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PubMed1985

Use of robust variance components models to analyse triglyceride data in families.

A robust approach for analysis of variance components models is presented which does not rely on the assumption of multivariate normality for its validity. This approach uses the multivariated normal distribution as a 'working model' but obtains standard errors for the final estimators which do not depend on this underlying distribution. By using the observed variance in the first derivatives of the multivariate normal 'working model' to modify the conventional score test, hypotheses regarding specific components can also be tested without relying directly on the assumption of multivariate normality. A special case is presented where both the modified score test and the likelihood ratio test are equally robust, and simulated data are used to illustrate this situation. Measurements of triglyceride levels in 391 individuals in 60 families randomly selected from the membership of a health maintenance organization are used to illustrate this robust approach to variance components.

Genetic Variation↗
PubMed2002

Developmental robustness.

Developmental robustness, the capacity to stay "on track" despite the myriad vicissitudes that inevitably plague a developing organism, is, I argue, a prerequisite for natural selection and key to our understanding of the evolution of developmental processes. But how is such robustness achieved? And how can we reconcile this property with the delicate precision that seems to characterize so many developmental mechanisms, with what Michael Behe calls "irreducible complexity"? By looking at context, I argue. Developmental mechanisms must be robust with respect to the kinds of insults they are most likely to face, but with respect to less likely vicissitudes, they can be fragile. More specifically, I examine the relative absence of reaction-diffusion mechanisms in development and suggest that such mechanisms, theoretically attractive though they may be, have been judged by evolution to be ill suited for providing protection against the kinds of vicissitudes developing organisms are most likely to face, and have been supplanted by more intricate mechanisms that are protected from insult by structural design.

Adaptation, Physiological↗
PubMed2001

Robustness to head misalignment of virtual sound imaging systems.

When binaural sound signals are presented with two loudspeakers, the listener's ears are required to be in the relatively small region which is under control of the system. Misalignment of the head results in inaccurate synthesis of the binaural signals. Consequently, directional information associated with the acoustic signals is inaccurately reproduced. When the two loudspeakers are placed close together, the spatial rate of change of the generated sound field is much smaller than that generated by two loudspeakers spaced apart. Therefore, the performance of such a system is expected to be more robust to misalignment of the listener's head. Robustness of performance is investigated here with respect to head displacement in three translational and three rotational directions. A comparison is given between systems consisting of two loudspeakers either placed close together or spaced apart. The extent of effective control with head displacement and the resulting deterioration in directional information is investigated in the temporal and spectral domain by analyzing synthesized binaural signals. Subjective localization experiments are performed for cases in which notable differences in performance are expected from the previous analysis. It is shown that the system comprising two loudspeakers that are close together is very robust to misalignment of the listener's head.

Acoustics↗
PubMed2002

Robust active control of broadband noise in finite ducts.

This study focuses on robust active control of broadband noise in finite ducts. Our analytical and experimental studies suggest the existence of several technical flaws in the path models of conventional active noise control (ANC) systems. These are sensitivity of the path model with respect to boundary conditions, and nonminimum phase (NMP) secondary and reference paths. For finite ducts with small cross sections, the traveling wave model (TWM) may be adopted to find an effective solution to these problems and lead to a robust ANC system. Since many practical "noisy" ducts are finite with small cross sections, the proposed ANC has many practical applications. Its robustness and ability to suppress broadband noise will be explained theoretically and verified experimentally.

Journal Article↗
PubMed2004

An efficient robust sound classification algorithm for hearing aids.

An efficient robust sound classification algorithm based on hidden Markov models is presented. The system would enable a hearing aid to automatically change its behavior for differing listening environments according to the user's preferences. This work attempts to distinguish between three listening environment categories: speech in traffic noise, speech in babble, and clean speech, regardless of the signal-to-noise ratio. The classifier uses only the modulation characteristics of the signal. The classifier ignores the absolute sound pressure level and the absolute spectrum shape, resulting in an algorithm that is robust against irrelevant acoustic variations. The measured classification hit rate was 96.7%-99.5% when the classifier was tested with sounds representing one of the three environment categories included in the classifier. False-alarm rates were 0.2%-1.7% in these tests. The algorithm is robust and efficient and consumes a small amount of instructions and memory. It is fully possible to implement the classifier in a DSP-based hearing instrument.

Acoustic Stimulation↗
PubMed2005

Optimal design of loudspeaker arrays for robust cross-talk cancellation using the Taguchi method and the genetic algorithm.

An optimal design technique of loudspeaker arrays for cross-talk cancellation with application in three-dimensional audio is presented. An array focusing scheme is presented on the basis of the inverse propagation that relates the transducers to a set of chosen control points. Tikhonov regularization is employed in designing the inverse cancellation filters. An extensive analysis is conducted to explore the cancellation performance and robustness issues. To best compromise the performance and robustness of the cross-talk cancellation system, optimal configurations are obtained with the aid of the Taguchi method and the genetic algorithm (GA). The proposed systems are further justified by physical as well as subjective experiments. The results reveal that large number of loudspeakers, closely spaced configuration, and optimal control point design all contribute to the robustness of cross-talk cancellation systems (CCS) against head misalignment.

Algorithms↗
PubMed1996

A robust sequential test for text-independent speaker verification.

A robust speaker verification algorithm based on sequential hypothesis testing is presented. In speaker verification, the system performance is severely degraded by deviations from the nominal statistical speaker models caused by insufficient training data, varying microphone and transmission line characteristics, and different levels and types of background noise. Historically, this problem has been addressed by using an empirical method to determine an adequate decision threshold for a desired operating point. The robust detection algorithm presented here is based on a minimax criterion, such that the worst-case performance over a class of distributions is minimized. The sequential test provides further robustness by using additional data if a decision cannot be reached with the desired level of confidence. The sequential detector has been implemented and tested on a realistic database collected specifically for this purpose, and the performance has been shown to be comparable to or better than that of the corresponding heuristic detectors previously described in the literature.

Algorithms↗
PubMed2000

Control performance and robustness of an active noise control system for uncertain primary sound fields

In this work, the control performance and robustness of an active noise control system subjected to uncertain primary sound fields are investigated. For this purpose, the performance index, residual potential energy in a desired quiet zone, is derived as a function of sound field variables, quiet zone variables, and control system variables. In the presence of uncertainty, typical measures of the robustness and performance of a control system, maximum, minimum, mean, and variance of the performance index are derived theoretically. In addition, based on the least-squares orthogonality principle, the condition for implementing the best-oriented control system, which is robust and can maximize the control performance by using a given number of control sources and sensors, is investigated. Finally, numerical simulations are carried out to illustrate and verify the proposed theory.

Journal Article↗
PubMed1995

Determination of robust ocular pharmacokinetic parameters in serum and vitreous humor of albino rabbits following systemic administration of ciprofloxacin from sparse data sets by using IT2S, a population pharmacokinetic modeling program.

Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of concentrations of anti-infective agents is limited. Advances in pharmacodynamics have pointed out the importance of understanding the profiles of drugs in the plasma and in specialized compartments in order to dose the drugs to obtain the best patient outcomes. Advances in population pharmacokinetic modeling hold the promise of allowing proper estimation of drug penetration into the vitreous (or other specialized compartment) with only a single vitreous sample, in conjunction with plasma sampling. We have developed a rabbit model which allows multiple samples of vitreous to be obtained without breaking down the blood-vitreous barrier. We have employed this model to test the hypothesis that robust estimates of vitreous penetration by the fluoroquinolone ciprofloxacin can be obtained from a traditional intensive plasma sampling set plus a single vitreous sample. We studied 33 rabbits which were receiving 40 mg of ciprofloxacin per kg of body weight intravenously as short infusions and from which multiple plasma and vitreous samples were obtained and assayed for ciprofloxacin content by high-performance liquid chromatography. Data were analyzed by the iterative two-stage population modeling technique (IT2S), employing the iterative two-stage program of Forrest et al. (Antimicrob. Agents Chemother. 37:1065-1072, 1993). Two data sets were analyzed: all plasma and vitreous samples versus all plasma samples and the initially obtained single vitreous sample. The pharmacokinetic parameter values identified were used to calculate the percent vitreous penetration as the ratio of the area under the concentration-time curve for the vitreous to that for the plasma. The values identified, 4% penetration for the full data set versus 3% penetration for the single vitreous sample data set, and their corresponding estimates were not statistically significantly different. We conclude that population modeling holds promise for the analysis of penetration of antimicrobiol agents into specialized spaces from which only single samples can be obtained, particularly for patients with whom robust plasma sampling can be performed.

Animals↗
PubMed2005

Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfected human hepatoma cells.

Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide, with an increased risk of developing cirrhosis and hepatocellular carcinoma. The study of HCV replication and pathogenesis has been hampered by the lack of an efficient stable cell culture system and small-animal models of HCV infection and propagation. In an effort to develop a robust HCV infection system, we constructed stable human hepatoma cell lines that contain a chromosomally integrated genotype 2a HCV cDNA and constitutively produce infectious virus. Transcriptional expression of the full-length HCV RNA genome is under the control of a cellular Pol II polymerase promoter at the 5' end and a hepatitis delta virus ribozyme at the 3' end. The resulting HCV RNA was expressed and replicated efficiently, as shown by the presence of high levels of HCV proteins as well as both positive- and negative-strand RNAs in the stable Huh7 cell lines. Stable cell lines robustly produce HCV virions with up to 10(8) copies of HCV viral RNA per milliliter (ml) of the culture medium. Subsequent infection of naïve Huh7.5 cells with HCV released from the stable cell lines resulted in high levels of HCV proteins and RNAs. Additionally, HCV infection was inhibited by monoclonal antibodies specific to CD81 and the HCV envelope glycoproteins E1 and E2, and HCV replication was suppressed by alpha interferon. Collectively, these results demonstrate the establishment of a stable HCV culture system that robustly produces infectious virus, which will allow the study of each aspect of the entire HCV life cycle.

Animals↗
PubMed2004

Global robust stability for shunting inhibitory CNNs with delays.

In this paper, the problem of global robust stability for shunting inhibitory cellular neural networks (SICNNs) is studied. A sufficient condition guaranteeing the network's global robust stability is established. The result can easily be used to verify globally robust stable networks. An example is given to illustrate that the conditions of our results are feasible.

Animals↗
PubMed2006

Applying Robust Directional Similarity based Clustering approach RDSC to classification of gene expression data.

Despite the fact that the classification of gene expression data from a cDNA microarrays has been extensively studied, nowadays a robust clustering method, which can estimate an appropriate number of clusters and be insensitive to its initialization has not yet been developed. In this work, a novel Robust Clustering approach, RDSC, based on the new Directional Similarity measure is presented. This new approach RDSC, which integrates the Directional Similarity based Clustering Algorithm, DSC, with the Agglomerative Hierarchical Clustering Algorithm, AHC, exhibits its robustness to initialization and its capability to determine the appropriate number of clusters reasonably. RDSC has been successfully employed to both artificial and benchmarking gene expression datasets. Our experimental results demonstrate its distinctive superiority over the conventional method Kmeans and the two typical directional clustering algorithms SPKmeans and moVMF.

Algorithms↗
PubMed2006

Hypoxia-inducible factor-1 inhibition in combination with temozolomide treatment exhibits robust antitumor efficacy in vivo.

PURPOSE: Inhibiting hypoxia-inducible factor-1 (HIF-1) represents a unique mechanism for cancer therapy. It is conceived that HIF-1 inhibitors may synergize with many classes of cancer therapeutic agents, such as angiogenesis inhibitors and cytotoxic drugs, to achieve a more robust tumor response. However, these hypotheses have not been rigorously tested in tumor models in vivo. The present study was carried out to evaluate the antitumor efficacy of combining HIF-1 inhibition with angiogenesis inhibitors or cytotoxic agents. EXPERIMENTAL DESIGN: Using a D54MG-derived tumor model that allows knockdown of HIF-1alpha on doxycycline treatment, we examined the tumor responses to chemotherapeutic agents, including the angiogenesis inhibitor ABT-869 and cytotoxic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and temozolomide, in the presence or absence of an intact HIF-1 pathway. RESULTS: Surprisingly, inhibiting HIF-1 in tumors treated with the angiogenesis inhibitor ABT-869 did not produce much added benefit compared with ABT-869 treatment alone, suggesting that the combination of an angiogenesis inhibitor with a HIF-1 inhibitor may not be a robust therapeutic regimen. In contrast, the cytotoxic drug temozolomide, when used in combination with HIF-1alpha knockdown, exhibited a superadditive and likely synergistic therapeutic effect compared with the monotherapy of either treatment alone in the D54MG glioma model. CONCLUSIONS: Our results show that the DNA alkylating agent temozolomide exhibits robust antitumor efficacy when used in combination with HIF-1 inhibition in D54MG-derived tumors, suggesting that the combination of temozolomide with HIF-1 inhibitors might be an effective regimen for cancer therapy. In addition, our results also show that the RNA interference-based inducible knockdown model can be a valuable platform for further evaluation of the combination treatment of other cancer therapeutics with HIF-1 inhibition.

Administration, Oral↗
PubMed2002

Trend tests for case-control studies of genetic markers: power, sample size and robustness.

The Cochran-Armitage trend test is commonly used as a genotype-based test for candidate gene association. Corresponding to each underlying genetic model there is a particular set of scores assigned to the genotypes that maximizes its power. When the variance of the test statistic is known, the formulas for approximate power and associated sample size are readily obtained. In practice, however, the variance of the test statistic needs to be estimated. We present formulas for the required sample size to achieve a prespecified power that account for the need to estimate the variance of the test statistic. When the underlying genetic model is unknown one can incur a substantial loss of power when a test suitable for one mode of inheritance is used where another mode is the true one. Thus, tests having good power properties relative to the optimal tests for each model are useful. These tests are called efficiency robust and we study two of them: the maximin efficiency robust test is a linear combination of the standardized optimal tests that has high efficiency and the MAX test, the maximum of the standardized optimal tests. Simulation results of the robustness of these two tests indicate that the more computationally involved MAX test is preferable.

Case-Control Studies↗
PubMedDate not supplied

Aging and attenuated processing robustness. Evidence from cognitive and sensorimotor functioning.

BACKGROUND: Within-person, across-time variations in processes and performance are intrinsic to all aspects of human functioning. OBJECTIVE: This article starts with a brief taxonomy of intraindividual dynamics. There are adaptive as well as non-adaptive types of intraindividual variations that unfold with different degrees of reversibility on different time scales and involve either single, or systems of, functions. METHODS: Empirical findings regarding aging and a specific type of intraindividual variation, namely attenuated processing robustness, are then presented with respect to cognitive and sensorimotor functioning. RESULTS: In both domains of functioning, old adults exhibit less robust functioning with a greater amount of week-to-week, day-to-day, or trial-by-trial fluctuations in their cognitive, walking, and postural control performances. CONCLUSION: Currently, the causes for the attenuation of processing robustness in cognitive and sensorimotor functioning are not well understood. Neurocomputational models are useful tools for exploring the tripartite relationships between the aging of neural information-processing fidelity, and cognitive, and sensorimotor processes.

Aging↗
PubMed2007

Robust multipoint simultaneous identical-by-descent mapping for two linked loci.

A challenging issue in genetic mapping of complex human diseases is localizing disease susceptibility genes when the genetic effects are small to moderate. There are greater complexities when multiple loci are linked to a chromosomal region. Liang et al. [Hum Hered 2001;51:64-78] proposed a robust multipoint method that can simultaneously estimate both the position of a trait locus and its effect on disease status by using affected sib pairs (ASPs). Based on the framework of generalized estimating equations (GEEs), the estimate and standard error of the position of a trait locus are robust to different genetic models. To utilize other relative pairs collected in pedigree data, Schaid et al. [Am J Hum Genet 2005;76:128-138] extended Liang's method to various types of affected relative pairs (ARPs) by two approaches: unconstrained and constrained methods. However, the above methods are limited to situations in which only one trait locus exists on the chromosome of interest. The mean functions are no longer correctly specified when there are multiple causative loci linked to a chromosomal region. To overcome this, Biernacka et al. [Genet Epidemiol 2005;28:33-47] considered the multipoint methods for ASPs to allow for two linked disease genes. We further generalize the approach to cover other types of ARPs. To reflect realistic situations for complex human diseases, we set modest sizes of genetic effects in our simulation. Our results suggest that several hundred independent pedigrees are needed, and markers with high information, to provide reliable estimates of trait locus positions and their confidence intervals. Bootstrap resampling can correct the downward bias of the robust variance for location estimates. These methods are applied to a prostate cancer linkage study on chromosome 20 and compared with the results for the one-locus model [Am J Hum Genet 2005;76:128-138]. We have implemented the multipoint IBD mapping for one and two linked loci in our software GEEARP, which allows analyses for five general types of ARPs.

Bias↗
PubMed1986

Robust spectral analysis of the EEG.

Robust methods for the spectral analysis of time series are briefly reviewed and seen to have applications in the field of EEG. After presenting two simple schemes for outliers (artifacts) generation and discussing their implications for estimation of the spectral density, the robust filtering algorithm of Kleiner et al. [J.R. Statist. Soc. Ser. B, 41: 313-351, 1979] is introduced and shown to work well for simulated data and for true EEG data containing artifacts. A new use of the robust methods for the detection of artifacts and possibly other transients in long-time EEG recordings is suggested and a preliminary implementation illustrated.

Electroencephalography↗
PubMed1997

Comparison of the bone robusticity index and bone weight/bone length index with the results of bone densitometry and bone histomorphometry in experimental studies.

In experimental studies of bone in rats, two morphometric indices reflecting bone density have been proposed, the bone robusticity index and bone weight/bone length index. In rats, the bone mineral content (BMC) and bone mineral density (BMD) of a selected bone can be determined using dual-energy X-ray absorptiometry (DXA); bone volume can be measured by histomorphometry and other techniques. This study was undertaken to compare two morphometric indices (bone robusticity and bone weight/bone length) with the results of DXA and histomorphometry. Forty female Wistar rats (100 days old, mean weight 239+/-12 g) were studied: 20 controls and 20 ovariectomized rats (OVX). The morphometric indices and BMD differed significantly (Friedman test) in the overall group of rats; no differences were observed in the control group, but significant differences were apparent in the OVX group (p<0.0001). The morphometric indices correlated more closely with BMC than with BMD; the femur length/ femur weight index had closer correlations than the robusticity index. Nonetheless, both morphometric indices differed significantly from BMD determined by DXA under abnormal conditions, which makes them unreliable for use in these circumstances.

Absorptiometry, Photon↗