Robustness

鲁棒性
  • 文章类型: Journal Article
    本文旨在评估哮喘和非哮喘儿童和青少年的空气污染暴露与第一秒用力呼气量(FEV1)之间的统计关联。其中响应变量FEV1每月重复测量,表征纵向实验。由于数据的性质,鲁棒线性混合模型(RLMM),结合稳健的主成分分析(RPCA),建议处理协变量之间的多重共线性以及极端观测值(高水平的空气污染物)对估计值的影响。考虑Huber和Tukey损失函数以获得线性混合模型(LMM)中参数的鲁棒估计。在协变量遵循线性时间序列模型的情况下,进行了有限的样本量调查,其中有和没有加性异常值(AO)。研究了时间相关性和异常值对LMM中固定效应参数估计的影响。在真实的数据分析中,稳健的模型策略证明,RPCA表现出三个主成分(PC),主要与相对湿度(Hmd)有关,直径小于10μm的颗粒物(PM10)和直径小于2.5μm的颗粒物(PM2.5)。
    This paper aims to evaluate the statistical association between exposure to air pollution and forced expiratory volume in the first second (FEV1) in both asthmatic and non-asthmatic children and teenagers, in which the response variable FEV1 was repeatedly measured on a monthly basis, characterizing a longitudinal experiment. Due to the nature of the data, an robust linear mixed model (RLMM), combined with a robust principal component analysis (RPCA), is proposed to handle the multicollinearity among the covariates and the impact of extreme observations (high levels of air contaminants) on the estimates. The Huber and Tukey loss functions are considered to obtain robust estimators of the parameters in the linear mixed model (LMM). A finite sample size investigation is conducted under the scenario where the covariates follow linear time series models with and without additive outliers (AO). The impact of the time-correlation and the outliers on the estimates of the fixed effect parameters in the LMM is investigated. In the real data analysis, the robust model strategy evidenced that RPCA exhibits three principal component (PC), mainly related to relative humidity (Hmd), particulate matter with a diameter smaller than 10 μm (PM10) and particulate matter with a diameter smaller than 2.5 μm (PM2.5).
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  • 文章类型: Journal Article
    现代神经网络对随机噪声和蓄意攻击的脆弱性引起了人们对其鲁棒性的担忧,特别是它们越来越多地用于安全和安全关键应用。尽管最近的研究努力通过对抗性示例的重新训练或采用数据增强技术来增强鲁棒性,对训练数据扰动对模型鲁棒性的影响的全面研究仍然缺乏。本文提出了第一个广泛的实证研究,调查了模型再训练过程中数据扰动的影响。实验分析侧重于随机和对抗鲁棒性,遵循稳健性分析领域的既定做法。探索了数据集不同方面的各种类型的扰动,包括输入,标签,和抽样分布。进行单因素和多因素实验来评估个体扰动及其组合。这些发现为构建高质量的训练数据集提供了见解,以优化鲁棒性,并推荐适当程度的训练集扰动,以平衡鲁棒性和正确性,并有助于理解深度学习中的模型鲁棒性,并为通过扰动再训练增强模型性能提供实践指导,促进为安全关键型应用开发更可靠、更值得信赖的深度学习系统。
    The vulnerability of modern neural networks to random noise and deliberate attacks has raised concerns about their robustness, particularly as they are increasingly utilized in safety- and security-critical applications. Although recent research efforts were made to enhance robustness through retraining with adversarial examples or employing data augmentation techniques, a comprehensive investigation into the effects of training data perturbations on model robustness remains lacking. This paper presents the first extensive empirical study investigating the influence of data perturbations during model retraining. The experimental analysis focuses on both random and adversarial robustness, following established practices in the field of robustness analysis. Various types of perturbations in different aspects of the dataset are explored, including input, label, and sampling distribution. Single-factor and multi-factor experiments are conducted to assess individual perturbations and their combinations. The findings provide insights into constructing high-quality training datasets for optimizing robustness and recommend the appropriate degree of training set perturbations that balance robustness and correctness, and contribute to understanding model robustness in deep learning and offer practical guidance for enhancing model performance through perturbed retraining, promoting the development of more reliable and trustworthy deep learning systems for safety-critical applications.
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  • 文章类型: Journal Article
    锁定的视野计划可以使左乳腺癌的心脏和肺器官剂量。
    本研究的目的是比较左侧乳腺癌调强放疗中场锁定和场分裂计划之间的剂量学差异,为了探索场锁定对低剂量区的影响,并评估其对放射治疗目标的鲁棒性,为临床放疗方案的选择提供参考。
    共选择了30例左乳癌根治术后的患者,并制定了7场锁定场和分裂场计划,以比较目标区域和每个危险器官之间的剂量差异(ΔD),并在六个方向上引入3、5和7毫米的偏移量,并重新计算扰动的剂量分布,并根据计划的鲁棒性比较原始计划和扰动计划之间的ΔD。
    结果显示,D98%,两种计划的计划目标体积(PTV)的D95%和D平均值差异不大,没有统计学差异。锁定的野外计划为左肺提供了更好的保护,右肺,心,右乳和左冠状动脉前降支。对于PTVΔD98%,PTVΔD95%,PTVΔDmean,锁定字段计划的ΔD较高,对于LungLΔ5、LungLΔ20和心脏Δ平均值,与原计划相比,ΔD较高。
    得出的结论是,磁场锁定计划可以减少受影响肺的低剂量区域,并为其余的关键器官提供更好的保护,并且现场锁定计划在保护关键器官方面更加强大。同时,现场锁定计划对目标PTV的位置偏差显示出更高的敏感性。
    UNASSIGNED: The locked vision plan can make the left breast cancer heart and lung organs dose.
    UNASSIGNED: The aim of the present study was to compare the dosimetric differences between field-locked and field-split plans in intensity-modulated radiotherapy for left-sided breast cancer, to explore the effect of field-locking on the low-dose region, and to evaluate its robustness to the radiotherapy target, in order to provide a reference for the selection of clinical radiotherapy protocols.
    UNASSIGNED: A total of 30 patients were selected after radical left breast cancer surgery, and 7-field locked-field and split-field plans were developed to compare the dose difference (∆D) between the target area and each organ at risk, and to introduce offsets of 3, 5 and 7 mm in six directions and recalculate the perturbed dose distributions, and to compare the ∆D between the original and the perturbed plans according to the robustness of the plans.
    UNASSIGNED: The results revealed that the D98%, D95% and Dmean values of the planning target volume (PTV) of the two plans differed little and were not statistically different. The locked field plan provided better protection for the left lung, right lung, heart, right breast and left anterior descending coronary artery. For PTV∆D98%, PTV∆D95%, PTV∆Dmean, the ∆D was higher for the Locked Fields plan, and for LungL∆5, LungL∆20 and Heart∆mean, the ∆D was higher for the original plan.
    UNASSIGNED: It was concluded that the field-locking plan could reduce the low-dose area of the affected lung and provide improved protection to the remaining critical organs, and the field-locking plan was more robust in protecting critical organs. Meanwhile, the field-locking plan showed higher sensitivity to positional deviation for target PTV.
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  • 文章类型: Journal Article
    我们最近揭示了各种蛋白质组学设施中蛋白质电晕表征的显着变异性,这表明独立研究之间的数据集没有可比性。这种异质性主要来自样品制备方案的差异,质谱工作流程,和原始数据处理。为了解决这个问题,我们制定了标准化的协议和统一的样品制备工作流程,从我们之前的研究中,将均匀的蛋白质电晕消化物分配到几个表现最好的蛋白质组学中心。我们还研究了使用类似的质谱仪器对数据均匀性,标准化的数据库搜索参数和数据处理工作流程的影响。我们的发现揭示了蛋白质电晕数据均匀性的显着逐步改善,使用类似的仪器和通过统一的数据库搜索,在不同的设施中,蛋白质鉴定的重叠度从11%增加到40%。我们确定了数据异质性背后的关键参数,并为设计实验提供了建议。我们的发现将显着提高蛋白质电晕分析在诊断和治疗应用中的稳健性。
    We recently revealed significant variability in protein corona characterization across various proteomics facilities, indicating that data sets are not comparable between independent studies. This heterogeneity mainly arises from differences in sample preparation protocols, mass spectrometry workflows, and raw data processing. To address this issue, we developed standardized protocols and unified sample preparation workflows, distributing uniform protein corona digests to several top-performing proteomics centers from our previous study. We also examined the influence of using similar mass spectrometry instruments on data homogeneity and standardized database search parameters and data processing workflows. Our findings reveal a remarkable stepwise improvement in protein corona data uniformity, increasing overlaps in protein identification from 11% to 40% across facilities using similar instruments and through a uniform database search. We identify the key parameters behind data heterogeneity and provide recommendations for designing experiments. Our findings should significantly advance the robustness of protein corona analysis for diagnostic and therapeutics applications.
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  • 文章类型: Journal Article
    背景:强度调节质子治疗(IMPT)的准确性受到治疗过程中可能发生的解剖结构变化的极大影响。已经提出了在线计划适应作为一旦检测到解剖结构变化就在治疗会话期间迅速干预的解决方案。在线自适应质子治疗(OAPT)的实施仍然受到工作流程中耗时任务的阻碍。
    目的:该研究引入了部分适应的新概念,旨在研究其作为OAPT工作流程中并行化任务的潜在解决方案的可行性,以节省宝贵的室内时间。
    方法:原理验证模拟研究包括来自六名头颈部癌症(HNC)患者的数据集,每个由一个计划CT(pCT)和三个轮廓控制CT(cCT)组成。在具有标准化场配置的pCT上生成了稳健的3场正常分割的初始IMT计划,提供66Gy和54Gy到高风险和低风险临床目标量(CTVHigh和CTVLow),分别。对于每个cCT,应用了基于剂量模拟的部分自适应:在当前解剖结构上对两个场进行了自适应,同时考虑了假定同时递送的第一个非自适应场的背景剂量.将部分适应计划与不同的首次(非适应)场分配产生的cCT上的分数剂量与未适应和完全适应计划中的剂量进行比较,涉及目标覆盖率和风险器官(OAR)保留。还评估了部分适应计划的稳健性。
    结果:部分适应计划显示出与完全适应计划相当的结果,并且在目标覆盖率和OAR节约方面都优于非适应计划。非适应计划中的目标覆盖率下降(中位数D98%:CTVLow和CTVHigh的95.9%和97.5%,分别)与初始计划(98.7%和98.8%)相比,部分(98.0%和98.5%)和完全适应(98.2%和98.7%)均恢复。CTVHigh的初始热点剂量(中位数D2%:101.8%)在非适应性计划中增加(102.9%),并通过适应性策略恢复(部分:102.5%,满:101.9%)。对于所有研究的剂量分布,脑干和脊髓的接近最大剂量(D0.01cc)在临床限制范围内,但在没有适应的情况下明显增加,在(部分和完全)适应的计划中,相对于非适应的计划有所改善。腮腺中值剂量(D50)主要是患者特异性的,取决于与目标区域的接近程度,但无论如何,与未适应的计划相比,部分和完全适应的计划要低。与完全适应相比,部分适应计划的OAR节省得到了进一步改善。在所有评估的方案中都保留了目标剂量指标的稳健性。
    结论:对于HNC患者的OAPT,部分适应能够产生与非适应计划的一致性优越的计划,与完全适应计划的一致性相当的计划,同时有可能加快在线自适应工作流程。因此,部分自适应代表一种中间方法,直到快速在线自适应工作流程变得可用。此外,它可以应用于在线治疗验证停止交付并触发剩余部分的在线适应的工作流程。
    BACKGROUND: The accuracy of intensity-modulated proton therapy (IMPT) is greatly affected by anatomy variations that might occur during the treatment course. Online plan adaptations have been proposed as a solution to intervene promptly during a treatment session once the anatomy changes are detected. The implementation of online-adaptive proton therapy (OAPT) is still hindered by time-consuming tasks in the workflow.
    OBJECTIVE: The study introduces the novel concept of partial adaptation and aims at investigating its feasibility as a potential solution to parallelize tasks during an OAPT workflow for saving valuable in-room time.
    METHODS: The proof-of-principle simulation study includes datasets from six head and neck cancer (HNC) patients, each consisting of one planning CT (pCT) and three contoured control CTs (cCTs). Robust 3-field normo-fractionated initial IMPT plans were generated on the pCTs with a standardized field configuration, delivering 66 Gy and 54 Gy to the high-risk and low-risk clinical target volume (CTVHigh and CTVLow), respectively. For each cCT, a dose-mimicking-based partial adaptation was applied: two fields were adapted on the current anatomy taking into account the background dose of the first non-adapted field supposedly delivered in the meantime. Fraction doses on the cCTs resulting from partially adapted plans with different first (non-adapted) field assignments were compared against those from non-adapted and fully adapted plans regarding target coverage and organs at risk (OARs) sparing. The robustness of partially adapted plans was also evaluated.
    RESULTS: Partially adapted plans showed comparable results to fully adapted plans and were superior to non-adapted plans for both target coverage and OAR sparing. Target coverage degradation in the non-adapted plans (median D98%: 95.9% and 97.5% for CTVLow and CTVHigh, respectively) was recovered by both partial (98.0% and 98.5%) and full adaptation (98.2% and 98.7%) in comparison to the initial plans (98.7% and 98.8%). The initial hotspot dose for the CTVHigh (median D2%: 101.8%) increased in the non-adapted plans (102.9%) and was recovered by the adaptive strategies (partial: 102.5%, full: 101.9%). The near-maximum dose (D0.01cc) to brainstem and spinal cord was within clinical constraints for all investigated dose distributions, but clearly increased for no adaptation and improved in the (both partially and fully) adapted plans with respect to the non-adapted ones. The parotids\' median doses (D50) were mainly patient-specific depending on the proximity to the target region, but anyway lower for the partially and fully adapted plans compared to the non-adapted ones. OAR sparing was furthermore improved for the partially adapted plans in comparison to full adaptation. Robustness of the target dose metrics was preserved in all evaluated scenarios.
    CONCLUSIONS: For OAPT of HNC patients, partial adaptation is able to generate plans of superior conformity to non-adapted plans and of comparable conformity as fully adapted plans, while having the potential to speed up the online-adaptive workflows. Thus, partial adaptation represents an intermediate approach until fast online adaptation workflows become available. Furthermore, it can be applied in workflows where online treatment verification stops the delivery and triggers an online adaptation for the remaining fraction.
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  • 文章类型: Journal Article
    这项工作的目的是开发一种超临界流体色谱方法,以研究这种新兴技术对大麻素分析的适用性,并展示其优势。在方法开发过程中,作者重点研究了九种植物大麻素,以评估可能对每种大麻素进行定量所需的选择性.方法开发后,在此方法上进行了鲁棒性研究,以获得有关其定性行为的更多信息(在临界分辨率方面),当改变一些关键参数(添加剂的浓度,柱温,起始梯度条件和色谱柱批次)。一旦对稳健性进行了评估,并对影响选定反应最大的参数进行了个性化,SFC方法用于模拟常规用途,以产生有关实际大麻样品中主要大麻素浓度的定量结果.还通过目前在实验室中用于相同目的的超高效液相色谱法分析样品。最后,比较两种分析方法获得的结果,以评估其一致性。Bland-Altman方法用作统计策略,以评估生成的结果之间的一致程度,并在差异图中显示数据。超高效超临界流体色谱定量结果与超高效液相色谱定量结果,证明该技术适用于大麻素分析。
    The aim of this work was to develop a supercritical fluid chromatographic method to study the applicability of this emerging technique to cannabinoid analysis and showcase its advantages. During method development, the authors focused on nine phyto-cannabinoids to assess the selectivity needed to potentially perform the quantitation of each cannabinoid. After method development, robustness studies were carried out on this method to gain more information about its qualitative behavior (in terms of critical resolutions) when varying some crucial parameters (concentration of additive, column temperature, starting gradient conditions and column batch). Once the robustness was evaluated and the parameters most affecting the selected responses were individuated, the SFC method was applied for a simulated routine use to generate quantitative results concerning the concentrations of the main cannabinoids in real cannabis samples. The samples were also analyzed by means of an ultra-high-performance liquid chromatographic method currently used in the laboratory for the same objective. Finally, the results obtained with both analytical methods were compared to evaluate their accordance. The Bland-Altman method was applied as a statistical strategy to evaluate the degree of accordance between the results generated and display the data in a difference plot. The ultra-high performance supercritical fluid chromatography quantitative results were in accordance with the ultra-high performance liquid chromatography results, demonstrating the applicability of this technique for cannabinoid analysis.
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  • 文章类型: Journal Article
    这项研究调查了ComBat协调对从不同扫描仪上获取的磁共振图像(MRI)中提取的放射学特征的可重复性的影响,使用各种数据采集参数和使用专用MRI体模的多个图像预处理技术。作为TCIARIDER数据库的一部分,使用了四个扫描仪来获取非解剖体模的MRI。在快速自旋回波反转恢复(IR)序列中,采用了几个反转持续时间,包括50、100、250、500、750、1000、1500、2000、2500和3000ms。此外,3D快速破坏梯度召回回波(FSPGR)序列用于研究几个翻转角(FA):2,5,10,15,20,25和30度。手动分割了19个体模隔室。使用不同的方法对每个图像进行预处理:Bin离散化,小波滤波器,高斯拉普拉斯算子,对数,正方形,平方根,和梯度。总的来说,92第一次-,第二-,并提取高阶统计影像组学特征。ComBat协调也应用于提取的放射学特征。最后,实施了组内相关系数(ICC)和Kruskal-Wallis's(KW)测试以评估放射学特征的稳健性。对于各种扫描仪,KW测试中的非重要特征数量介于0-5和29-74之间,31-91和37-92三次测试,FAs的0-33到34-90,ComBat协调前后的IRs为3-68至65-89,使用不同的图像预处理技术,分别。对于各种扫描仪,具有ICC的功能数量超过90%,范围在0-8和6-60之间,11-75和17-80进行三次测试,FAs的3-83到9-84,ComBat协调前后的IRs为3-49至3-63,使用不同的图像预处理技术,分别。各种扫描仪的使用,IRs,和FAs对放射学特征有很大影响。然而,大多数扫描仪鲁棒特征对IR和FA也是鲁棒的。在MR图像中的有效参数中,一个扫描仪中的几个测试对放射学特征的影响可以忽略不计。使用各种图像预处理的不同扫描仪和采集参数可能在很大程度上影响放射学特征。ComBat协调可能会显着影响MRI影像特征的可重复性。
    This study investigated the impact of ComBat harmonization on the reproducibility of radiomic features extracted from magnetic resonance images (MRI) acquired on different scanners, using various data acquisition parameters and multiple image pre-processing techniques using a dedicated MRI phantom. Four scanners were used to acquire an MRI of a nonanatomic phantom as part of the TCIA RIDER database. In fast spin-echo inversion recovery (IR) sequences, several inversion durations were employed, including 50, 100, 250, 500, 750, 1000, 1500, 2000, 2500, and 3000 ms. In addition, a 3D fast spoiled gradient recalled echo (FSPGR) sequence was used to investigate several flip angles (FA): 2, 5, 10, 15, 20, 25, and 30 degrees. Nineteen phantom compartments were manually segmented. Different approaches were used to pre-process each image: Bin discretization, Wavelet filter, Laplacian of Gaussian, logarithm, square, square root, and gradient. Overall, 92 first-, second-, and higher-order statistical radiomic features were extracted. ComBat harmonization was also applied to the extracted radiomic features. Finally, the Intraclass Correlation Coefficient (ICC) and Kruskal-Wallis\'s (KW) tests were implemented to assess the robustness of radiomic features. The number of non-significant features in the KW test ranged between 0-5 and 29-74 for various scanners, 31-91 and 37-92 for three times tests, 0-33 to 34-90 for FAs, and 3-68 to 65-89 for IRs before and after ComBat harmonization, with different image pre-processing techniques, respectively. The number of features with ICC over 90% ranged between 0-8 and 6-60 for various scanners, 11-75 and 17-80 for three times tests, 3-83 to 9-84 for FAs, and 3-49 to 3-63 for IRs before and after ComBat harmonization, with different image pre-processing techniques, respectively. The use of various scanners, IRs, and FAs has a great impact on radiomic features. However, the majority of scanner-robust features is also robust to IR and FA. Among the effective parameters in MR images, several tests in one scanner have a negligible impact on radiomic features. Different scanners and acquisition parameters using various image pre-processing might affect radiomic features to a large extent. ComBat harmonization might significantly impact the reproducibility of MRI radiomic features.
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  • 文章类型: Journal Article
    综合多项研究的结果是提高科学发现稳健性的一种流行方法。最著名的方法是荟萃分析。然而,因为荟萃分析需要具有相同统计形式的概念上可比的效应大小,当研究的研究设计高度多样化时,荟萃分析可能是不可能的,参与者特征,或关键变量的可操作性。在这些情况下,贝叶斯证据综合可能构成一种灵活可行的替代方案,因为这种方法结合了假设水平的研究,而不是效应大小水平的研究。因此,这种方法对要合并的研究提出了较少的限制。在这项研究中,我们引入贝叶斯证据综合,并通过模拟显示该方法何时偏离荟萃分析中的预期,以帮助研究人员正确解释综合结果.作为经验证明,我们还将贝叶斯证据综合应用于已发表的关于有和没有发育性语言障碍的人的统计学习的荟萃分析。我们强调了所提出方法的优缺点,并为未来的研究提供了建议。
    Synthesizing results across multiple studies is a popular way to increase the robustness of scientific findings. The most well-known method for doing this is meta-analysis. However, because meta-analysis requires conceptually comparable effect sizes with the same statistical form, meta-analysis may not be possible when studies are highly diverse in terms of their research design, participant characteristics, or operationalization of key variables. In these situations, Bayesian evidence synthesis may constitute a flexible and feasible alternative, as this method combines studies at the hypothesis level rather than at the level of the effect size. This method therefore poses less constraints on the studies to be combined. In this study, we introduce Bayesian evidence synthesis and show through simulations when this method diverges from what would be expected in a meta-analysis to help researchers correctly interpret the synthesis results. As an empirical demonstration, we also apply Bayesian evidence synthesis to a published meta-analysis on statistical learning in people with and without developmental language disorder. We highlight the strengths and weaknesses of the proposed method and offer suggestions for future research.
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  • 文章类型: Clinical Trial, Phase II
    在2期临床试验中,我们希望在中期分析(IA)期间做出正确的Go或No-Go决定,并在正确的时间做出此决定。IA的最佳时间通常是根据效用函数确定的。在以前的大多数研究中,效用函数旨在最小化验证性试验中的预期样本量或总成本.然而,选择的时间可以根据不同的替代假设而变化。本文为贝叶斯2期探索性临床试验提出了一种新的效用函数。它评估了IA期间做出的Go和No-Go决定的可预测性和稳健性。我们可以根据函数对IA进行稳健的时间选择,而不考虑治疗效果的假设。
    In phase 2 clinical trials, we expect to make a right Go or No-Go decision during the interim analysis (IA) and make this decision at the right time. The optimal time for IA is usually determined based on a utility function. In most previous research, utility functions aim to minimize the expected sample size or total cost in confirmatory trials. However, the selected time can vary depending on different alternative hypotheses. This paper proposes a new utility function for Bayesian phase 2 exploratory clinical trials. It evaluates the predictability and robustness of the Go and No-Go decision made during the IA. We can make a robust time selection for the IA based on the function regardless of the treatment effect assumptions.
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  • 文章类型: Review
    有机体行为,其巨大的复杂性和多样性,是由许多协调作用的生理系统产生的。了解这些系统如何进化以支持物种内部和物种之间的行为差异是生物学的一个长期目标,它吸引了从事多种分类群工作的研究人员的想象力。包括人类。特别重要的是行为进化的生理决定因素,这有时被忽视,因为我们缺乏一个强大的概念框架来研究适应和行为多样化的机制。这里,我们讨论了这样一个分析的框架,该框架将“系统视图”应用于我们对行为控制的理解。这种方法涉及将将行为和生理学视为自己的网络的单独模型链接到单个垂直集成的行为控制系统中。在这样做的时候,荷尔蒙通常作为纽带脱颖而出,或边缘,在这个系统中的节点之间。以我们的讨论为基础,我们专注于对马纳金(Pipridae)的研究,一个新热带鸟类家族。这些物种具有许多生理和内分泌专长,可以支持其精心制作的生殖表现。因此,manakins提供了一个有用的例子来帮助想象和可视化系统概念可以告知我们对行为进化的欣赏。特别是,manakins有助于阐明生理系统之间的连通性-通过内分泌信号传导维持-增强和/或限制复杂行为的进化,以产生跨分类群的行为差异。最终,我们希望这次审查将继续激发人们的想法,讨论,研究的出现集中在行为生态学和内分泌学的综合表型上。
    Organismal behavior, with its tremendous complexity and diversity, is generated by numerous physiological systems acting in coordination. Understanding how these systems evolve to support differences in behavior within and among species is a longstanding goal in biology that has captured the imagination of researchers who work on a multitude of taxa, including humans. Of particular importance are the physiological determinants of behavioral evolution, which are sometimes overlooked because we lack a robust conceptual framework to study mechanisms underlying adaptation and diversification of behavior. Here, we discuss a framework for such an analysis that applies a \"systems view\" to our understanding of behavioral control. This approach involves linking separate models that consider behavior and physiology as their own networks into a singular vertically integrated behavioral control system. In doing so, hormones commonly stand out as the links, or edges, among nodes within this system. To ground our discussion, we focus on studies of manakins (Pipridae), a family of Neotropical birds. These species have numerous physiological and endocrine specializations that support their elaborate reproductive displays. As a result, manakins provide a useful example to help imagine and visualize the way systems concepts can inform our appreciation of behavioral evolution. In particular, manakins help clarify how connectedness among physiological systems-which is maintained through endocrine signaling-potentiate and/or constrain the evolution of complex behavior to yield behavioral differences across taxa. Ultimately, we hope this review will continue to stimulate thought, discussion, and the emergence of research focused on integrated phenotypes in behavioral ecology and endocrinology.
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