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Coefficient of cross correlation and the time domain correspondence.

Time histories of neuromuscular and mechanical variables of human motion are often compared by using discrete timing events (onset, offset, time to peak, zero crossing, etc). The determination of these discrete timing points is often subjective and their interpretation can cause confusion when attempting to compare patterns. In this technical note, cross correlation and the 95% confidence interval of its maximum value are proposed as an objective means of pattern recognition and comparison. EMG patterns of cycling at different cadences were used as an example to demonstrate the effectiveness of this cross correlation method in identification of changes between conditions. Using a standard method of threshold identification, different onset and offset values can be found by using different thresholds, and the sequence of the offset timings between conditions can change. This is a clear indication of the inherent subjectivity with these discrete timing methods. In contrast, calculation of cross correlation for incremental phase shifts permits the identification of a maximal value that is an objective measure of the actual phase shifting between the two time series. Further, calculation of the 95% confidence interval allows one to determine whether the phase shifting is statistically significant. The application of this method is not limited to EMG pattern comparison, and can also be applied to other time histories such as kinematic and kinetic parameters of human motion.

Algorithms↗

Fog-induced respiratory responses are attenuated by nedocromil sodium in humans.

Fog inhalation induces cough and bronchoconstriction in patients with asthma, but only cough in normal subjects; whether it also influences the pattern of breathing is unclear. Nedocromil sodium (NCS) inhibits the cough response to inhalation of several pharmacological agents but its effects on fog-induced cough and changes in the pattern of breathing are unknown. We evaluated the effects of no drug, placebo, and 4- and 8-mg NCS administration on the cough threshold and changes in the pattern of breathing during fog inhalation in 14 healthy subjects. Measurements of tidal volume (VT), duration of inspiratory and expiratory times (TI and TE, respectively), total duration of the respiratory cycle (TT), mean inspiratory flow (VT/TI), duty cycle (TI/TT), respiratory frequency (f, 60/TT), and inspiratory minute ventilation (V I) were obtained by inductive plethysmography. Median cough threshold values were unaffected by placebo, but were increased (p < 0.01) by both NCS doses. In no-drug and placebo trials, inhalation of the threshold fog concentration caused increases in both VT/TI and V I (p always < 0.05) due to selective increases (p < 0.01) in VT. These changes were markedly attenuated by both NCS doses administration. Thus, fog induces coughing and increases in VT, VT/ TI, and V I in healthy subjects; NCS possesses antitussive effects and attenuates fog-induced changes in the pattern of breathing, possibly through inhibition of rapidly adapting "irritant" receptors.

Adult↗

Transfer effects of endurance training with the arms and legs.

The purpose of this study was to examine whether endurance training in the form of arm or leg cycling resulted in significant transfer effects when exercise was performed with the untrained muscle group. Sixteen middle-aged male volunteers completed 24 training sessions over 8 wk on either an arm cycle ergometer (AG, N = 8, mean age = 35.2 +/- 6.6 yr) or a leg cycle ergometer (LG, N = 8, mean age = 41.0 +/- 4.7 yr). The two groups were initially equated for their pre-training peak oxygen uptake (pVO2) determined during leg cycling (44.5 +/- 5.0 and 43.8 +/- 7.7 ml.kg-1.min-1 for the AG and LG, respectively). Training was performed at an intensity that was mid-way between the pre-training ventilatory threshold (VT) and the pVO2 for both cycling methods. Significant increases (P less than .05) were observed in the relative values of the oxygen uptake at the VT and the pVO2 as a result of both these methods of training, but these elevations were specific to the muscle groups that were trained. This specificity of training was also evident in the cardiorespiratory and metabolic measurements obtained during submaximal steady state exercise performed at the power output corresponding to the pre-training VT during arm and leg exercise. Hence, it was concluded that improvements in exercise performance resulting from short-term aerobic training with the arms or legs in middle-aged males with relatively high aerobic powers are due primarily to peripheral adaptations in the trained muscles.

Adult↗

Action of lycurim and pyrazofurin on hepatoma 3924A cells in culture.

The purpose of this study was to test for a possible synergism in the antitumor action of the antimetabolite pyrazofurin (PF) and the alkylating agent lycurim (LY) [1,4-di(2'-mesyloxy-ethylamino)-1,4-dideoxy-m-erythritol dimethylsulfonate] on proliferating and resting rat hepatoma 3924A cells in tissue culture. Earlier studies showed that PF killed hepatoma cells only in the logarithmic phase of growth as determined by colony-forming ability. Now we report that LY killed hepatoma cells in both the exponential and plateau phases. Treatment of cultures in each phase for 1 or 2 hrs resulted in threshold exponential type dose-response curves, yielding Do values of 3 and 1 microM, respectively. LY is a cycle-specific drug, although fluctuations in cell age-dependent survival were also demonstrated. In synchronized cultures, cells were most sensitive to 0.1 microM LY in early G1 phase, but in higher concentration (5 microM), LY killed the cells during the entire cell cycle, especially in G1, early and mid S phases, and M phase. Lycurim and PF given together in their IC50 concentrations (0.016 and 0.085 microM, respectively) yielded synergistic cell kill in 7-day treatment of proliferating cultures. Two-hour treatment of exponentially growing cells with LY and PF at their IC50 concentrations (1 and 20 microM, respectively) also yielded synergistic killing action, but in plateau-phase cells only summation was observed. Synergistic activity of LY and PF in hepatoma 3924A cells was dependent on drug concentration and incubation time.

Amides↗

Extinction dynamics in experimental metapopulations.

Metapopulation theory provides a framework for understanding population persistence in fragmented landscapes and as such has been widely used in conservation biology to inform management of fragmented populations. However, classical metapopulation theory [Levins, R. (1970) Lect. Notes Math. 2, 75-107] ignores metapopulation structure and local population dynamics, both of which may affect extinction dynamics. Here, we investigate metapopulation dynamics in populations that are subject to different migration rates by using experimental metapopulations of the annual plant Cardamine pensylvanica. As predicted by classical metapopulation theory, connected populations persisted longer than did isolated populations, but the relationship between migration and persistence time was nonlinear. Extinction risk sharply increased as the distance between local populations increased above a threshold value that was consistent with stochastic simulations and calculation of metapopulation capacity [Hanski, I. & Ovaskainen, O. (2000) Nature 404, 755-758]. In addition, the most connected metapopulations did not have the highest persistence levels. Stochastic simulations indicated an increase in extinction risk with the highest migration rates. Moreover, calculation of population coherence [Earn, D. J. D., Levin, S. A. & Rohani, P. (2000) Science 290, 1360-1364], a metric that predicts synchronous cycles, indicated that continuous populations should cycle in phase, resulting in an increased extinction risk. Determining empirically the optimal migration level to improve survival chances will be challenging for any natural population. Migration rates that would not increase migration above the threshold value would be ineffectual, but migration rates that would homogenize local densities could increase the risk of coherent oscillations and enhance extinction risk.

Ecology↗

Increasing exercise duration does not affect the postexercise elevation in esophageal temperature.

It has previously been observed that (a) following 15 min of intense exercise, esophageal temperature (Tes) remains elevated at a plateau value equal to that at which active vasodilation had occurred during exercise (i.e., esophageal temperature threshold for cutaneous vasodilation [ThVD]); and (b) exercise/recovery cycles of identical intensity and duration, when sequential, result in progressively higher Tes at the beginning and end of exercise. In the latter case, parallel increases in both the exercise ThVD and postexercise plateau of Tes were noted. This study was conducted to determine if the elevated postexercise Tes is related to increases in whole-body heat content. On separate occasions, 9 subjects completed 3 bouts of treadmill exercise at 70% VO2 max, 29 degrees C ambient temperature. Each exercise bout lasted either 15, 30, or 45 min and was followed by 60 min of inactive recovery. Esophageal temperatures were similar at the start of each exercise bout, but the rise in Tes during exercise nearly doubled from 1.0 degree C after 15 min of exercise to 1.9 degrees C after 45 min of exercise. There were no intercondition differences among the exercise ThVD (approximately 0.36 degree C above baseline) or postexercise plateau values for Tes (approximately 0.40 degree C above baseline). Thus the relationship between the ThVD during exercise and the postexercise Tes did not appear to be dependent on changes in whole-body heat content as produced by endogenous heating during exercise of different duration.

Adult↗

Ventilatory threshold and work efficiency during exercise on a cycle and rowing ergometer.

The purpose of this investigation was to determine the effects of increasing specific (rowing ergometer) and non-specific (cycle ergometer) workloads on parameters relating to the ventilatory threshold (Tvent) and work efficiency. When highly trained male rowers were tested using non-specific workloads, their %VO2 max values at Tvent were close to those characteristic of untrained subjects (74.6 +/- 6.2% VO2 max). However, when we tested the same subjects using specific workloads, we recorded values typical of highly trained athletes (85.0 +/- 4.4% VO2 max). For the non-specific exercise on the cycle ergometer, we recorded work efficiency values close to those of untrained subjects (22.8 +/- 2.1%); however, for the specific exercise on the rowing ergometer, we recorded much lower values (16.4 +/- 3.1%). Because of the results of the non-specific submaximal exercise tests, we suggest caution in the interpretation of physiological variables that may be sensitive to training status. The evaluation of Tvent and work efficiency as supplementary parameters during laboratory studies will enable researchers to ascertain the effectiveness of the training process used, as well as indicating the specificity of the loading apparatus.

Adaptation, Physiological↗

Spatial frequency discrimination in cyclopean vision.

It is well known that inspecting a cyclopean grating causes threshold for detecting a subsequently presented test cyclopean grating to be elevated, and that the threshold elevation is greatest at the adapting frequency. We report here that spatial frequency discrimination threshold is also elevated, but the elevation is greatest at frequencies offset from the adapting frequency, and the elevation at the adapting frequency is near-zero. We conclude that discrimination threshold is determined by the relative activity of cyclopean frequency-tuned channels, and suggest that relative activity is computed at an opponent-frequency stage. Discrimination threshold for cyclopean gratings was 2.5-4% for two observers, and remained approximately constant over the range 0.16-2.0 cycles/ degrees. Discrimination threshold for luminance-defined gratings was only slightly lower. Discrimination threshold was approximately independent of the grating's peak-to-peak disparity over a range of 45:1 for one observer and 17:1 for another. This finding as well as the low value of discrimination threshold are consistent with an opponent-process model. The dot density of every cyclopean grating used was chosen bearing in mind our finding that three or more spatial samples per grating cycle are required before sampling effects can be ignored.

Adult↗

Moderate exercise increases the post exercise resting warm thermoregulatory response thresholds.

BACKGROUND: The purpose of this study was to evaluate the effect of exercise on the subsequent post-exercise core temperature thresholds for vasodilation and sweating. METHODS: On two separate days, with 6 subjects (3 males and 3 females), a whole-body water-perfused suit decreased mean skin temperature until the threshold for vasoconstriction was demonstrated. Mean skin temperature was then slowly increased (approximately 5.0 degrees C x h(-1)) until thresholds for vasodilation and sweating were clearly established. Subjects were cooled by decreasing water temperature until both esophageal and mean skin temperatures returned to near baseline values. Subjects then either performed 15 min of cycle ergometry (60% V(O2max)) followed by 30 min of recovery (Exercise), or remained seated with no exercise for 45 min (Control). Subjects were then cooled again until the onset of cutaneous vasoconstriction followed by a second warming period. The core temperature thresholds for vasodilation and sweating increased significantly by 0.49 degrees C and 0.19 degrees C post-exercise, respectively (p < 0.05). In order to compare thresholds between conditions in which both esophageal and mean skin temperatures were changing, we mathematically compensated for changes in skin temperatures using the established linear cutaneous contribution of skin to the control of vasodilation and sweating (10%). RESULTS: The calculated core temperature threshold (at a designated skin temperature of 36.0 degrees C) for vasodilation increased significantly from 36.56 +/- 0.12 degrees C to 37.11 +/- 0.21 degrees C post-exercise (p < 0.01). Likewise, the sweating threshold increased from 36.79 +/- 0.18 degrees C to 37.05 +/- 0.23 degrees C postexercise (p < 0.01). In contrast, sequential measurements, without exercise, demonstrate a time-dependent decrease (0.18 degrees C) in the sweating threshold, with no difference in the vasodilation threshold. CONCLUSION: These data indicate that exercise has a prolonged effect by increasing the post-exercise thresholds for both warm thermoregulatory responses.

Body Temperature Regulation↗

A comparison of modality-specific somatosensory changes during menstruation in dysmenorrheic and nondysmenorrheic women.

OBJECTIVE: The objective was to evaluate somatosensory thresholds to a multimodality stimulation regimen applied both within and outside areas of referred menstrual pain in dysmenorrheic women, over four phases of confirmed ovulatory cycles, and to compare them with thresholds in nondysmenorrheic women during menstruation. DESIGN: Twenty dysmenorrheic women with menstrual pain scoring 5.45 +/- 0.39 cm (mean +/- standard error of mean) on a visual analog scale (10 cm) participated. Fifteen nondysmenorrheic women with a menstrual pain score of 0.4 +/- 0.2 cm participated as controls. Ovulation was confirmed by an enzyme-multiplied immunoassay technique. Menstrual pain was described with the McGill Pain Questionnaire. Areas within menstrual pain referral were two abdominal sites and the midline of the low back, and the arm and thigh were the control areas. The pressure pain threshold (PPT) and pinch pain threshold were determined by a hand-held electronic pressure algometer, the heat pain threshold (HPT) by a contact thermode, and the tactile threshold with von Frey hairs. RESULTS: In dysmenorrheic women the McGill Pain Questionnaire showed a larger sensory and affective component of pain than the evaluative and miscellaneous groups. The HPT and PPT were lower in the menstrual phase than in the ovulatory, luteal, and premenstrual phases, both within and outside areas of referred menstrual pain (p <0.01), with a more pronounced decrease at the referral pain areas. The pinch pain threshold was lower in the menstrual phase than in the ovulatory phase (p <0.02), and the tactile threshold did not differ significantly across the menstrual phases or within any site. Dysmenorrheic women had a lower HPT at the control sites and a lower PPT at the abdomen, back, and control sites, than in those of nondysmenorrheic women in the menstrual phase. CONCLUSIONS: The results show reduced somatosensory pain thresholds during menstruation to heat and pressure stimulation, both within and outside areas of referred menstrual pain in dysmenorrheic women. Dysmenorrheic women showed a lower HPT at the control sites and a lower PPT at all the sites than those for nondysmenorrheic women in the menstrual phase. The altered somatosensory thresholds may be dependent on a spinal mechanism of central hyperexcitability, induced by recurrent moderate to severe menstrual pain.

Adult↗

Comparison of physiologic dead space/tidal volume ratio and alveolar-arterial PO2 difference during incremental and constant work exercise.

We prefer 1-min incremental exercise testing on a cycle ergometer rather than constant work studies because of its speed, repeatability, and ease of identification of the anaerobic threshold. Although values such as VO2 and anaerobic threshold from both types of studies are reported to be comparable, we questioned whether VD/VT and AaPO2, which depend on simultaneous arterial blood and mixed expired gas sampling, would also be reliable during incremental testing. In 23 patients we did both a constant work test at below the anaerobic threshold and a 1-min incremental test. At matched VO2 we found no difference between VD/VT and AaPO2 despite anticipated differences in VE, VCO2, and R because of differences in their rates of increase. We conclude that VD/VT and AaPO2, determined during 1-min incremental exercise tests, are equivalent to those from constant work tests and that a separate constant work study is not needed for these measurements if determined below the anaerobic threshold.

Adult↗

Biologically relevant environmental data: macros to make the most of microclimate recordings.

The increased availability and use of automatic data loggers has made collection of microclimatic data cheap and easy. I present macros for the quantitative analysis and comparison of microclimatic (particularly temperature) data in the spreadsheet package Microsoft Excel. The macros presented will (1) collate maximum and minimum values of temperature (or other) cycles, (2) provide a count of the number of times a temperature recording crosses a given threshold, (3) measure the period of time spent above or below a given threshold, and (4) measure the rate of change of a data set as it approaches a threshold. A case study of the freeze tolerant grasshopper Sigaus australis (Orthoptera: Acrididae) and winter temperatures from its alpine habitat is used to demonstrate the macros.

Adaptation, Physiological↗

Variability of serum prolactin and progesterone levels in normal women: the relevance of single hormone measurements in the clinical setting.

In order to delineate factors contributing to variation in hormone levels, progesterone and prolactin (PRL) levels from 28 normal women, obtained daily during one menstrual cycle and every 20 minutes during a midluteal 24-hour admission in a subgroup of five subjects, provided a data base for analysis of these variables. Pulsatile analysis of the 24-hour data was conducted using an adaptive-threshold algorithm, and normal reference ranges were generated from randomly selected daily hormone values. Our data verify that inherent variation can significantly alter single random serum levels of reproductive hormones. These variations included menstrual cycle day, circadian influence, pulsatile secretion, assay error, and biologic heterogeneity. Besides the expected day-to-day change in progesterone levels during the luteal phase, seven of ten women exhibited a significant circadian variation in progesterone; however, the time of day of the peak level was not consistent among women. Prolactin levels did not demonstrate any clinically relevant change over the menstrual cycle, but did have a consistent circadian pattern (nocturnal rise) over the 24-hour study period. Pulsatile variation occurred in both progesterone and PRL levels during the 24-hour admission. Five different reference ranges were generated from randomly selected single daily values from the 28 normal menstrual cycles. Although the mean levels calculated for each reference range were similar, the reference ranges demonstrated considerable variation due to the random sampling. In the five progesterone reference ranges, the lower limit of the range varied from 2.7-6.1 ng/mL, whereas the upper limit varied from 24.2-42.1 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm.

OBJECTIVE: To compare World Health Organization threshold values for normal sperm with the initial sperm quality necessary for successful IUI. DESIGN: Retrospective study. SETTING: Private fertility clinic. PATIENT(S): One thousand eight hundred forty-one couples undergoing 4,056 cycles of IUI. INTERVENTION(S): Intrauterine insemination. MAIN OUTCOME MEASURE(S): Relation of initial sperm quality to fecundity. RESULT(S): Progressive motility and total motile sperm count were the initial sperm characteristics most closely related to pregnancy on discriminant analysis. The per-cycle pregnancy rate averaged 11.1% during the first three IUI cycles. Pregnancy rates were > or = 8.2% per cycle when the initial sperm values were a concentration of > or = 5 X 10(6)/mL, a total count of > or = 10 X 10(6), progressive motility of > or = 30%, or a total motile sperm count of > or = 5 x 10(6). Minimal increases in fecundity occurred when initial values were greater than these threshold levels. The lowest initial values that resulted in pregnancy were a concentration of 2 x 10(6)/mL, a total count of 5 x 10(6). motility of 17%, and a total motile sperm count of 1.6 X 10(6). Pregnancy rates were <3.6% when initial values were between the threshold levels and the lowest levels. CONCLUSION(S): The sperm quality that is necessary for successful IUI is lower than World Health Organization threshold values for normal sperm. Intrauterine insemination is effective therapy for male factor infertility when initial sperm motility is > or = 30% and the total motile sperm count is > or = 5 X 10(6). When initial values are lower, IUI has little chance of success.

Adult↗

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

BACKGROUND: It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. METHODS: A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. RESULTS: The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. CONCLUSIONS: Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

Adult↗

Fuzzy C-means method for clustering microarray data.

MOTIVATION: Clustering analysis of data from DNA microarray hybridization studies is essential for identifying biologically relevant groups of genes. Partitional clustering methods such as K-means or self-organizing maps assign each gene to a single cluster. However, these methods do not provide information about the influence of a given gene for the overall shape of clusters. Here we apply a fuzzy partitioning method, Fuzzy C-means (FCM), to attribute cluster membership values to genes. RESULTS: A major problem in applying the FCM method for clustering microarray data is the choice of the fuzziness parameter m. We show that the commonly used value m = 2 is not appropriate for some data sets, and that optimal values for m vary widely from one data set to another. We propose an empirical method, based on the distribution of distances between genes in a given data set, to determine an adequate value for m. By setting threshold levels for the membership values, genes which are tigthly associated to a given cluster can be selected. Using a yeast cell cycle data set as an example, we show that this selection increases the overall biological significance of the genes within the cluster. AVAILABILITY: Supplementary text and Matlab functions are available at http://www-igbmc.u-strasbg.fr/fcm/

Algorithms↗

Changes in firing rate of human motor units during linearly changing voluntary contractions.

1. Human subjects generated approximately linearly increasing or decreasing voluntary, isometric contractions using the first dorsal interosseus muscle of the hand.2. Single motor units began firing at 8.4+/-1.3 impulses/sec (mean +/- S.D. of an observation) and increased their firing rate 1.4+/-0.6 impulses/sec for each change of 100 g in voluntary force. These values were independent of the threshold force for recruiting motor units.3. At intermediate rates of increasing and decreasing voluntary force (one complete cycle every 10 sec) the firing rate of single motor units varied linearly with force over the entire range of forces studied. However, during slow increases in voluntary force, the firing rate tended to reach a plateau, while during rapid increases an initial train of impulses at a roughly constant rate was observed.4. The relative importance of recruitment and increased firing rate, as mechanisms for increasing the force of voluntary contraction, was determined. Only at low levels of force is recuitment the major mechanism. Increased firing rate becomes the more important mechanism at intermediate force levels and contributes the large majority of force if the entire physiological range is considered.

Action Potentials↗

Supernormal muscle fiber conduction velocity during intermittent isometric exercise in human muscle.

Muscle fiber conduction velocity (MFCV) and surface electromyographic parameters were studied in the brachial biceps muscle of healthy males during voluntary intermittent isometric contractions at 50% of maximum force. Recovery in the following 15 min was then observed. The measurements were performed during duty cycles of 33, 25, and 20%. The main finding was a supernormal MFCV during the exercise phase when the duty cycle was 25 and 20%. The level continued to increase during the recovery phase. During the exercise phase when the duty cycle was 33%, the MFCV decreased slightly (suggesting that the local anaerobic threshold had been surpassed) but increased during recovery to supernormal values. The ratio of median frequency to MFCV was constant during all experiments, indicating that the changes in median frequency reflect those in MFCV. We suggest that the supernormal MFCV was due to a combination of altered membrane properties, muscle fiber swelling, and temperature increase and hypothesize that the changes of electrical properties formed part of an adaptive mechanism of the muscle fiber membrane during exercise. In that respect, the increase of the MFCV could be a component of the well-known warm-up effect.

Adult↗