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We studied determinants of plasma beta-carotene in a sample of 98 normal volunteers. Blood samples were collected and 4-day weighed dietary records kept for each season of the year. Information on tobacco use and demographic and socio-economic data was elicited at the first interview. There was a peak of plasma beta-carotene in the fall, whereas the dietary beta-carotene peak occurred in summer. In a regression analysis involving a variety of independent variables, the only statistically significant determinants of plasma beta-carotene for non-smokers were dietary beta-carotene, sex, serum cholesterol and triglycerides. The number of cigarettes/day was introduced into the model for smokers and a significant negative coefficient was obtained for this variable. Interaction between dietary beta-carotene and tobacco use was shown to be a significant determinant of plasma beta-carotene for the total sample.
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The purpose of this study was to compare the mechanical properties of the heel pads of adults and children, using ultrasound to assess the responses of the heel pad during compression. Thirty volunteers without heel problems, aged from 4 to 36 years, were recruited. There were 10 children (< 15 years old) and 20 adults (> 18 years old). A 7.5-MHz linear array ultrasound transducer was incorporated into a specially designed device to measure the thickness of the heel pad under different loads. The load on the heel pad was increased serially in increments of 0.5 kg, to a maximum of 3 kg, and then reduced sequentially. The load-displacement curve of the heel pad during a loading-unloading cycle was then plotted. Mechanical properties of the heel, including unloaded heel-pad thickness (UHPT), compressibility index, elastic modulus, and energy dissipation ratio (EDR), were calculated from the load-displacement curves. The average UHPT was 1.53 +/- 0.09 cm in children and 1.76 +/- 0.20 cm in adults (p < 0.001). The EDR, which represents the shock absorbency of the heel pad, was 13.5 +/- 2.0% in the children and 23.7 +/- 6.9% in adults (p < 0.001). The average compressibility index and elastic modulus were also higher in adults than in children, although the differences were not statistically significant. These findings suggest that the mechanical properties of the heel pad change from childhood to adulthood. Less energy is absorbed in the heel pad of children, which may partially explain why children tend to have fewer heel problems than adults.
PURPOSE: The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. METHODS AND MATERIALS: For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the "real" shape variation. RESULTS: No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the vesicles (SD = 2.0 mm), smallest at the left and right side of the prostate (SD = 1.0 mm), and average elsewhere (SD = 1.5 mm). At the left, right, and cranial sides of the prostate, the intraobserver variation was of the same order of magnitude as the measured shape variation; elsewhere it was smaller. However, the accuracy of the estimated SD for intraobserver variation was about half of the accuracy of the estimated SD for the measured shape variation, giving an overall uncertainty of maximum 0.6 mm SD in the estimate of the "real" shape variation. The "real" shape variation was small at the left, right, and cranial side of the prostate (SD <0.5 mm) and between 0.5 mm and 1.6 mm elsewhere. CONCLUSIONS: We developed a method to quantify shape variation of organs with a complex shape and applied it to a GTV consisting of prostate and seminal vesicles. Deformation of prostate and seminal vesicles during the course of radiotherapy is small (relative to organ motion). Therefore, it is a valid approximation in image-guided radiotherapy of prostate cancer, in first order, to correct only for setup errors and organ motion. Prostate and seminal vesicles deformation can be considered as a second-order effect.
Five pathologists estimated with point counting the amount of amyloid in heart muscle autopsy samples from 19 patients who suffered from amyloidosis. The serial sections had been stained with 5 different methods. The different variation sources involved in a quantitative study on amyloid and the interstain reproducibility between the results given by these 5 stains were analyzed. The volume fractions of amyloid after different stains were subjected to correlation analysis. In our test system about a third (34%) of the variation was due to the point counting method. Sirius red had the lowest and Congo red the highest variation due to point counting, since Sirius red gave the most intense staining and highest volume fractions for amyloid. The volume fractions were lowest in Congo red. About 40% of the total variation was composed of the field variation. This variation includes the variation due to variation between fields, field selection and subjective intraobserver variation. Sirius red showed the smallest field variation in respect to the total variation. Congo red, on the other hand, had the highest variation. The variation caused by pure interobserver variation is presented by the difference between total variation and the calculated field variation. This was largest with Sirius red and smallest with Congo red. The pure interobserver variation accounted for about 26% of the total variation. The high reproducibility with Sirius stain is most probably due to the high volume fractions of positively stained material after this stain, not to low interobserver variation. Congo red seems to have low interobserver variation. The senior pathologists were more reliable in measuring the amyloid deposits than the junior pathologists as suggested by interstain reproducibility and variation.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.
BACKGROUND: There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. METHODS: HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. RESULTS: Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. CONCLUSIONS: Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.
Glucose level varies over time due to a number of complex physiologic processes. Evidence suggests variation in glucose level contributes to risk of complications. The timescale associated with variation in glucose level is on the order of seconds to minutes, yet diabetes complications stem from years of cumulative effects. This difference between timescale suggests a slower timescale may better represent the influential component of variation. We hypothesize variation in glycated hemoglobin captures the component of variation associated with future complications. Moreover, we hypothesize that patient-management strategies influence variation in glycated hemoglobin level. From a systems control perspective, increasing variation may well reflect a policy of closed loop feedback control where changes in patient glycated hemoglobin are addressed after the fact. Such a strategy attends to problems as they arise. In contrast, decreasing variation may result from a clinical strategy that is anticipatory and proactive. A physician using a proactive strategy will base current moves on anticipation of future states, controlling variation in patient outcomes such as glycated hemoglobin. We motivate our discussion using observational data from a large multispecialty medical group in Minnesota: we characterize the within-patient trend and variation of glycated hemoglobin in adults with type 2 diabetes, describe patterns of variation, and identify factors associated with variation. Our hypotheses imply: (1) patterns of variation in glycated hemoglobin reflect physician treatment strategy; (2) variation provides an independent contribution to risk of diabetes complications; (3) the development of treatment strategies that control variation may be a beneficial goal in the management of type 2 diabetes.
The objectives of this study were to determine whether total interindividual variation in blood pressure (BP) differs between inactive and active hours of the day, to identify predictors of interindividual variation in BP, and to assess whether variation associated with any of these identified predictors is greater (or less) during inactive hours than during active hours of the day. We obtained ambulatory BP recordings over 20 consecutive hours (12 active, out of bed [daytime]; and 8 inactive, in bed [nighttime]) in a sample of 240 unrelated, non-Hispanic white adults (138 men; 102 women). We estimated total interindividual variation in BP, and the percentage of interindividual variation associated with measures of age and body size, metabolic traits, catecholamines, erythrocyte cation transport, and renal function. We used linear regression to assess changes in the hourly estimates of total interindividual variation and in variation attributable to each set of predictor traits over the 20 h. In both men and women, total interindividual variation in systolic BP was significantly greater (not less) during inactive hours than during active hours. In addition, in women, total interindividual variation in diastolic BP was as great during inactive hours as during active hours. Each set of traits considered predicted a statistically significant percentage of interindividual variation in BP. None of the sets of traits predicted a greater percentage of interindividual variation during the inactive hours than during the active hours. Measures of age and body size, catecholamines, cation transport and renal function traits predicted significantly less interindividual variation during inactive hours than during active hours of the day. That total interindividual variation in BP is as great or greater during inactive hours than during active hours of the day emphasizes the potential for differences in nighttime BP to contribute to the development of cardiovascular disease. In as much as the predictors of interindividual variation in BP differ between the daytime and nighttime, the causes of variation during these two times may also differ.
Conventional dioptric power, including refractive status and keratometric measurements, can vary in a large variety of ways. The three-dimensional character of this type of power implies that six numbers are required for the complete representation of its variance: three variances and three covariances. Curves (called profiles) that show how these numbers compare in different meridians (or transverse directions) of the eye provide a useful graphical picture of the variation and its nature. This paper explores an important subclass of types of variation in which the variation is the same for all meridians. In this subclass the variation of power is said to be uniform across all meridians of the eye. It turns out that the uniformity may be either complete or partial. In the former case all aspects of the variation are the same. In the latter case certain aspects of the variation are the same across all meridians whereas others are not; in particular the variance of the torsional component of power is the same for every meridian whereas the variance of the curvital component changes from meridian to meridian. There is a range of types of completely uniform variation from spherical variation at one extreme to Jacksonian variation at the other. All types of uniform variation (partial or complete) are characterized by two indices called the jacksonian index and the completeness index. The types can be represented geometrically as points on the triangle of uniformity. Samples of measurements of dioptric power are selected to illustrate various types of uniform variation. Methods are presented for detecting and classifying uniform variation from profiles of variation and also from the variance-covariance matrix. Examples are given of uniform variation of refractive status and of keratometry of an eye. The variation is analyzed and classified. The concepts and methods are proving to be of fundamental importance in the study of the nature and underlying causes of fluctuations of refractive status and keratometric measurements.
The surgical findings in 147 consecutive hands that underwent primary carpal tunnel release between 1983 and 1993 were reviewed for anatomic variation. A classification is introduced for the two major types of variations found. The variations found within the carpal tunnel, termed intrinsic or Type I, were space-occupying lesions of muscular, bony, or varied soft tissue origin. The variations overlying the transverse carpal ligament, termed extrinsic or Type II, were nearly all muscular in origin. Seventy-four variations were found in 60 hands. Overall, an underlying variation was found in 41% of the hands. After applying a logistic model, it was found that patient age and hand dominance were important factors in predicting the presence of an anatomic variation. For patients 40 years of age or younger, the odds of observing an anatomic variation were 3.2 times higher than the odds of observing a variation in patients older than 40 years. The odds of observing an anatomic variation in the dominant hand were 2.3 times higher when compared with the odds of observing a variation in the nondominant hand. In patients 40 years of age or younger, with dominant side involvement, an anatomic variation was found in 71% of hands. In patients older than 40 years with nondominant side involvement, an anatomic variation was found in 24% of hands. Taking into account not only anatomic variations but also underlying medical disease and local injury, at least one was identified in 86% of hands.
Heterochrony is widely regarded as an important evolutionary mechanism, one that may underlie most, if not all, morphological evolution, yet relatively few studies have examined variation in the sequence of development. Even fewer studies have been designed so that intraspecific variation in the relative sequence of developmental events can be assessed, although this variation must be the basis for evolutionary change. Intraspecific variation in developmental ossification sequences was documented from the zebrafish (Danio rerio) by Cubbage and Mabee (1996) and from the Siamese fighting fish (Betta splendens) by Mabee and Trendler (1996), but a quantitative analysis of the patterns within this variation was not made. Here, we quantify the effect of rearing temperature on the sequence of ossification and characterize the levels and patterns of intraspecific variation in these fishes. For Danio, there were no temperature effects on the sequence of bone development across the cranium, cranial region development, cartilage versus dermal bones, or lateral line bone versus nonassociated bones. Likewise the level of variation in relative sequence (position) of ossification was low, about two ranks, across temperatures. At higher temperatures, we found higher levels of variation in iterated cranial bones and less in bones forming early in the sequence. No temperature effects on variation were found among regions, between lateral line-associated bones and nonassociated bones, between median and paired bones, or across the entire sequence, indicating concordant variability among the three temperatures. Individual bones with the highest levels of variability were not consistent among temperatures. Baseline patterns of intraspecific variation in Danio were compared to those of Betta. For both species, the level of intraspecific variation in sequence position was low and the variability of cranial bones was concordant. Individual bones with the highest levels of variability were not consistent between species. In both species, variation was widespread (distributed evenly across the sequence). We used comparisons (among regions, between dermal and cartilage bones, between lateral line-associated and other bones, between median and paired bones, between iterated and noniterated bones, between feeding-associated bones and others) to see which subsets were most variable and thus potentially useful in predicting high levels of evolutionary change. The only subset of bones that was significantly more variable than others was cartilage bones. If interspecific patterns are parallel to these intraspecific differences, cartilage bones would be expected to show higher levels of heterochrony. Although concordance across the cranial ossification sequence and among regions in Danio, Betta, and two other teleosts, Oryzias and Barbus, suggests an evolutionarily conserved pattern of ossification, identity in sequence position across taxa was not observed for any bone. Thus, variation existed in sequence position across temperatures and species. Intraspecific variation of this sort may influence the morphological outcome and evolutionary trajectories of species.
The degree of size and shape variation in the A. afarensis fossil sample has been interpreted in a variety of ways. Size variation has been described as exceeding that of extant hominoids, similar to that of strongly sexually dimorphic hominoids, and best matched to modern humans. The degree of shape variation has been characterized both as great and negligible. Recent fieldwork has increased the proximal femoral sample, providing new data with which to examine variation. The proximal femur of A. afarensis is analyzed in a comparative framework in order to gauge the magnitude of size and shape variation in this element. Seven of the best-preserved A. afarensis proximal femora contribute to the analysis (A.L. 128-1, A.L. 152-2, A.L. 211-1, A.L. 288-1ap, A.L. 333-3, A.L. 333-123, A.L. 827-1). Comparative samples from Pan, Pongo, Gorilla, and Homo provide context for interpreting variation among the fossils. The coefficient of variation (CV) of linear measurements is used to estimate size variation. Bootstrap resampling of CVs from extant hominoids provides distributions for comparison to A. afarensis CVs. Ratios of linear measurements provide scale-free shape variables that are used in pairwise comparisons. The Euclidean distance between pairs of A. afarensis are compared to the Euclidean distances between extant hominoid pairs. As found in some earlier analyses, size variation in A. afarensis is accommodated best in gorillas and orangutans. The magnitude of difference in shape between A. afarensis pairs is exceeded by most taxa, indicating that shape variation is not extreme. These general findings are contradicted by a few instances of excessive size and shape variation. These are uncharacteristic results and could point to temporal bias, although other alternatives are explored. The signal from the proximal femur is that size variation in A. afarensis is like that of the strongly sexually dimorphic apes, and shape variation is well within the range of most hominoids irrespective of their degree of size dimorphism.
It has previously been shown that the frequency of pilin antigenic variation in Neisseria gonorrhoeae (the gonococcus, Gc) is regulated by iron availability. To identify factors involved in pilin variation in an iron-dependent or an iron-independent manner, we conducted a genetic screen of transposon-mutated gonococci using a pilus-dependent colony morphology phenotype to detect antigenic variation deficient mutants. Forty-six total mutants representing insertions in 30 different genes were shown to have reduced colony morphology changes resulting from impaired pilin variation. Five mutants exhibited an iron-dependent decrease in pilin variation, while the remaining 41 displayed an iron-independent decrease in pilin variation. Based on the levels of antigenic variation impairment, we defined the genes as being essential for, important for, or involved in antigenic variation. DNA repair and DNA transformation frequencies of each mutant were measured to determine whether other recombination-based processes were also affected in the mutants. Each mutant was placed into one of six classes based on their pilin variation, DNA repair and DNA transformation phenotypes. Among the many genes identified, recR is shown to be an additional member of the gonococcal RecF-like recombination pathway. In addition, recG and ruvA represent the first evidence that the processing of Holliday junctions is required for pilin antigenic variation. Moreover, two independent insertions in a non-coding region upstream of the pilE gene suggest that cis-acting sequences important for pilin variation are found in that region. Finally, insertions that effect expression of the thrB and thrC genes suggest that molecules in the threonine biosynthetic pathway are important for pilin variation. Many of the other genes identified in this genetic screen do not have an obvious role in pilin variation, DNA repair, or DNA transformation.
PURPOSE: We evaluated the daily biological variation of serum prostate specific antigen (PSA) concentrations to determine the critical difference required between 2 consecutive PSA measurements that would indicate a significant elevation. MATERIALS AND METHODS: A total of 24 men, grouped according to clinical diagnosis and PSA, underwent phlebotomy for 10 consecutive weekdays. Duplicate serum samples were measured using 3 separate lots of Tandem-E and IMx PSA assays. The biological variation was calculated and the 2 PSA assay systems were compared. The critical difference was examined to determine the percent elevation necessary to indicate (with 95% confidence) that PSA had increased beyond what would be expected from biological and analytical variation. RESULTS: The biological variation, defined in terms of percent coefficient of variation, had a log-normal distribution with a geometric mean of 7.3% coefficient of variation and a 95th percentile value of 19.2% coefficient of variation using the Tandem-E PSA assay. Assuming an analytical variation of 5% coefficient of variation, the median critical difference was 20.5% and the 95th percentile critical difference was 45.8%. There was no significant difference between the 2 PSA assay systems in biological variation. However, PSA concentrations measured by the IMx assay were consistently lower compared to values measured by the Tandem-E assay. CONCLUSIONS: Characterizing the biological variation of serum PSA assists in evaluating the significance of changes in serial PSA measurements. The degree of biological variation differs among patients, such that an increase between 2 consecutive PSA levels that is less than 20 to 46% may be due to biological and analytical variation. These data influence interpretation of repeated measurements of serum PSA with time.