Do growth chart centiles need a face lift?

European height and weight growth charts commonly extend from the 3rd to the 97th centile, whereas in North America the extremes are usually the 5th and 95th centiles. There is no good reason for the difference, and neither chart is particularly useful for screening owing to the high false positive rate associated with a cut off based on the lowest centile. The World Health Organisation''s international growth reference uses cut offs based on standard deviation scores rather than centiles, which are more suitable for the extremes of growth status seen in the developing world. This chart, however, is incompatible with charts based on centiles. Here a unified growth chart is proposed: it has nine rather than seven centiles, and they are spaced two thirds of a standard deviation score apart rather than the more usual unit spacing. This gives a set of curves very like the conventional 3rd to 97th centiles, but with additional curves at 2.67 standard deviation below and above the mean (roughly the 0.4th and 99.6th centiles). The 0.4th centile is a more practical cut off for screening purposes than the 3rd or 5th centile.     

A method of detecting conserved and variable segments in the amino acid sequences of homologous proteins

A set of aligned homologous protein sequences is divided into two groups consisting of m and n sequences. Each group contains sequences from the most related organisms. Value of the position dissimilarity of proteins from different groups of m and n sequences is defined as a number of mismatches in comparison of all possible m X n pairs of amino acid residues in the position (each from different group) divided by m X n. Ten position average of dissimilarity values is plotted vs. the first position number. Area of the figure between the profile of dissimilarity values and its mean value line characterizes the overall irregularity of amino acid substitutions along the protein sequences. If the area is greater than the average area for 1000 random profiles by more than two standard deviation units, the profile extrema containing the "surplus" of area are cut off. The cut-off stretches are likely to be variable and constant regions. If necessary, each of stretches may be separately tested and statistically estimated using a standard size sample of artificial protein families. Intergroup comparison of protein sequences reveals high overall irregularity of amino acid substitutions and identifies variable and conservative regions for all considered families of proteins: phospholipases A2, aspartate aminotransferases, alpha-subunits of Na+, K(+)-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre, human rhodopsins.     

Graphic identification of conservative and variable segments in the amino acid sequences of homologous proteins

An algorithm is presented for localizing variable and constant regions in homologous protein sequences. A set of aligned protein sequences is divided into two groups consisting of m and n sequences. Each group contains sequences of most related species. Value of the position dissimilarity of proteins from different groups of m and n sequences is defined as a number of failures to coincide in comparison with all possible mXn pairs of amino acid residues in the position (each from different group) divided by mXn. The position dissimilarity value of m protein sequences within a group is defined as the number of failures to coincide in comparison with all possible mX X(m-1)/2 pairs of amino acid residues divided by mX(m-1)/2. Ten position average of dissimilarity values is plotted vs. the first position number. Area of the figure included between the profile of dissimilarity values and its mean value line characterizes the overall irregularity of amino acid substitutions along the protein sequences. If the area value is greater than the average area for 1000 random profile by more than two standard deviation units, the profile extrema containing the "surplus" of area are cut off. The cut off stretches are likely to be variable and constant regions. In case of "between groups" comparisons it is found that the overall irregularity of amino acid substitutions is very high for all considered families of proteins; phospholipases A2, aspartate aminotransferases, alpha-subunits of Na+,K(+)-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre, human rhodopsins.     

Pulmonary arterial transit times

To begin to characterize the pulmonary arterial transport function we rapidly injected a bolus containing a radiopaque dye and a fluorescence dye into the right atrium of anesthetized dogs. The concentrations of the dye indicators were measured in the main pulmonary artery (fluoroscopically) and in a subpleural pulmonary arteriole (by fluorescence microscopy). The resulting concentration vs. time curves were subjected to numerical deconvolution and moment analysis to determine how the bolus was dispersed as it traveled through the arteriole stream tube from the main pulmonary artery to the arteriole. The mean transit time and standard deviation of the transport function from the main pulmonary artery to the arterioles studied averaged 1.94 and 1.23 s, respectively, and the relative dispersion (ratio of standard deviation to mean transit time) was approximately 64%. This relative dispersion is at least as large as those reported for the whole dog lung, indicating that relative to their respective mean transit times the dispersion upstream from the arterioles is comparable to that taking place in capillaries and/or veins. The standard deviations of the transport functions were proportional to their mean transit times. Thus the relative dispersion from the main pulmonary artery to the various arterioles studied was fairly consistent. However, there were variations in mean transit time even between closely adjacent arterioles, suggesting that variations in mean transit times between arteriole stream tubes also contribute to the dispersion in the pulmonary arterial tree.     

Determination of typical patterns from strongly varying signals

Forces measured in human joints vary considerably when an activity such as walking is carried out by different subjects or when it is repeated. ‘Typical’ standardised force–time patterns are needed to test and improve joint implants. Mechanically most important for their endurance are the magnitudes and times of force maxima and minima. They should equal the arithmetic means from the single measurements. Similar problems exist when evaluating other strongly varying signals, as in gait analysis. The new method to calculate typical signals (TSs) enhances existing dynamic time warping (DTW) procedures. It allows us to combine any number of signals. The sequence of input signals – used for calculating the TS – has only a minor influence. The accuracy of the method was tested numerically on signals for which the typical patterns could be defined exactly, and also on real joint forces that varied to different extents.     

Determination of typical patterns from strongly varying signals

Forces measured in human joints vary considerably when an activity such as walking is carried out by different subjects or when it is repeated. 'Typical' standardised force-time patterns are needed to test and improve joint implants. Mechanically most important for their endurance are the magnitudes and times of force maxima and minima. They should equal the arithmetic means from the single measurements. Similar problems exist when evaluating other strongly varying signals, as in gait analysis. The new method to calculate typical signals (TSs) enhances existing dynamic time warping (DTW) procedures. It allows us to combine any number of signals. The sequence of input signals--used for calculating the TS--has only a minor influence. The accuracy of the method was tested numerically on signals for which the typical patterns could be defined exactly, and also on real joint forces that varied to different extents.     

Localization of conserved and variable segments in amino acid sequences of homologous proteins using a personal computer]

A set of aligned homologous protein sequences is divided into two groups consisting of the most related sequences m and k. The value of the position variability of homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible k x m pairs of amino acid residues in that position divided by k x m. The position variability value plotted vs the sequence position number with a window of 10 positions gives the intergroup local variability profile. The area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area S(r) for 1000 random homologous protein families. If S is greater than S(r) by more than 2 standard deviation units sigma r the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(S(r) + 2 sigma r) are cut off by two straight lines to locate significant regions. The numerical experiment on the family of homologous phospholipases A2 revealed the linear dependence of the values S(r) and sigma r upon the position variability standard deviation sigma v of the homologous sequences. Furthermore, it was shown for protein families of various length (rhodopsins, aspartate aminotransferases, cytochromes b, L- and M-subunits of photosynthetic bacteria photoreaction centre and alpha-subunits of Na, K-ATPase), that delta S = S - n(S'r + 2 sigma r), where S - the area of the local variability profile, n = L/l (L - the length of the given protein family and l - the length of the hypothetical protein domain). If l = 250 then S'r = -1.42 + 62.56 sigma v and sigma'r = -0.14 + 7.46 sigma v.     

Uneven distribution of amino acid substitutions throughout the amino acid sequence of homologous proteins]

A set of aligned homologous protein sequences is divided into two groups consisting of m and n most related sequences. The value of position variability for homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible m*n pairs of amino acid residues in that position divided by m*n. The position variability value plotted versus the sequence position number with a window of 10 positions gives the intergroup local variability profile. Area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area Sr for 1000 random homologous protein families. If S is greater than Sr by more than 2 standard deviation units sigma r, the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(Sr+ 2 sigma r) are cut off by two straight lines to locate significant regions. The difference (S-Sr) given in standard deviation units sigma r is believed to be the amino acid substitution overall irregularity along the homologous protein sequences OI = (S-Sr)/sigma r. The significant conservative and variable regions of six homologous sequence families (phospholipase A2, cytochromes b, alpha-subunits of Na,K-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre and human rhodopsins) were identified. It was shown that for artificial homologous protein sequences derived by k-fold lengthening of natural protein sequences, the OI value rises as square root of k. To compare the degree of substitution irregularity in homologous protein sequence families of different lengths L the value of standard substitution overall irregularity for L = 250 is proposed.     

Distribution of mutants in aggregates of cultured cells

The analysis of the distribution of mutants in an exponentially growing culture of cells that are aggregated into clumps of homogeneous size is described, given the mutation rate and a random process by which clumps divide to produce progeny. The mean and standard deviation of the proportion of clumps with a given number of mutant cells at a particular time are calculated. Since the standard deviation tends to be much smaller than the mean, the following conclusions can be drawn. Aggregation lowers the number of mutant-containing clumps in cultures grown to a standard number of cells, but raises the number of mutant-containing clumps in cultures grown to a standard number of clumps. In the absence of mutation, or at low mutation rates, clumps tend to become pure types (normal or mutant). The probability of finding pure, nonmutant-containing clumps, however, is approximately the initial fraction of nonmutant cells (given realistic forward and back mutation rates). Also, in terms of the given process, it is possible to compute the probability that all the cells in an aggregate descend from a single, common parent cell within a given number of generations, and thus to calculate the probability that all the cells in a clone grown from an aggregate descend from a single cell within a known number of generations.     

Trunk and hip muscle activity in early walkers with and without cerebral palsy – A frequency analysis

Poor control of postural muscles is a primary impairment in cerebral palsy (CP), yet core trunk and hip muscle activity has not been thoroughly investigated. Frequency analysis of electromyographic (EMG) signals provides insight about the intensity and pattern of muscle activation, correlates with functional measures in CP, and is sensitive to change after intervention. The objective of this study was to investigate differences in trunk and hip muscle activation frequency in children with CP compared to children with similar amounts of walking experience and typical development (TD). EMG data from 31 children (15 with CP, 16 with TD) were recorded from 16 trunk and hip muscles bilaterally. A time–frequency pattern was generated using the continuous wavelet transform and instantaneous mean frequency (IMNF) was calculated at each interval of the gait cycle. Functional principal component analysis (PCA) revealed that IMNF was significantly higher in the CP group throughout the gait cycle for all muscles. Additionally, stride-to-stride variability was higher in the CP group. This evidence demonstrated altered patterns of trunk and hip muscle activation in CP, including increased rates of motor unit firing, increased number of recruited motor units, and/or decreased synchrony of motor units. These altered muscle activation patterns likely contribute to muscle fatigue and decreased biomechanical efficiency in children with CP.     

Phenotypic expression of a genetic property introduced by deoxyribonucleate

The time course of the appearance of cells showing a new phenotype, following treatment with a specific DNA, has been analyzed. A plot as a function of time of the number of cells showing the new property closely resembles the summation under a normal distribution curve. Describing the appearance of the new phenotype in these terms permits the definition of two parameters, the mean time, and the standard deviation of the distribution curve. This distribution is not affected either by the DNA concentration with which the transformable population has been treated, or by the streptomycin concentration with which the transformed population has been challenged. Interruptions of the expression process, by cooling to 20° or 0°C., serve only to displace the expression curves, without changing their shape, while small reductions in temperature change both the mean time of expression and the standard deviation of the distribution curve. On the basis of these observations a number of hypotheses have been examined concerning the mechanism whereby transforming DNA manifests a phenotypic alteration in the transformed cells. It can be concluded that there exist at least two stages in the process of expression. The completion of the first stage, causing the randomization, occurs with a mean time of about 60 minutes, and a terminal step, that of the transition of phenotype, occurs in less than 3 minutes.     

Effect of walking speed and severity of hip osteoarthritis on gait variability

Gait analysis in orthopaedic and neurological examinations is important; however, few studies assess gait variability at different walking speeds in patients with varying degrees of hip osteoarthritis. We aimed to clarify (1) how different controlled speeds and (2) various severities of hip osteoarthritis influence gait variability. Gait variability was described by the standard deviation (SD) of the spatial–temporal and mean standard deviation (MeanSD) of angular parameters. The spatial positions of the anatomical points for calculating gait parameters were determined in 20 healthy elderly controls and 20 patients with moderate and 20 patients with severe hip osteoarthritis with a zebris CMS-HS ultrasound-based motion analysis system at three walking speeds. The SD of the spatial–temporal and MeanSD of angular parameters of gait, which together describe gait variability, significantly depended on speed and osteoarthritis severity. The lowest variability in the gait was found near the self-selected walking speeds. Hip joint degeneration significantly worsened variability on the affected side, with non-affected joints and the pelvis compensating by increasing flexibility and adapting to step-by-step motions. Particular attention must be paid to improving gait stability and the reliability of limb movements in the presence of and increasing severity of osteoarthritis.     

Probability Density Function of the Red Cell Membrane Permeability Coefficient

The distribution of a random variable is determined by the probability density functions (PDF) of all other random variables with which the variable in question is jointly distributed. If the PDF of the random variable of interest is normal, or skewed normal, then the distributions with which it is jointly distributed determine its mean and standard deviation. In the case described here (where hemolysis time of the red blood cell is a function of the permeability coefficient and geometric variables of the cell) the mean and standard deviation of the permeability coefficient and the known distributions of the geometric variables on which the hemolysis time depends determine a predicted distribution of hemolysis time. An observed distribution of the hemolysis time is obtained spectrophotometrically. By choosing the mean and standard deviation of the permeability coefficient so that the predicted PDF of the hemolysis time matches the observed PDF best by least-squares criterion, the complete distribution of the permeability coefficient is determined.     

Timing light height affects sprint times

Timing light systems are commonly used to measure sprint times of athletes. In this study, the reliability and effect of timing light height on sprint times was investigated. Two sets of timing lights set at hip and shoulder height, simultaneously timed subjects over 10 and 20 meters. The within-trial variation of both timing light heights were equally consistent; all coefficients of variation (CV) less than 1.2% with less variability associated with the longer (20 m) distances (CV < 0.85%). The typical error between the two timing light heights for both distances was small (< or = 1.3%). The mean difference between the two heights was significantly different (0.7 second, 95% CL = 0.05-0.10 second) at both the 10 and 20 m distances. Faster times were recorded at hip height as opposed to shoulder due to the legs breaking the beam before the upper body. It is suggested that standardized procedures are necessary for speed assessment using timing lights in order for comparisons to be made between athletic populations.     

Improving estimates of the basic reproductive ratio: using both the mean and the dispersal of transition times

In both within-host and epidemiological models of pathogen dynamics, the basic reproductive ratio, R(0), is a powerful tool for gauging the risk associated with an emerging pathogen, or for estimating the magnitude of required control measures. Techniques for estimating R(0), either from incidence data or in-host clinical measures, often rely on estimates of mean transition times, that is, the mean time before recovery, death or quarantine occurs. In many cases, however, either data or intuition may provide additional information about the dispersal of these transition times about the mean, even if the precise form of the underlying probability distribution remains unknown. For example, we may know that recovery typically occurs within a few days of the mean recovery time. In this paper we elucidate common situations in which R(0) is sensitive to the dispersal of transition times about their respective means. We then provide simple correction factors that may be applied to improve estimates of R(0) when not only the mean but also the standard deviation of transition times out of the infectious state can be estimated.     

Changes in evoked potentials during systematic exposure to a series of similar signals with variable intersignal intervals]

Series of clicks, standard by the number of stimuli and greatly varying by the length of interstimuli intervals in each series, were systematically presented to dogs without reinforcement. Evoked potentiale (EP) in the cortical auditory zone were recorded. It has been found that a typical U-shaped distribution of amplitude values of averaged EP is elaborated in the series in the course of repeated presentations; a maximal amplitude is observed in response to the first and last clicks, and a minimal, in the middle of the series. Such a regularity was previously found for the action of standard series with a constant interstimuli interval. It is assumed that an estimation may take place in the dog CNS of the number of signals used in a series, whose mechanism is not necessarily based on the time factor. The ability to estimate the number of signals in the series may be regarded as an elementary model of counting in the dogs' CNS.     

Effects of low-pass filter combinations on lower extremity joint moments in distance running

Inverse dynamics is a standard tool in biomechanics, which requires low-pass filtering of external force and kinematic signals. Unmatched filtering procedures are reported to affect joint moment amplitudes in high impact movements, like landing or cutting, but are also common in the analysis of distance running. We analyzed the effects of cut-off frequencies in 94 rearfoot runners at a speed of 3.5 m/s. Additionally, we investigated whether the evaluation of footwear interventions is affected by the choice of cut-off frequencies. We performed 3D inverse dynamics for the hip, knee and ankle joints using different low-pass filter cut-off frequency combinations for a recursive fourth-order Butterworth filter. We observed fluctuations of joint moment curves in the first half of stance, which were most pronounced for the most unmatched cut-off frequency combination (kinematics: 10 Hz; ground reaction forces (GRFs): 100 Hz) and for more proximal joints. Peak sagittal plane hip joint moments were altered by 94% on average. We observed a change in the ranking of subjects based on joint moment amplitude. We found significant (p < 0.001) footwear by cut-off frequency combination interaction effects for most peak joint moments. These findings highlight the importance of cut-off frequency choice in the analysis of joint moments and the assessment of footwear interventions in distance running. Based on our results, we propose to use matched cut-off frequencies around 20 Hz in order to avoid large artificial fluctuations in joint moment curves while at the same time avoiding a severe removal of physiological high-frequency signal content from the GRF signals.     

Estimation of parameters in population models for Schizosaccharomyces pombe from chemostat data

The integro-differential growth model of Eakman, Fredriekson, and Tsuehiya has been employed to fit cell size distribution data for Schizosaccharomyces pombe grown in a chemostat under severe product inhibition by ethanol. The distributions were obtained with a Coulter aperture and an electronic system patterned after that of Harvey and Marr. Four parameters—mean cell division size, cell division size standard deviation, daughter cell size standard deviation, and a growth rate coefficient—were calculated for models where the cell growth rate was inversely proportional to size, constant, and proportional to size. A fourth model, one where sigmoidal growth behavior was simulated by two linear growth segments, was also investigated. Linear and sigmoidal models fit the distribution data best. While the mean cell division size remained relatively constant at all growth rates, standard deviation of division size distribution increased with increasing holding times. Standard deviation of the daughter size distribution remained small at all dilution rates. Unlike previous findings with other organisms, the average cell size of Schizosaccharomyces pobme increased at low growth rates.     

Proton NMR and spin lattice relaxation study of nucleoside di- and triphosphates in neutral aqueous solutions

The average conformations of adenosine, inosine and guanosine di- and triphosphates in neutral aqueous solution have been investigated by 1H vicinal couplings, chemical shifts and T1 relaxation time measurements at 250 MHz. Comparison of chemical shifts with those of the corresponding nucleotide monophosphates suggests that the beta-phosphate group is in all cases oriented towards the base and close to H3'. The vicinal coupling constants indicate that the proportion of the S conformer of the ribose moiety is 55--60% and that the gauche-gauche rotamer of the CH2-OP exocyclic group is predominant. The preferential orientations of the base have been determined by minimization of the standard deviation about the mean of the molecular reorientation correlation times derived from the H8, H1', H2' and H3' relaxation times and computed interproton distances. The problem of the correlation between the syn-anti equilibrium and the N equilibrium S interconversion has been examined. Typical magnetization recovery curves after a 180 degree pulse have been simulated in the case of ATP, taking into account cross relaxation effects. It is shown that in most of the molecules under consideration the syn orientation of the base is predominant whereas for ATP the syn and anti are equivalent.