Treadmill-based system for postural studies: Design and validation.

Computer-controlled treadmills are common in many gait labs and offer great potential for conducting perturbation-based postural studies. However, the time-course of these disturbances can be too brief to be controlled manually through product software. Here we present a system that combines a Bertec® split-belt treadmill with custom hardware and software to deliver postural disturbances during standing and record data from multiple sources simultaneously. We used this system to administer to 15 healthy participants an 8-session perturbation-based training protocol in which they learned to respond without stepping to progressively larger perturbations. Kinematic, electromyographic, and force data were collected throughout. Motion capture was used to characterize the accuracy and repeatability of the treadmill-delivered perturbations with respect to duration, displacement, and peak velocity. These (observed) data were compared to that expected based on software commands and the known constraints of the treadmill (i.e., 10 Hz operating speed). We found perturbation durations to be as expected. Peak velocities and displacements were slightly higher than expected (average increases were 0.59 cm/s and 1.76 cm, respectively). Because this increase in magnitude was consistent, it did not impede training or affect data analysis. Treadmill behavior was repeatable across 95 % of trials.

Sfold Tools for MicroRNA Target Prediction.

Computational prediction of miRNA binding sites on target mRNAs facilitates experimental investigation of miRNA functions. In this chapter, we describe STarMir and STarMirDB, two application modules of the Sfold RNA package. STarMir is a Web server for performing miRNA binding site predictions for mRNA and target sequences submitted by users. STarMirDB is a database of precomputed transcriptome-scale predictions. Both STarMir and STarMirDB provide comprehensive sequence, thermodynamic, and target structure features, a logistic probability as a measure of confidence for each predicted site, and a publication-quality diagram of the predicted miRNA-target hybrid. In addition, STarMir now offers a new quantitative score to address combined regulatory effects of multiple seed and seedless sites. This score provides a quantitative measure of the overall regulatory effects of both seed and seedless sites on the target. STarMir and STarMirDB are freely available to all through the Sfold Web application server at http://sfold.wadsworth.org .

Hispanic mothers' beliefs regarding HPV vaccine series completion in their adolescent daughters.

Rates of human papillomavirus (HPV) vaccine series completion among adolescent Hispanic females in Texas in 2014 (∼39%) lag behind the Healthy People 2020 goal (80%). This qualitative study identifies Hispanic mothers' salient behavioral, normative and control beliefs regarding having their adolescent daughters complete the vaccine series. Thirty-two mothers of girls (aged 11-17) that had received at least one dose of the HPV vaccine, completed in-depth interviews. Six girls had received one dose of the HPV vaccine, 10 girls had received two doses, and 16 girls had received all three doses. The questions elicited salient: (i) experiential and instrumental attitudes (behavioral beliefs); (ii) supporters and non-supporters (normative beliefs) and (iii) facilitators and barriers (control beliefs). Directed content analysis was employed to select the most salient beliefs. Mothers: (i) expressed salient positive feelings (e.g. good, secure, happy and satisfied); (ii) believed that completing the series resulted in positive effects (e.g. protection, prevention); (iii) believed that the main supporters were themselves, their daughter's father and doctor with some of their friends not supporting series completion and (iv) believed that vaccine affordability, information, transportation, ease of scheduling and keeping vaccination appointments and taking their daughter's immunization card to appointments were facilitators. This study represents the first step in building theory-based framework of vaccine series completion for this population. The beliefs identified provide guidance for health care providers and intervention developers.

STarMir Tools for Prediction of microRNA Binding Sites.

MicroRNAs (miRNAs) are a class of endogenous short noncoding RNAs that regulate gene expression by targeting messenger RNAs (mRNAs), which results in translational repression and/or mRNA degradation. As regulatory molecules, miRNAs are involved in many mammalian biological processes and also in the manifestation of certain human diseases. As miRNAs play central role in the regulation of gene expression, understanding miRNA-binding patterns is essential to gain an insight of miRNA mediated gene regulation and also holds promise for therapeutic applications. Computational prediction of miRNA binding sites on target mRNAs facilitates experimental investigation of miRNA functions. This chapter provides protocols for using the STarMir web server for improved predictions of miRNA binding sites on a target mRNA. As an application module of the Sfold RNA package, the current version of STarMir is an implementation of logistic prediction models developed with high-throughput miRNA binding data from cross-linking immunoprecipitation (CLIP) studies. The models incorporated comprehensive thermodynamic, structural, and sequence features, and were found to make improved predictions of both seed and seedless sites, in comparison to the established algorithms (Liu et al., Nucleic Acids Res 41:e138, 2013). Their broad applicability was indicated by their good performance in cross-species validation. STarMir is freely available at http://sfold.wadsworth.org/starmir.html .

STarMirDB: A database of microRNA binding sites.

microRNAs (miRNAs) are an abundant class of small endogenous non-coding RNAs (ncRNAs) of ∼22 nucleotides (nts) in length. These small regulatory molecules are involved in diverse developmental, physiological and pathological processes. miRNAs target mRNAs (mRNAs) for translational repression and/or mRNA degradation. Predictions of miRNA binding sites facilitate experimental validation of miRNA targets. Models developed with data from CLIP studies have been used for predictions of miRNA binding sites in the whole transcriptomes of human, mouse and worm. The prediction results have been assembled into STarMirDB, a new database of miRNA binding sites available at http://sfold.wadsworth.org/starmirDB.php . STarMirDB can be searched by miRNAs or mRNAs separately or in combination. The search results are categorized into seed and seedless sites in 3' UTR, CDS and 5' UTR. For each predicted site, STarMirDB provides a comprehensive list of sequence, thermodynamic and target structural features that are known to influence miRNA: target interaction. A high resolution PDF diagram of the conformation of the miRNA:target hybrid is also available for visualization and publication. The results of a database search are available through both an interactive viewer and downloadable text files.

Effects of genetic variations on microRNA: target interactions.

Genetic variations within microRNA (miRNA) binding sites can affect miRNA-mediated gene regulation, which may lead to phenotypes and diseases. We perform a transcriptome-scale analysis of genetic variants and miRNA:target interactions identified by CLASH. This analysis reveals that rare variants tend to reside in CDSs, whereas common variants tend to reside in the 3' UTRs. miRNA binding sites are more likely to reside within those targets in the transcriptome with lower variant densities, especially target regions in which nucleotides have low mutation frequencies. Furthermore, an overwhelming majority of genetic variants within or near miRNA binding sites can alter not only the potential of miRNA:target hybridization but also the structural accessibility of the binding sites and flanking regions. These suggest an interpretation for certain associations between genetic variants and diseases, i.e. modulation of miRNA-mediated gene regulation by common or rare variants within or near miRNA binding sites, likely through target structure alterations. Our data will be valuable for discovering new associations among miRNAs, genetic variations and human diseases.

STarMir: a web server for prediction of microRNA binding sites.

STarMir web server predicts microRNA (miRNA) binding sites on a target ribonucleic acid (RNA). STarMir is an implementation of logistic prediction models developed with miRNA binding data from crosslinking immunoprecipitation (CLIP) studies (Liu,C., Mallick, B., Long, D., Rennie, W.A., Wolenc, A., Carmack, C.S. and Ding, Y. (2013). CLIP-based prediction of mammalian microRNA binding sites. Nucleic Acids Res., 41(14), e138). In both intra-dataset and inter-dataset validations, the models showed major improvements over established algorithms in predictions of both seed and seedless sites. General applicability of the models was indicated by good performance in cross-species validations. The input data for STarMir is processed by the web server to perform prediction of miRNA binding sites, compute comprehensive sequence, thermodynamic and target structure features and a logistic probability as a measure of confidence for each predicted site. For each of seed and seedless sites and for all three regions of a mRNA (3' UTR, CDS and 5' UTR), STarMir output includes the computed binding site features, the logistic probability and a publication-quality diagram of the predicted miRNA:target hybrid. The prediction results are available through both an interactive viewer and downloadable text files. As an application module of the Sfold RNA package (http://sfold.wadsworth.org), STarMir is freely available to all at http://sfold.wadsworth.org/starmir.html.

MicroRNA binding sites in C. elegans 3' UTRs.

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Since the discovery of lin-4, the founding member of the miRNA family, over 360 miRNAs have been identified for Caenorhabditis elegans (C. elegans). Prediction and validation of targets are essential for elucidation of regulatory functions of these miRNAs. For C. elegans, crosslinking immunoprecipitation (CLIP) has been successfully performed for the identification of target mRNA sequences bound by Argonaute protein ALG-1. In addition, reliable annotation of the 3' untranslated regions (3' UTRs) as well as developmental stage-specific expression profiles for both miRNAs and 3' UTR isoforms are available. By utilizing these data, we developed statistical models and bioinformatics tools for both transcriptome-scale and developmental stage-specific predictions of miRNA binding sites in C. elegans 3' UTRs. In performance evaluation via cross validation on the ALG-1 CLIP data, the models were found to offer major improvements over established algorithms for predicting both seed sites and seedless sites. In particular, our top-ranked predictions have a substantially higher true positive rate, suggesting a much higher likelihood of positive experimental validation. A gene ontology analysis of stage-specific predictions suggests that miRNAs are involved in dynamic regulation of biological functions during C. elegans development. In particular, miRNAs preferentially target genes related to development, cell cycle, trafficking, and cell signaling processes. A database for both transcriptome-scale and stage-specific predictions and software for implementing the prediction models are available through the Sfold web server at http://sfold.wadsworth.org.

Response to an exercise intervention after endometrial cancer: differences between obese and non-obese survivors.

OBJECTIVE: The objective of this paper is to describe baseline differences between obese and non-obese endometrial cancer survivor in anthropometrics, exercise behavior, fitness, heart rate and blood pressure, and quality of life, and to analyze whether the effect of a home-based exercise intervention on these outcomes differed for obese and non-obese participants. METHODS: One hundred post-treatment Stage I-IIIa endometrial cancer survivors participated in a single arm 6month study in which they received a home-based exercise intervention. Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured every two months, and quality of life (QOL) and psychological distress were measured at baseline and 6months. RESULTS: Adjusting for potential confounders, at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher systolic blood pressure (p=.018), and lower physical functioning (p<.001) and ratings of general health (p=.002), and more pain (p=.037) and somatization (.002). Significant improvements were seen in exercise behavior, resting heart rate, systolic blood pressure, and multiple QOL domains over the course of the intervention. Obese survivors had less improvement in exercise behavior and cardiorespiratory fitness than non-obese survivors, but there were no differences with regard to improvements in QOL and stress. CONCLUSIONS: Home based exercise interventions are beneficial to endometrial cancer survivors, including those whose BMI is in the obese range. While obese survivors have lower levels of physical activity and fitness, they experienced similar activity, fitness, quality of life and mental health benefits. Exercise should be encouraged in endometrial cancer survivors, including those who are obese.

Brain-computer interface (BCI) evaluation in people with amyotrophic lateral sclerosis.

Brain-computer interfaces (BCIs) might restore communication to people severely disabled by amyotrophic lateral sclerosis (ALS) or other disorders. We sought to: 1) define a protocol for determining whether a person with ALS can use a visual P300-based BCI; 2) determine what proportion of this population can use the BCI; and 3) identify factors affecting BCI performance. Twenty-five individuals with ALS completed an evaluation protocol using a standard 6 × 6 matrix and parameters selected by stepwise linear discrimination. With an 8-channel EEG montage, the subjects fell into two groups in BCI accuracy (chance accuracy 3%). Seventeen averaged 92 (± 3)% (range 71-100%), which is adequate for communication (G70 group). Eight averaged 12 (± 6)% (range 0-36%), inadequate for communication (L40 subject group). Performance did not correlate with disability: 11/17 (65%) of G70 subjects were severely disabled (i.e. ALSFRS-R < 5). All L40 subjects had visual impairments (e.g. nystagmus, diplopia, ptosis). P300 was larger and more anterior in G70 subjects. A 16-channel montage did not significantly improve accuracy. In conclusion, most people severely disabled by ALS could use a visual P300-based BCI for communication. In those who could not, visual impairment was the principal obstacle. For these individuals, auditory P300-based BCIs might be effective.

CLIP-based prediction of mammalian microRNA binding sites.

Prediction and validation of microRNA (miRNA) targets are essential for understanding functions of miRNAs in gene regulation. Crosslinking immunoprecipitation (CLIP) allows direct identification of a huge number of Argonaute-bound target sequences that contain miRNA binding sites. By analysing data from CLIP studies, we identified a comprehensive list of sequence, thermodynamic and target structure features that are essential for target binding by miRNAs in the 3' untranslated region (3' UTR), coding sequence (CDS) region and 5' untranslated region (5' UTR) of target messenger RNA (mRNA). The total energy of miRNA:target hybridization, a measure of target structural accessibility, is the only essential feature common for both seed and seedless sites in all three target regions. Furthermore, evolutionary conservation is an important discriminating feature for both seed and seedless sites. These features enabled us to develop novel statistical models for the predictions of both seed sites and broad classes of seedless sites. Through both intra-dataset validation and inter-dataset validation, our approach showed major improvements over established algorithms for predicting seed sites and a class of seedless sites. Furthermore, we observed good performance from cross-species validation, suggesting that our prediction framework can be valuable for broad application to other mammalian species and beyond. Transcriptome-wide binding site predictions enabled by our approach will greatly complement the available CLIP data, which only cover small fractions of transcriptomes and known miRNAs due to non-detectable levels of expression. Software and database tools based on the prediction models have been developed and are available through Sfold web server at http://sfold.wadsworth.org.

Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ζ 2 renders tumor cells dependent on its paralogous gene COPZ1.

Anticancer drugs are effective against tumors that depend on the molecular target of the drug. Known targets of cytotoxic anticancer drugs are involved in cell proliferation; drugs acting on such targets are ineffective against nonproliferating tumor cells, survival of which leads to eventual therapy failure. Function-based genomic screening identified the coatomer protein complex ζ1 (COPZ1) gene as essential for different tumor cell types but not for normal cells. COPZ1 encodes a subunit of coatomer protein complex 1 (COPI) involved in intracellular traffic and autophagy. The knockdown of COPZ1, but not of COPZ2 encoding isoform coatomer protein complex ζ2, caused Golgi apparatus collapse, blocked autophagy, and induced apoptosis in both proliferating and nondividing tumor cells. In contrast, inhibition of normal cell growth required simultaneous knockdown of both COPZ1 and COPZ2. COPZ2 (but not COPZ1) was down-regulated in the majority of tumor cell lines and in clinical samples of different cancer types. Reexpression of COPZ2 protected tumor cells from killing by COPZ1 knockdown, indicating that tumor cell dependence on COPZ1 is the result of COPZ2 silencing. COPZ2 displays no tumor-suppressive activities, but it harbors microRNA 152, which is silenced in tumor cells concurrently with COPZ2 and acts as a tumor suppressor in vitro and in vivo. Silencing of microRNA 152 in different cancers and the ensuing down-regulation of its host gene COPZ2 offer a therapeutic opportunity for proliferation-independent selective killing of tumor cells by COPZ1-targeting agents.

Function-based gene identification using enzymatically generated normalized shRNA library and massive parallel sequencing.

As a general strategy for function-based gene identification, an shRNA library containing approximately 150 shRNAs per gene was enzymatically generated from normalized (reduced-redundance) human cDNA. The library was constructed in an inducible lentiviral vector, enabling propagation of growth-inhibiting shRNAs and controlled activity measurements. RNAi activities were measured for 101 shRNA clones representing 100 human genes and for 201 shRNAs derived from a firefly luciferase gene. Structure-activity analysis of these two datasets yielded a set of structural criteria for shRNA efficacy, increasing the frequencies of active shRNAs up to 5-fold relative to random sampling. The same library was used to select shRNAs that inhibit breast carcinoma cell growth by targeting potential oncogenes. Genes targeted by the selected shRNAs were enriched for 10 pathways, 9 of which have been previously associated with various cancers, cell cycle progression, or apoptosis. One hundred nineteen genes, enriched through this selection and represented by two to six shRNAs each, were identified as potential cancer drug targets. Short interfering RNAs against 19 of 22 tested genes in this group inhibited cell growth, validating the efficiency of this strategy for high-throughput target gene identification.

A structural interpretation of the effect of GC-content on efficiency of RNA interference.

BACKGROUND: RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) has become a powerful technique for eukaryotic gene knockdown. siRNA GC-content negatively correlates with RNAi efficiency, and it is of interest to have a convincing mechanistic interpretation of this observation. We here examine this issue by considering the secondary structures for both the target messenger RNA (mRNA) and the siRNA guide strand. RESULTS: By analyzing a unique homogeneous data set of 101 shRNAs targeted to 100 endogenous human genes, we find that: 1) target site accessibility is more important than GC-content for efficient RNAi; 2) there is an appreciable negative correlation between GC-content and RNAi activity; 3) for the predicted structure of the siRNA guide strand, there is a lack of correlation between RNAi activity and either the stability or the number of free dangling nucleotides at an end of the structure; 4) there is a high correlation between target site accessibility and GC-content. For a set of representative structural RNAs, the GC content of 62.6% for paired bases is significantly higher than the GC content of 38.7% for unpaired bases. Thus, for a structured RNA, a region with higher GC content is likely to have more stable secondary structure. Furthermore, by partial correlation analysis, the correlation for GC-content is almost completely diminished, when the effect of target accessibility is controlled. CONCLUSION: These findings provide a target-structure-based interpretation and mechanistic insight for the effect of GC-content on RNAi efficiency.

mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts.

Target prediction for animal microRNAs (miRNAs) has been hindered by the small number of verified targets available to evaluate the accuracy of predicted miRNA-target interactions. Recently, a dataset of 3,404 miRNA-associated mRNA transcripts was identified by immunoprecipitation of the RNA-induced silencing complex components AIN-1 and AIN-2. Our analysis of this AIN-IP dataset revealed enrichment for defining characteristics of functional miRNA-target interactions, including structural accessibility of target sequences, total free energy of miRNA-target hybridization and topology of base-pairing to the 5' seed region of the miRNA. We used these enriched characteristics as the basis for a quantitative miRNA target prediction method, miRNA targets by weighting immunoprecipitation-enriched parameters (mirWIP), which optimizes sensitivity to verified miRNA-target interactions and specificity to the AIN-IP dataset. MirWIP can be used to capture all known conserved miRNA-mRNA target relationships in Caenorhabditis elegans at a lower false-positive rate than can the current standard methods.

Detection of a de novo interstitial 2q microdeletion by CGH microarray analysis in a patient with limb malformations, microcephaly and mental retardation.

We describe the cytogenetic diagnosis using BAC- and oligonucleotide microarrays of a 16-year-old Laotian-American female, who first presented at 2 1/2 years of age with microcephaly, developmental retardation, and skeletal abnormalities of the upper limb including mild syndactyly of the second and third and the third and fourth fingers, short middle phalanges and clinodactyly of the fifth digit at the distal interphalangel joint on both hands, and symphalangism of the metacarpal-phalangeal joints of the second and fifth digits bilaterally. Her lower limbs displayed symphalangism of the metatarsal-phalangeal joint of the second, third, and fourth digits on both feet, with fusion of the middle and distal phalanges of the second and fifth digits and hallux valgus bilaterally. G-banded chromosomal study at age 4 was normal. However, comparative genomic hybridization at age 15 with the Spectral Genomics 1 Mb Hu BAC array platform indicated a microdeletion involving two BAC clones, RP11-451F14 --> RP11-12N7 at 2q31.1. The maximal deletion on initial analysis comprised the HOXD cluster, which is implicated in limb development. Fluorescence in situ hybridization (FISH) using the RP11-451F14 probe confirmed the deletion. Both parents were negative for the deletion. Additional FISH using BAC RP11-387A1, covering the HOXD cluster, limited the maximal deletion to approximately 2.518 Mb, and excluded involvement of the HOXD cluster. The Agilent 44K and 244K platforms demonstrated a deletion of approximately 2,011,000 bp, which did not include the HOXD cluster. The malformations in our patient may be caused by deletion of a regulatory element far upstream of the HOXD cluster.

PhyloScan: identification of transcription factor binding sites using cross-species evidence.

BACKGROUND: When transcription factor binding sites are known for a particular transcription factor, it is possible to construct a motif model that can be used to scan sequences for additional sites. However, few statistically significant sites are revealed when a transcription factor binding site motif model is used to scan a genome-scale database. METHODS: We have developed a scanning algorithm, PhyloScan, which combines evidence from matching sites found in orthologous data from several related species with evidence from multiple sites within an intergenic region, to better detect regulons. The orthologous sequence data may be multiply aligned, unaligned, or a combination of aligned and unaligned. In aligned data, PhyloScan statistically accounts for the phylogenetic dependence of the species contributing data to the alignment and, in unaligned data, the evidence for sites is combined assuming phylogenetic independence of the species. The statistical significance of the gene predictions is calculated directly, without employing training sets. RESULTS: In a test of our methodology on synthetic data modeled on seven Enterobacteriales, four Vibrionales, and three Pasteurellales species, PhyloScan produces better sensitivity and specificity than MONKEY, an advanced scanning approach that also searches a genome for transcription factor binding sites using phylogenetic information. The application of the algorithm to real sequence data from seven Enterobacteriales species identifies novel Crp and PurR transcription factor binding sites, thus providing several new potential sites for these transcription factors. These sites enable targeted experimental validation and thus further delineation of the Crp and PurR regulons in E. coli. CONCLUSION: Better sensitivity and specificity can be achieved through a combination of (1) using mixed alignable and non-alignable sequence data and (2) combining evidence from multiple sites within an intergenic region.

Factors influencing the identification of transcription factor binding sites by cross-species comparison.

As the number of sequenced genomes has grown, the questions of which species are most useful and how many genomes are sufficient for comparison have become increasingly important for comparative genomics studies. We have systematically addressed these questions with respect to phylogenetic footprinting of transcription factor (TF) binding sites in the gamma-proteobacteria, and have evaluated the statistical significance of our motif predictions. We used a study set of 166 Escherichia coli genes that have experimentally identified TF binding sites upstream of the gene, with orthologous data from nine additional gamma-proteobacteria for phylogenetic footprinting. Just three species were sufficient for approximately 74.0% of the motif predictions to correspond to the experimentally reported E. coli sites, and important characteristics to consider when choosing species were phylogenetic distance, genome size, and natural habitat. We also performed simulations using randomized data to determine the critical maximum a posteriori probability (MAP) values for statistical significance of our motif predictions (P = 0.05). Approximately 60% of motif predictions containing sites from just three species had average MAP values above these critical MAP values. The inclusion of a species very closely related to E. coli increased the number of statistically significant motif predictions, despite substantially increasing the critical MAP value.

Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes.

Toward the goal of identifying complete sets of transcription factor (TF)-binding sites in the genomes of several gamma proteobacteria, and hence describing their transcription regulatory networks, we present a phylogenetic footprinting method for identifying these sites. Probable transcription regulatory sites upstream of Escherichia coli genes were identified by cross-species comparison using an extended Gibbs sampling algorithm. Close examination of a study set of 184 genes with documented transcription regulatory sites revealed that when orthologous data were available from at least two other gamma proteobacterial species, 81% of our predictions corresponded with the documented sites, and 67% corresponded when data from only one other species were available. That the remaining predictions included bona fide TF-binding sites was proven by affinity purification of a putative transcription factor (YijC) bound to such a site upstream of the fabA gene. Predicted regulatory sites for 2097 E.coli genes are available at http://www.wadsworth.org/resnres/bioinfo/.

Depression, anxiety, and quality of life in patients with epithelial ovarian cancer.

OBJECTIVE: The aims of this study were to evaluate psychological distress and quality of life (QOL) in patients with epithelial ovarian cancer (EOC) and to examine the relationship between these problems and health and demographic variables. METHODS: Of 344 consecutive patients identified, 246 completed questionnaires. Four dimensions of QOL were assessed including physical, functional, emotional, and social/family well-being, as well as concerns specific to ovarian cancer patients. Depression was measured with the Center for Epidemiologic Studies-Depression (CES-D) scale and anxiety was measured by the State Anxiety Subscale of the Spielberger State-Trait Anxiety Inventory. Performance status was evaluated by the Zubrod score. RESULTS: Sixty-five patients (26%) had early stage disease; 181 (74%) had advanced disease. One hundred twenty-one patients (49%) were under active treatment, while 124 (51%) were seen for posttherapy surveillance. Forty-eight (21%) met CES-D cutoff criteria for a clinical evaluation for depression, and 29% scored above the 75th percentile for anxiety. Performance status was related to depression, anxiety, and QOL problems, except in the domain of social well-being. CONCLUSIONS: Clinically significant depression and anxiety may be more prevalent in patients with EOC than previously reported. Future studies of screening for and treating psychological distress are being designed to improve QOL in these women.