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Graphical generalized residuals in fitting distributions: applications to epidemiological follow-up data.

Three kinds of generalized residuals based on probability integral transformation are defined and their roles in graphical goodness of fit testing are discussed. Although they are useful in fitting parametric distributions, their value is questionable, however, in fitting Cox's proportional hazard rate (PHR) models. They almost always appear to give a good fit because of (a) almost non-parametric nature of the PHR models; (b) heavy right-hand censoring in epidemiological data; and (c) scale adjustment in graphical presentation. Thus, the apparent overall fit has little inferential meaning, but the residuals are useful in exploratory analysis. A simple method, based on non-parametric stratified residual plots, for selection of risk factors is discussed. It is, in fact, equivalent to comparison of several empirical survival functions, one for each set of values (stratum) of a covariable under consideration. It is also suggested that for the preliminary PHR model, the continuous variables should be discretized and indicator variables used in the model to check analytically the graphical perception of the possible functional form of the contribution of each covariable to the PHR model.

Analysis of Variance↗

Determination of RNase A/2'-cytidine monophosphate binding affinity and enthalpy by a global fit of thermal unfolding curves.

A spectropolarimeter was used to measure the thermal response curves of RNase A in the presence and absence of the ligand cytidine 2'-monophosphate. A coupled equilibrium model was used to describe the dissociation of the protein-ligand complex (NL<==>N + L) and the thermal unfolding of the free protein (N<==>U). The unfolding curves of the protein in the presence of several different concentrations of ligand were fit to this coupled equilibrium model using global linkage analysis. The best-fitted values for the thermal unfolding of the apo-protein were 60.9 +/- 0.2 degrees C (T(m)) and 105.5 +/- 1.4 kcal/mol (DeltaH), while the fitted values for the dissociation of the protein-ligand complex were 1.6 +/- 0.4 microM (K(D)) and 18.7 +/- 1.0 kcal mol(-1) (DeltaH(L)). These values were in excellent agreement with values obtained by other methods. The sensitivity of the data fitting was compared using linear or quadratic temperature dependence for the response curves of the free ligand (L), native apo-protein (N), native ligand-bound protein (NL), and unfolded apo-protein (U). There was no significant improvement in the precision of the fitted data when the temperature-dependent response for each species (N, L, NL, and U) was expressed as quadratic functions of temperature.

Binding Sites↗

Duration and fitness dependence of quasispecies memory.

The duration and fitness dependence of memory in viral quasispecies evolving in cell culture have been investigated using two genetic markers of foot-and-mouth disease virus (FMDV). In lineages of antigenic variant FMDV RED, which reverted to FMDV RGD, memory FMDV RED genomes were detected after 50 infectious cycles, and memory level was fitness dependent. In growth-competition experiments between a reference FMDV RGD and two different FMDV RED populations, a 7.6-fold higher fitness of the initial FMDV RED population resulted in 30 to 100-fold higher memory level. In lineages of low-fitness clones containing an elongated internal polyadenylate tract, revertants lacking excess adenylate residues became dominant by passage 20. However, genomes including a larger number of adenylate residues were detected as memory genomes after at least 150 infectious cycles. Thus, quasispecies memory can be durable and is fitness dependent, as predicted from the growth competition of two mutant forms of a genome. An understanding of factors influencing quasispecies memory levels and duration may have implications for the extended diagnosis of viruses based on the quantification of minority genomes.

Animals↗

The fitness of citrus tristeza virus defective RNAs is affected by the lengths of their 5'- and 3'-termini and by the coding capacity.

Populations of the Closterovirus Citrus tristeza virus (CTV) generally contain defective RNAs (dRNAs) that vary in size, abundance, and sequence. The variation in abundance of the different dRNAs in a population suggests selection for those of higher fitness. To examine factors affecting fitness of dRNAs, we investigated a series of in vitro constructed dRNAs for their ability to be amplified in protoplasts by an efficiently replicated CTV deletion mutant. The minimal sequences required for accumulation of the dRNAs were within the genomic 5' proximal approximately 1 kb and the 3' 270 nucleotides. However, other factors were involved, because a dRNA with only the minimal sequences failed to be replicated. Rescue of a nonviable dRNA by insertion of nonviral sequences between the termini suggested that "spacing" between terminal cis-acting signals influenced fitness. A continuous open reading frame (ORF) through most of the sequences derived from the 5' of the genome was a requirement for dRNA amplification. In general, insertions, deletions, or nucleotide substitutions were tolerated in the dRNAs as long as an ORF was retained, whereas dRNAs with mutations that prematurely terminated the ORF were not viable. To discriminate between a requirement for an essential protein and ribosomal travel, perhaps to present replication signals to the replicase complex, mutations were made to modify the potential protein but still maintain an ORF. Deletions, insertions of nonviral sequences, or switching of reading frames that altered the amino acid sequence of the protein, except the N-terminal 161 amino acids, did not destroy the fitness of the dRNAs. Yet termination of the ORF in the middle of nonviral sequences did destroy the ability of the dRNAs to be amplified. These results suggest that even though a continuous ORF was needed for fitness, its protein product did not affect the amplification of the dRNAs.

Closterovirus↗

Modelling whole blood oxygen equilibrium: comparison of nine different models fitted to normal human data.

The ability of nine different models, prominent in the literature, to meaningfully characterize the oxygen-hemoglobin equilibrium curve (OHEC) of normal individuals was examined. Previously reported data (N = 33), obtained using the DCA-1 (Radiometer, Copenhagen), and new data (N = 8), obtained using the Hemox-Analyzer (TCS, Southampton, PA), from blood samples of normal, non-smoking volunteers were used and these devices were found to give statistically similar results. The OHECs were digitized and fitted to the models using least-squares techniques developed in this laboratory. The "goodness-of-fit" was determined by the root-mean-squared (RMS) error, the number of parameters, and the parameter redundancy, i.e., correlation between the parameters. The best RMS error did not necessarily indicate the best model. Most literature models consist of ratios of similar-order polynomials. These showed considerable parameter redundancy which made the curve fitting difficult. The best fits gave RMS errors as low as 0.2% saturation. The Hill model gave a good characterization over the saturation range 20%-98% with RMS errors of about 0.6% saturation. On the other hand, good characterizations over the entire range were given by several other models. The relative advantages and disadvantages of each model have been compared as well as the difficulties in fitting several of the models. No single model is best under all circumstances. The best model depends upon the particular circumstances for which it is to be utilized.

Hemoglobins↗

[Preparoxysmal fits of laughter from misformation of the hypothalamus (author's transl)].

Fits of laughter have been described in a number of instances with a differentiation made between primary and secondary fits. Fits of laughter in the case of pubertas praecox resulting from a hyperplastic deformation at the base of the IIIrd ventricle have not been observed as yet. The case here described shows that fits of laughter of this type can be observed prior to commencement of the actual epileptic fit itself. A short description if given of how normal laughing and crying comes into being, referring to the relevant literature.

Brain Neoplasms↗

[Contact surface and pressure load at implant-bone interface in press-fit cups compared to natural hip joints].

The implantation of an endoprosthetic socket into the acetabulum alters the mechanical stresses in the periacetabular region in a significant manner compared with the natural hip joint. In this way, a remodelling process is initiated. Primary stability to achieve osseointegration and a loading of the acetabulum owing to the biomechanical interaction between cup and bone that is similar to the natural joint, are important prerequisites for a long-term bony integration of the implant. Therefore, the intra-articular pressure distribution in eight hip joints of fresh-frozen human pelvic cadavers and in the bone/implant interface of two press-fit cups was investigated using pressure-sensitive Prescale films. A modular cup with a pure hemispherical shape (PCA cup) and a monoblock cup with a biradial surface and flattening of the pole (press-fit cup) were tested. Loads of up to twice body weight were introduced into the sacrum, simulating a single-leg stance with the hip in neutral flexion. The results were extracted from the pressure prints applying digital image processing methods. It was demonstrated that intra-articular contact occurs over the whole articular surface of the joint, with contact areas between 39.0% and 56.9% of the hemisphere, showing zones of higher pressures where the acetabulum is supported by the iliac, ischial and pubic bone. The biradial press-fit cup showed mean contact areas of 44.7% of its surface when inserted under press-fit only. This area was enlarged to 53.0% and to 64.2% with increasing load. The corresponding figures for the PCA cup are 45.1%, 48.9% and 57.1%. The low-profile PCA cup produces a small band of high pressure near the periphery, and with increasing load its pole area comes into contact with the acetabular fossa. Occasionally, irregular gaps do occur. The press-fit cup enlarges the contact area from the periphery to the pole within its optimised biradial contact zone until the lunar surface is loaded. The acetabular fossa remains unloaded owing to the flattening of the pole. This load distribution is close to that of the natural hip joint. The pressure distribution of both cups is also characterised by three zones at the iliac, ischial and pubic bones showing a higher load transmission.

Acetabulum↗

Analysis of initial fixation strength of press-fit fixation technique in anterior cruciate ligament reconstruction. A comparative study with titanium and bioabsorbable interference screw using porcine lower limb.

We performed a controlled laboratory study to evaluate the initial fixation strength of press-fit technique. Forty porcine lower limbs were used and divided into four groups according to the method of fixation; group 1 (press-fit+1.4 mm), in which the diameter difference between the bone plug and the femoral tunnel was 1.4 mm; group 2 (press-fit+1.4 mm, 30 degrees), in which the diameter difference was the same with group 1, but the tensile loading axis was 30 degrees away from the long axis of the femoral tunnel; group 3 (titanium), in which a titanium interference screw was used for fixation; group 4 (bioabsorbable), in which a bioabsorbable interference screw was used for fixation. The graft in the press-fit group was harvested with a hollow oscillating saw with inner diameter of 9.4 mm to obtain consistent and completely circular shape of the bone plug. The femoral tunnel with diameter of 8 mm was drilled at the original ACL insertion. Following the bone plug insertion into the femoral tunnel and applying a preload of 20 N, the specimen underwent 500 loading cycles between 0 and 2 mm of displacement. Thereafter the specimen was loaded to failure. There was no fixation site failure during the cyclic loading test. Significant differences in the stiffness, linear load, or failure mode among the groups were not found. The average ultimate failure load of group 1 and group 2 were not significantly different from those of group 3 and group 4. The press-fit groups demonstrated sufficient fixation strength for the rehabilitation and interference screw groups. The completely circular shape of the bone plug and increased diameter difference between the bone plug and the femoral tunnel seemed to contribute to the strong fixation.

Animals↗

Tensile properties of an anterior cruciate ligament graft after bone-patellar tendon-bone press-fit fixation.

Hardware used for fixation of ACL autografts in bone tunnels frequently complicates revision surgery, requiring two-stage procedures when a bone-patellar tendon-bone (B-PT-B) autograft is used for ACL reconstruction. Therefore alternative procedures that eliminate hardware have been advocated. This study compared the mechanical behavior of two fixation procedures: a widely used interference screw (IFS) fixation and a press-fit fixation that is hardware free. Twenty hind limbs from skeletally mature Saanen breed goats were used in this study, ten each in IFS and press-fit groups. After ACL reconstruction the specimens were dissected, leaving a femur-ACL graft-tibia complex (FATC) for uniaxial tensile testing. The tests included a series of three cyclic creep tests (C1-C3) for the evaluation of residual elongation followed by a tensile load to failure test to obtain linear stiffness and ultimate load of the FATCs. Four of ten specimens failed during the cyclic creep test for the press-fit group, compared to one for the IFS group. For the remaining specimens residual elongation following three cyclic creep tests (C1-C3) was 1.7+/-0.5 mm in the press-fit group compared to 1.3+/-0.6 mm in the IFS group, and there was no statistical significant difference between the two fixations. In the load to failure test there was also no statistical significant difference in linear stiffness between the two fixations. However, the ultimate load for the press-fit group (215+/-75 N) was significantly lower than that for the IFS group (328+/-103 N). These results provide the basis for future studies involving the time course of healing of these two procedures using the goat model.

Animals↗

Biomechanical evaluation of press-fit femoral fixation technique in ACL reconstruction.

In this experimental study, the authors evaluated the biomechanical properties of the femoral press-fit graft fixation technique in ACL reconstruction. 20 fresh frozen distal femurs, patellae and patellar ligaments were used from 10 cadaver specimens. Three bone-patellar tendon grafts of 10 mm width were prepared from each sample; altogether 60 bone-patellar tendon grafts were prepared for the experiment. Three 9 mm wide tunnels were drilled in each distal femur at different angles (0, 15, 30, 45, and 60 degrees). This means that 60 tunnels were drilled into the 20 femurs, 12 at each angle. The trapezoid bone blocks were impacted into the holes. The primary stability and stiffness of this press-fit fixation method were measured with a Zwick 020 computer-controlled testing device using maximum-failure tensile-strength tests. The ultimate tensile strength was the greatest at 45 degrees (534+/-20 N, range 507-554), with 118+/-10 N/mm (range 99-126) stiffness, followed by 485+/-35 N (range 416-510) with 122+/-13 N/mm (range 104-136) stiffness at 30 degrees, 353+/-18 N (range 320-371) with 113+/-13 N/mm (range 83-124) stiffness at 15 degrees, and 312+/-30 N (range 261-343) with 89+/-14 N/mm (ranged:68-103) stiffness at 0 degrees. In the cases of 0, 15, 30 and 45 degrees the bone blocks were pulled out of the drilled holes, but at 60 degrees rupture of the patellar tendon or breakage of the bone block occurred more frequently. It can be seen that the ultimate tensile strength increased with the angle between the loading direction and the bone block. When compared to data in the literature, these data showed similar and satisfying biomechanical properties of femoral press-fit fixation. Because of the known advantages of an implantation-free fixation technique, the femoral press-fit fixation technique can be a good alternative in ACL surgery. These results provide the basis for future studies involving the postoperative healing process of this femoral press-fit fixation technique in porcine knees.

Adult↗

Long-term results of HA coated threaded versus HA coated hemispheric press fit cups: 287 hips followed for 11 to 16 years.

INTRODUCTION: There are many studies on the short and medium term results of hydroxyapatite (HA) coated acetabular components, but information on survival in the longer run is sparse. In this paper, we report 11 to 16 years follow up results of HA coated threaded versus HA coated hemispherical press fit cups. PATIENTS AND METHODS: During the years 1988-1993, we performed 323 primary total hip replacements in 276 patients with an HA coated acetabular component. In 128 cases we used a HA coated threaded cup, and in 195 cases a HA coated hemispherical press fit cup was inserted. There were 189 women and 87 men aged 15-79 (mean 48) years. During follow-up, 14 patients died and 21 patients would not come for the follow-up examination as they were doing quite well with their prostheses. These patients were censored at their last control examination. This left 241 patients (287 hips) followed for 11 to 16 (mean 13) years after the operation. RESULTS: During the follow-up period 48 press fit cups and 9 threaded cups were revised, none because of infection. Survival analyses indicated a cumulative survival of the threaded HA coated cup of 0.91 (95% CI: 0.86-0.97) at 16 years with one patient at risk. The cumulative survival of the HA coated press fit cup was 0.74 (0.69-0.80) at 15 years with no patient at risk. The difference is significant (P = 0.0002). Wear and age was significantly associated with revision (P < 0.0001 and 0.0002, respectively), and wear was significantly (P < 0.0001) associated with osteolysis. CONCLUSION: These results indicate that HA coated threaded cups provide satisfactory bony interlock to resist force loads in the long run whereas the HA coated hemispherical press fit cups do not.

Acetabulum↗

Fitting the two-stage model of carcinogenesis to nested case-control data on the Colorado Plateau uranium miners: dependence on data assumptions.

This paper investigates some problems with the Colorado Plateau uranium miners cohort when fitting the mechanistic model of carcinogenesis of Moolgavkar et al. (MVK model) to nested case-control data for lung cancers. The influence of data for hard rock mining and work histories on the model fitting is examined and found to be highly influential. The question of selecting the most appropriate number of controls per case is also considered. Analyses were carried out assuming that the hard rock mining exposure occurred prior to all other work histories and that miners received no exposure between work histories. The use of less than 15 controls per case was found to seriously restrict the quality of fit of the models. The best fitting, most reliable model contained linear effects of radon exposure on the first mutation rate, the rate of differentiation, and the rate of death of the intermediate cells. An effect of smoking on the growth of the intermediate cells was also included in the model. It is concluded that owing to the complexity of the MVK model and the limited amount of information in this dataset, the reliability of the Colorado Plateau dataset for fitting this type of model, particularly in a case-control format, is questionable.

Case-Control Studies↗

Non-additive effects of herbivores and pollinators on Erysimum mediohispanicum (Cruciferae) fitness.

In this study, the non-additivity of effects of herbivores and pollinator on fitness of the plant Erysimum mediohispanicum (Cruciferae) has been experimentally tested. The abundance and diversity of the pollinator assemblage of plants excluded from and exposed to mammalian herbivores, and the combined effect of pollinators and herbivores on plant reproduction were determined over a period of 2 years. Pollinator abundance was higher and diversity was lower on plants excluded from herbivores. Furthermore, the experimental exclusions demonstrated that both pollinators and herbivores affected plant fitness, but their effects were not independent. Herbivores only had a detrimental effect on plant fitness when pollinators were present. Similarly, pollinators enhanced fitness only when herbivores were excluded. This outcome demonstrates that the importance of pollinators for plant fitness depends on the occurrence of herbivores, and suggests that herbivores may hamper pollinator-mediated adaptation in plants.

Analysis of Variance↗

Energetic efficiency under stress underlies positive genetic correlations between longevity and other fitness traits in natural populations.

Evolutionary relationships among fitness traits are considered in terms of the near-to-universal scenario of stressful environments leading to a resource-deficient and hence energy-deficient world. Fitness approximates to energetic (and metabolic) efficiency under this environmental model. When fitness is high, stress resistance (reducible to oxidative-stress resistance) and metabolic stability are maximal, and energy expenditure is minimal. Rapid development should then be favored followed by a long lifespan and high adult survival. Positive associations among diverse fitness or life-history traits are expected, controlled by stress-resistant 'good genotypes'. Heterozygotes tend to show higher energetic efficiency and hence higher fitness than do corresponding homozygotes under extreme environments, and to give parallel associations among life-history traits. Energy budgets under abiotic environments are pivotal for integrative evolutionary studies of life histories in natural populations.

Animals↗

Genic heterozygosity, chromosomal interchanges and fitness in rye: any relationship?

Relationship between heterozygosity at allozyme loci, chromosomal interchanges and fitness was analyzed in a rye cultivar showing a polymorphism for such rearrangements. Nine allozyme systems (ACO, ACPH, GOT, GPI, LAP, MDH, PER, PGD and PGM) and five components of fitness (number of fertile tillers, total offspring, egg cell fertility, flowers/ear and seeds/ear) were studied. The estimated selection coefficients against interchange heterozygotes ranged from s = 0.12 to s = 0.34. A significant effect of the genic heterozygosity on some fitness components was observed in interchange heterozygotes (tillering and total offspring), in their standard homozygous sibs (flowers/ear and seeds/ear) and in the descendants of the crosses between standard karyotypes (flowers/ear, seeds/ear and egg cell fertility). However, the main effect was linked to genetic background associated to different crosses. Significant differences for Acph-1, Gpi-1, Lap-1, Mdh-1, Mdh-4, Pgd-2 and Pgm-1 loci were also found in some of these crosses although these differences were inconsistent. This suggests that probably the allozyme loci analyzed were not directly contributing to the fitness and that they are linked, in some cases, to different deleterious alleles depending on both cross and locus. This fact could support the local effect hypothesis as explanation although we do not discard the existence of some inbreeding level (general effect hypothesis) since all crosses and loci studied show a overall consistent trend of increased fitness with increased heterozygosity.

Alleles↗

Error thresholds in a mutation-selection model with Hopfield-type fitness.

The deterministic limit of a Hopfield-type mutation-selection model in the sequence space approach is investigated. Genotypes are identified with two-letter sequences. Mutation is modelled as a Markov process, fitness functions are of Hopfield type, where the fitness of a sequence is determined by the Hamming distances to a number of predefined patterns. Using a maximum principle for the population mean fitness in equilibrium, the error threshold phenomenon is studied for quadratic Hopfield-type fitness functions with small numbers of patterns. Different from previous investigations of the Hopfield model, the system shows error threshold behaviour not for all fitness functions, but only for certain parameter values.

Algorithms↗

Assessment of some aspects of physical fitness.

Fitness assessment protocols are continually being modified to satisfy current needs of both athletic and non-athletic groups. Laboratory facilities for assessing aerobic fitness have become highly sophisticated with exercise test modalities matched as closely as possible to specific sports. Similar developments have applied to tests of anaerobic power. Among non-athletic populations there is a demand for indirect methods of assessing work capacity by means of submaximal responses and field tests. Such test are now available for use with subjects varying in age, sex, level of fitness and training status. Physical fitness is a multivariate concept and consequently is not amenable to characterisation in a single fitness test.

Journal Article↗

Non-linear curve-fitting programs for Phadezyme IgE PRIST using a Hewlett-Packard HP-97 and a Texas Instruments TI-59 with a PC-100A printer.

A non-linear curve-fitting program using a modified Hoerl's function on the Hewlett-Packard HP-97 and Texas Instruments TI-59 programmable calculators for the determination of Phadezaym IgE PRIST (IgE) results is described. Excellent correlation between the reference serum concentration and the curve fit concentration results were obtained. The equation used in the curve fit is ln y = A + B ln x + CxD, where A, B, C and an accuracy of fit term R are calculated by the program. The value of D must be specified by the user before the curve fit is performed.

Computers↗