11 results on '"Fernandez, Soledad A."'
Search Results
2. Performance of model-based vs. permutation tests in the HEALing (Helping to End Addiction Long-termSM) Communities Study, a covariate-constrained cluster randomized trial
- Author
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Tang, Xiaoyu, Heeren, Timothy, Westgate, Philip M., Feaster, Daniel J., Fernandez, Soledad A., Vandergrift, Nathan, and Cheng, Debbie M.
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- 2022
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3. Power analysis for RNA-Seq differential expression studies using generalized linear mixed effects models
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Yu, Lianbo, Fernandez, Soledad, and Brock, Guy
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- 2020
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4. A pan-cancer study of class-3 semaphorins as therapeutic targets in cancer
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Zhang, Xiaoli, Klamer, Brett, Li, Jin, Fernandez, Soledad, and Li, Lang
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- 2020
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5. Fully moderated t-statistic in linear modeling of mixed effects for differential expression analysis
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Yu, Lianbo, Zhang, Jianying, Brock, Guy, and Fernandez, Soledad
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- 2019
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6. Performance of model-based vs. permutation tests in the HEALing (Helping to End Addiction Long-termSM) Communities Study, a covariate-constrained cluster randomized trial.
- Author
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Tang, Xiaoyu, Heeren, Timothy, Westgate, Philip M., Feaster, Daniel J., Fernandez, Soledad A., Vandergrift, Nathan, and Cheng, Debbie M.
- Subjects
CLUSTER randomized controlled trials ,COMMUNITIES ,FALSE positive error ,T-test (Statistics) ,HEALING ,PERMUTATIONS ,ERROR rates - Abstract
Background: The HEALing (Helping to End Addiction Long-termSM) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests.Methods: The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups.Results: Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA).Conclusions: Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study.Trial Registration: ClinicalTrials.gov http://www.Clinicaltrials: gov ; Identifier: NCT04111939. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Power analysis for RNA-Seq differential expression studies.
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Lianbo Yu, Fernandez, Soledad, and Brock, Guy
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RNA sequencing , *GENE expression , *GENETICS of breast cancer , *RNA analysis , *MOLECULAR genetics - Abstract
Background: Sample size calculation and power estimation are essential components of experimental designs in biomedical research. It is very challenging to estimate power for RNA-Seq differential expression under complex experimental designs. Moreover, the dependency among genes should be taken into account in order to obtain accurate results. Results: In this paper, we propose a simulation based procedure for power estimation using the negative binomial distribution and assuming a generalized linear model (at the gene level) that considers the dependence between gene expression level and its variance (dispersion) and also allows equal or unequal dispersion across conditions. We compared the performance of both Wald test and likelihood ratio test under different scenarios. The null distribution of the test statistics was simulated for the desired false positive control to avoid excess false positives with the usage of an asymptotic chi-square distribution. We applied this method to the TCGA breast cancer data set. Conclusions: We provide a framework for power estimation of RNA-Seq data. The proposed procedure is able to properly control the false positive error rate at the nominal level. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Aprepitant versus ondansetron in preoperative triple-therapy treatment of nausea and vomiting in neurosurgery patients: study protocol for a randomized controlled trial.
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Bergese, Sergio, Viloria, Adolfo, Uribe, Alberto, Antor, Alejandra, and Fernandez, Soledad
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POSTOPERATIVE nausea & vomiting ,NAUSEA ,NEUROSURGERY ,POSTOPERATIVE care ,RANDOMIZED controlled trials - Abstract
Background: The incidence of postoperative nausea and vomiting (PONV) is 50% to 80% after neurosurgery. The common prophylactic treatment for postoperative nausea and vomiting is a triple therapy of droperidol, promethazine and dexamethasone. Newer, more effectives methods of prophylaxis are being investigated. We designed this prospective, double-blind, single-center study to compare the efficacy of ondansetron, a neurokinin-1 antagonist, and aprepitant, as a substitute for droperidol, in the prophylactic treatment of postoperative nausea and vomiting after neurosurgery. Methods: After obtaining institutional review board approval; 176 patients, 18 to 85 years of age with American Society of Anesthesiologists (ASA) classifications I to III, who did not receive antiemetics 24 h before surgery and were expected to undergo general anesthesia for neurosurgery lasting longer than 2 h were included in this study. After meeting the inclusion and exclusion criteria and providing written informed consent, patients were randomly assigned in a 1:1 ratio to one of two treatment groups: aprepitant or ondansetron. The objective of this study was to conduct a randomized, double-blind, double-dummy, parallel-group and single-center trial to compare and evaluate the efficacies of aprepitant versus ondansetron. Patients received oral aprepitant 40 mg OR oral dummy pill within 2 h prior to induction. At induction, a combination of intravenous dexamethasone 10 mg, promethazine 25 mg, and ondansetron 4 mg OR dummy injection was administered. Therefore, all patients received one dummy treatment and three active PONV prophylactic medications: dexamethasone 10 mg, promethazine 25 mg, and either aprepitant 40 mg OR ondansetron 4 mg infusion. The primary outcome measures were the episodes and severity of nausea and vomiting; administration of rescue antiemetic; and opioid consumption for 120 h postoperatively. Standard safety assessments included adverse event reports, physical and laboratory data, awakening time and duration of recovery from anesthesia. Discussion: The results of this comparative study could potentially identify an improved treatment regimen that may decrease the incidence and severity of postoperative nausea and vomiting in patients undergoing neurosurgery. Also, this will serve to enhance patient recovery and overall satisfaction of neurosurgical patients in the immediate postoperative period. [ABSTRACT FROM AUTHOR]
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- 2012
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9. Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: Implications for transformation.
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Nadella, Murali V. P., Shu, Sherry T., Dirksen, Wessel P., Thudi, Nanda K., Nadella, Kiran S., Fernandez, Soledad A., Lairmore, Michael D., Green, Patrick L., and Rosol, Thomas J.
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GENE expression ,VIRAL proteins ,BLOOD cells ,HTLV ,CELL transformation ,T cells - Abstract
Background: Adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated. Results: We report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, cotransfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/ or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1α (MIP-1α), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection. Conclusion: These data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process. [ABSTRACT FROM AUTHOR]
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- 2008
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10. Modeling and detection of respiratory-related outbreak signatures.
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Craigmile, Peter F., Namhee Kim, Fernandez, Soledad A., and Bonsu, Bema K.
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DISEASE outbreaks ,TIME series analysis ,MEDICAL informatics ,EPIDEMIOLOGY ,RADIOGRAPHY ,COMPUTERS in medicine - Abstract
Background: Time series methods are commonly used to detect disease outbreak signatures (e.g., signals due to influenza outbreaks and anthrax attacks) from varying respiratory-related diagnostic or syndromic data sources. Typically this involves two components: (i) Using time series methods to model the baseline background distribution (the time series process that is assumed to contain no outbreak signatures), (ii) Detecting outbreak signatures using filter-based time series methods. Methods: We consider time series models for chest radiograph data obtained from Midwest children's emergency departments. These models incorporate available covariate information such as patient visit counts and smoothed ambient temperature series, as well as time series dependencies on daily and weekly seasonal scales. Respiratory-related outbreak signature detection is based on filtering the one-step-ahead prediction errors obtained from the time series models for the respiratory-complaint background. Results: Using simulation experiments based on a stochastic model for an anthrax attack, we illustrate the effect of the choice of filter and the statistical models upon radiograph-attributed outbreak signature detection. Conclusion: We demonstrate the importance of using seasonal autoregressive integrated average time series models (SARIMA) with covariates in the modeling of respiratory-related time series data. We find some homogeneity in the time series models for the respiratory-complaint backgrounds across the Midwest emergency departments studied. Our simulations show that the balance between specificity, sensitivity, and timeliness to detect an outbreak signature differs by the emergency department and the choice of filter. The linear and exponential filters provide a good balance. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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11. Coordinate enhancement of transgene transcription and translation in a lentiviral vector.
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Yilmaz, Alper, Fernandez, Soledad, Lairmore, Michael D., and Boris-Lawrie, Kathleen
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TRANSGENES , *GENETIC translation , *GENETIC transcription , *LENTIVIRUS diseases , *LENTIVIRUSES , *CELL membranes - Abstract
Background: Coordinate enhancement of transgene transcription and translation would be a potent approach to significantly improve protein output in a broad array of viral vectors and nonviral expression systems. Many vector transgenes are complementary DNA (cDNA). The lack of splicing can significantly reduce the efficiency of their translation. Some retroviruses contain a 5' terminal post-transcriptional control element (PCE) that facilitates translation of unspliced mRNA. Here we evaluated the potential for spleen necrosis virus PCE to stimulate protein production from HIV-1 based lentiviral vector by: 1) improving translation of the internal transgene transcript; and 2) functionally synergizing with a transcriptional enhancer to achieve coordinate increases in RNA synthesis and translation. Results: Derivatives of HIV-1 SIN self-inactivating lentiviral vector were created that contain PCE and cytomegalovirus immediate early enhancer (CMV IE). Results from transfected cells and four different transduced cell types indicate that: 1) PCE enhanced transgene protein synthesis; 2) transcription from the internal promoter is enhanced by CMV IE; 3) PCE and CMV IE functioned synergistically to significantly increase transgene protein yield; 4) the magnitude of translation enhancement by PCE was similar in transfected and transduced cells; 5) differences were observed in steady state level of PCE vector RNA in transfected and transduced cells; 6) the lower steady state was not attributable to reduced RNA stability, but to lower cytoplasmic accumulation in transduced cells. Conclusion: PCE is a useful tool to improve post-transcriptional expression of lentiviral vector transgene. Coordinate enhancement of transcription and translation is conferred by the combination of PCE with CMV IE transcriptional enhancer and increased protein yield up to 11 to 17-fold in transfected cells. The incorporation of the vector provirus into chromatin correlated with reduced cytoplasmic accumulation of PCE transgene RNA. We speculate that epigenetic modulation of promoter activity altered cotranscriptional recruitment of RNA processing factors and reduced the availability of fully processed transcript or the efficiency of export from the nucleus. Our results provide an example of the dynamic interplay between the transcription and post-transcription steps of gene expression and document that introduction of heterologous gene expression signals can yield disparate effects in transfected versus transduced cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
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