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Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs.

This report investigates the power issue in applying the non-parametric linkage analysis of affected sib-pairs (ASP) [Kruglyak and Lander, 1995: Am J Hum Genet 57:439-454] to localize genes that contribute to human longevity using long-lived sib-pairs. Data were simulated by introducing a recently developed statistical model for measuring marker-longevity associations [Yashin et al., 1999: Am J Hum Genet 65:1178-1193], enabling direct power comparison between linkage and association approaches. The non-parametric linkage (NPL) scores estimated in the region harboring the causal allele are evaluated to assess the statistical power for different genetic (allele frequency and risk) and heterogeneity parameters under various sampling schemes (age-cut and sample size). Based on the genotype-specific survival function, we derived a heritability calculation as an overall measurement for the effect of causal genes with different parameter settings so that the power can be compared for different modes (dominant, recessive) of inheritance. Our results show that the ASP approach is a powerful tool in mapping very strong effect genes, both dominant and recessive. To map a rare dominant genetic variation that reduces hazard of death by half, a large sample (above 600 pairs) with at least one extremely long-lived (over age 99) sib in each pair is needed. Again, with large sample size and high age cut-off, the method is able to localize recessive genes with relatively small effects, but the power is very limited in case of a dominant effect. Although the power issue may depend heavily on the true genetic nature in maintaining survival, our study suggests that results from small-scale sib-pair investigations should be referred with caution, given the complexity of human longevity.

Age Factors↗

Estimating the power of variance component linkage analysis in large pedigrees.

Variance component linkage analysis is commonly used to map quantitative trait loci (QTLs) in general pedigrees. Large pedigrees are especially attractive for these studies because they provide greater power per genotyped individual than small pedigrees. We propose accurate and computationally efficient methods to calculate the analytical power of variance component linkage analysis that can accommodate large pedigrees. Our analytical power computation involves the approximation of the noncentrality parameter for the likelihood-ratio test by its Taylor expansions. We develop efficient algorithms to compute the second and third moments of the identical by descent (IBD) sharing distribution and enable rapid computation of the Taylor expansions. Our algorithms take advantage of natural symmetries in pedigrees and can accurately analyze many large pedigrees in a few seconds. We verify the accuracy of our power calculation via simulation in pedigrees with 2-5 generations and 2-8 siblings per sibship. We apply this proposed analytical power calculation to 98 quantitative traits in a cohort study of 6,148 Sardinians in which the largest pedigree includes 625 phenotyped individuals. Simulations based on eight representative traits show that the difference between our analytical estimation of the expected LOD score and the average of simulated LOD scores is less than 0.05 (1.5%). Although our analytical calculations are for a fully informative marker locus, in the settings we examined power was similar to what could be attained with a single nucleotide polymorphism (SNP) mapping panel (with >1 SNP/cM). Our algorithms for power analysis together with polygenic analysis are implemented in a freely available computer program, POLY.

Chromosome Mapping↗

Analysis of theta power in hippocampal EEG during bar pressing and running behavior in rats during distinct behavioral contexts.

These experiments examine changes in theta power as measured by wavelet analysis in five rats performing a conditional visual discrimination task and a simple running task. In the conditional task, rats were trained to press one lever to initiate a trial and then to press one of two choice levers, each corresponding to one of two cue lights. Analysis of theta power in this operant task found a large decrease in theta power during the choice bar presses, in contrast to the increase in theta power during trial initiation bar presses. This result seems to stand counter to results that propose consistent relationships between motor actions and theta power (Vanderwolf, EEG Clin Neurophys 26:407-418, 1969), as well as studies suggesting that the lack of bar-press theta is the result of habituation. However, these data can be seen as being in broad agreement with the theoretical framework of sensorimotor integration (Bland and Oddie, Behav Brain Res 127:119-136, 2001). To investigate further the power of theta observed at the termination of type 1 motor activity, a runway task was devised in which rats ran back and forth between two ends of a linear track, one of which was always rewarded and the other never rewarded. Theta power decreased sharply 240 ms before movement ended at the rewarded end, but not at the unrewarded end of the track. These data extend the current scope of theory in demonstrating that hippocampal theta activity can end abruptly 200-400 ms prior to the end of type 1 motor movement when approaching the end of a motor sequence.

Action Potentials↗

Prostate cancer mortality reduction by screening: power and time frame with complete enrollment in the European Randomised Screening for Prostate Cancer (ERSPC) trial.

From 1992-2001, 7 countries in Europe gradually recruited men for the European Randomised Screening for Prostate Cancer (ERSPC) trial. Centres recruit different age groups and have different designs for recruiting and countries have different underlying risks for prostate cancer. Recruitment has reached 163,126 men aged 55-69 at entry now. Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected. Recruitment data were collected from the screening centres. We calculated the expected number of prostate cancer deaths in each follow-up year, based on national statistics and expected rate in trial entrants. The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials. With an assumed 25% intervention effect in men actually screened and a 20% contamination rate, the trial will reach a power of 0.86 in 2008. With an assumed intervention effect of 40%, the power reaches 0.90 in 2003-2004. Pooling data with those of the Prostate, Lung, Colorectal and Ovary (PLCO) trial early is expected to improve the power to 79% (20% intervention effect) to 92% (40% intervention effect PLCO). Adding more centres with compliance rates lower than 45% decreases the power of the trial. The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25% or more or if contamination remains limited to 10% if the true effect is 20% or more. If early detection and treatment turns out to have a stronger effect as may be suggested by observational data, the ERSPC trial is likely to conclusively show that within the next 5 years.

Aged↗

The power density of a surgical laser beam: its meaning and measurement.

This paper discusses the fundamental concepts of matter, energy, power, and power density, with specific emphasis on the power density of a laser. It points out that a laser beam does not have a single, unique value of diameter within which all of its radiation is confined. Therefore, a computation of power density requires both a value of diameter, and the value of the fraction of total power which is transmitted within that diameter. Some possible means of measuring diameter, power, and power density are presented.

Biophysical Phenomena↗

Low power laser irradiation alters the rate of regeneration of the rat facial nerve.

Low power laser irradiation has been reported to cause biological effects due to the photochemical and/or photophysical action of the radiation. This study determined quantitatively if transcutaneous low power laser irradiation can affect the regeneration of the rat facial nerve. The facial nerve was crushed unilaterally in anesthetized rats and transcutaneously irradiated daily with a laser beam directed at the area of the crush injury. Laser treatment began on the day of the crush injury and was continued daily for 7, 8, or 9 days. Preliminary experiments determined the most effective wavelength, laser power, length of irradiation, and treatment schedule. The wavelengths examined were 361, 457, 514, 633, 720, and 1064. The laser powers and lengths of irradiation examined ranged from 8.5 to 40 mW and 13 to 120 min. Irradiation treatment was done daily, on alternating days and on the first 4 days postcrush. The most effective laser parameters for the low power treatment included daily irradiation with a helium-neon (HeNe) or argon pumped tunable dye laser a wavelength of 633 nm, with a power of 8.5 mW for 90 minutes (45.9 J, 162.4 J/cm2). The number of horseradish peroxidase (HRP) labeled neurons in the facial motor nucleus was used as an assay of the degree of regeneration. In rats in which the facial nerve was crushed but not irradiated, the average number of HRP labeled neurons in the facial nucleus was 22 on day 7 postcrush, 54 on day 8, 116 on day 9, and 1,149 on day 10. After HeNe or argon pumped tunable dye laser irradiation, the average number of HRP-labeled neurons increased to 34 on day 7 postcrush, 148 on day 8, and 1,725 on day 9. There was a statistically significant difference between the control and irradiated rats on day 9 postcrush (P < 0.01). These data indicate that transcutaneous low power irradiation with the lasers and parameters involved in this study increased the rate of regeneration of rat facial nerve following crush injury.

Animals↗

High power Ho:YAG laser ablation of intervertebral discs: effects on ablation rates and temperature profile.

BACKGROUND AND OBJECTIVE: As the Ho:YAG laser gained increasing importance in recent experimental and clinical investigations, this study was performed to investigate the effect of power on ablation rates and temperature during disc ablation with a high power Ho:Yag laser under simulated clinical conditions. STUDY DESIGN/MATERIALS AND METHODS: A high power Ho:YAG laser was used to investigate the influence of increasing power from 10 to 32 Watt on ablation rate (mg) and temperature (degree C). Ablation weight was measured by a precision scale calculating the difference of the pre- and postlasing weight of the specimen after application of total energies of 1,000, 1,500, and 2,000 J. Temperatures were measured by thermoprobes, which were connected via a thermomodule to an amplifier and the signal was plotted by a computer with appropriate software. RESULTS: Whereas ablation rate rose almost linearly with total energy, increasing power above 20 W did not essentially improve ablation rate. Temperatures reached their highest values after application of a total energy of 500 J and did not rise further, whereas increasing power did not induce a rise in temperature. CONCLUSIONS: Regarding the chosen experimental setting, maximum temperatures are reached after application of 500 J, and increasing power does not induce a rise in temperature.

Animals↗

Peak power of muscles injured by lengthening contractions.

Excessive or extreme lengthening contractions have a well-characterized depressive effect on skeletal muscle isometric force. In addition to producing force, active muscles must often shorten in order to meet the power requirements of locomotion and other physical activities. However, the impact of lengthening contractions on muscle power is poorly understood. We evaluated the effect of 20 isometric contractions or 20 lengthening contractions (20% strain at 1.5 fiber lengths/s) on the force-velocity-power relationships of mouse soleus muscles in vitro at 35 degrees C. Pre- and posttreatment data were obtained as the muscles shortened through their optimal length (Lo). The isometric treatment did not alter Lo, the curvature of the force-velocity relationship (a/Po), or soleus maximal shortening velocity (Vmax), whereas peak force (Po) displayed a slow, time-dependent decline of 10% across the experiments. Following the lengthening treatment, Lo increased by 6%, a/Po increased by 22%, and Vmax and Po fell by 24% and 26%, respectively. Under optimal conditions for producing power, muscles damaged by lengthening contractions attained 22% less force and shortened 20% more slowly than before damage. Consequently, soleus peak power fell 37% after lengthening, a 2.5-fold greater decline than noted for the isometric treatment. Under the conditions studied here, the excessive power loss following lengthening contractions was due to force and velocity deficits of approximately equal relative magnitude. Because power represents the ability of the muscle to perform work, reductions in both force and shortening velocity should be considered when evaluating and treating lengthening-induced skeletal muscle injuries.

Animals↗

Power of testing proportions in small two-sample studies when sample sizes are equal.

In planning experiments having two groups of equal but small size, investigators face the uncertainty of power calculations that rely on asymptotic methods. This paper presents a method for determining power for two-sided tests. I compare two randomization tests, Fisher's exact test (FET), and the mid-P (MID), with the uncorrected chi-square test (CHI). Results show power as a function of relative risk for these methods, and assesses their relative power and type I error rates. MID is shown to have intermediate power between CHI, which is the most powerful, and FET, the least powerful. Situations are shown in which CHI and MID occasionally exceed the nominal level of alpha.

Data Interpretation, Statistical↗

Efficient power computation for exact and mid-P tests for the common odds ratio in several 2 x 2 tables.

When designing a study that may generate a set of sparse 2 x 2 tables, or when confronted with 'negative' results upon exact analysis of such tables, we need to compute the power of exact tests. In this paper we provide an efficient approach for computing exact unconditional power for four exact tests on the common odds ratio in a series of 2 x 2 tables. These tests are the traditional exact test; a test based on a probability ordering of the sample space; and two tests based on ordering the sample space according to distance from the mean, or median. For each test, we consider both a conservative version and a mid-P adjusted version. We explore three computational options for power determination: exact power computation, calculation of exact upper and lower bounds for power, and Monte Carlo confidence bounds for power. We present an interactive program implementing these options. For study design, the program may be run several times to arrive at a sample configuration with adequate power.

Case-Control Studies↗

Effects of cocaine on the EEG power spectrum of rats are significantly altered after its repeated administration: do they reflect sensitization phenomena?

It was previously shown that a moderate dose of cocaine (10 mg/kg i.p.) produces a pattern in the EEG power spectrum which indicates a preferential activation of dopamine D1-like receptors, namely a decrease of power in most of the frequency bands. In contrast, a large dose of cocaine (30 mg/kg i.p.) produces a decrease of power in most of the frequency bands as well, but a selective increase in the alpha-1 band, characteristic for an additional activation of dopamine D2-like receptors. In the present experiments, it was studied in rats, if in the course of sensitization, a shift from D1-like to additional D2-like receptor activation will occur or not. For this study, the animals were treated 10 times with cocaine (either 10 or 20 mg/kg) and, after a drug free interval of 4 days, tested with the same dose administered previously. Acute administration of 10 mg/kg of cocaine increased the locomotor activity slightly and its effect tended to be enhanced after repeated administration. Twenty mg/kg cocaine increased the locomotor activity more than the 10 mg/kg dose and its effect was significantly enhanced after repeated treatment. In addition, it was shown that the dose of 10 mg/kg of cocaine which activates D1- but not D2-like receptors is sufficient to elicit conditioned place preference. Ten mg/kg of cocaine produced a decrease of power in most of the frequency bands and this effect was slightly more pronounced after repeated treatment. Twenty mg/kg of cocaine acutely also produced a decrease in power in most of the frequency bands, but did not decrease the power in the alpha-1 band, being just at the threshold of activating D2-like receptors as well. Repeated administration led to a significant increase in power in the alpha-1 band and a less pronounced one in the alpha-2 band. This observation demonstrates that sensitization to cocaine can be manifest in the EEG and that after a certain dosage, a shift from an activation of D1-like dopamine receptors to an additional activation of D2-like receptors becomes obvious.

Analysis of Variance↗

Electromyogram power spectrum during dynamic contractions at different intensities of exercise.

During dynamic contractions performed on a cycle ergometer, we studied the influence of motor unit (MU) recruitment on the electromyographic (EMG) spectral content by exerting mechanical power of different intensities, which was chosen to remain below the maximal aerobic power (VO2max). The spectral parameters: EMG total power (PEMG), mean (MPF) and median (MED) power frequencies, which are the most representative of the EMG spectral content, were calculated according to the EMG activity of the vastus medialis muscle (VM) and soleus muscle (SOL) of the right leg. For VM and SOL, PEMG increased linearly with exerted power demonstrating an enhancement of MU recruitment. Moreover these relationships were less scattered when exerted power was expressed as a percentage of VO2max. Changes in MPF and MED with varying exercise intensities were different from one subject to another. For a set of subjects, MPF and MED were found to be independent of exerted power. Although VM and SOL muscles are different in fibre type composition, similar results were obtained for both EMG activities. We have concluded that for dynamic contractions performed at different intensities below VO2max, the recruitment of the MU has a poor effect on the EMG spectral content whatever the predominant type of fibre.

Adult↗

Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density.

The relation between EEG power density during slow wave sleep (SWS) deprivation and power density during subsequent sleep was investigated. Nine young male adults slept in the laboratory for 3 consecutive nights. Spectral analysis of the EEG on the 2nd (baseline) night revealed an exponential decline in mean EEG power density (0.25-15.0 Hz) over successive nonrapid eye movement--rapid eye movement sleep cycles. During the first 3 h of the 3rd night the subjects were deprived of SWS by means of acoustic stimuli, which did not induce wakefulness. During SWS deprivation an attenuation of EEG power densities was observed in the delta frequencies, as well as in the theta band. In the hours of sleep following SWS deprivation both the power densities in the frequency range from 1 to 7 Hz and the amount of SWS were enhanced, relative to the same period of the baseline night. Both the amount of EEG energy accumulating subsequent to SWS deprivation and its time course could be predicted accurately from the EEG energy deficit caused by SWS deprivation. The data show that the level of integral EEG power density during a certain period after sleep onset depends on the amount of EEG energy accumulated during the preceding sleep rather than on the time elapsed since sleep onset. In terms of the two-process model of sleep regulation (Borbély 1982; Daan et al. 1984) this finding indicates that EEG power density reflects the rate of decay of the regulating variable, S, rather than S itself, as was originally postulated.

Acoustic Stimulation↗

A simple method for measurement of mechanical power in jumping.

A simple test for the measurement of mechanical power during a vertical rebound jump series has been devised. The test consists of measuring the flight time with a digital timer (+/- 0.001 s) and counting the number of jumps performed during a certain period of time (e.g., 15-60 s). Formulae for calculation of mechanical power from the measured parameters were derived. The relationship between this mechanical power and a modification of the Wingate test (r = 0.87, n = 12 males) and 60 m dash (r = 0.84, n = 12 males) were very close. The mechanical power in a 60 s jumping test demonstrated higher values (20 W X kgBW-1) than the power in a modified (60 s) Wingate test (7 W X kgBW-1) and a Margaria test (14 W X kgBW-1). The estimated powers demonstrated different values because both bicycle riding and the Margaria test reflect primarily chemo-mechanical conversion during muscle contraction, whereas in the jumping test elastic energy is also utilized. Therefore the new jumping test seems suitable to evaluate the power output of leg extensor muscles during natural motion. Because of its high reproducibility (r = 0.95) and simplicity, the test is suitable for laboratory and field conditions.

Biomechanical Phenomena↗

A comparison of the effect of external loading upon power output in stair climbing and running up a ramp.

Previous studies have shown that external loading increases the power output measured during stair climbing. However, it was noted in an earlier study that stairtreads form mechanical contraints which limit the extent to which a subject can be externally loaded, and, thereby, make it impossible to observe maximal power output for this type of activity. The purpose of this study was to compare the effects of external loading upon power output when running up stairs or a ramp. Since a ramp is free of the mechanical constraints of stairtreads, it was felt that higher power output values would be achieved using the ramp, and that it would be possible to observe an asymptote in power output which could not be obtained for stair climbing. Seven male subjects performed maximal ramp and stair climbing tests under five experimental loading conditions (no external load, 10.1, 19.2, 24.2, and 29.2 kg). For the ramp, it was possible to employ a sixth loading condition of 34.2 kg. For stair climbing, the mean (+/- SD) power output values under the five experimental conditions were 16.6 +/- 0.7, 17.3 +/- 1.3, 18.5 +/- 1.0, 18.6 +/- 1.5, and 18.9 +/- 1.7 W X kg-1, respectively. In contrast, the mean (+/- SD) power output values observed while running up the ramp were 18.8 +/- 1.4, 19.9 +/- 1.6, 20.5 +/- 1.6, 20.1 +/- 2.1, 20.3 +/- 2.1, and 19.8 +/- 1.9 W X kg-1, respectively. At each experimental condition, the differences between the ramp and stairs was significant (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Functional torque-velocity and power-velocity characteristics of elite athletes.

Technical limitations of some isokinetic dynamometers have called into question the validity of some data on human muscle mechanics. The Biodex dynamometer has been shown to minimize the impact artefact while permitting automatic gravity correction. This dynamometer was used to study quadriceps muscle torque and power generation in elite power (n = 6) and elite endurance (n = 7) athletes over 12 randomly assigned isokinetic velocities from 30 degrees.s-1 to 300 degrees.s-1. The angle at peak torque varied as a negative, linear function of angular velocity, with the average angle across test velocities being 59.5 degrees (SD 10.2 degrees). Power athletes developed greater peak torque at each angular velocity (P less than 0.05) and experienced a 39.7% decrement in torque over the velocity range tested. Endurance athletes encountered a 38.8% decline in peak torque. Torques measured at 60 degrees of knee flexion followed a similar trend in both groups; however the greatest torques were recorded at 60 degrees.s-1 rather than at 30 degrees.s-1. Leg extensor muscle power increased monotonically with angular velocity in both power (r2 = 0.728) and endurance athletes (r2 = 0.839); however these curves diverged significantly so that the power athletes produced progressively more power with each velocity increment. These inter group differences probably reflected a combination of natural selection and training adaptation.

Adult↗

Power and work produced in different leg muscle groups when rising from a chair.

The aim of this study was to determine the power output and work done by different muscle groups at the hip and knee joints during a rising movement, to be able to tell the degree of activation of the muscle groups and the relationship between concentric and eccentric work. Nine healthy male subjects rose from a chair with the seat at knee level. The moments of force about the hip and knee joints were calculated semidynamically. The power output (P) and work in the different muscle groups surrounding the joints was calculated as moment of force times joint angular velocity. Work was calculated as: work = integral of P dt. The mean peak concentric power output was for the hip extensors 49.9 W, hip flexors 7.9 W and knee extensor 89.5 W. This power output corresponded to a net concentric work of 20.7 J, 1.0 J and 55.6 J, respectively. There was no concentric power output from the knee flexor muscles. Energy absorption through eccentric muscle action was produced by the hip extensors and hip flexors with a mean peak power output of 4.8 W and 7.4 W, respectively. It was concluded that during rising, the hip and knee muscles mainly worked concentrically and that the greatest power output and work were produced during concentric contraction of the knee and hip extensor muscles. There was however also a demand for eccentric work by the hip extensors as well as both concentric and eccentric work by the hip flexors. The knee flexor muscles were unloaded.

Adult↗

Gender differences in anaerobic power tests.

The purpose of this study was to determine if the differences in anaerobic power between males and females could be accounted for by differences in body composition, strength, and neuromuscular function. A total of 82 untrained men and 99 women took part in the study. Body composition, somatotype, isometric strength, neuromuscular function were measured, and four anaerobic power tests performed. The men were significantly different from the women on all strength, power, and neuromuscular measurements except reaction time and on all anthropometric and somatotype dimensions except ectomorphy. Strength and anthropometric dimensions were similarly related to anaerobic power values within each sex. Relative fat (%fat) exerted different degrees of influence on sprint and jump performances in each sex. Removing the influence of anthropometric, strength, and neuromuscular differences by analysis of covariance reduced, but did not remove, the significant differences between the sexes. Therefore, factors other than lean body mass, leg strength, and neuromuscular function may be operating in short-term, explosive power performances to account for the differences between the sexes. The task-specific nature of anaerobic power tests and the relatively large influence of anthropometric factors on power production were confirmed.

Adult↗