612 Background: Observation of heterogeneity in breast pathology has been a consistent theme but ... more 612 Background: Observation of heterogeneity in breast pathology has been a consistent theme but one that has had little detailed analysis and/or interpretation. Typically, this research has been limited due to variation in pathology description by different pathologists. We have utilized a unique breast disease tissue and data repository to infer multiple pathways from breast disease to breast cancer. Methods: Breast pathology diagnoses are drawn from 1029 standardized and highly expanded pathology reports. A single pathologist records the occurrence of any and all pathologies seen in a patient’s breast biopsy. This co-occurrence data is analyzed using a Bayesian network learning algorithm that links data observations in a probabilistic order of events. The resultant Bayesian network is a visualization of how breast disease diagnoses can predict the presence or absence of other diagnoses. For example, a connection between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) visualizes the statement: the presence of DCIS alters the likelihood of the presence of IDC. Results: Separate progression pathways are implicated for DCIS comedo to IDC and DCIS non-comedo to IDC. Multiple breast lesions predict DCIS non-comedo occurrence. One pathway inferred from these predictive lesions is: columnar cell hyperplasia-florid ductal hyperplasia-atypical ductal hyperplasia-DCIS non-comedo-IDC. In contrast, no hyperplasia or atypical lesion can predict DCIS comedo occurrence. That DCIS comedo and DCIS non-comedo have very different progression pathways implies these two pathologies may be two separate diseases. Parallel genomic studies at our institute provide strong evidence that DCIS non-comedo and DCIS comedo are two separate genomic entities. Conclusions: Bayesian network analysis provides a mechanism for the use of heterogeneity in breast disease pathology to predict multiple breast disease progression pathways. Using novel bioinformatic techniques and traditional genomic analysis methods we have gathered compelling evidence that DCIS progression follows two separate pathways. No significant financial relationships to disclose.
Breast cancer presents as part of a heterogeneous mix of breast disease pathologies whose biologi... more Breast cancer presents as part of a heterogeneous mix of breast disease pathologies whose biological origins are poorly understood. A systematic and quantitative study of heterogeneity in breast tissue would enable us to characterize the disease states present, and use that characterization to guide further research into the complex pathologic associations within breast tissue and between patients. Initially we focus
At Windber Research Institute we have started research programs that use artificial neural networ... more At Windber Research Institute we have started research programs that use artificial neural networks (ANNs) in the study of breast cancer in order to identify heterogeneous data predictors of patient disease stages. As an initial effort, we have chosen matrix metalloproteinases (MMPs) as potential biomarker predictors. MMPs have been implicated in the early and late stage development of breast cancer.
Objective To define pregnancy episodes and estimate gestational aging within electronic health re... more Objective To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results We identified 628,165 pregnant persons with 816,471 pregnancy episodes, o...
There is a growing emphasis on diversity and its impact on health care. Our research has focused ... more There is a growing emphasis on diversity and its impact on health care. Our research has focused on migrants who are Mandarin speaking Chinese and Puerto Rican. Through a series of focus groups conducted in their native languages we discovered that barriers to service access differ across the two groups. In addition, many of these services are administered by individual states rather than the federal government. The diversity across migrant groups and state policies creates a challenge in using findings to establish national or international standards for best practices with older migrants. How then can we apply lessons about diversity and the impact of programs on a national and international scale? We propose the use of Social Interaction Modeling as a method for understanding patterns of behavior at both national and international levels, while preserving the unique character of each migrant group and the context within which they live.
Research on older migrants often starts with a set of assumptions- including the importance of la... more Research on older migrants often starts with a set of assumptions- including the importance of language as a barrier to care. A comparative approach allows us to examine these assumptions as they impact access to services for older migrants. Our study compared two groups of older migrants – Mandarin speaking Chinese and Spanish speakers from Puerto Rico. Through a series of focus groups we learned that although language can be a barrier to service access, the more important element in reducing disparities for older migrants is the level of trust between older adult and provider. For the older Chinese participants, the presence of a native speaker whom they trust is contrasted with a lack of trusted native Spanish speakers available to Puerto Rican elders, who must often rely on translators from various providers. We will use this example to help explain the differences in service use by these two communities. Part of a symposium sponsored by the International Aging and Migration Int...
An online issue tracking (QAIT) system was developed to support the QA of questionnaire-based cli... more An online issue tracking (QAIT) system was developed to support the QA of questionnaire-based clinical data and tissue banking in the Clinical Breast Care Project (CBCP). The web-based system provides a centralized storage and management of QA issues and role-based access to related information and functions via internet. The QAIT system greatly improved the QA process for the CBCP clinical data and tissue banking and can be easily adapted to other applications.
Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide... more Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide determination of DNA copy number alterations. This technology has tremendous potential for disease-gene discovery in cancer and developmental disorders as well as numerous other applications. However, widespread utilization of a CGH has been limited by the lack of well characterized, high-resolution clone sets optimized for consistent performance in aCGH assays and specifically designed analytic software. We have assembled a set of ∼4100 publicly available human bacterial artificial chromosome (BAC) clones evenly spaced at ∼1-Mb resolution across the genome, which includes direct coverage of ∼400 known cancer genes. This aCGH-optimized clone set was compiled from five existing sets, experimentally refined, and supplemented for higher resolution and enhancing mapping capabilities. This clone set is associated with a public online resource containing detailed clone mapping data, protocols...
612 Background: Observation of heterogeneity in breast pathology has been a consistent theme but ... more 612 Background: Observation of heterogeneity in breast pathology has been a consistent theme but one that has had little detailed analysis and/or interpretation. Typically, this research has been limited due to variation in pathology description by different pathologists. We have utilized a unique breast disease tissue and data repository to infer multiple pathways from breast disease to breast cancer. Methods: Breast pathology diagnoses are drawn from 1029 standardized and highly expanded pathology reports. A single pathologist records the occurrence of any and all pathologies seen in a patient’s breast biopsy. This co-occurrence data is analyzed using a Bayesian network learning algorithm that links data observations in a probabilistic order of events. The resultant Bayesian network is a visualization of how breast disease diagnoses can predict the presence or absence of other diagnoses. For example, a connection between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) visualizes the statement: the presence of DCIS alters the likelihood of the presence of IDC. Results: Separate progression pathways are implicated for DCIS comedo to IDC and DCIS non-comedo to IDC. Multiple breast lesions predict DCIS non-comedo occurrence. One pathway inferred from these predictive lesions is: columnar cell hyperplasia-florid ductal hyperplasia-atypical ductal hyperplasia-DCIS non-comedo-IDC. In contrast, no hyperplasia or atypical lesion can predict DCIS comedo occurrence. That DCIS comedo and DCIS non-comedo have very different progression pathways implies these two pathologies may be two separate diseases. Parallel genomic studies at our institute provide strong evidence that DCIS non-comedo and DCIS comedo are two separate genomic entities. Conclusions: Bayesian network analysis provides a mechanism for the use of heterogeneity in breast disease pathology to predict multiple breast disease progression pathways. Using novel bioinformatic techniques and traditional genomic analysis methods we have gathered compelling evidence that DCIS progression follows two separate pathways. No significant financial relationships to disclose.
Breast cancer presents as part of a heterogeneous mix of breast disease pathologies whose biologi... more Breast cancer presents as part of a heterogeneous mix of breast disease pathologies whose biological origins are poorly understood. A systematic and quantitative study of heterogeneity in breast tissue would enable us to characterize the disease states present, and use that characterization to guide further research into the complex pathologic associations within breast tissue and between patients. Initially we focus
At Windber Research Institute we have started research programs that use artificial neural networ... more At Windber Research Institute we have started research programs that use artificial neural networks (ANNs) in the study of breast cancer in order to identify heterogeneous data predictors of patient disease stages. As an initial effort, we have chosen matrix metalloproteinases (MMPs) as potential biomarker predictors. MMPs have been implicated in the early and late stage development of breast cancer.
Objective To define pregnancy episodes and estimate gestational aging within electronic health re... more Objective To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results We identified 628,165 pregnant persons with 816,471 pregnancy episodes, o...
There is a growing emphasis on diversity and its impact on health care. Our research has focused ... more There is a growing emphasis on diversity and its impact on health care. Our research has focused on migrants who are Mandarin speaking Chinese and Puerto Rican. Through a series of focus groups conducted in their native languages we discovered that barriers to service access differ across the two groups. In addition, many of these services are administered by individual states rather than the federal government. The diversity across migrant groups and state policies creates a challenge in using findings to establish national or international standards for best practices with older migrants. How then can we apply lessons about diversity and the impact of programs on a national and international scale? We propose the use of Social Interaction Modeling as a method for understanding patterns of behavior at both national and international levels, while preserving the unique character of each migrant group and the context within which they live.
Research on older migrants often starts with a set of assumptions- including the importance of la... more Research on older migrants often starts with a set of assumptions- including the importance of language as a barrier to care. A comparative approach allows us to examine these assumptions as they impact access to services for older migrants. Our study compared two groups of older migrants – Mandarin speaking Chinese and Spanish speakers from Puerto Rico. Through a series of focus groups we learned that although language can be a barrier to service access, the more important element in reducing disparities for older migrants is the level of trust between older adult and provider. For the older Chinese participants, the presence of a native speaker whom they trust is contrasted with a lack of trusted native Spanish speakers available to Puerto Rican elders, who must often rely on translators from various providers. We will use this example to help explain the differences in service use by these two communities. Part of a symposium sponsored by the International Aging and Migration Int...
An online issue tracking (QAIT) system was developed to support the QA of questionnaire-based cli... more An online issue tracking (QAIT) system was developed to support the QA of questionnaire-based clinical data and tissue banking in the Clinical Breast Care Project (CBCP). The web-based system provides a centralized storage and management of QA issues and role-based access to related information and functions via internet. The QAIT system greatly improved the QA process for the CBCP clinical data and tissue banking and can be easily adapted to other applications.
Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide... more Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide determination of DNA copy number alterations. This technology has tremendous potential for disease-gene discovery in cancer and developmental disorders as well as numerous other applications. However, widespread utilization of a CGH has been limited by the lack of well characterized, high-resolution clone sets optimized for consistent performance in aCGH assays and specifically designed analytic software. We have assembled a set of ∼4100 publicly available human bacterial artificial chromosome (BAC) clones evenly spaced at ∼1-Mb resolution across the genome, which includes direct coverage of ∼400 known cancer genes. This aCGH-optimized clone set was compiled from five existing sets, experimentally refined, and supplemented for higher resolution and enhancing mapping capabilities. This clone set is associated with a public online resource containing detailed clone mapping data, protocols...
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