35 research outputs found

    Electronic Health Record Phenotyping in Cardiovascular Epidemiology

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    The secondary use of EHR data for research is a cost-effective resource for a variety of research questions and domains; however, there are many challenges when using electronic health record (EHR) data for epidemiologic research.This dissertation quantified differences in prevalence for acute myocardial infarction (MI) and heart failure (HF) using phenotyping algorithms differing in diagnosis position of ICD-10-CM codes and the inclusion of clinical components. The period of interest was January 1, 2016 to December 31, 2019 for UNC Clinical Data Warehouse for Health data and October 1, 2015 and December 31, 2019 for Atherosclerosis Risk in Communities (ARIC) Study data, the latter used for validation analyses. During the period of interest, 13,200 acute MI cases and 53,545 HF cases were identified in the UNC data. Age-standardized prevalence of acute MI and HF were highest using Any Diagnosis Position algorithm and lowest for acute MI using 1st or 2nd Diagnosis Position with Lab or Procedure and 1st Diagnosis Position for HF. Projected differences in healthcare expenditures by algorithm as well as patient and clinical characteristics, such as event severity and mortality, were also estimated. When compared to physician-adjudicated hospitalizations in the ARIC study, the phenotyping algorithms used for the UNC analysis performed well given their simplicity. The algorithm with the highest sensitivity was Any Diagnosis Position for acute MI and HF at 75.5% and 70.5%. Specificity, PPV, and NPV ranged from 80-99% for all algorithms. Requiring clinical components had little effect except for increasing PPV slightly, while restricting diagnosis position to 1st or 2nd position decreased sensitivity and increased PPV. The impact of clinical components or diagnosis position did not differ by race, age, or sex subgroups.The results from this dissertation can be used by researchers using EHR data for a variety of reasons from informing their own analytic decisions to validating their study findings. The continued use of EHR data for research requires transparency to facilitate reproducibility as well as studies focused on what we are measuring.Doctor of Philosoph

    International Conference on Mathematical Analysis and Applications in Science and Engineering – Book of Extended Abstracts

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    The present volume on Mathematical Analysis and Applications in Science and Engineering - Book of Extended Abstracts of the ICMASC’2022 collects the extended abstracts of the talks presented at the International Conference on Mathematical Analysis and Applications in Science and Engineering – ICMA2SC'22 that took place at the beautiful city of Porto, Portugal, in June 27th-June 29th 2022 (3 days). Its aim was to bring together researchers in every discipline of applied mathematics, science, engineering, industry, and technology, to discuss the development of new mathematical models, theories, and applications that contribute to the advancement of scientific knowledge and practice. Authors proposed research in topics including partial and ordinary differential equations, integer and fractional order equations, linear algebra, numerical analysis, operations research, discrete mathematics, optimization, control, probability, computational mathematics, amongst others. The conference was designed to maximize the involvement of all participants and will present the state-of- the-art research and the latest achievements.info:eu-repo/semantics/publishedVersio

    SIS 2017. Statistics and Data Science: new challenges, new generations

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    The 2017 SIS Conference aims to highlight the crucial role of the Statistics in Data Science. In this new domain of ‘meaning’ extracted from the data, the increasing amount of produced and available data in databases, nowadays, has brought new challenges. That involves different fields of statistics, machine learning, information and computer science, optimization, pattern recognition. These afford together a considerable contribute in the analysis of ‘Big data’, open data, relational and complex data, structured and no-structured. The interest is to collect the contributes which provide from the different domains of Statistics, in the high dimensional data quality validation, sampling extraction, dimensional reduction, pattern selection, data modelling, testing hypotheses and confirming conclusions drawn from the data

    Recent Advances in Industrial and Applied Mathematics

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    This open access book contains review papers authored by thirteen plenary invited speakers to the 9th International Congress on Industrial and Applied Mathematics (Valencia, July 15-19, 2019). Written by top-level scientists recognized worldwide, the scientific contributions cover a wide range of cutting-edge topics of industrial and applied mathematics: mathematical modeling, industrial and environmental mathematics, mathematical biology and medicine, reduced-order modeling and cryptography. The book also includes an introductory chapter summarizing the main features of the congress. This is the first volume of a thematic series dedicated to research results presented at ICIAM 2019-Valencia Congress

    Discovery of Type 2 Diabetes Trajectories from Electronic Health Records

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    University of Minnesota Ph.D. dissertation. September 2020. Major: Health Informatics. Advisor: Gyorgy Simon. 1 computer file (PDF); xiii, 110 pages.Type 2 diabetes (T2D) is one of the fastest growing public health concerns in the United States. There were 30.3 million patients (9.4% of the US populations) suffering from diabetes in 2015. Diabetes, which is the seventh leading cause of death in the United States, is known to be a non-reversible (incurable) chronic disease, leading to severe complications, including chronic kidney disease, amputation, blindness, and various cardiac and vascular diseases. Early identification of patients at high risk is regarded as the most effective clinical tool to prevent or delay the development of diabetes, allowing patients to change their life style or to receive medication earlier. In turn, these interventions can help decrease the risk of diabetes by 30-60%. Many studies have been conducted aiming at the early identification of patients at high risk in the clinical settings. These studies typically only consider the patient's current state at the time of the assessment and do not fully utilize all available information such as patient's medical history. Past history is important. It has been shown that laboratory results and vital signs can differ between diabetic and non-diabetic patients as many as 15-20 years before the onset of diabetes. We have also shown in our study that the order in which patients develop diabetes-related comorbidities is predictive of their diabetes risk even after adjusting for the severity of the comorbidities. In this thesis, we develop multiple novel methods to discover T2D trajectories from Electronic Health Records (EHR). We define trajectory as an order of in which diseases developed. We aim to discover typical and atypical trajectories where typical trajectories represent predominant patterns of progressions and atypical trajectories refer to the rest of the trajectories. Revealing trajectories can allow us to divide patients into subpopulations that can uncover the underlying etiology of diabetes. More importantly, by assessing the risk correctly and by a better understanding of the heterogeneity of diabetes, we can provide better care. Since data collected from EHR poses several challenges to directly identify trajectories from EHR data, we devise four specific studies to address the challenges: First, we propose a new knowledge-driven representation for clinical data mining, second, we demonstrate a method for estimating the onset time of slow-onset diseases from intermittently observable laboratory results in the specific context of T2D, third, we present a method to infer trajectories, the sequence of comorbidities potentially leading up to a particular disease of interest, and finally, we propose a novel method to discover multiple trajectories from EHR data. The patterns we discovered from above four studies address a clinical issue, are clinically verifiable and are amenable to deployment in practice to improve the quality of individual patient care towards promoting public health in the United States

    Machine Learning Applications for Drug Repurposing

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    The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected until a very late stage of the drug discovery, where the discovery of drug-induced side effects and potential drug resistance can decrease the value of the drug and even completely invalidate the use of the drug. Thus, a new paradigm in drug discovery is needed. Structural systems pharmacology is a new paradigm in drug discovery that the drug activities are studied by data-driven large-scale models with considerations of the structures and drugs. Structural systems pharmacology will model, on a genome scale, the energetic and dynamic modifications of protein targets by drug molecules as well as the subsequent collective effects of drug-target interactions on the phenotypic drug responses. To date, however, few experimental and computational methods can determine genome-wide protein-ligand interaction networks and the clinical outcomes mediated by them. As a result, the majority of proteins have not been charted for their small molecular ligands; we have a limited understanding of drug actions. To address the challenge, this dissertation seeks to develop and experimentally validate innovative computational methods to infer genome-wide protein-ligand interactions and multi-scale drug-phenotype associations, including drug-induced side effects. The hypothesis is that the integration of data-driven bioinformatics tools with structure-and-mechanism-based molecular modeling methods will lead to an optimal tool for accurately predicting drug actions and drug associated phenotypic responses, such as side effects. This dissertation starts by reviewing the current status of computational drug discovery for complex diseases in Chapter 1. In Chapter 2, we present REMAP, a one-class collaborative filtering method to predict off-target interactions from protein-ligand interaction network. In our later work, REMAP was integrated with structural genomics and statistical machine learning methods to design a dual-indication polypharmacological anticancer therapy. In Chapter 3, we extend REMAP, the core method in Chapter 2, into a multi-ranked collaborative filtering algorithm, WINTF, and present relevant mathematical justifications. Chapter 4 is an application of WINTF to repurpose an FDA-approved drug diazoxide as a potential treatment for triple negative breast cancer, a deadly subtype of breast cancer. In Chapter 5, we present a multilayer extension of REMAP, applied to predict drug-induced side effects and the associated biological pathways. In Chapter 6, we close this dissertation by presenting a deep learning application to learn biochemical features from protein sequence representation using a natural language processing method

    A comparison of the CAR and DAGAR spatial random effects models with an application to diabetics rate estimation in Belgium

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    When hierarchically modelling an epidemiological phenomenon on a finite collection of sites in space, one must always take a latent spatial effect into account in order to capture the correlation structure that links the phenomenon to the territory. In this work, we compare two autoregressive spatial models that can be used for this purpose: the classical CAR model and the more recent DAGAR model. Differently from the former, the latter has a desirable property: its ρ parameter can be naturally interpreted as the average neighbor pair correlation and, in addition, this parameter can be directly estimated when the effect is modelled using a DAGAR rather than a CAR structure. As an application, we model the diabetics rate in Belgium in 2014 and show the adequacy of these models in predicting the response variable when no covariates are available

    A Statistical Approach to the Alignment of fMRI Data

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    Multi-subject functional Magnetic Resonance Image studies are critical. The anatomical and functional structure varies across subjects, so the image alignment is necessary. We define a probabilistic model to describe functional alignment. Imposing a prior distribution, as the matrix Fisher Von Mises distribution, of the orthogonal transformation parameter, the anatomical information is embedded in the estimation of the parameters, i.e., penalizing the combination of spatially distant voxels. Real applications show an improvement in the classification and interpretability of the results compared to various functional alignment methods
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