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PubMed2001

The quality of clinical fit of stainless steel bands used in endodontics.

Stainless steel bands are commonly advocated to protect posterior teeth against fracture during endodontic treatment and before final restoration. A poorly fitting band, however, may lead to a compromised coronal seal and gingival irritation. This radiographic study assessed the quality of fit and marginal adaptation in the proximal area of stainless steel bands placed during routine endodontic treatment. Clinical radiographs of 120 maxillary and mandibular premolars and molars were evaluated. All radiographs were taken during routine clinical endodontic treatment and randomly selected from cases completed by ten operators. Approximately one-half of cases did not meet the criteria of adequate marginal seal (mesial: 65/120; distal: 49/120). Only 11 teeth were found to have adequate fit of the band on both mesial and distal aspects of the tooth. The most common reason for inadequacy of fit was lack of band adaptation to the tooth contour in the cervical region. Stainless steel bands have a high possibility of poor marginal fit and should be used with the awareness that they may produce other clinical problems.

Bicuspid↗
PubMed1993

Person-environment fit: using commensurate scales to predict student stress.

The relationship between person-environment fit and stress was examined for two samples of university students (N = 55 and 79). The Kirton Adaption-Innovation Inventory (KAI) was modified to assess the students' perceptions of the adaptor-innovator style required by their course, the styles they exhibited in the course, and their ideal style preferences. To ascertain fit, the KAI total scores and subscale scores (Originality, Efficiency, and Rule/Group Conformity) were used to classify students on three dimensions: (1) perception of what style their course required, adaptive or innovative; (2) congruence between the style the course required and the style they exhibited in the course; and (3) the magnitude of the difference, if any, between the required style and the exhibited style. Points two and three are measures of fit. The dependent variable was stress. Also the students' ideal style scores, KAI total and subscales, were substituted for the exhibited scores and the classification and analyses were repeated. Analysis of the total scores revealed that a course requiring adaptive behaviours was perceived as more stressful than a course requiring innovative behaviours. Similarly, an analysis of the Rule/Group Conformity scores revealed that the greater the conformity required the greater the stress. Also the less originality demanded in the course the greater was the perceived stress. For the KAI total scores and Rule/Group Conformity scores, the two measures of fit (incongruity and magnitude of the incongruity) were not related to stress. However, analyses of the Originality and Efficiency subscales supported the importance of the P-E fit position. For both subscales, stress was associated with the magnitude of the difference between what was required in the course and what students exhibited in the course. Educational implications derived from these findings as well as recommendations for future research are discussed.

Adaptation, Psychological↗
PubMed2000

Fitting and benchmarking of dosimetry data for new brachytherapy sources.

New source designs of encapsulated low-energy gamma emitting nuclides for permanent implants require dosimetric analysis and calibration standardization. The dosimetry measurements can be incorporated into a treatment planning system by fitting the data. The use of a fitting function whose behavior at range limits mimics the physical phenomena, using as few parameters as possible, eliminates noisy outliers and lends credence to calculations beyond the measured range. Clinical implementation of the new sources also requires benchmarking against existing sources, where the current clinical experience lies. We present an analysis of measured dosimetry data for three brachytherapy sources recently available from North American Scientific, Inc. (North Hollywood, CA): 103Pd source model MED3633 ("PdGold"), 125I source models MED3631-A/M ("IoGold-AM") and MED3631-A/S ("IoGold-AS"). Using the formalism of the Interstitial Collaborative Working Group (ICWG) the radial dose function, g(r), the anisotropy function, F(r, theta), and the anisotropy factor, phi an(r), were previously evaluated from measurements of each source design. In this report we use fitting functions whose forms are chosen to approach reasonable values at data limits. These forms are quite similar to those used in a previous analysis of TG43 Iodine and palladium compendium data. Fitting parameter results for each function are provided for each brachytherapy source model. Fit-data discrepancies are smaller than measurement uncertainties, meaning that incorporation into treatment planning systems will not introduce significant errors in clinical use. Current clinical experience is based on the Theragenics (Norcross, GA) 103Pd seed ("PdThera"), and the Nycomed-Amersham (Arlington Heights, IL) 125I seed models 6711 ("6711") and 6702 ("6702"). The new sources are benchmarked against these seeds.

Anisotropy↗
PubMed2001

Fitted dosimetric parameters of high dose-rate 192Ir sources according to the AAPM TG43 formalism.

The purpose of this study is to find fitted functional forms to the anisotropy function, F(r, theta), and the radial dose function, g(r), in order to characterize dose-rate distributions around all the high-intensity 192Ir sources currently in use. Dosimetry data are at present available as tables for: the microSelectron HDR ("classic" and "new" design models), the PDR source, and the VariSource HDR source, expressed in terms of the AAPM Task Group No. 43 recommendations. There is only one paper out which introduces a functional form to fit the anisotropy function, but only for symmetric sources with respect to the transverse axis. However, dosimetric data of the HDR and PDR sources mentioned above cannot be reproduced with these functional forms. In our study F(r,theta) and g(r) published data are fitted with functional forms in such a way that appropriate limits are reached for both functions and the maximum fit error approaches the data uncertainty. The average fit error is less than 1% in all cases. These functional forms make handling data easier within the treatment planning system, avoiding the use of tabulated data.

Anisotropy↗
PubMedDate not supplied

Measurement of the presampling modulation transfer function of film digitizers using a curve fitting technique.

A curve fitting technique combined with an angulated slit image has been developed for the measurement of the presampling modulation transfer function (MTF) of film digitizers. The noisy line spread functions (LSFs) acquired from an angulated slit image are fitted using a combination of two functions by means of a nonlinear least-square fitting technique. The parameters in the model function for each LSF are obtained by minimizing the residual root mean square (RMS), and then averaged over all the LSF fittings. The resulting analytical function is representative of the continuous presampled LSF. We have found that a combination of Gaussian and exponential functions provides a good fit to the LSFs obtained with film digitizers. The corresponding analytical Fourier transformation of the model function yields the presampling MTF, without Nyquist frequency limitation. Measurements of spatial resolution properties using this method were performed for two laser scanners and an optical drum scanner.

Biophysical Phenomena↗
PubMed1999

Functional fitting of interstitial brachytherapy dosimetry data recommended by the AAPM Radiation Therapy Committee Task Group 43. American Association of Physicists in Medicine.

This work was undertaken to expedite implementation of the AAPM Task Group 43 recommendations, which call for significant modifications in the way dose is calculated for interstitial sources of 192Ir, 125I, and 103Pd as well as significant changes in the dose rate constant for 125I sources. The TG43 recommendations include a new formalism for dose calculation at points defined by the radial distance, r, from the source center and the angle, theta, that such a radius makes with the source axis. For each source type, values are tabulated for the radial dose function, the anisotropy function, and the anisotropy factor. The TG43 report includes fitting functions for the radial dose function in the form of polynomials, which are poorly behaved outside the range of fitted data. No functions are offered for the anisotropy function data or the anisotropy factor data, both of which could profit from some smoothing by such functions. We have found a double exponential fit to the radial dose function that not only approximates the data adequately but also appropriately approaches zero for very large distances. The anisotropy function is conveniently fit with a form of type 1 - f(r,theta)cos(theta)e(cr), which is exactly 1 at theta=90 degrees and approaches 1 for large r (for c<0), where f(r,theta) is a selected polynomial in the two variables. The form chosen for the anisotropy factor was 1 - (a+br)e(cr), which appropriately approaches 1 for large r (and c<0). Functional fits of these types are expected to facilitate implementation of TG43 recommendations, in that they may be either incorporated into dose algorithms or used to generate lookup tables of either the x, y or the r, theta format.

Algorithms↗
PubMed1982

A computer program for fitting a master hearing aid to the residual hearing characteristics of individual patients.

The electroacoustic characteristics of an experimental master hearing aid are determined by the choice of transducers and settings of 26 controls which include a preamplifier, the gains and limiting levels in each of 12 channels as well as the gain of a final power amplifier. Here, a computer program which aids in the fitting of the electroacoustic characteristics of this aid to the characteristics of a patient's residual hearing is described. The patient's audiologic data and the hearing-aid parameters are entered into the computer and the gain and limiting level of each channel of the hearing aid are adjusted until an appropriate fit is achieved. The results of the fitting procedure are displayed on a graphics terminal. Permanent copies of the results can be produced on a printer-plotter. Included in the results for each of 12 channels are (1) the discomfort level, most comfortable listening level, and hearing threshold of the patient, and (2) the maximum output and noise floor of the hearing aid as well as the aided speech level. This approach has simplified the problem of fitting a complicated hearing aid to a patient's residual hearing and seems to offer attractive possibilities for fitting commercial hearing aids in the future.

Acoustics↗
PubMed1998

Development of a new standard laboratory protocol for estimating the field attenuation of hearing protection devices. Part III. The validity of using subject-fit data.

The mandate of ASA Working Group S12/WG11 has been to develop "laboratory and/or field procedure(s) that yield useful estimates of field performance" of hearing protection devices (HPDs). A real-ear attenuation at threshold procedure was selected, devised, tested via an interlaboratory study, and incorporated into a draft standard that was approved in 1997 [J. D. Royster et at., "Development of a new standard laboratory protocol for estimating the field attenuation of hearing protection devices. Part I. Research of Working Group 11, Accredited Standards Committee S12, Noise," J. Acoust. Soc. Am. 99, 1506-1526 (1996); ANSI S12.6-1997, "American National Standard Methods for Measuring Real-Ear Attenuation of Hearing Protectors" (American National Standards Institute, New York, 1997)]. The real-world estimation procedure utilizes a subject-fit methodology with listeners who are audiometrically proficient, but inexperienced in the use of HPDs. A key factor in the decision to utilize the subject-fit method was an evaluation of the representativeness of the laboratory data vis-à-vis attenuation values achieved by workers in practice. Twenty-two field studies were reviewed to develop a data base for comparison purposes. Results indicated that laboratory subject-fit attenuation values were typically equivalent to or greater than the field attenuation values, and yielded a better estimate of those values than did experimenter-fit or experimenter-supervised fit types of results. Recent data which are discussed in the paper, but which were not available at the time of the original analyses, confirm the findings.

Auditory Threshold↗
PubMed2006

Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae.

The fitness cost of the genes responsible for resistance to fluoroquinolones in clinical isolates of Streptococcus pneumoniae were estimated in vitro in a common genetic background. Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations. The fitness of these transformants was estimated by pairwise competition experiments with a common R6 strain. On average, single par and gyr mutants responsible for low-level MIC resistance (first-step resistance) impose a fitness burden of approximately 8%. Some of these mutants engender no measurable cost, while one, a parE mutant, reduces the fitness of these bacteria by more than 40%. Most interestingly, the addition of the second par or gyr mutations required for clinically significant, high-MIC fluoroquinolone resistance does not increase the fitness burden imposed by these single genes and can even reduce it. We discuss the implications of these results for the epidemiology of fluoroquinolone resistance and the evolution of acquired resistance in treated patients.

DNA Gyrase↗
PubMed2002

Mutations in cytochrome b resulting in atovaquone resistance are associated with loss of fitness in Plasmodium falciparum.

Drug resistance in malarial parasites has become a major obstacle in the control of the disease. Strategies are urgently needed to control the development of resistance and to possibly reverse existing resistance. One key element required to reverse malaria drug resistance is for the parasites to "pay" a biological "cost" or suffer a loss of fitness when acquiring resistance to antimalarial drugs. Such a situation would be a disadvantage to the resistant parasites in the absence of drug pressure. We compared here the relative fitness of atovaquone-resistant Plasmodium falciparum K1 clones with single and double base mutations in their cytochrome b genes to their parent clones during erythrocytic stages in the absence of drug pressure. We found that the double amino acid mutation (M133I and G280D) is associated with a 5 to 9% loss of fitness and that the single amino acid change of M133I did not result in any detectable loss of fitness. Molecular modeling of the interaction of P. falciparum cytochrome b with ubiquinone led to the prediction that a loss of fitness of the malaria parasites would result from the G280D mutation due to its close proximity to the putative ubiquinone-binding site. This appears to have resulted in a weakening of the cytochrome b-ubiquinone complex, thereby causing the electron transport chain to become less efficient. Our results suggest that the prevalence of resistant parasites may decrease after the drug usage is discontinued.

Amino Acid Substitution↗
PubMed2003

Fusidic acid-resistant mutants of Salmonella enterica serovar Typhimurium with low fitness in vivo are defective in RpoS induction.

Mutants of Salmonella enterica serovar Typhimurium resistant to fusidic acid (Fusr) have mutations in fusA, the gene encoding translation elongation factor G (EF-G). Most Fusr mutants have reduced fitness in vitro and in vivo, in part explained by mutant EF-G slowing the rate of protein synthesis and growth. However, some Fusr mutants with normal rates of protein synthesis still suffer from reduced fitness in vivo. As shown here, Fusr mutants could be similarly ranked in their relative fitness in mouse infection models, in a macrophage infection model, in their relative hypersensitivity to hydrogen peroxide in vivo and in vitro, and in the amount of RpoS production induced upon entry into the stationary phase. We identify a reduced ability to induce production of RpoS (sigmas) as a defect associated with Fusr strains. Because RpoS is a regulator of the general stress response, and an important virulence factor in Salmonella, an inability to produce RpoS in appropriate amounts can explain the low fitness of Fusr strains in vivo. The unfit Fusr mutants also produce reduced levels of the regulatory molecule ppGpp in response to starvation. Because ppGpp is a positive regulator of RpoS production, we suggest that a possible cause of the reduced levels of RpoS is the reduction in ppGpp production associated with mutant EF-G. The low fitness of Fusr mutants in vivo suggests that drugs that can alter the levels of global regulators of gene expression deserve attention as potential antimicrobial agents.

Animals↗
PubMed1994

Survival, Growth, and Localization of Epiphytic Fitness Mutants of Pseudomonas syringae on Leaves.

Among 82 epiphytic fitness mutants of a Pseudomonas syringae pv. syringae strain that were characterized in a previous study, 4 mutants were particularly intolerant of the stresses associated with dry leaf surfaces. These four mutants each exhibited distinctive behaviors when inoculated onto and into plant leaves. For example, while none showed measurable growth on dry potato leaf surfaces, they grew to different population sizes in the intercellular spaces of bean leaves and on dry bean leaf surfaces, and one mutant appeared incapable of growth in both environments although it grew well on moist bean leaves. The presence of the parental strain did not influence the survival of the mutants immediately following exposure of leaves to dry, high-light incubation conditions, suggesting that the reduced survival of the mutants did not result from an inability to produce extracellular factors in planta. On moist bean leaves that were colonized by either a mutant or the wild type, the proportion of the total epiphytic population that was located in sites protected from a surface sterilant was smaller for the mutants than for the wild type, indicating that the mutants were reduced in their ability to locate, multiply in, and/or survive in such protected sites. This reduced ability was only one of possibly several factors contributing to the reduced epiphytic fitness of each mutant. Their reduced fitness was not specific to the host plant bean, since they also exhibited reduced fitness on the nonhost plant potato; the functions altered in these strains are thus of interest for their contribution to the general fitness of bacterial epiphytes.

Journal Article↗
PubMed1998

Effect of Insertion Site and Metabolic Load on the Environmental Fitness of a Genetically Modified Pseudomonas fluorescens Isolate.

An isolate of Pseudomonas fluorescens (SBW25) was modified with different marker genes (lacZY, aph-1, and xylE). These marker genes were inserted singly or in combination into two separate (1 Mbp apart) and presumably nonessential sites (-6- and Ee) on the chromosome of SBW25. This allowed the production of a range of genetically modified SBW25 variants that differed with respect to insertion site of the marker genes and metabolic burden. The environmental fitness of the different SBW25 variants was tested in soil, in the rhizosphere of wheat and pea, and on the phylloplane of wheat. Reduced environmental fitness of the different variants was mainly attributed to the extra metabolic burden of novel gene expression, whereas choice of insertion site was of little significance. Changes in environmental fitness were dependent on the environmental conditions; an environment, such as soil, with a low microbial carrying capacity had a negative effect on the environmental fitness of variants with a large metabolic load. In environments with a larger carrying capacity, such as the rhizosphere of pea, environmental fitness of variants with a large metabolic load was not significantly different from that of variants with a smaller metabolic burden.

Journal Article↗
PubMed2006

Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1.

Resistance to zidovudine (ZDV) results from thymidine analog resistance mutations (TAMs) at human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) codons 41, 67, 70, 210, 215, and 219. Two mutations are possible at codon 215: Y or F. Whereas T215Y occurs alone or with M41L and L210W (TAM-1 pattern), T215F rarely occurs with these mutations or by itself; it is found instead with D67N, K70R, and K219Q (TAM-2 pattern). The L210W mutation most often occurs with M41L and T215Y and rarely occurs with the T215F or TAM-2 mutation. To explain these associations, TAMs were introduced into HIV-1(Hxb2) by site-directed mutagenesis and expressed in recombinant viruses. Viral replication kinetics, relative fitness, and infectivity were tested in the absence or presence of ZDV. Viruses carrying the 215Y mutation showed faster replication kinetics and greater relative fitness than did T215F mutants in the absence or presence of ZDV. In addition, T215Y mutants showed greater infectivity than did wild-type HIV-1 over a range of ZDV concentrations, but T215F mutants had only a modest advantage over the wild-type virus. Whereas introduction of L210W improved the relative fitness of an M41L/T215Y mutant in the presence of ZDV, introduction of this mutation into a D67N/K70R/K219Q background resulted in decreased relative fitness in the presence or absence of drug. By contrast, introduction of T215F into the D67N/K70R/K219Q background increased viral fitness in the presence of ZDV. These results help explain why T215Y but not T215F usually emerges as the first major TAM, as well as the clustering of L210W with TAM-1 mutations and T215F with TAM-2 mutations.

Amino Acid Substitution↗
PubMed1991

Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses.

We describe a sensitive, internally controlled method for comparing the genetic adaptability and relative fitness of virus populations in constant or changing host environments. Certain monoclonal antibody-resistant mutants of vesicular stomatitis virus can compete equally during serial passages in mixtures with the parental wild-type clone from which they were derived. These genetically marked "surrogate wild-type" neutral mutants, when mixed with wild-type virus, allow reliable measurement of changes in virus fitness and of virus adaptation to different host environments. Quantitative fitness vector plots demonstrate graphically that even clones of an RNA virus are composed of complex variant populations (quasispecies). Variants of greater fitness (competitive replication ability) were selected within very few passages of virus clones in new host cells or animals. Even clones which were well adapted to BHK21 cells gained further fitness during repeated passages in BHK21 cells.

Animals↗
PubMed1995

Extreme fitness differences in mammalian and insect hosts after continuous replication of vesicular stomatitis virus in sandfly cells.

Continuous, persistent replication of a wild-type strain of vesicular stomatitis virus in cultured sandfly cells for 10 months profoundly decreased virus replicative fitness in mammalian cells and greatly increased fitness in sandfly cells. After persistent infection of sandfly cells, fitness was over 2,000,000-fold greater than that in mammalian cells, indicating extreme selective differences in the environmental conditions provided by insect and mammalian cells. The sandfly-adapted virus also showed extremely low fitness in mouse brain cells (comparable to that in mammalian cell cultures). It also showed an attenuated phenotype, requiring a nearly millionfold higher intracranial dose than that of its parent clone to kill mice. A single passage of this adapted virus in BHK-21 cells at 37 degrees C restored fitness to near neutrality and also restored mouse neurovirulence. These results clearly illustrate the enormous capacity of RNA viruses to adapt to changing selective environments.

Animals↗
PubMed2002

Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation.

Recent studies have shown that the accumulation of multiple mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance may be grouped as multi-NRTI resistance (MNR) complexes. In this study, we have examined the viral fitness of recombinant viruses carrying the reverse transcriptase (RT) of a human immunodeficiency virus type 1 (HIV-1) primary isolate harboring mutations comprising the MNR 69 insertion complex. Different RT mutants were prepared in the sequence context of either the wild-type RT sequence of the HIV-1(BH10) isolate or the sequence found in a clinical HIV-1 isolate with the MNR 69 insertion mutation. As expected, in the presence of zidovudine, recombinant viruses harboring the MNR RT from the patient were more fit than wild-type viruses. However, in the absence of drug, the virus with the RT from the original clinical isolate (SS) was more fit than (i) the wild-type virus with an engineered serine insertion between residues 69 and 70 (T69SSS) and (ii) the recombinant virus with the MNR RT where the insertion was removed (2S0S). These results suggest that RT insertions, in the right sequence context (i.e., additional mutations contained in the MNR 69 insertion complex), enhance NRTI resistance and may improve viral fitness. Thus, comparing complex mutation patterns with viral fitness may help to elucidate the role of uncharacterized drug resistance mutations in antiretroviral treatment failure.

Adult↗
PubMed2003

Role of the human immunodeficiency virus type 1 envelope gene in viral fitness.

A human host offers a variety of microenvironments to the infecting human immunodeficiency virus type 1 (HIV-1), resulting in various selective pressures, most of them directed against the envelope (env) gene. Therefore, it seems evident that the replicative capacity of the virus is largely related to viral entry. In this study we have used growth competition experiments and TaqMan real-time PCR detection to measure the fitness of subtype B HIV-1 primary isolates and autologous env-recombinant viruses in order to analyze the contribution of wild-type env sequences to overall HIV-1 fitness. A significant correlation was observed between fitness values obtained for wild-type HIV-1 isolates and those for the corresponding env-recombinant viruses (r = 0.93; P = 0.002). Our results suggest that the env gene, which is linked to a myriad of viral characteristics (e.g., entry into the host cell, transmission, coreceptor usage, and tropism), plays a major role in fitness of wild-type HIV-1. In addition, this new recombinant assay may be useful for measuring the contribution of HIV-1 env to fitness in viruses resistant to novel antiretroviral entry inhibitors.

Base Sequence↗