haploid genome, a negative correlation between the number of TE insertions and both fitness and egg hatchability were found. Neither correlation was significant for the Harwich replicates, which have only diverged by 30 TE copies. The average deleterious effect of a TE insertion on fitness and its components was estimated as 0.004. Both homozygous and heterozygous TE insertions were shown to have deleterious effects on fitness and its components.

Analysis of Variance↗

Adaptations to increasing hydraulic stress: morphology, hydrodynamics and fitness of two higher aquatic plant species.

Sessile organisms often exhibit morphological changes in response to permanent exposure to mechanical stimulation (wind or water movements). The adaptive value of these morphological changes (hydrodynamic performance and consequences on fitness) has not been studied extensively, particularly for higher plants submitted to flow stress. The aim was to determine the adaptive value of morphological patterns observed within two higher aquatic plant species, Berula erecta and Mentha aquatica, growing along a natural flow stress gradient. The hydrodynamic ability of each ramet was investigated through quantitative variables (drag coefficient and E-value). Fitness-related traits based on vegetative growth and clonal multiplication were assessed for each individual. For both species, the drag coefficient and the E-value were explained only to a limited extent by the morphological traits used. B. erecta exhibited a reduction in size and low overall plant drag at higher flow velocities, despite high drag values relative to leaf area, due to a low flexibility. The plants maintained their fitness, at least in part, through biomass reallocation: one tall ramet at low velocity, but shorter individuals with many interconnected stolons when flow velocity increased. For M. aquatica, morphological differences along the velocity gradient did not lead to greater hydrodynamic performance. Plant size increased with increasing velocities, suggesting the indirect effects of current favouring growth in high velocities. The fitness-related traits did not demonstrate lower plant fitness for high velocities. Different developmental constraints linked to plant morphology and trade-offs between major plant functions probably lead to different plant responses to flow stress.

Adaptation, Physiological↗

Quantitative analysis of electrophoresis data: novel curve fitting methodology and its application to the determination of a protein-DNA binding constant.

A computer program, GelExplorer, which uses a new methodology for obtaining quantitative information about electrophoresis has been developed. It provides a straightforward, easy-to-use graphical interface, and includes a number of features which offer significant advantages over existing methods for quantitative gel analysis. The method uses curve fitting with a nonlinear least-squares optimization to deconvolute overlapping bands. Unlike most curve fitting approaches, the data is treated in two dimensions, fitting all the data across the entire width of the lane. This allows for accurate determination of the intensities of individual, overlapping bands, and in particular allows imperfectly shaped bands to be accurately modeled. Experiments described in this paper demonstrate empirically that the Lorentzian lineshape reproduces the contours of an individual gel band and provides a better model than the Gaussian function for curve fitting of electrophoresis bands. Results from several fitting applications are presented and a discussion of the sources and magnitudes of uncertainties in the results is included. Finally, the method is applied to the quantitative analysis of a hydroxyl radical footprint titration experiment to obtain the free energy of binding of the lambda repressor protein to the OR1 operator DNA sequence.

Bacteriophage lambda↗

The effect of fitting procedure on hearing protector attenuation.

Realistically evaluating the effectiveness of hearing protectors continues to be a major problem in hearing conservation. The purpose of this study was to examine a laboratory-based fitting procedure (User Fit) that was designed to yield hearing protector attenuation values similar to that derived from field studies. Ten subjects who were naive to hearing protectors were used in a repeated measures design that measured real ear attenuation at threshold for two types of plugs. Each subject was tested in two fitting conditions that varied based on the type and degree of assistance given to the subjects by the experimenter. The results showed significant differences in attenuation based on the fitting procedure used, with the User Fit best approximating field data. In addition, a generalized learning effect was noted. The results suggest that any experience with earplugs leads to subsequent improvement in attenuation despite the type of earplug used. Further testing is planned with greater numbers of subjects and additional types of hearing protectors.

Adult↗

Unreamed locked tight-fitting nailing for acute tibial fractures.

OBJECTIVES: Treatment of tibial fractures by unreamed locked nailing with loose-fitting nails has previously been shown to be associated with a low union rate and high implant failure rate. This report describes the authors' experience in using tight-fitting nails that were relatively larger than loose-fitting nails. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: Forty-eight consecutive patients with fifty-two tibial fractures (excluding open IIIC fractures and those with bone loss) were studied: thirty-four men and fourteen women, with a mean age of 38 years. There were twenty-five closed fractures, nine Type I, eight Type II, four Type IIIA, and six Type IIIB open fractures. INTERVENTION: Unreamed nailing with tight-fitting nails using the Russell-Taylor system. OUTCOME MEASURES: Union rate, time to union, complication rate, and functional recovery, as well as nailing time, hospital time, and crutch-walking time were recorded. RESULTS: Union occurred in forty-eight of fifty-two fractures (92%) with a mean time to union of 18.2 weeks. Compartment syndrome occurred in three patients. Deep infection occurred in one Type II and one Type IIIB open fracture. Four fractures required additional exchange nailing or bone grafting to achieve union: one Type II, one Type IIIA, and two Type IIIB open fractures. Three malalignments resulted from operative technical error. The rate of both intraoperative bony split and screw breakage was 3.8% (2 of 52), but neither complication interfered with fracture healing. Recovery of joint motion was essentially normal in those patients without knee or ankle injury. CONCLUSIONS: Unreamed locked nailing with tight-fitting nails can produce satisfactory clinical results for acute tibial fractures. It has the advantages of technical simplicity and an acceptable risk of implant failure.

Acute Disease↗

Fit and match hypothesis for kidney transplantation.

The importance of HLA matching for cadaver-donor transplants is often ignored due to the small (10%) difference in graft survival rates between the best and worst matched pairs. A new "fit and match" hypothesis is proposed to improve the predictive value of matching. Graft and functional survival rates of kidney transplants were calculated for living and cadaver-donors by the standard Kaplan and Meier methods. Mean discharge serum creatinine (SCr) values were computed after excluding patients who died or lost their grafts before discharge. Donor size, recipient size, age of donor kidney, damage caused by cold ischemia time, and mode of donor death all had substantial effects on the average SCr levels at discharge. These SCr levels correlated with one- and five-year graft survival rates. Transplants that had extremely different graft survival rates, such as those from living donors and cadaver donors, were found to have similar rates when reclassified by SCr levels at discharge. By examining the combined effects of the fit and match factors, transplants with the best fit and match exhibited a 95% one-year graft survival rate, whereas those with the worst fit and match had a 75% survival rate. This 20% difference increased to 36% after five years (84% vs. 48%). We conclude that the fit and match hypothesis provides a theoretical basis for devising a more critical method of predicting cadaver kidney transplant survival rates. Furthermore, it suggests a vital need to develop methods for estimating functional donor renal mass.

Age Factors↗

Fitting relationships between exposure and standardized mortality ratios.

Practical methods are described for formal fitting of simple (linear) relationships between exposures in several subgroups and standardized mortality (or morbidity) ratios (SMRs) for these groups, whether derived from a cohort study by the person-years method or otherwise. The observed events are assumed to have Poisson variation about the fitted relationships. Procedures are outlined for obtaining parameter estimates by iterative weighted least squares regression, which is not only equivalent to, but also the simplest form of maximum likelihood estimation. A test of fit is available in a chi 2 statistic for deviations of observed data from "fitted" values. A further test allows one to examine whether the SMR at zero exposure is different from unity. The concept of relative slopes is discussed, and methods are given for obtaining estimates and confidence intervals. Generalizations to more than one exposure, and to quadratic and other relationships, are explained. Steps for computing the basic fits are detailed, and instructions for adapting packaged computer programs given. Illustrations are provided from data of lung cancer SMRs in relation to exposure to asbestos and to smoking.

Asbestosis↗

Pessary treatment of pelvic relaxation: factors affecting successful fitting and continued use.

OBJECTIVES: The aims of this study were to determine predictors of successful pessary fitting and continued pessary use in patients with pelvic relaxation. DESIGN: Retrospective observational study. SETTING AND SUBJECTS: The medical records of 130 consecutive patients evaluated for pessary treatment of pelvic relaxation by a single specially trained nurse practitioner (CRJ) at Kaiser Foundation Hospital, Harbor City, Calif, between May 1, 1997, and June 30, 2002, were retrospectively reviewed. INSTRUMENTS: Voiding diaries, data collection sheet, and questionnaires. METHODS: The medical records of the 130 patients were retrospectively reviewed, and data were recorded on data collection sheets. Patients using pessaries completed a questionnaire to assess treatment effectiveness. RESULTS: Coexisting stress urinary incontinence and previous prolapse and cystocele/rectocele repairs were each found to be independent predictors of unsuccessful pessary fitting. Fifty percent of successfully fitted patients had discontinued pessary use by 24 months. Current pessary users were more likely to have undergone prior pelvic reconstructive surgery (37% vs 13%, P = .02), less likely to require a space-filling pessary (13% vs 37%, P = .03), and more likely to recommend pessary to their friends or family (87% vs 50%, P = .007) compared to patients who discontinued pessary use. CONCLUSIONS: Prior pelvic reconstructive surgery is associated with an increased risk of unsuccessful pessary fitting; however, those patients who are successfully fitted tend to continue pessary use.

Aged↗

Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time.

BACKGROUND: Changes in virulence during an epidemic are common among pathogens, but still unexplored in the case of HIV-1. Here we used primary human cells to study the replicative fitness of primary HIV-1 isolates from untreated patients, comparing historical (1986-1989) and recent samples (2002-2003). METHODS: Head-to-head dual virus infection/competition assays were performed in both peripheral blood mononuclear cells and human dendritic cell/T-cell co-cultures with pairs of 12 carefully matched historical and recent HIV-1 isolates from untreated patients. Sensitivity to inhibition by lamivudine (3TC) and TAK-779 of historical and recent R5 HIV-1 isolates was measured in a subset of samples. RESULTS: Overall, the historical HIV-1 out-competed the recent HIV-1 isolates in 176 of 238 competitions and in 9 of 12 competitions carefully matched for CD4 cell count. The mean relative replicative fitness (W) of all historical HIV-1 strains was significantly greater than that of recent HIV-1 isolates (W(1986-1989) = 1.395 and W(2002-2003) = 0.545, P < 0.001 (t test)). The more fit viruses (mean W > 1) from 1986-1989 appeared less sensitive to TAK-779 and 3TC than did the less fit (mean W < 1) 2002-2003 viruses. CONCLUSIONS: These findings suggest that HIV-1 replicative fitness may have decreased in the human population since the start of the pandemic. This 'attenuation' could be the consequence of serial bottlenecks during transmission and result in adaptation of HIV-1 to the human host.

Amides↗

Adaptability of myopic children to progressive addition lenses with a modified fitting protocol in the Correction of Myopia Evaluation Trial (COMET).

PURPOSE: The purpose of this study was to evaluate the adaptability of myopic children participating in the Correction of Myopia Evaluation Trial (COMET) to the use of progressive addition lenses (PALs) with a modified fitting protocol of setting the distance fitting cross 4 mm above the pupil center. METHODS: COMET was a multicenter, randomized clinical trial to evaluate whether PALs vs. single-vision lenses (SVLs) slowed the rate of progression in children with juvenile-onset myopia over 3 years. Of the 469 children enrolled, 234 were assigned to SVLs and 235 were assigned to PALs (+2.00 D near addition), which were fit according to a standard study protocol with the fitting cross positioned 4 mm above the pupil center. The children's adaptability to the use of PALs was evaluated by comparing the frequency and reasons for problem visits, visual symptoms, cover test results, and adherence to wearing glasses between treatment groups. RESULTS: During the first 3 years of follow-up, no differences were observed between children wearing PALs and those wearing SVLs with respect to the number or reasons for problem visits. One week after receipt of the study glasses, children wearing PALs showed a higher frequency of three visual symptoms related to adaptability: looking down from the blackboard and getting items on their desk in focus (p = 0.001), blur when reading (p = 0.003), and difficulty going down steps (p = 0.02). Children wearing PALs were more likely to report at least one adaptation symptom at 1 week: odds ratio of 2.76 (95% confidence interval = 1.28-5.95). By 1 month, these differences disappeared and the frequency of all visual symptoms remained low and similar for both treatment groups over 3 years. Strabismus was observed on cover test in five children (three SVLs, two PALs). None of the children had to be changed from PALs to SVLs, whereas two of the children were changed from SVLs to PALs as a result of binocular vision problems. The children and parents reported adherence to wearing the eyeglasses approached 100% compliance throughout the follow-up period for both groups. Most (98%) of the 235 children assigned to PALs maintained the modified fitting protocol without any problems over 3 years. CONCLUSION: These data show that children can safely and comfortably wear PALs for at least 3 years.

Adaptation, Physiological↗

Predation risk and longevity influence variation in fitness of female roe deer (Capreolus capreolus L.).

We studied the effects of population density, red fox predation risk, individual body mass and longevity on female fitness in a free-ranging roe deer population. During the study, population density varied from 9.3 to 36.1 deer km(-2), and red fox abundance varied strongly over years owing to a sarcoptic mange outbreak. In support of our predictions, long-lived females had higher fitness than short-lived ones. Further, fortunate female roe deer that gave birth in years of low red fox abundance attained much higher fitness than those that gave birth in years of high red fox abundance. Longevity and predation risk explained more than half the variation in fitness observed among roe deer females. As a possible effect of small sample size, we found no effect of female body mass or population density at birth. Our study demonstrates that predation risk, a component of environmental stochasticity, may prevent directional selection even when phenotypic quality influences individual fitness.

Animals↗