<b>Copyright information:</b>Taken from "Classification methods for the developm... more <b>Copyright information:</b>Taken from "Classification methods for the development of genomic signatures from high-dimensional data"Genome Biology 2006;7(12):R121-R121.Published online 20 Dec 2006PMCID:PMC1794434.
In microbial and chemical risk assessments, careful dose-response modeling is emphasized because ... more In microbial and chemical risk assessments, careful dose-response modeling is emphasized because a target risk level (probability of infection or illness) is often in the low benchmark response range of 1% to 10%. To address model uncertainty at low doses and enhance diversity and flexibility for model-averaging, a set of fractional polynomial dose-response models can be considered. However, elicitation of an informative prior in Bayesian approach is difficult in those models because their parameters are not interpretable. This paper illustrates a method of elicitating informative prior known using data augmentation prior.
Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-s... more Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-stage lung cancer patients that are most likely to benefit from adjuvant chemotherapy with surgery (ACT). Background: Receiving ACT appears to have a better prognosis for more severe early-stage non-small cell lung cancer patients than surgical resection only. However, not all patients benefit from chemotherapy. Objective: Preliminary studies suggest that the application of ACT is associated with a better prognosis for more severe NSCLC patients compared to those who only underwent surgical resection. Given the immense personal and financial costs associated with ACT, finding the patients who are most likely to benefit from ACT is paramount. Thus, the purpose of this research is to utilize gene expression and clinical data from lung cancer patients to find treatment-associated genomic biomarkers. Methods: To investigate the treatment effect, a modified-covariate regularized Cox regression...
Wounds : a compendium of clinical research and practice, 2016
Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healin... more Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healing challenges of diabetic foot ulcers (DFUs). This paper reports the occurrences of these factors that the authors label the "Troublesome Triad" (TT) in a prospective series of 62 patients with diabetes mellitus (DM), who were hospitalized because of their DFUs. With Institutional Review Board approval, the authors gathered data in a prospective series of patients hospitalized because of lower extremity wounds. From this data, they analyzed the DFU cohort for the incidence of each of the components of the TT. The severity of the wound was graded with the authors' 0 to 10 Wound Score in the patients who had components of the TT and compared with those who did not. One or more components of the TT were observed in 57 patients (91.9%). As the number of confounders increased, mean Wound Scores decreased from 5.2 for 1 confounder to 2.9 for 3 confounders (P = 0.003). Most patient...
A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting... more A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting tumor growth is sufficient intracellular drug accumulation. We hypothesized that membrane transporters on tumor cells determine at least in part the response to GA analogues. To facilitate a systematic study of chemosensitivity across a group of GA analogues with similar chemical structures, we correlated mRNA expression profiles of most known transporters with growth inhibitory potencies of compounds in 60 tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays. Geldanamycin analogues displayed a range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein) expression. Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity to GA analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of daunorubicin in K562/DOX cells could be blocked markedly by GA analogues in a dose-dependent fashion. The IC(50) values (half-maximum inhibition of daunorubicin efflux) were 5.5, 7.3 and 12 muM for macbecin II (NSC330500), 17-AAG (NSC330507) and GA, respectively. These observations demonstrate that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that drug interactions between GA analogues and other agents that are ABCB1 substrates may occur via ABCB1 in normal or tumor cells.
<b>Copyright information:</b>Taken from "Classification methods for the developm... more <b>Copyright information:</b>Taken from "Classification methods for the development of genomic signatures from high-dimensional data"Genome Biology 2006;7(12):R121-R121.Published online 20 Dec 2006PMCID:PMC1794434. [17] data.
Wounds : a compendium of clinical research and practice, Jan 21, 2018
This study demonstrates the applicability of an innovative wound score that summates 5 assessment... more This study demonstrates the applicability of an innovative wound score that summates 5 assessments using 2-point (best) to 0-point (worst) grades based on specific findings to generate a 0- to 10-point wound score for categorizing diabetic foot ulcers as well as validates its effectiveness. Long Beach Wound Scores (LBWS) were determined prospectively over an 18-month period in 105 hospitalized patients, with or without diabetes, with lower extremity wounds. Wounds were categorized as healthy, problem, or end-stage from their initial LBWS. Outcomes were graded as good or poor using a 5-level scale. Outcome information was available and statistically analyzed for comparisons with initial evaluation LBWSs in 85 patients. In the healthy category, 66.7% healed or improved and were designated as good outcomes. In the problem category, 83.3% had good outcomes. In the end-stage category, 50.0% had good outcomes. Outliers for poor outcomes in the healthy category were due to the patients'...
Journal of biopharmaceutical statistics, Jan 20, 2017
In treating patients diagnosed with early Stage I non-small-cell lung cancer (NSCLC), doctors mus... more In treating patients diagnosed with early Stage I non-small-cell lung cancer (NSCLC), doctors must choose surgery alone, Adjuvant Cisplatin-Based Chemotherapy (ACT) alone or both. For patients with resected stages IB to IIIA, clinical trials have shown a survival advantage from 4-15% with the adoption of ACT. However, due to the inherent toxicity of chemotherapy, it is necessary for doctors to identify patients whose chance of success with ACT is sufficient to justify the risks. This research seeks to use gene expression profiling in the development of a statistical decision-making algorithm to identify patients whose survival rates will improve from ACT treatment. Using the data from the National Cancer Institute, the lasso method in the Cox-Proportional-Hazards regression model is used as the main method to determine a feasible number of genes that are strongly associated with the treatment-related patient survival. Considering treatment groups separately, the patients are assigne...
Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc
In 2002 Fife and Strauss (Fife, et al. Wound Rep Reg, 10:198-207; Strauss, et al. Foot Ankle Intl... more In 2002 Fife and Strauss (Fife, et al. Wound Rep Reg, 10:198-207; Strauss, et al. Foot Ankle Intl, 23:933-937) studied the predictability of transcutaneous oxygen measurements (TCOMs) for healing diabetic foot ulcers (DFUs). This paper analyzes the validity of the two studies and combines their information to predict which DFU will heal with adjunctive hyperbaric oxygen (HBO₂) treatments. A statistical review of the Fife and Strauss papers was performed. The numbers presented in the papers were subjected to analyses to compare like by like data as well as test for p-values and odds ratios for predicting healing of DFUs with HBO₂. In the Strauss paper 143 subjects were studied in retrospective and prospective series. In those TCOMs which exceed 200 mmHg with HBO₂ healing occurred in 87.5% even if the room air TCOM was ⟨ 30 mmHg (p ⟨ 0.001). The Fife paper studied retrospectively a subset of 221 patients who had TCOMs with HBO₂. Failure rates for healing decreased progressively from 3...
Wounds : a compendium of clinical research and practice, 2016
The authors describe an innovative wound score and demonstrate its versatility for scoring a vari... more The authors describe an innovative wound score and demonstrate its versatility for scoring a variety of wound types in addition to diabetic foot ulcers (DFUs). To further test its merits, they determined its interobserver reliability in a prospective series of patients. The Wound Score system the authors created integrates the most important features of 4 predominantly used wound scoring systems. It utilizes a logical 0 to 10 format based on 5 assessments each graded from 2 (best) to 0 (worst). The versatility and reliability of the Wound Score were studied in a prospective series of 94 patients with lower extremity wounds. The Wound Score was quick to determine, applicable to a variety of wound types and locations, and highly objective for grading the severity of each of the 5 assessments. The Wound Score categorized wound types as "healthy," "problem," or "futile" for evaluation and management. Diabetes was present in 75.9%, with 70% of the DFUs scori...
Standard classification algorithms are generally designed to maximize the number of correct predi... more Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher&#39;s linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.
In chemical and microbial risk assessments, risk assessors fit dose-response models to high-dose ... more In chemical and microbial risk assessments, risk assessors fit dose-response models to high-dose data and extrapolate downward to risk levels in the range of 1-10%. Although multiple dose-response models may be able to fit the data adequately in the experimental range, the estimated effective dose (ED) corresponding to an extremely small risk can be substantially different from model to model. In this respect, model averaging (MA) provides more robustness than a single dose-response model in the point and interval estimation of an ED. In MA, accounting for both data uncertainty and model uncertainty is crucial, but addressing model uncertainty is not achieved simply by increasing the number of models in a model space. A plausible set of models for MA can be characterized by goodness of fit and diversity surrounding the truth. We propose a diversity index (DI) to balance between these two characteristics in model space selection. It addresses a collective property of a model space rather than individual performance of each model. Tuning parameters in the DI control the size of the model space for MA.
Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, ... more Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, steering away from the traditional view of one-size-fits-all medicine. A premise of this study is that the sex of a patient influences difference in disease characteristics and risk factors. In this study, we intend to exploit and to obtain better sex-specific biomarkers from gene-expression data. We propose a procedure to isolate a set of important genes as sex-specific genomic biomarkers, which may enable more effective patient treatment. A set of sex-specific genes is obtained by a variable importance ranking using a combination of cross-validation methods. The proposed procedure is applied to three gene-expression datasets.
<b>Copyright information:</b>Taken from "Classification methods for the developm... more <b>Copyright information:</b>Taken from "Classification methods for the development of genomic signatures from high-dimensional data"Genome Biology 2006;7(12):R121-R121.Published online 20 Dec 2006PMCID:PMC1794434.
In microbial and chemical risk assessments, careful dose-response modeling is emphasized because ... more In microbial and chemical risk assessments, careful dose-response modeling is emphasized because a target risk level (probability of infection or illness) is often in the low benchmark response range of 1% to 10%. To address model uncertainty at low doses and enhance diversity and flexibility for model-averaging, a set of fractional polynomial dose-response models can be considered. However, elicitation of an informative prior in Bayesian approach is difficult in those models because their parameters are not interpretable. This paper illustrates a method of elicitating informative prior known using data augmentation prior.
Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-s... more Aims: Our goal is to find predictive genomic biomarkers in order to identify subgroups of early-stage lung cancer patients that are most likely to benefit from adjuvant chemotherapy with surgery (ACT). Background: Receiving ACT appears to have a better prognosis for more severe early-stage non-small cell lung cancer patients than surgical resection only. However, not all patients benefit from chemotherapy. Objective: Preliminary studies suggest that the application of ACT is associated with a better prognosis for more severe NSCLC patients compared to those who only underwent surgical resection. Given the immense personal and financial costs associated with ACT, finding the patients who are most likely to benefit from ACT is paramount. Thus, the purpose of this research is to utilize gene expression and clinical data from lung cancer patients to find treatment-associated genomic biomarkers. Methods: To investigate the treatment effect, a modified-covariate regularized Cox regression...
Wounds : a compendium of clinical research and practice, 2016
Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healin... more Uncontrolled deformity, deep infection, and/or ischemia-hypoxia are highly associated with healing challenges of diabetic foot ulcers (DFUs). This paper reports the occurrences of these factors that the authors label the "Troublesome Triad" (TT) in a prospective series of 62 patients with diabetes mellitus (DM), who were hospitalized because of their DFUs. With Institutional Review Board approval, the authors gathered data in a prospective series of patients hospitalized because of lower extremity wounds. From this data, they analyzed the DFU cohort for the incidence of each of the components of the TT. The severity of the wound was graded with the authors' 0 to 10 Wound Score in the patients who had components of the TT and compared with those who did not. One or more components of the TT were observed in 57 patients (91.9%). As the number of confounders increased, mean Wound Scores decreased from 5.2 for 1 confounder to 2.9 for 3 confounders (P = 0.003). Most patient...
A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting... more A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting tumor growth is sufficient intracellular drug accumulation. We hypothesized that membrane transporters on tumor cells determine at least in part the response to GA analogues. To facilitate a systematic study of chemosensitivity across a group of GA analogues with similar chemical structures, we correlated mRNA expression profiles of most known transporters with growth inhibitory potencies of compounds in 60 tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays. Geldanamycin analogues displayed a range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein) expression. Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity to GA analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of daunorubicin in K562/DOX cells could be blocked markedly by GA analogues in a dose-dependent fashion. The IC(50) values (half-maximum inhibition of daunorubicin efflux) were 5.5, 7.3 and 12 muM for macbecin II (NSC330500), 17-AAG (NSC330507) and GA, respectively. These observations demonstrate that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that drug interactions between GA analogues and other agents that are ABCB1 substrates may occur via ABCB1 in normal or tumor cells.
<b>Copyright information:</b>Taken from "Classification methods for the developm... more <b>Copyright information:</b>Taken from "Classification methods for the development of genomic signatures from high-dimensional data"Genome Biology 2006;7(12):R121-R121.Published online 20 Dec 2006PMCID:PMC1794434. [17] data.
Wounds : a compendium of clinical research and practice, Jan 21, 2018
This study demonstrates the applicability of an innovative wound score that summates 5 assessment... more This study demonstrates the applicability of an innovative wound score that summates 5 assessments using 2-point (best) to 0-point (worst) grades based on specific findings to generate a 0- to 10-point wound score for categorizing diabetic foot ulcers as well as validates its effectiveness. Long Beach Wound Scores (LBWS) were determined prospectively over an 18-month period in 105 hospitalized patients, with or without diabetes, with lower extremity wounds. Wounds were categorized as healthy, problem, or end-stage from their initial LBWS. Outcomes were graded as good or poor using a 5-level scale. Outcome information was available and statistically analyzed for comparisons with initial evaluation LBWSs in 85 patients. In the healthy category, 66.7% healed or improved and were designated as good outcomes. In the problem category, 83.3% had good outcomes. In the end-stage category, 50.0% had good outcomes. Outliers for poor outcomes in the healthy category were due to the patients'...
Journal of biopharmaceutical statistics, Jan 20, 2017
In treating patients diagnosed with early Stage I non-small-cell lung cancer (NSCLC), doctors mus... more In treating patients diagnosed with early Stage I non-small-cell lung cancer (NSCLC), doctors must choose surgery alone, Adjuvant Cisplatin-Based Chemotherapy (ACT) alone or both. For patients with resected stages IB to IIIA, clinical trials have shown a survival advantage from 4-15% with the adoption of ACT. However, due to the inherent toxicity of chemotherapy, it is necessary for doctors to identify patients whose chance of success with ACT is sufficient to justify the risks. This research seeks to use gene expression profiling in the development of a statistical decision-making algorithm to identify patients whose survival rates will improve from ACT treatment. Using the data from the National Cancer Institute, the lasso method in the Cox-Proportional-Hazards regression model is used as the main method to determine a feasible number of genes that are strongly associated with the treatment-related patient survival. Considering treatment groups separately, the patients are assigne...
Undersea & hyperbaric medicine : journal of the Undersea and Hyperbaric Medical Society, Inc
In 2002 Fife and Strauss (Fife, et al. Wound Rep Reg, 10:198-207; Strauss, et al. Foot Ankle Intl... more In 2002 Fife and Strauss (Fife, et al. Wound Rep Reg, 10:198-207; Strauss, et al. Foot Ankle Intl, 23:933-937) studied the predictability of transcutaneous oxygen measurements (TCOMs) for healing diabetic foot ulcers (DFUs). This paper analyzes the validity of the two studies and combines their information to predict which DFU will heal with adjunctive hyperbaric oxygen (HBO₂) treatments. A statistical review of the Fife and Strauss papers was performed. The numbers presented in the papers were subjected to analyses to compare like by like data as well as test for p-values and odds ratios for predicting healing of DFUs with HBO₂. In the Strauss paper 143 subjects were studied in retrospective and prospective series. In those TCOMs which exceed 200 mmHg with HBO₂ healing occurred in 87.5% even if the room air TCOM was ⟨ 30 mmHg (p ⟨ 0.001). The Fife paper studied retrospectively a subset of 221 patients who had TCOMs with HBO₂. Failure rates for healing decreased progressively from 3...
Wounds : a compendium of clinical research and practice, 2016
The authors describe an innovative wound score and demonstrate its versatility for scoring a vari... more The authors describe an innovative wound score and demonstrate its versatility for scoring a variety of wound types in addition to diabetic foot ulcers (DFUs). To further test its merits, they determined its interobserver reliability in a prospective series of patients. The Wound Score system the authors created integrates the most important features of 4 predominantly used wound scoring systems. It utilizes a logical 0 to 10 format based on 5 assessments each graded from 2 (best) to 0 (worst). The versatility and reliability of the Wound Score were studied in a prospective series of 94 patients with lower extremity wounds. The Wound Score was quick to determine, applicable to a variety of wound types and locations, and highly objective for grading the severity of each of the 5 assessments. The Wound Score categorized wound types as "healthy," "problem," or "futile" for evaluation and management. Diabetes was present in 75.9%, with 70% of the DFUs scori...
Standard classification algorithms are generally designed to maximize the number of correct predi... more Standard classification algorithms are generally designed to maximize the number of correct predictions (concordance). The criterion of maximizing the concordance may not be appropriate in certain applications. In practice, some applications may emphasize high sensitivity (e.g., clinical diagnostic tests) and others may emphasize high specificity (e.g., epidemiology screening studies). This paper considers effects of the decision threshold on sensitivity, specificity, and concordance for four classification methods: logistic regression, classification tree, Fisher&#39;s linear discriminant analysis, and a weighted k-nearest neighbor. We investigated the use of decision threshold adjustment to improve performance of either sensitivity or specificity of a classifier under specific conditions. We conducted a Monte Carlo simulation showing that as the decision threshold increases, the sensitivity decreases and the specificity increases; but, the concordance values in an interval around the maximum concordance are similar. For specified sensitivity and specificity levels, an optimal decision threshold might be determined in an interval around the maximum concordance that meets the specified requirement. Three example data sets were analyzed for illustrations.
In chemical and microbial risk assessments, risk assessors fit dose-response models to high-dose ... more In chemical and microbial risk assessments, risk assessors fit dose-response models to high-dose data and extrapolate downward to risk levels in the range of 1-10%. Although multiple dose-response models may be able to fit the data adequately in the experimental range, the estimated effective dose (ED) corresponding to an extremely small risk can be substantially different from model to model. In this respect, model averaging (MA) provides more robustness than a single dose-response model in the point and interval estimation of an ED. In MA, accounting for both data uncertainty and model uncertainty is crucial, but addressing model uncertainty is not achieved simply by increasing the number of models in a model space. A plausible set of models for MA can be characterized by goodness of fit and diversity surrounding the truth. We propose a diversity index (DI) to balance between these two characteristics in model space selection. It addresses a collective property of a model space rather than individual performance of each model. Tuning parameters in the DI control the size of the model space for MA.
Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, ... more Numerous studies have demonstrated sex differences in drug reactions to the same drug treatment, steering away from the traditional view of one-size-fits-all medicine. A premise of this study is that the sex of a patient influences difference in disease characteristics and risk factors. In this study, we intend to exploit and to obtain better sex-specific biomarkers from gene-expression data. We propose a procedure to isolate a set of important genes as sex-specific genomic biomarkers, which may enable more effective patient treatment. A set of sex-specific genes is obtained by a variable importance ranking using a combination of cross-validation methods. The proposed procedure is applied to three gene-expression datasets.
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Papers by Hojin Moon