Variability

变异性
  • 文章类型: Journal Article
    局部共振超材料(LRM)最近出现在寻找轻质噪声和振动解决方案中。这些材料具有产生阻带的能力,这是由相同谐振器的亚波长添加到主体结构中引起的,并导致强烈的振动衰减。然而,它们的制造不可避免地引入可变性,使得所制造的系统通常显著偏离原始的设计。这会降低衰减性能,但也可能扩大衰减带。这项工作的重点是谐振器特性公差范围内的可变性对超材料梁中振动衰减的影响。经过定性的预研究,两种非侵入式不确定性传播方法被用来找到三个性能指标的上限和下限,通过评估不确定性参数定义为区间变量的确定性超材料模型。使用全局搜索方法,并将其与基于机器学习(ML)的不确定性传播方法进行比较,从而大大减少了所需的模拟数量。发现谐振器刚度和质量的变化具有最高的影响。谐振器位置的变化仅对较不深的亚波长设计具有相当的影响。在宽带优化中利用了变化的谐振器特性的展宽潜力,并评估了优化的超材料的鲁棒性。本文是“弹性和声学超材料科学的当前发展(第2部分)”主题的一部分。
    Locally resonant metamaterials (LRMs) have recently emerged in the search for lightweight noise and vibration solutions. These materials have the ability to create stop bands, which arise from the sub-wavelength addition of identical resonators to a host structure and result in strong vibration attenuation. However, their manufacturing inevitably introduces variability such that the system as-manufactured often deviates significantly from the original as-designed. This can reduce attenuation performance, but may also broaden the attenuation band. This work focuses on the impact of variability within tolerance ranges in resonator properties on the vibration attenuation in metamaterial beams. Following a qualitative pre-study, two non-intrusive uncertainty propagation approaches are applied to find the upper and lower bounds of three performance metrics, by evaluating deterministic metamaterial models with uncertain parameters defined as interval variables. A global search approach is used and compared with a machine learning (ML)-based uncertainty propagation approach which significantly reduces the required number of simulations. Variability in resonator stiffnesses and masses is found to have the highest impact. Variability in the resonator positions only has a comparable impact for less deep sub-wavelength designs. The broadening potential of varying resonator properties is exploited in broadband optimization and the robustness of the optimized metamaterial is assessed.This article is part of the theme issue \'Current developments in elastic and acoustic metamaterials science (Part 2)\'.
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  • 文章类型: Journal Article
    土壤-水特征曲线(SWCC)定义了土壤中的水量与土壤吸力之间的关系。SWCC通常用于估计水力传导率函数(HCF)和剪切强度函数(SSF)。因此,SWCC的准确确定对于实施非饱和土力学原理至关重要。SWCC通常由有限数量的实验数据确定,因为SWCC测量是耗时且昂贵的。因此,当考虑到所确定的SWCC的准确性和实验费用时,所需土壤标本的最小数量对于SWCC测试至关重要。在这项研究中,选择了由沙子和高岭土混合物制成的材料,以及新加坡BukitTimah组的残留土壤,以准备用于SWCC测量的土壤标本。从具有工程土壤的标本中获得的SWCC是一致的,而那些来自残留土壤的标本则略有分散。这表明一个样本足以确定工程土壤样品的SWCC,同时,应至少准备两个标本,以确定来自BukitTimah组的残留土壤样品的SWCC。
    The soil‒water characteristic curve (SWCC) defines the relationship between the amount of water in soil and soil suction. The SWCC is commonly used to estimate the hydraulic conductivity function (HCF) and the shear strength function (SSF). Therefore, an accurate determination of the SWCC is crucial for implementing the principles of unsaturated soil mechanics. The SWCC is commonly determined from a limited number of experimental data because SWCC measurements are time-consuming and costly. As a result, the minimum number of required soil specimens is crucial for a SWCC test when considering the accuracy of the determined SWCC and the experimental expenses. In this study, both engineered from sand and kaolin mixtures and residual soils from Bukit Timah Formation in Singapore are selected to prepare soil specimens for SWCC measurements. The SWCCs obtained from the specimens with engineered soil are consistent, while those from specimens with residual soil are slightly scattered. This indicates that one specimen is sufficient to determine the SWCC for engineered soil samples, while a minimum of two specimens should be prepared for the determination of SWCC for residual soil samples from Bukit Timah Formation.
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  • 文章类型: Journal Article
    背景:当前最好的证据支持神经肌肉训练在降低受伤风险方面的有效性;但是,前交叉韧带(ACL)损伤的发生率仍然很高。神经认知训练(NT)已经成功地改善了生物力学的危险因素,但是只有少数研究考虑过它们。
    目的:回顾文献,以确定NT对运动员ACL损伤相关生物力学危险因素的影响。
    方法:我们搜索了PubMed,谷歌学者,Scopus,科学直接,和物理治疗证据数据库从开始到2011年8月。我们纳入了使用运动学习方法和损伤预防计划来调查与ACL损伤相关的运动学和动力学风险因素的随机对照试验。通过物理治疗证据数据库量表评估每个临床试验研究的质量。资格标准是根据PICOS(人群,干预,比较,结果,和研究类型)框架。
    结果:共有9项研究纳入最终分析。运动学习方法包括内部和外部关注焦点,双重任务,视觉运动训练,自我控制反馈,差分学习,线性和非线性教学法,结合锻炼计划。在大多数使用NT的研究中,膝关节外翻显著减少;胫骨外展和外旋;地面反作用力;膝盖增加,主干-,hip-,并观察到膝关节屈曲力矩。
    结论:在经典NT中,与理想运动模式的偏差,尤其是强调变异性和自我发现过程在预防损伤中起作用,并可能减轻运动员ACL损伤的生物力学风险因素。建议从业者将运动特定的认知任务与神经肌肉训练相结合,以模拟竞争环境的负荷。这可以改善ACL损伤风险降低和康复计划。
    BACKGROUND: The best current evidence supports the effectiveness of neuromuscular training in reducing the risk of injury; however, the rate of anterior cruciate ligament (ACL) injuries is still high. Neurocognitive training (NT) has successfully improved biomechanical risk factors, but they have been considered in only a few studies.
    OBJECTIVE: To review the literature to determine the effect of NT on biomechanical risk factors related to ACL injury in athletes.
    METHODS: We searched PubMed, Google Scholar, Scopus, Science Direct, and the Physiotherapy Evidence Database from inception to August 2011. We included randomized controlled trials that used motor learning approaches and injury prevention programs to investigate kinematic and kinetic risk factors related to ACL injury. The quality of each clinical trial study was evaluated by the Physiotherapy Evidence Database scale. The eligibility criteria were checked based on the PICOS (population, intervention, comparison, outcome, and study type) framework.
    RESULTS: A total of 9 studies were included in the final analysis. Motor learning approaches include internal and external focus of attention, dual tasks, visual motor training, self-control feedback, differential learning, and linear and nonlinear pedagogy, combined with exercise programs. In most of the studies that used NT, a significant decrease in knee valgus; tibial abduction and external rotation; ground reaction force; and an increase in knee-, trunk-, hip-, and knee-flexion moment was observed.
    CONCLUSIONS: In classical NT, deviation from the ideal movement pattern especially emphasizing variability and self-discovery processes is functional in injury prevention and may mitigate biomechanical risk factors of ACL injuries in athletes. Practitioners are advised to use sport-specific cognitive tasks in combination with neuromuscular training to simulate loads of the competitive environment. This may improve ACL injury risk reduction and rehabilitation programs.
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  • 文章类型: Journal Article
    沉思是导致抑郁和焦虑严重程度的公认因素。它是未知的,然而,随着时间的推移,沉思的时间动态中的个体差异是否可以预测抑郁或焦虑的纵向增加。
    当前的研究检查了通过生态瞬时评估在14天内评估的反思性惯性和变异性的动态指标是否可以预测抑郁症状的变化,一般焦虑,以及90天随访时的社交焦虑(n=115)。
    控制反思性变异性,因变量的基线水平,性别,和平均短暂的沉思水平,反思性惯性并不能预测抑郁症状的变化,一般焦虑,或者在90天的随访中出现社交焦虑。相比之下,更高的反思性变异性预测抑郁症和社交焦虑症状的增加,但在随访时不是一般焦虑。支持较高基线水平的抑郁症状的个体在其瞬时反思性中表现出更大的惯性和变异性。更大的反思性变异性而不是惯性也与更高的一般焦虑和社交焦虑基线水平相关。
    这些结果表明,反思性变异性可能是抑郁症和社交焦虑症状随时间增加的危险因素,并且是临床干预的潜在有用目标。
    UNASSIGNED: Rumination is a well-established contributor to the severity of depression and anxiety. It is unknown, however, whether individual differences in the temporal dynamics of rumination over time predict longitudinal increases in depression or anxiety.
    UNASSIGNED: The current study examined whether the dynamic indices of ruminative inertia and variability assessed over 14 days via ecological momentary assessment predicted change in symptoms of depression, general anxiety, and social anxiety at a 90-day follow-up (n = 115).
    UNASSIGNED: Controlling for ruminative variability, baseline levels of the dependent variable, sex, and mean levels of momentary rumination, ruminative inertia did not predict change in symptoms of depression, general anxiety, or social anxiety at the 90-day follow-up. In contrast, greater ruminative variability predicted increases in symptoms of both depression and social anxiety but not general anxiety at follow-up. Individuals endorsing higher baseline levels of depressive symptoms demonstrated greater amounts of inertia and variability in their momentary rumination. Greater ruminative variability but not inertia was also associated with higher baseline levels of general anxiety and social anxiety.
    UNASSIGNED: These results suggest that ruminative variability may be a risk factor for increases in symptoms of depression and social anxiety over time and a potentially useful target for clinical intervention.
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  • 文章类型: Journal Article
    背景:自杀矛盾情绪越来越被理解为两种相互冲突的动机取向相互作用的结果,希望死亡(WTD)和希望生活(WTL)。然而,关于他们关系性质的研究很少,它们的时间结构,以及它们在预测自杀欲望中的相关性。
    方法:50名心身/精神病住院患者(17名报告自杀未遂)参加了一项密集的纵向设计,在10天内每天进行10次信号提示;评估WTD,WTL,自杀的欲望。我们计算了WTD的平均值和变异性,WTL,自杀的矛盾心理,和自杀欲望,并测试了自杀欲望的混合效应模型。
    结果:回答提示的平均次数为40.98(SD=21.68)。WTD和WTL的重复测量相关性为r=-0.60。有自杀未遂史的患者报告WTD较高,较低的WTL,更多的自杀矛盾心理,更强烈的自杀欲望,并在所有构建体中显示出较高的变异性。在同样的评估中,WTD是自杀欲望的最强统计预测因子。只有WTL以及WTD和WTL的相互作用可以前瞻性地预测自杀欲望。
    结论:希望死亡和WTL可能是两个不同的(尽管相关)构建体,不应减少到单个矛盾得分。更加关注WTL具有自杀研究和实践的潜力。
    BACKGROUND: Suicidal ambivalence is increasingly understood as the result of the interplay of two conflicting motivational orientations, the wish to die (WTD) and wish to live (WTL). However, research is scarce regarding the nature of their relationship, their temporal structure, and their relevance in predicting suicidal desire.
    METHODS: Fifty psychosomatic/psychiatric inpatients (17 reporting suicide attempts) took part in an intensive longitudinal design with 10 signal-contingent prompts per day over 10 days; assessing WTD, WTL, and suicidal desire. We calculated mean values and variability of WTD, WTL, suicidal ambivalence, and suicidal desire and tested mixed-effects models of suicidal desire.
    RESULTS: The mean number of answered prompts was 40.98 (SD = 21.68). Repeated-measures correlation of WTD and WTL was r = -0.60. Patients with a history of suicide attempts reported higher WTD, lower WTL, more suicidal ambivalence, stronger suicidal desire, and showed higher variability in all constructs. At the same assessment, WTD was the strongest statistical predictor of suicidal desire. Only WTL and the interaction of WTD and WTL predicted suicidal desire prospectively.
    CONCLUSIONS: Wish to die and WTL are likely two distinct (although correlated) constructs that should not be reduced to a single ambivalence score. A stronger focus on WTL holds potential for suicide research and practice.
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  • 文章类型: Journal Article
    背景:Mabegondo农业研究中心(XuntadeGalicia,科鲁尼亚,西班牙)保存了来自西班牙西北部的生态型和草地物种自然种群的最重要的植物遗传资源之一,其中包括黑麦草种群(黑麦草属。),世界上栽培最多的牧草之一。本研究的目的是评估具有表型性状和分子标记的商业品种和天然黑麦草种群之间的多样性。
    结果:使用11个多态微卫星基因座分析了58个生态型和10个品种(总共680个DNA样品),区分了673个基因型。通过结构分析检测到两个主要组,一个与黑麦草有关,另一个与多花黑麦草有关。第一组显示两个亚组,第二组显示三个亚组。多花乳杆菌簇显示两个与第三簇无关的亚组,包括商业品种,一个来自加那利群岛(包括黑麦草),另一个来自西班牙西北部,呈现特定的农业形态特征,例如较低的FES(从1月1日起的天数,当每株植物每个地块开花三个头时),CRE(开花时的生长,以干物质为单位),和AIN(每株植物的花序数)。
    结论:这是首次分析来自伊比利亚半岛的大量黑麦草数据,从分析的商业品种中获得自生品种的明显遗传分化。此外,在生态型中发现的遗传结构与分析的表型变异有关。对保护生物多样性和获得更好适应的黑麦草品种感兴趣,由于其特定的表型特征,例如较低的FES,CRE和AIN。
    BACKGROUND: The Agricultural Research Centre of Mabegondo (Xunta de Galicia, A Coruña, Spain) conserves one of the most important collections of phytogenetic resources of ecotypes and natural populations of grassland species from northwestern Spain, among them populations of ryegrass (Lolium spp.), one of the most cultivated forage grasses in the world. The objective of the present study was to evaluate the diversity among commercial cultivars and natural ryegrass populations with phenotypic traits and molecular markers.
    RESULTS: Eleven polymorphic microsatellites loci were used to analyze 58 ecotypes and 10 cultivars (680 DNA samples in total) differentiating 673 genotypes. Two main groups were detected by the Structure analysis, one related to Lolium perenne and a second to Lolium multiflorum. The first group showed two subgroups and the second three. The cluster of L. multiflorum showed two subgroups not related with the third cluster including commercial varieties, one from the Canary Islands (with Lolium rigidum included) and a second one from northwestern Spain, which presented specific agromorphological characteristics, such as lower FES (number of days from 1 January, when three heads per plant were flowering per plot), CRE (growth in flowering, in g of dry matter), and AIN (number of inflorescences per plant).
    CONCLUSIONS: This is the first time that a large amount of data on ryegrass from the Iberian Peninsula has been analyzed, obtaining a clear genetic differentiation of the autochthonous varieties from the commercial varieties analyzed. In addition, the genetic structure found in the ecotypes was related to the phenotypic variation analyzed. Being of interest in the conservation of biodiversity and in obtaining better adapted varieties of ryegrasses, due to their specific phenotypic traits, such as a lower FES, CRE and AIN.
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  • 文章类型: Journal Article
    心脏震颤(SCG)信号是由心脏活动引起的胸壁振动,可能对心脏监测和诊断有用。观察到SCG波形随呼吸而变化,但是这些变化的机制很少被理解为自主神经张力的改变,肺容积,心脏位置和胸内压在呼吸周期中都是变化的。了解SCG变异性及其来源可能有助于减少变异性并增加SCG临床实用性。这项研究调查了屏气(BH)在两个不同的肺容积(即,结束吸气和结束呼气)和五个气道压力(即0,±2-4和±15-20cmH2O)。还研究了在将SCG搏动分组为相似波形形态的两个集群的情况下(以无监督的机器学习方式使用K-medoid算法执行)的情况下正常呼吸期间的变异性。这项研究包括15名健康受试者(11名女性和4名男性,年龄:21±2岁),其中SCG,心电图,和肺活量测定同时获得。在每个实验状态下计算SCG波形变异性(即,肺容量和气道压力)。结果表明,屏气比聚类正常呼吸数据更有效地降低了SCG的状态内变异性。对于BH州来说,状态内变异性随着气道压力偏离零而增加。BH状态的听觉与听觉能量比随着气道压力降低到零以下而增加,这可能与胸内压力对心脏后负荷和血液喷射的影响有关。当将吸气末和呼气末(气道压力相同)的BH波形合并为一组时,州内变异性增加,这表明肺容积和心脏位置的相关变化是变异性的重要来源。发现气道压力和波形变化之间的线性趋势对于呼气末的BH具有统计学意义。为了证实这些发现,对于更多数量的气道压力水平和更多数量的受试者,需要更多的研究.
    Seismocardiographic (SCG) signals are chest wall vibrations induced by cardiac activity and are potentially useful for cardiac monitoring and diagnosis. SCG waveform is observed to vary with respiration, but the mechanism of these changes is poorly understood as alterations in autonomic tone, lung volume, heart location and intrathoracic pressure are all varying during the respiratory cycle. Understanding SCG variability and its sources may help reduce variability and increase SCG clinical utility. This study investigated SCG variability during breath holding (BH) at two different lung volumes (i.e., end inspiration and end expiration) and five airway pressures (i.e., 0, ± 2-4, and ± 15-20 cm H2O). Variability during normal breathing was also studied with and without grouping SCG beats into two clusters of similar waveform morphologies (performed using the K-medoid algorithm in an unsupervised machine learning fashion). The study included 15 healthy subjects (11 Females and 4 males, Age: 21 ± 2 y) where SCG, ECG, and spirometry were simultaneously acquired. SCG waveform variability was calculated at each experimental state (i.e., lung volume and airway pressure). Results showed that breath holding was more effective in reducing the intra-state variability of SCG than clustering normal breathing data. For the BH states, the intra-state variability increased as the airway pressure deviated from zero. The subaudible-to-audible energy ratio of the BH states increased as the airway pressure decreased below zero which may be related to the effect of the intrathoracic pressure on cardiac afterload and blood ejection. When combining the BH waveforms at end inspiration and end expiration states (at the same airway pressures) into one group, the intra-state variability increased, which suggests that the lung volume and associated change in heart location were a significant source of variability. The linear trend between airway pressure and waveform changes was found to be statistically significant for BH at end expiration. To confirm these findings, more studies are needed with a larger number of airway pressure levels and larger number of subjects.
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  • 文章类型: Journal Article
    目的:尽管正常人心脏的电活动通过心电图得到了很好的表征,缺乏通过非侵入性电解剖标测对受试者内部和受试者之间的心室激动和恢复变化的详细见解。我们使用非侵入性心电图成像(ECGI)作为更好地了解病理学的基础,对正常人体内和之间的人心外膜激活和恢复进行了表征。
    结果:通过ECGI评估了22名正常人的心外膜激活和恢复,4例束支传导阻滞(BBB)和4例长QT综合征(LQTS)。我们比较了心室的特征[左心室(LV)和右心室(RV)],性别,和年龄组(<50/≥50岁)。Pearson相关系数(CC)用于受试者内部和受试者之间的比较。正常人平均年龄49±14岁,6/22是男性,并且没有结构性/电性心脏病。LV的平均激活时间比RV长,但没有不同的性别或年龄。心室的电恢复情况相似,但开始较早,男性平均较短。ECG信号的受试者之间比较的中间CC,激活,和恢复模式分别为0.61、0.32和0.19。受试者内的搏动到搏动比较产生了更高的CC(分别为0.98、0.89和0.82)。BBB或LQTS患者的激活和/或恢复模式与正常人群中的激活和/或恢复模式形成显着对比。
    结论:正常受试者之间的激活和恢复模式差异很大,但是稳定的个体被击败,男性优势较短的恢复。基线时ECGI的个体特征可作为更好地理解出现的参考,programming,和治疗电心脏病。
    OBJECTIVE: Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology.
    RESULTS: Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS). We compared characteristics between the ventricles [left ventricle (LV) and right ventricle (RV)], sexes, and age groups (<50/≥50years). Pearson\'s correlation coefficient (CC) was used for within-subject and between-subject comparisons. Age of normal subjects averaged 49 ± 14 years, 6/22 were male, and no structural/electrical heart disease was present. The average activation time was longer in LV than in RV, but not different by sex or age. Electrical recovery was similar for the ventricles, but started earlier and was on average shorter in males. Median CCs of between-subject comparisons of the ECG signals, activation, and recovery patterns were 0.61, 0.32, and 0.19, respectively. Within-subject beat-to-beat comparisons yielded higher CCs (0.98, 0.89, and 0.82, respectively). Activation and/or recovery patterns of patients with BBB or LQTS contrasted significantly with those found in the normal population.
    CONCLUSIONS: Activation and recovery patterns vary profoundly between normal subjects, but are stable individually beat to beat, with a male preponderance to shorter recovery. Individual characterization by ECGI at baseline serves as reference to better understand the emergence, progression, and treatment of electrical heart disease.
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  • 文章类型: Journal Article
    这项研究旨在阐明网球上旋单手正手击球中速度-准确性关系的潜在机制。九名大学球员以三种不同的速度进行地面击球,将球着陆位置的可变性评估为准确性指标。球发射变量的变化(速度,发射角度,spin,等。)和从这些可变性到球着陆位置可变性的转换率进行了量化。这些变化和他们的转换比可能会受到不同的努力,以产生球速和不同的球轨迹所需的每个速度击中目标,分别。仅在击球方向上观察到速度-精度权衡。当自旋轴的可变性增加时,它对落球位置的影响很小。相反,速度仰角的撞击方向的转换比率显着增加,而其变异性保持不变。因此,球轨迹的几何要求可以负责速度精度的权衡。因此,即使是技术熟练的球员,无论击球速度如何,都能保持一致的球发射变量,也应故意选择适度较慢的球速度,以避免由于几何要求而不可避免地增加球着陆位置的可变性。
    This study aimed to elucidate the mechanisms underlying the speed-accuracy relationship in a tennis topspin single-handed forehand groundstroke. Groundstrokes at three different speeds by nine college players were captured, with the variability of the ball landing position evaluated as indices of accuracy. Variabilities of ball launch variables (speed, launch angle, spin, etc.) and conversion ratios from these variabilities to the variability of the ball landing position were quantified. These variabilities and their conversion ratios could be influenced by different efforts exerted to generate ball speeds and different ball trajectories required to hit a target at each speed, respectively. The speed-accuracy trade-off was observed only in the hitting direction. While the variability of the spin axis increased, it had minimal influence on the ball landing position. Conversely, the conversion ratio in the hitting direction of the velocity elevation angle significantly increased, while its variability remained unchanged. Consequently, the geometrical requirements of ball trajectories can be responsible for the speed-accuracy trade-off. Therefore, even skilled players capable of maintaining consistent ball launch variables regardless of the shot speed should deliberately choose a moderately slower ball speed to avoid an inevitable increase in the variability of the ball landing position due to geometrical requirements.
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  • 文章类型: Journal Article
    生物等效性研究在仿制药开发中至关重要,其中创新产品提供了治疗等效性。然而,由于与药物相关的多种因素的相互作用,生物等效性研究表现出显著的复杂性,配方,生理学,和药代动力学。诸如基于生理的生物制药建模(PBBM)之类的方法可以通过适当开发和验证的模型来实现虚拟生物等效性(VBE)评估。这些模型现在被广泛用于生物等效性风险评估,内部决策,以及与生物等效性相关的药物和制剂因素的评价。通过结合变异性和开发虚拟种群进行生物等效性评估来描述上述因素对于利用此类模型至关重要。在这份手稿中,我们已经描绘了我们目前对VBE的理解。提供了关于研究设计的详细解释,体内变异性,和生理的影响,药物,和制定VBE种群发展的因素。此外,建议将变异性纳入GastroPlus的策略,重点是受试者内和跨场合的变异性。描绘了两个与立即释放和改良释放制剂有关的工业案例研究,其中VBE用于决策和监管依据。最后,在VBE领域的监管理解,以及未来的前景,是详细的。
    Bioequivalence studies are pivotal in generic drug development wherein therapeutic equivalence is provided with an innovator product. However, bioequivalence studies represent significant complexities due to the interplay of multiple factors related to drug, formulation, physiology, and pharmacokinetics. Approaches such as physiologically based biopharmaceutics modeling (PBBM) can enable virtual bioequivalence (VBE) assessment through appropriately developed and validated models. Such models are now being extensively used for bioequivalence risk assessment, internal decision-making, and the evaluation of drug and formulation factors related to bioequivalence. Depiction of the above-mentioned factors through the incorporation of variability and development of a virtual population for bioequivalence assessment is of paramount importance in utilizing such models. In this manuscript, we have portrayed our current understanding of VBE. A detailed explanation was provided with respect to study designs, in vivo variability, and the impact of physiological, drug, and formulation factors on the development of the population for VBE. Furthermore, strategies are suggested to incorporate variability in GastroPlus with an emphasis on intra-subject and inter-occasion variability. Two industrial case studies pertaining to immediate and modified release formulation were portrayed wherein VBE was utilized for decision-making and regulatory justification. Finally, regulatory understanding in the area of VBE, along with future perspectives, was detailed.
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