A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Algorithms - Top 30 Publications

Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study.

Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors.Design Prospective open cohort study.Setting General practices in England providing data for the QResearch database.Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline.Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status.Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records.Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R(2), with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms.Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.

Spatial interpolation and radiological mapping of ambient gamma dose rate by using artificial neural networks and fuzzy logic methods.

The aim of this study was to determine spatial risk dispersion of ambient gamma dose rate (AGDR) by using both artificial neural network (ANN) and fuzzy logic (FL) methods, compare the performances of methods, make dose estimations for intermediate stations with no previous measurements and create dose rate risk maps of the study area. In order to determine the dose distribution by using artificial neural networks, two main networks and five different network structures were used; feed forward ANN; Multi-layer perceptron (MLP), Radial basis functional neural network (RBFNN), Quantile regression neural network (QRNN) and recurrent ANN; Jordan networks (JN), Elman networks (EN). In the evaluation of estimation performance obtained for the test data, all models appear to give similar results. According to the cross-validation results obtained for explaining AGDR distribution, Pearson's r coefficients were calculated as 0.94, 0.91, 0.89, 0.91, 0.91 and 0.92 and RMSE values were calculated as 34.78, 43.28, 63.92, 44.86, 46.77 and 37.92 for MLP, RBFNN, QRNN, JN, EN and FL, respectively. In addition, spatial risk maps showing distributions of AGDR of the study area were created by all models and results were compared with geological, topological and soil structure.

Evaluating Model-Data Fit by Comparing Parametric and Nonparametric Item Response Functions: Application of a Tukey-Hann Procedure.

This study describes an approach for examining model-data fit for the dichotomous Rasch model using Tukey-Hann item response functions (TH-IRFs). The procedure proposed in this paper is based on an iterative version of a smoothing technique proposed by Tukey (1977) for estimating nonparametric item response functions (IRFs). A root integrated squared error (RISE) statistic (Douglas and Cohen, 2001) is used to compare the TH-IRFs to the Rasch IRFs. Data from undergraduate students at a large university are used to demonstrate this iterative smoothing technique. The RISE statistic is used for comparing the item response functions to assess model-data fit. A comparison between the residual based Infit and Outfit statistics and RISE statistics are also examined. The results suggest that the RISE statistic and TH-IRFs provide a useful analytical and graphical approach for evaluating item fit. Implications for research, theory and practice related to model-data fit are discussed.

Scale Anchoring with the Rasch Model.

Scale anchoring is a method to provide additional meaning to particular scores at different points along a score scale by identifying representative items associated with the particular scores. These items are then analyzed to write statements of what types of performance can be expected of a person with the particular scores to help test takers and other stakeholders better understand what it means to achieve the different scores. This article provides simple formulas that can be used to identify possible items to serve as scale anchors with the Rasch model. Specific attention is given to practical considerations and challenges that may be encountered when applying the formulas in different contexts. An illustrative example using data from a medical imaging certification program demonstrates how the formulas can be applied in practice.

Comparing Imputation Methods for Trait Estimation Using the Rating Scale Model.

This study examined the performance of four methods of handling missing data for discrete response options on a questionnaire: (1) ignoring the missingness (using only the observed items to estimate trait levels); (2) nearest-neighbor hot deck imputation; (3) multiple hot deck imputation; and (4) semi-parametric multiple imputation. A simulation study examining three questionnaire lengths (41-, 20-, and 10-item) crossed with three levels of missingness (10, 25, and 40 percent) was conducted to see which methods best recovered trait estimates when data were missing completely at random and the polytomous items were scored with Andrich's (1978) rating scale model. The results showed that ignoring the missingness and semi-parametric imputation best recovered known trait levels across all conditions, with the semi-parametric technique providing the most precise trait estimates. This study demonstrates the power of specific objectivity in Rasch measurement, as ignoring the missingness leads to generally unbiased trait estimates.

Can we create a valid treatment algorithm for patients with drug resistant overactive bladder (OAB) syndrome or detrusor overactivity (DO)? Results from a think tank (ICI-RS 2015).

To review and assess the definitions of drug resistance and the evidence supporting treatment for drug resistant overactive bladder/detrusor overactivity (OAB/DO).

Genomic prediction from observed and imputed high-density ovine genotypes.

Genomic prediction using high-density (HD) marker genotypes is expected to lead to higher prediction accuracy, particularly for more heterogeneous multi-breed and crossbred populations such as those in sheep and beef cattle, due to providing stronger linkage disequilibrium between single nucleotide polymorphisms and quantitative trait loci controlling a trait. The objective of this study was to evaluate a possible improvement in genomic prediction accuracy of production traits in Australian sheep breeds based on HD genotypes (600k, both observed and imputed) compared to prediction based on 50k marker genotypes. In particular, we compared improvement in prediction accuracy of animals that are more distantly related to the reference population and across sheep breeds.

Machine Learning for Social Services: A Study of Prenatal Case Management in Illinois.

To evaluate the positive predictive value of machine learning algorithms for early assessment of adverse birth risk among pregnant women as a means of improving the allocation of social services.

AnkPlex: algorithmic structure for refinement of near-native ankyrin-protein docking.

Computational analysis of protein-protein interaction provided the crucial information to increase the binding affinity without a change in basic conformation. Several docking programs were used to predict the near-native poses of the protein-protein complex in 10 top-rankings. The universal criteria for discriminating the near-native pose are not available since there are several classes of recognition protein. Currently, the explicit criteria for identifying the near-native pose of ankyrin-protein complexes (APKs) have not been reported yet.

Electricity forecasting on the individual household level enhanced based on activity patterns.

Leveraging smart metering solutions to support energy efficiency on the individual household level poses novel research challenges in monitoring usage and providing accurate load forecasting. Forecasting electricity usage is an especially important component that can provide intelligence to smart meters. In this paper, we propose an enhanced approach for load forecasting at the household level. The impacts of residents' daily activities and appliance usages on the power consumption of the entire household are incorporated to improve the accuracy of the forecasting model. The contributions of this paper are threefold: (1) we addressed short-term electricity load forecasting for 24 hours ahead, not on the aggregate but on the individual household level, which fits into the Residential Power Load Forecasting (RPLF) methods; (2) for the forecasting, we utilized a household specific dataset of behaviors that influence power consumption, which was derived using segmentation and sequence mining algorithms; and (3) an extensive load forecasting study using different forecasting algorithms enhanced by the household activity patterns was undertaken.

A cross-sectional evaluation of meditation experience on electroencephalography data by artificial neural network and support vector machine classifiers.

To quantitate the meditation experience is a subjective and complex issue because it is confounded by many factors such as emotional state, method of meditation, and personal physical condition. In this study, we propose a strategy with a cross-sectional analysis to evaluate the meditation experience with 2 artificial intelligence techniques: artificial neural network and support vector machine. Within this analysis system, 3 features of the electroencephalography alpha spectrum and variant normalizing scaling are manipulated as the evaluating variables for the detection of accuracy. Thereafter, by modulating the sliding window (the period of the analyzed data) and shifting interval of the window (the time interval to shift the analyzed data), the effect of immediate analysis for the 2 methods is compared. This analysis system is performed on 3 meditation groups, categorizing their meditation experiences in 10-year intervals from novice to junior and to senior. After an exhausted calculation and cross-validation across all variables, the high accuracy rate >98% is achievable under the criterion of 0.5-minute sliding window and 2 seconds shifting interval for both methods. In a word, the minimum analyzable data length is 0.5 minute and the minimum recognizable temporal resolution is 2 seconds in the decision of meditative classification. Our proposed classifier of the meditation experience promotes a rapid evaluation system to distinguish meditation experience and a beneficial utilization of artificial techniques for the big-data analysis.

Identify High-Quality Protein Structural Models by Enhanced K-Means.

Background. One critical issue in protein three-dimensional structure prediction using either ab initio or comparative modeling involves identification of high-quality protein structural models from generated decoys. Currently, clustering algorithms are widely used to identify near-native models; however, their performance is dependent upon different conformational decoys, and, for some algorithms, the accuracy declines when the decoy population increases. Results. Here, we proposed two enhanced K-means clustering algorithms capable of robustly identifying high-quality protein structural models. The first one employs the clustering algorithm SPICKER to determine the initial centroids for basic K-means clustering (SK-means), whereas the other employs squared distance to optimize the initial centroids (K-means++). Our results showed that SK-means and K-means++ were more robust as compared with SPICKER alone, detecting 33 (59%) and 42 (75%) of 56 targets, respectively, with template modeling scores better than or equal to those of SPICKER. Conclusions. We observed that the classic K-means algorithm showed a similar performance to that of SPICKER, which is a widely used algorithm for protein-structure identification. Both SK-means and K-means++ demonstrated substantial improvements relative to results from SPICKER and classical K-means.

Influence of Retinal Pathology on the Reliability of Macular Thickness Measurement: A Comparison Between Optical Coherence Tomography Devices.

To evaluate the repeatability, reliability, and comparability of macular thickness measurements between three optical coherence tomography (OCT) machines in healthy eyes, eyes with diabetic macular edema (DME), and eyes with neovascular age-related macular degeneration (nAMD).

Correlation Between Mesopic Retinal Sensitivity and Optical Coherence Tomographic Metrics of the Outer Retina in Patients With Non-Atrophic Dry Age-Related Macular Degeneration.

To determine the correlation between mesopic retinal sensitivity and optical coherence tomographic metrics of the outer retina in patients with intermediate age-related macular degeneration (AMD).

Chemical-induced disease relation extraction via convolutional neural network.

This article describes our work on the BioCreative-V chemical-disease relation (CDR) extraction task, which employed a maximum entropy (ME) model and a convolutional neural network model for relation extraction at inter- and intra-sentence level, respectively. In our work, relation extraction between entity concepts in documents was simplified to relation extraction between entity mentions. We first constructed pairs of chemical and disease mentions as relation instances for training and testing stages, then we trained and applied the ME model and the convolutional neural network model for inter- and intra-sentence level, respectively. Finally, we merged the classification results from mention level to document level to acquire the final relations between chemical and disease concepts. The evaluation on the BioCreative-V CDR corpus shows the effectiveness of our proposed approach.

An algorithm for separation of mixed sparse and Gaussian sources.

Independent component analysis (ICA) is a ubiquitous method for decomposing complex signal mixtures into a small set of statistically independent source signals. However, in cases in which the signal mixture consists of both nongaussian and Gaussian sources, the Gaussian sources will not be recoverable by ICA and will pollute estimates of the nongaussian sources. Therefore, it is desirable to have methods for mixed ICA/PCA which can separate mixtures of Gaussian and nongaussian sources. For mixtures of purely Gaussian sources, principal component analysis (PCA) can provide a basis for the Gaussian subspace. We introduce a new method for mixed ICA/PCA which we call Mixed ICA/PCA via Reproducibility Stability (MIPReSt). Our method uses a repeated estimations technique to rank sources by reproducibility, combined with decomposition of multiple subsamplings of the original data matrix. These multiple decompositions allow us to assess component stability as the size of the data matrix changes, which can be used to determinine the dimension of the nongaussian subspace in a mixture. We demonstrate the utility of MIPReSt for signal mixtures consisting of simulated sources and real-word (speech) sources, as well as mixture of unknown composition.

MeSH Now: automatic MeSH indexing at PubMed scale via learning to rank.

MeSH indexing is the task of assigning relevant MeSH terms based on a manual reading of scholarly publications by human indexers. The task is highly important for improving literature retrieval and many other scientific investigations in biomedical research. Unfortunately, given its manual nature, the process of MeSH indexing is both time-consuming (new articles are not immediately indexed until 2 or 3 months later) and costly (approximately ten dollars per article). In response, automatic indexing by computers has been previously proposed and attempted but remains challenging. In order to advance the state of the art in automatic MeSH indexing, a community-wide shared task called BioASQ was recently organized.

Quantification of task-dependent cortical activation evoked by robotic continuous wrist joint manipulation in chronic hemiparetic stroke.

Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment.

Physical human-robot interaction of an active pelvis orthosis: toward ergonomic assessment of wearable robots.

In human-centered robotics, exoskeletons are becoming relevant for addressing needs in the healthcare and industrial domains. Owing to their close interaction with the user, the safety and ergonomics of these systems are critical design features that require systematic evaluation methodologies. Proper transfer of mechanical power requires optimal tuning of the kinematic coupling between the robotic and anatomical joint rotation axes. We present the methods and results of an experimental evaluation of the physical interaction with an active pelvis orthosis (APO). This device was designed to effectively assist in hip flexion-extension during locomotion with a minimum impact on the physiological human kinematics, owing to a set of passive degrees of freedom for self-alignment of the human and robotic hip flexion-extension axes.

Non-fragile mixed H∞ and passive synchronization of Markov jump neural networks with mixed time-varying delays and randomly occurring controller gain fluctuation.

This paper studies the non-fragile mixed H∞ and passive synchronization problem for Markov jump neural networks. The randomly occurring controller gain fluctuation phenomenon is investigated for non-fragile strategy. Moreover, the mixed time-varying delays composed of discrete and distributed delays are considered. By employing stochastic stability theory, synchronization criteria are developed for the Markov jump neural networks. On the basis of the derived criteria, the non-fragile synchronization controller is designed. Finally, an illustrative example is presented to demonstrate the validity of the control approach.

Mathematical algorithm for the automatic recognition of intestinal parasites.

Parasitic infections are generally diagnosed by professionals trained to recognize the morphological characteristics of the eggs in microscopic images of fecal smears. However, this laboratory diagnosis requires medical specialists which are lacking in many of the areas where these infections are most prevalent. In response to this public health issue, we developed a software based on pattern recognition analysis from microscopi digital images of fecal smears, capable of automatically recognizing and diagnosing common human intestinal parasites. To this end, we selected 229, 124, 217, and 229 objects from microscopic images of fecal smears positive for Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica, respectively. Representative photographs were selected by a parasitologist. We then implemented our algorithm in the open source program SCILAB. The algorithm processes the image by first converting to gray-scale, then applies a fourteen step filtering process, and produces a skeletonized and tri-colored image. The features extracted fall into two general categories: geometric characteristics and brightness descriptions. Individual characteristics were quantified and evaluated with a logistic regression to model their ability to correctly identify each parasite separately. Subsequently, all algorithms were evaluated for false positive cross reactivity with the other parasites studied, excepting Taenia sp. which shares very few morphological characteristics with the others. The principal result showed that our algorithm reached sensitivities between 99.10%-100% and specificities between 98.13%- 98.38% to detect each parasite separately. We did not find any cross-positivity in the algorithms for the three parasites evaluated. In conclusion, the results demonstrated the capacity of our computer algorithm to automatically recognize and diagnose Taenia sp., Trichuris trichiura, Diphyllobothrium latum, and Fasciola hepatica with a high sensitivity and specificity.

Depressive Symptoms and Their Interactions With Emotions and Personality Traits Over Time: Interaction Networks in a Psychiatric Clinic.

Associations between depression, personality traits, and emotions are complex and reciprocal. The aim of this study is to explore these interactions in dynamical networks and in a linear way over time depending on the severity of depression.

Learning from label proportions in brain-computer interfaces: Online unsupervised learning with guarantees.

Using traditional approaches, a brain-computer interface (BCI) requires the collection of calibration data for new subjects prior to online use. Calibration time can be reduced or eliminated e.g., by subject-to-subject transfer of a pre-trained classifier or unsupervised adaptive classification methods which learn from scratch and adapt over time. While such heuristics work well in practice, none of them can provide theoretical guarantees. Our objective is to modify an event-related potential (ERP) paradigm to work in unison with the machine learning decoder, and thus to achieve a reliable unsupervised calibrationless decoding with a guarantee to recover the true class means.

Differential transcriptome analysis supports Rhodnius montenegrensis and Rhodnius robustus (Hemiptera, Reduviidae, Triatominae) as distinct species.

Chagas disease is one of the main parasitic diseases found in Latin America and it is estimated that between six and seven million people are infected worldwide. Its etiologic agent, the protozoan Trypanosoma cruzi, is transmitted by triatomines, some of which from the genus Rhodnius. Twenty species are currently recognized in this genus, including some closely related species with low levels of morphological differentiation, such as Rhodnius montenegrensis and Rhodnius robustus. In order to investigate genetic differences between these two species, we generated large-scale RNA-sequencing data (consisting of four RNA-seq libraries) from the heads and salivary glands of males of R. montenegrensis and R. robustus. Transcriptome assemblies produced for each species resulted in 64,952 contigs for R. montenegrensis and 70,894 contigs for R. robustus, with N50 of approximately 2,100 for both species. SNP calling based on the more complete R. robustus assembly revealed 3,055 fixed interspecific differences and 216 transcripts with high levels of divergence which contained only fixed differences between the two species. A gene ontology enrichment analysis revealed that these highly differentiated transcripts were enriched for eight GO terms related to AP-2 adaptor complex, as well as other interesting genes that could be involved in their differentiation. The results show that R. montenegrensis and R. robustus have a substantial quantity of fixed interspecific polymorphisms, which suggests a high degree of genetic divergence between the two species and likely corroborates the species status of R. montenegrensis.

Continuous uniformly finite time exact disturbance observer based control for fixed-time stabilization of nonlinear systems with mismatched disturbances.

This paper presents a continuous composite control scheme to achieve fixed-time stabilization for nonlinear systems with mismatched disturbances. The composite controller is constructed in two steps: First, uniformly finite time exact disturbance observers are proposed to estimate and compensate the disturbances. Then, based on adding a power integrator technique and fixed-time stability theory, continuous fixed-time stable state feedback controller and Lyapunov functions are constructed to achieve global fixed-time system stabilization. The proposed control method extends the existing fixed-time stable control results to high order nonlinear systems with mismatched disturbances and achieves global fixed-time system stabilization. Besides, the proposed control scheme improves the disturbance rejection performance and achieves performance recovery of nominal system. Simulation results are provided to show the effectiveness, the superiority and the applicability of the proposed control scheme.

Predicting 3D lip shapes using facial surface EMG.

The aim of this study is to prove that facial surface electromyography (sEMG) conveys sufficient information to predict 3D lip shapes. High sEMG predictive accuracy implies we could train a neural control model for activation of biomechanical models by simultaneously recording sEMG signals and their associated motions.

Applications of fractional lower order S transform time frequency filtering algorithm to machine fault diagnosis.

Stockwell transform(ST) time-frequency representation(ST-TFR) is a time frequency analysis method which combines short time Fourier transform with wavelet transform, and ST time frequency filtering(ST-TFF) method which takes advantage of time-frequency localized spectra can separate the signals from Gaussian noise. The ST-TFR and ST-TFF methods are used to analyze the fault signals, which is reasonable and effective in general Gaussian noise cases. However, it is proved that the mechanical bearing fault signal belongs to Alpha(α) stable distribution process(1 < α < 2) in this paper, even the noise also is α stable distribution in some special cases. The performance of ST-TFR method will degrade under α stable distribution noise environment, following the ST-TFF method fail. Hence, a new fractional lower order ST time frequency representation(FLOST-TFR) method employing fractional lower order moment and ST and inverse FLOST(IFLOST) are proposed in this paper. A new FLOST time frequency filtering(FLOST-TFF) algorithm based on FLOST-TFR method and IFLOST is also proposed, whose simplified method is presented in this paper. The discrete implementation of FLOST-TFF algorithm is deduced, and relevant steps are summarized. Simulation results demonstrate that FLOST-TFR algorithm is obviously better than the existing ST-TFR algorithm under α stable distribution noise, which can work better under Gaussian noise environment, and is robust. The FLOST-TFF method can effectively filter out α stable distribution noise, and restore the original signal. The performance of FLOST-TFF algorithm is better than the ST-TFF method, employing which mixed MSEs are smaller when α and generalized signal noise ratio(GSNR) change. Finally, the FLOST-TFR and FLOST-TFF methods are applied to analyze the outer race fault signal and extract their fault features under α stable distribution noise, where excellent performances can be shown.

Predicting functional decline and survival in amyotrophic lateral sclerosis.

Better predictors of amyotrophic lateral sclerosis disease course could enable smaller and more targeted clinical trials. Partially to address this aim, the Prize for Life foundation collected de-identified records from amyotrophic lateral sclerosis sufferers who participated in clinical trials of investigational drugs and made them available to researchers in the PRO-ACT database.

HSTLBO: A hybrid algorithm based on Harmony Search and Teaching-Learning-Based Optimization for complex high-dimensional optimization problems.

Harmony Search (HS) and Teaching-Learning-Based Optimization (TLBO) as new swarm intelligent optimization algorithms have received much attention in recent years. Both of them have shown outstanding performance for solving NP-Hard optimization problems. However, they also suffer dramatic performance degradation for some complex high-dimensional optimization problems. Through a lot of experiments, we find that the HS and TLBO have strong complementarity each other. The HS has strong global exploration power but low convergence speed. Reversely, the TLBO has much fast convergence speed but it is easily trapped into local search. In this work, we propose a hybrid search algorithm named HSTLBO that merges the two algorithms together for synergistically solving complex optimization problems using a self-adaptive selection strategy. In the HSTLBO, both HS and TLBO are modified with the aim of balancing the global exploration and exploitation abilities, where the HS aims mainly to explore the unknown regions and the TLBO aims to rapidly exploit high-precision solutions in the known regions. Our experimental results demonstrate better performance and faster speed than five state-of-the-art HS variants and show better exploration power than five good TLBO variants with similar run time, which illustrates that our method is promising in solving complex high-dimensional optimization problems. The experiment on portfolio optimization problems also demonstrate that the HSTLBO is effective in solving complex read-world application.

Three-Dimensional Super-Resolution in Eukaryotic Cells Using the Double-Helix Point Spread Function.

Single-molecule localization microscopy, typically based on total internal reflection illumination, has taken our understanding of protein organization and dynamics in cells beyond the diffraction limit. However, biological systems exist in a complicated three-dimensional environment, which has required the development of new techniques, including the double-helix point spread function (DHPSF), to accurately visualize biological processes. The application of the DHPSF approach has so far been limited to the study of relatively small prokaryotic cells. By matching the refractive index of the objective lens immersion liquid to that of the sample media, we demonstrate DHPSF imaging of up to 15-μm-thick whole eukaryotic cell volumes in three to five imaging planes. We illustrate the capabilities of the DHPSF by exploring large-scale membrane reorganization in human T cells after receptor triggering, and by using single-particle tracking to image several mammalian proteins, including membrane, cytoplasmic, and nuclear proteins in T cells and embryonic stem cells.