Effects Of Different Magnitudes Research Articles

Acute Metabolic Changes with Lower Leg-Positioned Wearable Resistances during Submaximal Running in Endurance-Trained Runners.

The aim of this study was to determine the acute metabolic effects of different magnitudes of wearable resistance (WR) attached to the lower leg during submaximal running. Fifteen endurance-trained runners (37.8 ± 6.4 years; 1.77 ± 0.7 m; 72.5 ± 9.8 kg; 58.9 ± 7.4 L/min VO2max; 45.7 ± 5.8 min 10 K run time) completed seven submaximal running trials with WR loads of 0, 0.5, 1, 1.5, 2, 2.5 and 3% body mass (BM). Based on regression data, for every 1% BM increase of additional load, oxygen consumption (VO2) increased by 2.56% and heart rate increased by 1.16%. Inferential based analysis identified that ≤1% BM were enough to elicit responses in VO2, with a possible small increase (effect size (ES), 90% confidence interval (CI): 0.22, 0.17 to 0.39), while 3% BM loads produced a most likely very large increase (ES, 90% CI: 0.51, 0.42 to 0.60). A training load score was extrapolated using heart rate data to determine the amount of internal stress. An additional 1% BM resulted in an extra 0.39 (0.29 to 0.47) increase in internal stress over five minutes. Lower leg WR elicited substantial increases in lactate production from the lightest loading (0.5% BM), with a likely moderate increase (ES, 90% CI: 0.49, 0.30 to 0.95). Lower-leg positioned WR provides a running-specific overload with loads ≥ 1% BM resulting in substantial changes in metabolic responses.

Quantifying the hydrodynamic impacts of cumulative sand mining on a large river-connected floodplain lake: Poyang Lake

Sand mining has significant impacts on the hydrological and hydrodynamic regimes of river-lake systems. Recently, continuous sand mining has occurred in Poyang Lake, a large floodplain lake connected to the Yangtze River. Previous studies on the impact of sand mining in Poyang Lake focused on water level variations. However, the influence of different magnitudes of sand mining on the hydrological and hydrodynamic regimes in such a complex river-lake floodplain system is unclear. The current study aims to address this issue by combining a hydrodynamic model and hydrological data. Based on average conditions (2000–2010), the influences of 1–4 m uniform sand mining in the northern lake on water levels and outflows were quantified, and the spatial and temporal impacts of cumulative sand mining (1998–2010) on current speeds and residence times were further assessed. The results showed that the elevations of the thalwegs in the northern outlet channels decreased unevenly from 1998 to 2010. The water levels decreased cumulatively but nonlinearly with increasing sand mining. Mining 1–4 m of sand caused cumulative water level decreases of 0.55–2.14 m in the northern channels when the water levels were lower than 14 m. Due to cumulative sand mining from 1998 to 2010, the current speeds in the northern mining channels generally decreased, and those in the central channels mostly increased, with the majority varying from −0.4 to 0.4 m/s. The residence time changes were opposite to the current speed changes, with −4 to 10 day variations. The opposite outflow variations between uniform mining and realistic uneven mining indicated that outflow variations depended on the mining magnitudes and bed slope changes. The above results suggested that for this river-connected floodplain lake, sand mining in outlet channels enhanced the spatial and temporal heterogeneity of the lake hydrodynamics and that the blocking effect of the connected large river impacted the hydrodynamic variation patterns. This study leads to better understanding of the effects of different magnitudes of sand mining on the hydrologic and hydrodynamic regimes in Poyang Lake and provides a reference for quantifying similar human activities in complex floodplain lakes.

Acute Metabolic Changes with Thigh-Positioned Wearable Resistances during Submaximal Running in Endurance-Trained Runners

The aim of this study was to determine the acute metabolic effects of different magnitudes of wearable resistance (WR) attached to the thigh during submaximal running. Twenty endurance-trained runners (40.8 ± 8.2 years, 1.77 ± 0.7 m, 75.4 ± 9.2 kg) completed six submaximal eight-minute running trials unloaded and with WRs of 1%, 2%, 3%, 4% and 5% body mass (BM), in a random order. The use of a WR resulted in a 1.6 ± 0.6% increase in oxygen consumption (VO2) for every 1% BM of additional load. Inferential based analysis found that the loading of ≥3% BM was needed to elicit any substantial responses in VO2, with an increase that was likely to be moderate in scale (effect size (ES) ± 90% confidential interval (CI): 0.24 ± 0.07). Using heart rate data, a training load score was extrapolated to quantify the amount of internal stress. For every 1% BM of WR, there is an extra 0.17 ± 0.06 estimated increase in training load. A WR ≥3% of BM was needed to elicit substantial responses in lactate production, with an increase which was very likely to be large in scale (ES ± 90% CI: 0.41 ± 0.18). A thigh-positioned WR provides a running-specific overload with loads ≥3% BM, resulting in substantial changes in metabolic responses.

Effects of environmental flows in a restored floodplain system on the community composition of fish, macroinvertebrates and macrophytes

Floodplains were extensively altered by anthropogenic activities, resulting in modified flow dynamics essential for maintaining diverse riverine communities. There is growing interest in restoring environmental flows by artificially modulating discharge as a potential management option in regulated rivers. In the context of a large floodplain restoration project along the upper Danube, the effects of different magnitudes of discharge on fish, macroinvertebrates and macrophytes in different habitat types of the floodplain system were studied. Community composition of fishes and macroinvertebrates changed after peak-flows of up to a 20-fold increase of mean discharge, whereas species richness and coverage of macrophytes were hardly affected. Over all habitat types, similar community response patterns were evident for macroinvertebrates, whereas in fishes, the most pronounced changes occurred in floodplain ponds that only become connected to the main channel at high flows. Community changes for fish and macroinvertebrates were mostly attributed to higher numbers of individuals (3-fold increase for fishes) rather than to changes of species richness (maximum fish species richness change <10%), however, rheophilic specialists such as Barbus barbus were much more abundant after e-flows. These findings suggest that environmental flows can have meaningful and desired conservation effects on the aquatic community composition of fishes and macroinvertebrates, depending on the magnitude of the flow and on the specific habitat type. They also stress the importance of managing dynamic flow regimes that must comprise both minimum low flows as well as flood extremes to sustain freshwater biodiversity of high conservation value.

Generational Mean Analysis of Salt Tolerance during Osmotic Phase in Maize Seedling

This study details the nature and magnitude of the genetic effects associated with various quantitative characters (morphological and hydric relations) measured in maize seedlings during the osmotic phase of saline stress (100 mM NaCl). Three lines with differential behavior in salt stress: SC2 (tolerant), AFE (susceptible) and LP3 (moderately tolerant) were used to obtain contrasting crosses (SC2 × AFE) and (SC2 × LP3). An analysis of six generational means (P1, P2, F1, F2, BC1 and BC2) was applied for each cross. First a scaling test was applied and then a three and six-parameter genetic models were used to estimate various genetic components. In none of the traits studied there was evidence of adequacy to the three parameter model, which indicates important epistatic effects in genetic expression. The dominant genetic effects were greater than the additive ones for all the characters evaluated. LG showed positive and significant differences for [h] in both crosses, indicating the presence of hybrid vigor and its possible use in the improvement. Low value of [d] and high of [h] both significant in SC2 × AFE, indicates existence of genes dispersion between the parental lines. While, for the cross SC2 × LP3, the low and significant value of [d] and not significant value of [h], indicate greater genetic similarity. In the SC2 × LP3 cross, the negative interaction [l] confirms ambidirectional dominance, while for SC2 × LP3 the positive sign indicates directional dominance. The analysis of tolerance to salinity in the osmotic phase showed a complex polygenic inheritance for the traits used, determined by simple and interaction effects of different magnitudes and significance according to the cross considered.

The calcium transient characteristics induced by fluid shear stress affect the osteoblast proliferation

Ca2+ signaling is essential for bone metabolism. Fluid shear stress (FSS), which can induce a rapid release of calcium from endoplasmic reticulum (ER) to produce calcium transients, plays a significant role in osteoblast proliferation and differentiation. However, it is still unclear of how calcium transients induced by FSS activating a number of downstream signals which subsequently regulate cell functions. In this study, we performed a group of Ca2+ transients models, which were induced by FSS to investigate the effects of different magnitudes of Ca2+ transients in osteoblast proliferation. Further, we performed a global proteomic profile of MC3T3-E1 cells in different Ca2+ transients models stimulated by FSS. GO enrichment and KEGG pathway analysis revealed that the TCA cycle was activated in the proliferating process. The activation of TCA needed mitochondrial Ca2+ uptake which were influenced by the amplitude of Ca2+ transients induced by FSS. Our work elucidate that osteoblast proliferation induced by FSS was related to the magnitude of calcium transients, which further activated energetic metabolism signaling pathway. This work revealed further understanding the mechanism of osteoblast proliferation induced by mechanic loading and help us to design new methods for osteoporosis therapy.

Effects of consonant voicing on vocalic segment duration across resonants and prosodic boundaries

Most languages, and especially English, reduce the duration of vocalic segments before voiceless obstruents relative to voiced ones. Previous studies examined this effect for final singleton consonants in tauto- and heterosyllabic contexts within a word. Here, monosyllabic words are examined for the effect both across resonants (e.g., “code”/”coat” vs. “cold”/”colt”) and across word boundaries and stress conditions (e.g., “no CODE”/”NO code” vs. “no GOAD”/”NO goad”). Preliminary results showed a typical effect for singleton stops, with vocalic segment reduced 33.6% for the voiceless stop. Vocalic segments were somewhat reduced with an intervening resonant (26.4%) but the resonance itself was more reduced (57.3%); vocalic segment and resonance were approximately the same duration as the vocalic segments alone in singleton syllables. The vocalic segment of “no” decreased slightly with following voiceless stop (8.2% when unstressed, 10.2% when stressed); this was smaller than other studies’ effect across syllable boundaries within words. The results indicate that the word and syllable structure impose timing effects of different magnitudes on both vowels and resonants due to voicing of an adjacent stop. It is surprising that the effect occurs across word boundaries and further that stress makes little difference. [Work supported by NIH grant DC-002717.]

Time‐dependent velocity‐field controls on anomalous chemical transport in porous media

AbstractTemporal variations in the subsurface velocity field are often (if not always) present in the real world to at least some degree. However, an accounting of their effects on chemical transport has been largely neglected. Here we demonstrate experimentally the effects of a time‐varying velocity field on conservative chemical tracer transport in porous media, as compared to constant velocity conditions. We find that velocity‐field fluctuations increase chemical tracer spreading and residence time, which intensify the anomalous nature of the transport. This behavior is modeled by a continuous time random walk particle tracking method formulated to account for time‐dependent velocity fields. The model matches the experimental results with a parsimonious and consistent set of parameters. The model is then applied to study the effects of different magnitudes in velocity‐field fluctuations, as well as different degrees of porous media heterogeneity, on 1‐D and 2‐D spatiotemporal propagation of an injected, point‐source, chemical plume. Increased intensity of velocity‐field fluctuations, and increased porous medium heterogeneity, each serve to increase the extent of chemical spreading and anomalous behavior.

Increased Fatigue Response to Augmented Deceptive Feedback during Cycling Time Trial.

This study aimed to investigate the effect of different magnitudes of deception on performance and exercise-induced fatigue during cycling time trial. After three familiarization visits, three women and eight men performed three 5-km cycling time trials while following a simulated dynamic avatar reproducing either 100% (5K100%), 102% (5K102%), or 105% (5K105%) of the subject's previous fastest trial. Quadriceps muscle activation was quantified with surface electromyography. Fatigue was quantified by preexercise to postexercise (10 s through 15 min recovery) changes in quadriceps maximal voluntary contraction (MVC) force, potentiated twitch force evoked by electrical femoral nerve stimulation (QTSingle) and voluntary activation (VA, twitch interpolation technique). Greater quadriceps muscle activation in 5K102% versus 5K100% (12% ± 11%) was found in parallel with a 5% ± 2% and 2% ± 1% improvement in power output and completion time, respectively (P < 0.01). Exercise-induced reduction in MVC force and VA were 14% ± 19% and 28% ± 31% greater at exercise termination (at 10 s), whereas QTSingle recovery (from 10 s to 15 min) was 5% ± 5% less in 5K102% versus 5K100% (P < 0.01). No difference in performance or fatigue indices measured at exercise termination was found between 5K100% and 5K105%. Muscle activation and performance improvements during a deceptive cycling time trial were achieved only with a 2% magnitude of deception and were associated with a further impairment in MVC force, QTSingle recovery and VA compared to control. Performance improvement during cycling time trial with augmented deceptive feedback therefore resulted in exacerbated exercise-induced peripheral and central fatigue.

Exploring the performance reserve: Effect of different magnitudes of power output deception on 4,000 m cycling time-trial performance.

PurposeThe aim of the present study was to investigate whether a magnitude of deception of 5% in power output would lead to a greater reduction in the amount of time taken for participants to complete a 4000 m cycling TT than a magnitude of deception of 2% in power output, which we have previously shown can lead to a small change in 4000 m cycling TT performance.MethodsTen trained male cyclists completed four, 4000 m cycling TTs. The first served as a habituation and the second as a baseline for future trials. During trials three and four participants raced against a pacer which was set, in a randomized order, at a mean power output equal to 2% (+2% TT) or 5% (+5% TT) higher than their baseline performance. However participants were misled into believing that the power output of the pacer was an accurate representation of their baseline performance on both occasions. Cardiorespiratory responses were recorded throughout each TT, and used to estimate energy contribution from aerobic and anaerobic metabolism.ResultsParticipants were able to finish the +2% TT in a significantly shorter duration than at baseline (p = 0.01), with the difference in performance likely attributable to a greater anaerobic contribution to total power output (p = 0.06). There was no difference in performance between the +5% TT and +2% TT or baseline trials.ConclusionsResults suggest that a performance reserve is conserved, involving anaerobic energy contribution, which can be utilised given a belief that the exercise will be sustainable however there is an upper limit to how much deception can be tolerated. These findings have implications for performance enhancement in athletes and for our understanding of the nature of fatigue during high-intensity exercise.

Optimal measurements of hemodynamic response latency in fNIRS using the jackknife approach.

Functional near-infrared spectroscopy (fNIRS) permits measurements of changes in the concentration of oxygenated and deoxygenated hemoglobin, typically with a higher sampling rate than with other imaging methods based on the hemodynamic response. We examined the potential of the fNIRS technique to estimate variations in the latency of hemodynamic responses to experimental events and sought optimal methods to maximize the reliability and reproducibility of latency effects. We used Monte Carlo simulations using subsamples of real fNIRS measures to estimate the statistical power of different approaches (such as fixed threshold, percent of peak, fractional-area latency, for both individual-subject estimates and estimates from jackknife averages) to detect a known simulated latency shift. The simulations used measures of hemodynamic responses in the temporal lobe from two groups of young adult participants who listened to auditory stimuli, one with a blocked presentation design and one with an event-related design. We estimated the relative sensitivity of different latency measures and approaches to the measurement of latency effects of different magnitudes using realistic noise and signal-to-noise characteristics. In general, the jackknife approach provided the greatest statistical power to detect a known latency shift, without inflation of Type I error.

Maintaining a clinical weight loss after intensive lifestyle intervention is the key to cardiometabolic health

Intensive lifestyle interventions (ILI) are criticised for ineffective obesity treatment because weight loss over time is modest and thus of limited clinical relevance. However, a subgroup (5-30%) maintains a clinical weight loss >10%, but it is not clear if cardiometabolic health follows this pattern. The aim was to study the effect of different magnitudes of weight loss maintenance after ILI on cardiometabolic health. Eighty out of 2420 former participants (age: 36±1, BMI: 38±1, (means ±SE)) in an 11-12-week ILI were recruited into 3 groups; clinical weight loss maintenance (>10% weight loss), moderate maintenance (1-10%), and weight regain based on weight loss at follow-up (5.3±0.4years). Weight loss during the ILI was achieved by increased physical activity and hypo-caloric diet. Dual X-ray Absorptiometry, blood sample, skeletal muscle biopsy and VO2max test were used to determine cardiometabolic health at follow-up. At follow-up, the clinical weight loss maintenance group scored better in the following variables compared to the other groups: BMI (31±1, 33±2, 43±2kg/m2), composition (34±2, 40±1, 49±1% fat), visceral adipose tissue (0.8±0.2, 1.7±0.5, 2.4±0.4kg), plasma triglycerides (0.8±0.2, 1.3±0.4, 1.6±0.3mmol/L), plasma glucose (4.9±0.1, 5.9±0.4, 5.9±0.1mmol/L), Hb1Ac (5.1±0.0, 5.6±0.2, 5.8±0.2%), protein content in skeletal muscle of GLUT4 (1.5±0.2, 0.9±0.1, 1.0±0.1 AU) and hexokinase II (1.6±0.2, 1.0±0.2, 0.7±0.1 AU), citrate synthase activity (155±6, 130±5, 113±5μmol/g/min) and VO2max (49±1, 43±1, 41±1mL/min/FFM) (p<0.05). Cardiometabolic health is better in participants who have maintained >10% weight loss compared to moderate weight loss and weight regain.

Effects of Different Magnitudes of Whole-Body Vibration on Dynamic Squatting Performance.

The purpose of this study was to examine the effects (a) of different whole-body vibration (WBV) accelerations when applied simultaneously during a set of squats on performance and perceived exertion and (b) of different linear increases and decreases of vibrations during the squats. It is a randomized, crossover experimental design. Undergraduate students (3 female; 16 male) participated. Each participant completed 5 laboratory sessions in this study (4 familiarization and 1 test session). The test session then had each participant complete one 20-second set of dynamics quarter-squats for 5 separate conditions followed by 5 minutes of rest. Squatting was performed at maximum speed from full extension knee with plantar-flexion ankle to a knee angle of 70° (0° = anatomic position) with dorsiflexion ankle. All sets were performed on the WBV platform in random order, where the 5 different conditions were (a) no WBV-sham, (b) 30 Hz (30 Hz low amplitude), (c) 50 Hz (50 Hz high amplitude), (d) 30-50 Hz (increasing frequency from 30 to 50 Hz; 1 Hz per second with high amplitude), and (e) 50-30 Hz (decreasing frequency from 50 to 30 Hz; 1 Hz per second). There was a significant decrease in the mean velocity of squatting performed during the 30- to 50-Hz condition compared with all other conditions (p ≤ 0.05). There were a significantly lower amount of repetitions performed during the 30- to 50-Hz exposure compared with the no-WBV and 30-Hz conditions. There was a significantly lower Rating of Perceived Exertion (RPE) during the 30-Hz condition compared with the no-WBV, 50-Hz, 30-50-Hz, and 50-30-Hz conditions.

Does size matter? The effect of different magnitudes of prismatic adaptation on perceptual and motor biases.

Does size matter? The effect of different magnitudes of prismatic adaptation on perceptual and motor biases.

Three-dimensional phase-field simulation of microstructural evolution in three-phase materials with different diffusivities

The coarsening behavior of three-phase materials, such as eutectic material systems, is of high technological interest. Microstructure evolution simulations can help to understand the effect of different magnitudes of the diffusivities in the different phases. In this study, the evolution of a 3D three-phase morphology was modeled with equal interfacial energy and volume fraction and similar thermodynamic properties for the three phases, but the diffusion mobilities were taken different. It was observed that the phase with the lowest mobility has the highest growth rate and, on average, a larger number of grain faces, while the other two phases have a nearly equal growth rate and average number of grain faces. The simulation results are compared with results from experiments and simulation studies for single-phase and two-phase materials.

Quantifying the global carbon cycle response to volcanic stratospheric aerosol radiative forcing using Earth System Models

AbstractLarge volcanic eruptions can have a significant cooling effect on climate, which is evident in both modern and palaeo data. However, due to the difficulty of disentangling volcanic and other influences in the modern atmospheric CO2 record, and uncertainties associated with palaeo reconstructions of atmospheric CO2, the magnitude of the carbon cycle response to volcanically induced climatic changes is difficult to quantify. In this study, three Earth System Models (SIMEARTH, CLIMBER‐2, and CLIMBER LPJ) are used to simulate the effects of different magnitudes of volcanic eruption, from relatively small (e.g., Mount Pelée, 1902) to very large (e.g., the 1258 ice core event), on the coupled global climate‐carbon cycle system. These models each use different, but justifiable, parameterizations to simulate the global carbon cycle and climate. Key differences include how soil respiration and net primary productivity respond to temperature and atmospheric CO2. All models simulate global surface cooling in response to volcanic events. In response to a Mount Pinatubo‐equivalent eruption, the modelled temperature decrease is 0.3°C to 0.4°C and atmospheric CO2 decreases by 1.1 ppm to 3.4 ppm. The initial response time of climate to volcanic forcing and subsequent recovery time vary little with changes in the size of the forcing. Response times for vegetation and soil carbon are relatively consistent across forcings for each model. However, results indicate that there is significant uncertainty concerning the response of the carbon cycle to volcanic eruptions. Suggestions for future research directed at reducing this uncertainty are given.

Study of a spherical vibration-insensitive optical reference cavity

We have investigated the vibrational sensitivity of a horizontal-mounted spherical reference cavity, which can be applied to develop an ultra-stable laser. Effects of different magnitudes of height and area as well as acceleration of the cavity support points on the length variation of the cavity are studied. When the cavity support points are totally constrained, the vibration sensitivity can be reduced to below 3.0×10-10/g. After performing extensive numerical simulations, we can find the optimal support position. According to the obtained results we present the mounting scheme of the spherical cavity. Taking into consideration the machining errors, near-horizontal mounting, and unsymmetrical mounting of the cavity, we can describe quantitatively the length variation of the cavity caused by these three factors. We also discuss the contribution of the second order effect to the length variation of the cavity.

Body temperature control in patients with refractory septic shock: too much may be harmful

Background The lowering of body temperature is a common, almost reflexive step in the daily care of septic shock patient. However, the effect of different magnitudes of fever control on the outcome of refractory septic patients with a very poor outcome is controversial and has yet to be explored. Methods This prospective trial examined sixty-five refractory septic shock patients with a core temperature higher than 38.5°C. Patients were randomly assigned to a group achieving a “low temperature” range (LT group: 36.0-37.5 °C) or to a group achieving a “high temperature” range (HT group: 37.5-38.3 °C) by physical methods including a water-flow cooling blanket and ice packs. A target core temperature was achieved in 1-2 hours post-treatment, and maintained for 72 hours. Averaged values of core temperature as well as hemodynamic, respiratory, and laboratory variables were analyzed at baseline and during the first 72 hours after fever control. Results Thirty-four (52.31%) patients were assigned to the LT group and thirty-one (47.69%) patients were assigned to the HT group. The mean core temperature was significantly lower in the LT group than in the HT group (36.61 vs. 37.85 °C, respectively; P &lt; 0.0001). The average heart rate (HR) (75.5 vs. 91.9 beats/min, respectively; P &lt; 0.0001) and the mean cardiac output (CO) (5.35 vs. 6.45 L/min, respectively; P = 0.002) were also statistically significant lower in the LT group than in the HT group. The averaged serum lactate level was significantly higher in the LT group compared to the HT group (5.59 vs. 2.82 mmol/L, respectively; P=0.008). Fibrinogen and activated partial thromboplatin time were also different between the two groups. The 28 days mortality was significantly higher in the LT group than in the HT group (61.8 vs. 25.8%, respectively; P=0.003). A Cox-regression model analysis showed that mean core temperature during the 72 h period was an independent predictor of 28 days mortality (odds ratio (OR) = 0.42, 95%CI 0.25, 0.6; P=0.001). Conclusion Controlling fever to a lower range (36.0-37.5 °C) may be harmful to patients with refractory septic shock by worsening tissue perfusion, compared to controlling it within a higher range (37.5-38.3 °C). An understanding of the mechanisms responsible for these observations requires further investigation.

Investigation of free-spanned pipeline behavior due to axial forces and local loads

This paper presents an experimental study on the deformation behavior of pre-compression free-spanned steel tubular members under lateral loads due to an indenter. The tests were carried out on six similar pipes with an outer diameter of 139.9mm, a length of 2400mm and a thickness of 2.55mm, which are presented and discussed. The strains and deformations were determined in the local load-effected zone, and the effect of different magnitudes of compression pre-loading on the strength of samples against lateral load was investigated.The main advantage of the current investigation compared with those carried out previously and reported in literature is that both the pre-loading axial compression force and local load applied statically by an indenter are included experimentally in the study. From the results of the tests, it can be concluded that pre-loading has a marked effect on the lateral strength and deformation behavior of the pipes. Furthermore, finite element analyses for geometrically identical specimens are presented, and the analytical solutions are compared to the experimental results.

Estimating Genetic Effects and Quantifying Missing Heritability Explained by Identified Rare-Variant Associations

Next-generation sequencing has led to many complex-trait rare-variant (RV) association studies. Although single-variant association analysis can be performed, it is grossly underpowered. Therefore, researchers have developed many RV association tests that aggregate multiple variant sites across a genetic region (e.g., gene), and test for the association between the trait and the aggregated genotype. After these aggregate tests detect an association, it is only possible to estimate the average genetic effect for a group of RVs. As a result of the "winner's curse," such an estimate can be biased. Although for common variants one can obtain unbiased estimates of genetic parameters by analyzing a replication sample, for RVs it is desirable to obtain unbiased genetic estimates for the study where the association is identified. This is because there can be substantial heterogeneity of RV sites and frequencies even among closely related populations. In order to obtain an unbiased estimate for aggregated RV analysis, we developed bootstrap-sample-split algorithms to reduce the bias of the winner's curse. The unbiased estimates are greatly important for understanding the population-specific contribution of RVs to the heritability of complex traits. We also demonstrate both theoretically and via simulations that for aggregate RV analysis the genetic variance for a gene or region will always be underestimated, sometimes substantially, because of the presence of noncausal variants or because of the presence of causal variants with effects of different magnitudes or directions. Therefore, even if RVs play a major role in the complex-trait etiologies, a portion of the heritability will remain missing, and the contribution of RVs to the complex-trait etiologies will be underestimated.