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Power Doppler ultrasound evaluation of the shear rate and shear stress dependences of red blood cell aggregation.

The use of power Doppler ultrasound at 10 MHz is evaluated as a method to study the shear rate and the shear stress dependences of red blood cell aggregation. This evaluation was based on six in vitro experiments conducted in a 1.27-cm diameter tube under steady flow conditions. Porcine whole blood was circulated in the flow model at flow rates ranging between 125 to 1500 ml/min (mean shear rate across the tube ranging between 6 and 74 s-1). For each flow condition, the variation of the Doppler power across the tube and the velocity profile were measured by moving the Doppler sample volume across the tube diameter. For each radial position, the shear rate within the Doppler sample volume was also determined by considering the radial power pattern of the ultrasound beam. To estimate the shear stress within the Doppler sample volume, the apparent viscosity of blood samples withdrawn from the flow model was measured for each experiment. The variation of the Doppler power as a function of the shear rate within the sample volume showed a rapid reduction of the power between 1 and 5 s-1, a transition region between 5 and 10 s-1, and a very slow reduction beyond 10 s-1. Little variation of the Doppler power was measured for shear stress higher than 2 dyn/cm2. The maximum Doppler power for all flow rates was usually found near the center of the tube. Based on the ultrasonic scattering models, which predict that the Doppler power is related to the volume square of the scatterers, the method described in the present study showed a very high sensitivity to the presence of red blood cell aggregation for shear rates below 10 s-1.

Animals↗

The RF-powered surface wave sensor oscillator--a successful alternative to passive wireless sensing.

A novel, passive wireless surface acoustic wave (SAW) sensor providing a highly coherent measurand proportional frequency, frequency modulated (FM) with identification (ID) data and immune to interference with multiple-path signals is described. The sensor is appropriate for bandwidth-limited applications requiring high-frequency accuracy. It comprises a low-power oscillator, stabilized with the sensing SAW resonator and powered by the rectified radio frequency (RF) power of the interrogating signal received by an antenna on the sensor part. A few hundred microwatts of direct current (DC) power are enough to power the sensor oscillator and ID modulation circuit and achieve stable operation at 1.0 and 2.49 GHz. Reliable sensor interrogation was achieved over a distance of 0.45 m from a SAW-based interrogation unit providing 50 mW of continuous RF power at 915 MHz. The -30 to -35 dBm of returned sensor power was enough to receive the sensor signal over a long distance and through several walls with a simple superheterodyne FM receiver converting the sensor signal to a low measurand proportional intermediate frequency and retrieving the ID data through FM detection. Different sensor implementations, including continuous and pulsed power versions and the possibility of transmitting data from several measurands with a single sensor, are discussed.

Electronics↗

Consideration of the posterior corneal curvature for assessment of corneal power after myopic LASIK.

PURPOSE: To evaluate the effect of a separate measurement of the anterior and posterior corneal surface to calculate the total refractive power of the cornea after myopic laser in situ keratomileusis (LASIK). METHODS: A total of 39 eyes of 21 patients (aged 33 +/- 9 years) were included in this prospective, non-randomized, comparative study. These involved 19 myopic corrections (- 3.5 +/- 1.6 dioptres) and 23 refractive corrections of myopic astigmatism (sphere: - 3.7 +/- 1.6 D, cylinder: - 1.2 +/- 0.4 D). All procedures were accomplished with the Keratom II). Coherent-Schwind excimer laser and the Moria Model One) microkeratome (150 micro m head) at the Medical Education Centre, La Trinidad, Caracas, Venezuela. Subjective refractometry, Bausch & Lomb) keratometry and Orbscan) slit-scanning corneal topography analysis were performed before and 3 months after LASIK. Corneal power was assessed directly using keratometry (K1) and Orbscan videokeratography (T1). Corneal power was calculated using the preoperative keratometric (K2, 'gold standard', clinical history method) or topographic power (T2, clinical history method) and spherical equivalent change. A composite value was derived from the Orbscan anterior and posterior surface power and central pachymetry (T3). RESULTS: Three months postoperatively, corneal power ranged in a descending order from T1 (42.33 +/- 1.78 D), K1 (40.82 +/- 2.20 D), K2 (40.42 +/- 2.36 D), T2 (40.03 +/- 2.51 D) to T3 (38.78 +/- 2.23 D). On average, T1 exceeded the gold standard by 1.9 D and the gold standard exceeded T3 by 1.6 D. K2, T1, T2 and T3 correlated significantly with K1 (r = 0.975, p < 0.001; r = 0.909, p < 0.001; r = 0.963, p < 0.001; r = 0.853, p < 0.001, respectively). The differences T1-K2 (r = - 0.699, p < 0.001) and T3-K2 (r = - 0.499, p = 0.001) correlated highly inversely and K1-K2 correlated borderline inversely (r = - 0.325, p = 0.043) with the intended refractive correction. CONCLUSION: After myopic LASIK, refractive corneal power is overestimated by direct keratometric and especially videokeratoscopic measurements. The higher the intended refractive correction, the greater is this error. A separate measurement of both refractive surfaces of the cornea tends to underestimate but may enhance accuracy of the total refractive corneal power if the history of the patient is unknown.

Adult↗

Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: sample size and power calculations.

Association (e.g. case-control) studies are often used to finely map loci identified by linkage analysis. We investigated the influence of various parameters on power and sample size requirements for such a study. Calculations were performed for various values of a high-risk functional allele (fA), frequency of a marker allele associated with the high risk allele (f1), degree of linkage disquilibrium between functional and marker alleles (D') and trait heritability attributable to the functional locus (h2). The calculations show that if cases and controls are selected from equal but opposite extreme quantiles of a quantitative trait, the primary determinants of power are h2 and the specific quantiles selected. For a dichotomous trait, power also depends on population prevalence. Power is optimal if functional alleles are studied (fA= f1 and D'= 1.0) and can decrease substantially as D' diverges from 1.0 or as f(1) diverges from fA. These analyses suggest that association studies to finely map loci are most powerful if potential functional polymorphisms are identified a priori or if markers are typed to maximize haplotypic diversity. In the absence of such information, expected minimum power at a given location for a given sample size can be calculated by specifying a range of potential frequencies for fA (e.g. 0.1-0.9) and determining power for all markers within the region with specification of the expected D' between the markers and the functional locus. This method is illustrated for a fine-mapping project with 662 single nucleotide polymorphisms in 24 Mb. Regions differed by marker density and allele frequencies. Thus, in some, power was near its theoretical maximum and little additional information is expected from additional markers, while in others, additional markers appear to be necessary. These methods may be useful in the analysis and interpretation of fine-mapping studies.

Alleles↗

Effect of light power density on development of elastic modulus of a model light-activated composite during polymerization.

PURPOSE: Elastic modulus development during polymerization of a composite is a measure of the polymerization maturity and the restoration's ability to transfer stress to enamel and dentin. The characteristics of elastic modulus development in real time during cure are largely unknown. The purpose of this study was to evaluate the effect of light power density and total energy density on the early development of elastic modulus for a light-activated composite. METHODS: Cylindrical specimens of a model hybrid composite were tested in flexure in a dynamic mechanical analyzer (DMA). Specimens were light-activated (Variable Intensity Polymerizer, Bisco, Itasca, Illinois) for 60 seconds. Elastic modulus was measured continuously for 5 minutes from the start of light activation. Development of elastic modulus was assessed for six different light power densities and two reduced power density levels given at longer exposure duration to provide similar energy density values. One-way analysis of variance with Tukey's post hoc comparison test was used to evaluate significant differences of elastic modulus at p = .05. RESULTS: The rates of elastic modulus development and final moduli were dependent on the light power density applied. Composite specimens cured by equivalent energy densities using short times and high power density or long times and low power density produced equivalent elastic moduli. Elastic moduli for emitted power densities between 400 and 600 mW/cm2 (160-260 mW/cm2 measured at the specimen surface) were not significantly different (p > .05). CONCLUSIONS: Light power densities greater than 160 mW/cm2 measured at the specimen surface resulted in elastic moduli that were not significantly different. Equivalent energy densities produced comparable elastic moduli.

Analysis of Variance↗

Power flow in the equine forelimb.

A method is described for the estimation of segmental powers and power flow during the stance phase in the equine forelimb, to demonstrate the sources and paths of energy flow through the limb segments. S-VHS video and force platform data were collected for 5 walking trials in a sound Dutch Warmblood horse. Two camera views were combined using direct linear transformation and the resultant sagittal plane positional and angular data used together with the vertical and cranio-caudal ground reaction forces to calculate moments about the ends of the 4 lowermost segments of the forelimb, and the reaction forces at the segment ends. Power flows were calculated across the proximal and distal ends of each segment and total segmental power computed. During initial and terminal stance, power flowed into the cannon segment proximally, and out distally. For the rest of stance, the flow in the cannon was distal to proximal. At the pastern, power flowed in proximally during initial loading, and out distally. For most of the rest of stance, the pattern of flow was distal to proximal, except for terminal stance, when power flowed in through both ends. The largest effect at the hoof is a loss of energy in terminal stance as power flowed out proximally and into the pastern. The pastern appears to receive most of the energy during loading and pushoff and transfers this energy up the limb during midstance.

Animals↗

Influence of training on autonomic nervous function in horses: evaluation by power spectral analysis of heart rate variability.

We studied the influence of training on autonomic nervous function in the horse. For this purpose, Holter electrocardiogram (ECG) was recorded before and after training from 24 Thoroughbred horses (2-year-olds) and autonomic nervous function was evaluated by the power spectral analysis of heart rate (HR) variability. We obtained HR, low-frequency (LF) power, high-frequency (HF) power, and LF/HF ratio from recording. We set LF at 0.01-0.07 Hz and HF at 0.07-0.6 Hz. The HF power is thought to reflect primarily parasympathetic nervous function. Both the sympathetic and parasympathetic nervous systems have been shown to contribute to the LF power. The LF/HF ratio is considered as an index of the cardiac sympathovagal balance. Second degree atrioventricular blocks were found in the ECG of 3 and 5 horses before and after the training period, respectively. Ventricular premature depolarisations were detected in a horse after the training period. Heart rate decreased at night. The lowest HR values had a tendency to appear in the early morning. Both the LF and HF power tended to be higher at night. However, the LF/HF ratio was almost the same throughout the day. The HR was significantly decreased by training. Although the LF power and LF/HF ratio were significantly increased, the HF power was not changed by training. These results suggest that parasympathetic nervous activity may be fully activated even before training in this species.

Animals↗

Non-linear relationship between O2 uptake and power output at high intensities of exercise in humans.

1. A slow component to pulmonary oxygen uptake (VO2) is reported during prolonged high power exercise performed at constant power output at, or above, approximately 60% of the maximal oxygen uptake. The magnitude of the slow component is reported to be associated with the intensity of exercise and to be largely accounted for by an increased VO2 across the exercising legs. 2. On the assumption that the control mechanism responsible for the increased VO2 is intensity dependent we hypothesized that it should also be apparent in multi-stage incremental exercise tests with the result that the VO2-power output relationship would be curvilinear. 3. We further hypothesized that the change in the VO2-power output relationship could be related to the hierarchical recruitment of different muscle fibre types with a lower mechanical efficiency. 4. Six subjects each performed five incremental exercise tests, at pedalling rates of 40, 60, 80, 100 and 120 rev min-1, over which range we expected to vary the proportional contribution of different fibre types to the power output. Pulmonary VO2 was determined continuously and arterialized capillary blood was sampled and analysed for blood lactate concentration ([lactate]b). 5. Below the level at which a sustained increase in [lactate]b was observed pulmonary VO2 showed a linear relationship with power output; at high power outputs, however, there was an additional increase in VO2 above that expected from the extrapolation of that linear relationship, leading to a positive curvilinear VO2-power output relationship. 6. No systematic effect on the magnitude or onset of the 'extra' VO2 was found in relation to pedalling rate, which suggests that it is not related to the pattern of motor unit recruitment in any simple way.

Adult↗

Age-related differences in muscle power during single-step balance recovery.

The purpose of this study was to investigate age-related differences in muscle power during a surrogate task of trip recovery. Participants included 10 healthy young men (19-23 years old) and 10 healthy older men (65-83). The task involved releasing participants from a forward-leaning posture. After release, participants attempted to recover their balance using a single step of the right foot. Muscle power at the hip, knee, and ankle of the stepping limb were determined from the product of joint angular velocity and joint torque. Muscle powers during balance recovery followed a relatively consistent pattern in both young and older men, and showed effects of both lean and age. Interestingly, the effects of age did not always involve smaller peak power values in the older men as expected from the well-documented loss of muscle power with aging. Older men exhibited smaller peak muscle power at the knee and larger peak muscle power at the ankle and hip compared to young men. The increases in muscle power at the ankle and hip may result from a neuromuscular adaptation aimed at improving balance recovery ability by compensating for the age-related loss of muscle function.

Adult↗

Muscle power predicts freestyle swimming performance.

The purpose of this study was to determine the relationship between non-invasive laboratory measures of 'muscle power' and swim performance over sprint (50 m) and middle-distance (400 m) events. Twenty-two swimmers performed an upper and lower body Wingate Anaerobic Test (WAT) and a maximal sustained power output test (MPO) for the upper body. Peak power (PP) and mean power (MP) were determined for the WAT, while peak sustained workload (WLpeak) was determined for the MPO. Timed swims over 50 m and 400 m were undertaken by all swimmers during which the number of arm strokes per length was recorded. Highly significant relationships were found between sprint-swim speed (S50) and mean power of the arms (MP(arms)) (r = 0.63, P less than 0.01), between S50 and mean power of the legs (MP(legs)) (r = 0.76, P less than 0.001) and between S50 and the distance covered with each arm stroke (DS) (r = 0.91, P less than 0.001). Multiple regression analyses revealed that WAT power indices for the legs did not significantly increase explained variance in S50 above that of the arms. The relationship between WL(peak) and S400 was highly significant (r = 0.70, P less than 0.001) and indicates the importance of arm power in the longer distance swim events.

Adolescent↗

Time course of changes in bilateral arm power of swimmers during recovery from injury using a swim bench.

OBJECTIVES: There has been little research on the time course of recovery from injury in athletes. This is especially the case for recovery in arm power in injured swimmers. The purpose of this study was to compare the power output of the injured and non-injured arms of swimmers during recovery from injury by use of a maximal exercise test on a computer interfaced isokinetic swim bench. METHODS: Thirteen swimmers (five men and eight women; age 18.8 (3.2) years; stature 1.76 (0.05) m; body mass 61.7 (5.9) kg; mean (SD)) gave written informed consent and were recruited to this study throughout a three year period. All subjects had experienced non-aquatic soft tissue injury to their dominant-side shoulder or upper arm in the three months before participation, but had been allowed to return to swimming training. All of the subjects had injured their dominant arm and the mean time for absence from training was 3.7 (1.1) weeks. At return to training and at four, eight, and twelve weeks thereafter, subjects performed two all-out 30 second tests on the swim bench by simulating the swimming arm action. From these tests, peak power output (PPO), mean power output (MPO), and power decay (PD) for each arm during the 30 seconds of exercise could be determined by averaging the two tests. The differences between return to training and the four, eight, and twelve week periods were analysed using repeated measures analysis of variance with Tukey b post hoc test. RESULTS: The repeated testing showed 95% confidence intervals of +/- 11.4 W for PPO, +/- 9.5 W for MPO and +/- 0.5 for PD. When the swimmers returned to training the results showed that PPO was 179 (21.9) v 111 (18.1) W (P = 0.02), MPO was 122 (9.8) v 101 (8.8) W (P = 0.01), and PD was 2.5 (0.6) v 5.2 (1.9) (P = 0.001) for non-injured and injured arms respectively (all values mean (SEM)). There were similar differences at four weeks which disappeared after eight weeks, except for that of PPO which was still evident (187.3 (21.9) v 156.8 (18.1) W; P = 0.01). At 12 weeks there were no differences between the non-injured and injured arm on any of the indices of arm power (P > 0.05). CONCLUSIONS: These results suggest that, using the swim bench power test, differences in bilateral arm power output after injury persist for at least eight weeks after return to swimming training. These findings support the need for prolonged rehabilitation after such injury. This would best include physiotherapy and a training programme within which special consideration is given to the recuperation process.

Adolescent↗

Statistical power of MRI monitored trials in multiple sclerosis: new data and comparison with previous results.

OBJECTIVES: To evaluate the durations of the follow up and the reference population sizes needed to achieve optimal and stable statistical powers for two period cross over and parallel group design clinical trials in multiple sclerosis, when using the numbers of new enhancing lesions and the numbers of active scans as end point variables. METHODS: The statistical power was calculated by means of computer simulations performed using MRI data obtained from 65 untreated relapsing-remitting or secondary progressive patients who were scanned monthly for 9 months. The statistical power was calculated for follow up durations of 2, 3, 6, and 9 months and for sample sizes of 40-100 patients for parallel group and of 20-80 patients for two period cross over design studies. The stability of the estimated powers was evaluated by applying the same procedure on random subsets of the original data. RESULTS: When using the number of new enhancing lesions as the end point, the statistical power increased for all the simulated treatment effects with the duration of the follow up until 3 months for the parallel group design and until 6 months for the two period cross over design. Using the number of active scans as the end point, the statistical power steadily increased until 6 months for the parallel group design and until 9 months for the two period cross over design. The power estimates in the present sample and the comparisons of these results with those obtained by previous studies with smaller patient cohorts suggest that statistical power is significantly overestimated when the size of the reference data set decreases for parallel group design studies or the duration of the follow up decreases for two period cross over studies. CONCLUSIONS: These results should be used to determine the duration of the follow up and the sample size needed when planning MRI monitored clinical trials in multiple sclerosis.

Adolescent↗

Power outputs of slow and fast skeletal muscles of mice.

The purpose of this study was to contrast the frequency-power relationship of slow soleus and fast extensor digitorum longus (EDL) muscles to their frequency-force relationships and to investigate factors involved in the development of maximum power during a single contraction. Stimulation frequency-force and stimulation frequency-power relationships were determined for soleus and EDL muscles of the mouse for single contractions in situ at 35 degrees C. Power was measured during isovelocity shortening contractions with displacement through 10% of fiber length at the optimum velocity. Optimum velocity was defined as the shortening velocity for the generation of maximum power for a given stimulation frequency. Both force (N/cm2) and power (watts/kg) increased with stimulation frequency until a plateau was reached. For the frequency-force relationship, the curve for soleus muscles was merely shifted to the left of that for EDL muscles. In contrast, the power developed by EDL muscles was greater than that of soleus muscles (P less than 0.05) at each stimulation frequency. The higher power was a direct consequence of higher optimum velocities for EDL muscles compared with soleus muscles.

Animals↗

Effect of fatigue on maximal power output at different contraction velocities in humans.

The effect of fatigue as a result of a standard submaximal dynamic exercise on maximal short-term power output generated at different contraction velocities was studied in humans. Six subjects performed 25-s maximal efforts on an isokinetic cycle ergometer at five different pedaling rates (60, 75, 90, 105, and 120 rpm). Measurements of maximal power output were made under control conditions [after 6 min of cycling at 30% maximal O2 uptake (VO2max)] and after fatiguing exercise that consisted of 6 min of cycling at 90% VO2max with a pedaling rate of 90 rpm. Compared with control values, maximal peak power measured after fatiguing exercise was significantly reduced by 23 +/- 19, 28 +/- 11, and 25 +/- 11% at pedaling rates of 90, 105, and 120 rpm, respectively. Reductions in maximum peak power of 11 +/- 8 and 14 +/- 8% at 60 and 75 rpm, respectively, were not significant. The rate of decline in peak power during the 25-s control measurement was least at 60 rpm (5.1 +/- 2.3 W/s) and greatest at 120 rpm (26.3 +/- 13.9 W/s). After fatiguing exercise, the rate of decline in peak power at pedaling rates of 105 and 120 rpm decreased significantly from 21.5 +/- 9.0 and 26.3 +/- 13.9 W/s to 10.0 +/- 7.3 and 13.3 +/- 6.9 W/s, respectively. These experiments indicate that fatigue induced by submaximal dynamic exercise results in a velocity-dependent effect on muscle power. It is suggested that the reduced maximal power at the higher velocities was due to a selective effect of fatigue on the faster fatigue-sensitive fibers of the active muscle mass.

Adult↗

Within-night variation in respiratory effort preceding apnea termination and EEG delta power in sleep apnea.

We studied the within-night variability of the maximum esophageal pressure deflection before apnea termination (DPmax) in nine patients with severe obstructive sleep apnea as an index of the arousal threshold and the mean electroencephalogram (EEG) delta power for each 30 s as an index of the timing of sleep cycles. Periodicity in the time variation of delta power and DPmax was analyzed by determining their power spectral density and their relationship determined by cross correlation. DPmax and delta power varied cyclically and in phase with a major periodicity (major peak in power spectral density) of 117.6 +/- 8.8 (SE) min. The correlation between the values of DPmax and delta power was significant (P < 0.001) in each subject (mean r = 0.47 +/- 0.03), and the coherence between DPmax and delta power at their dominant frequency was high. Within cycles of non-rapid-eye-movement sleep, DPmax and delta power increased, reaching peak values on average at or after midcycle. These findings suggest that the arousal threshold to airway occlusion in patients with obstructive sleep apnea varies cyclically during the night synchronous to the underlying cycles of sleep.

Activity Cycles↗

Improving trial power through use of prognosis-adjusted end points.

BACKGROUND AND PURPOSE: The stroke patient population is heterogeneous, leading to wide variation in outcome caused by differences in age, initial severity, and presence of concomitant disease. Setting an identical recovery target for all patients in intervention trials may conceal individually important therapeutic treatment effects. Instead, a variable end point that takes severity or likely prognosis into account may be more informative. METHODS: We used data from the Glycine Antagonist in Neuroprotection (GAIN) International trial to assess statistical power of various primary end points for intervention trials. We selected prognosis-adjusted cut points based on Barthel Index (BI) or Rankin Scale (RS) using a prognostic model, or assigned a fixed end point within subgroups of patients defined by their Oxford category or National Institutes of Health Stroke Scale (NIHSS) score. We simulated a treatment effect and estimated statistical power with standard formulae. RESULTS: Assignment of end points using a prognostic model for individual patients increased statistical power, when compared with assigning end points using only the Oxford classification. For the BI, power was increased from 60% to 88% (equivalent to a 49% reduction in sample size if power remains unchanged). With the RS end points, power was increased from 84% to 92% (or a 24% reduction in sample size). Versus a fixed end point for all patients, model-based methods increased power by 22 percentage points for BI> or =95 and 14 percentage points for RS< or =1 (effective sample size reductions 43% and 34%). CONCLUSIONS: Prognosis-adjusted end points can increase statistical power compared with fixed end points. Assessment is based on realistic goals for individual patients and yet trial results remain generalizable.

Age Factors↗

Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials.

Inhomogeneous patient samples have been used in previous studies to determine the power of magnetic resonance imaging (MRI) for trial monitoring in multiple sclerosis (MS). These power-calculations might not be applicable to the active relapsing-remitting patient who is preferably included in trials. In order to reevaluate the power-calculations for MRI in the monitoring of treatment in strictly relapsing-remitting MS and to compare the power of different trial designs we studied 12 relapsing-remitting MS patients prospectively for a median period of 12 months using monthly clinical assessments and gadolinium-enhanced MRI. A median number of two clinical relapses/patient occurred of which a median of one was treated with steroids. A median of 1.59 new lesions/scan/patient was detected (range 0-8). The total number of new active lesions correlated significantly with study period relapses (SRCC = 0.72, P = 0.023). Computer simulations using the bootstrap technique yielded mostly lower power values for a parallel groups design than in previous studies except for short follow-periods in larger samples. In this-sample the open cross-over design was found to be between 20 and 40% more powerful. Results of power-calculations are clearly sample dependent implying that for treatment trial monitoring using MRI in relapsing-remitting MS conservative sample size estimates are to be used. In an active patient group open cross-over trial designs could be a very powerful alternative to parallel groups design.

Adult↗

Power and sample size calculations in the presence of phenotype errors for case/control genetic association studies.

BACKGROUND: Phenotype error causes reduction in power to detect genetic association. We present a quantification of phenotype error, also known as diagnostic error, on power and sample size calculations for case-control genetic association studies between a marker locus and a disease phenotype. We consider the classic Pearson chi-square test for independence as our test of genetic association. To determine asymptotic power analytically, we compute the distribution's non-centrality parameter, which is a function of the case and control sample sizes, genotype frequencies, disease prevalence, and phenotype misclassification probabilities. We derive the non-centrality parameter in the presence of phenotype errors and equivalent formulas for misclassification cost (the percentage increase in minimum sample size needed to maintain constant asymptotic power at a fixed significance level for each percentage increase in a given misclassification parameter). We use a linear Taylor Series approximation for the cost of phenotype misclassification to determine lower bounds for the relative costs of misclassifying a true affected (respectively, unaffected) as a control (respectively, case). Power is verified by computer simulation. RESULTS: Our major findings are that: (i) the median absolute difference between analytic power with our method and simulation power was 0.001 and the absolute difference was no larger than 0.011; (ii) as the disease prevalence approaches 0, the cost of misclassifying a unaffected as a case becomes infinitely large while the cost of misclassifying an affected as a control approaches 0. CONCLUSION: Our work enables researchers to specifically quantify power loss and minimum sample size requirements in the presence of phenotype errors, thereby allowing for more realistic study design. For most diseases of current interest, verifying that cases are correctly classified is of paramount importance.

Alzheimer Disease↗