subject:(personalized medicine)

1. Zhang, Patrick. Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.

Degree: School of Engineering, 2018, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:792824/

► Recent technological advancements in genetic testing and the growing accessibility of public genomic data provide researchers with a unique avenue to approach personalized medicine. This… (more)

Subjects/Keywords: Personalized medicine

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APA (6^th Edition):

Zhang, P. (2018). Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792824/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Patrick. “Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.” 2018. Thesis, Brown University. Accessed January 22, 2021. https://repository.library.brown.edu/studio/item/bdr:792824/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Patrick. “Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events.” 2018. Web. 22 Jan 2021.

Vancouver:

Zhang P. Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events. [Internet] [Thesis]. Brown University; 2018. [cited 2021 Jan 22]. Available from: https://repository.library.brown.edu/studio/item/bdr:792824/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang P. Exploring the Potential of Direct-To-Consumer Genomic Test Data for Predicting Adverse Drug Events. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792824/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Scherholz, Megerle, 1986-. Enabling personalized medicine through pharmacokinetic modeling.

Degree: PhD, Chemical and Biochemical Engineering, 2019, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/60057/

► Personalized medicine strives to deliver the ‘right drug’ at the ‘right dose’ at the ‘right time’ by considering the unique characteristics that define specialized populations… (more)

▼ Personalized medicine strives to deliver the ‘right drug’ at the ‘right dose’ at the ‘right time’ by considering the unique characteristics that define specialized populations of patients and contribute to inter-individual variability, a leading cause of therapeutic failure when not properly considered. Given the challenges of studying specialized patient subgroups in clinical trials as well as the high degree of control necessary to tease out differences across populations, physiologically based pharmacokinetic (PBPK) modeling emerged as a key tool to evaluate complex clinical phenotypes and to predict the potential distribution of patient responses. Unfortunately, the inherent variability of biological systems and knowledge gaps in physiological data often limit confidence in model predictions for special populations. Thus, a critical step in model development for special populations involves an in-depth analysis of estimated model input and evaluation of the underlying physiological mechanisms leading to variability in pharmacokinetics, both of which may be guided by global sensitivity analysis and advanced statistical techniques. The benefits of global sensitivity as a means to refine parameter estimates and to understand how model behavior depended on the input parameter space were demonstrated using GastroPlus™ model, a well-known commercially available platform. Global sensitivity analysis was performed in two stages using the Morris Method to screen for significant factors followed by quantitative assessment of variability using Sobol’s sensitivity analysis. The 2-staged approach significantly reduced computational cost without sacrificing interpretation of model behavior, revealing nonlinearities and parameter interactions that would have been missed by local approaches. Furthermore, the utility of pharmacokinetic models to study the underlying and complex physiological mechanisms contributing to clinical differences across patient subgroups was revealed using Monte Carlo simulations by restricting model input to parameter combinations that described only biologically plausible model output. Through an integrated approach using a support vector machine, principal component analysis and global sensitivity analysis, specific combinations of parameters were shown to give rise to clinical phenotype, while individual parameters influenced the shape of the exposure profile. Augmenting analysis of the model input with global sensitivity analysis enabled an understanding of sexual dimorphism and inter-individual variability in pharmacokinetics. Finally, a dynamic semi-mechanstici model that considered pharmacokinetics and pharmacodynamics was used to demonstrate how patients benefit from careful timing of drug delivery. In this study, a mathematical model was developed to explore chronopharmacological dosing of synthetic glucocorticoids and its influence on the endogenous glucocorticoid secretion. Considering the central regulatory function of endogenous glucocorticoids for metabolic, anti-inflammatory,… Advisors/Committee Members: Androulakis, Ioannis P (chair), Ierapetritou, Marianthi (internal member), Ramachandran, Rohit (internal member), Sinko, Patrick (outside member), Zheng, Ming (outside member), School of Graduate Studies.

Subjects/Keywords: Pharmacokinetics; Personalized medicine

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APA (6^th Edition):

Scherholz, Megerle, 1. (2019). Enabling personalized medicine through pharmacokinetic modeling. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60057/

Chicago Manual of Style (16^th Edition):

Scherholz, Megerle, 1986-. “Enabling personalized medicine through pharmacokinetic modeling.” 2019. Doctoral Dissertation, Rutgers University. Accessed January 22, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/60057/.

MLA Handbook (7^th Edition):

Scherholz, Megerle, 1986-. “Enabling personalized medicine through pharmacokinetic modeling.” 2019. Web. 22 Jan 2021.

Vancouver:

Scherholz, Megerle 1. Enabling personalized medicine through pharmacokinetic modeling. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2021 Jan 22]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60057/.

Council of Science Editors:

Scherholz, Megerle 1. Enabling personalized medicine through pharmacokinetic modeling. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60057/

Columbia University

3. Oh, Eun Jeong. Optimal Treatment Regimes for Personalized Medicine and Mobile Health.

Degree: 2020, Columbia University

URL: https://doi.org/10.7916/d8-vvh2-3080

► There has been increasing development in personalized interventions that are tailored to uniquely evolving health status of each patient over time. In this dissertation, we… (more)

▼ There has been increasing development in personalized interventions that are tailored to uniquely evolving health status of each patient over time. In this dissertation, we investigate two problems: (1) the construction of individualized mobile health (mHealth) application recommender system; and (2) the estimation of optimal dynamic treatment regimes (DTRs) from a multi-stage clinical trial study. The dissertation is organized as follows. In Chapter 1, we provide a brief background on personalized medicine and two motivating examples which illustrate the needs and benefits of individualized treatment policies. We then introduce reinforcement learning and various methods to obtain the optimal DTRs as well as Q-learning procedure which is a popular method in the DTR literature. In Chapter 2, we propose a partial regularization via orthogonality using the adaptive Lasso (PRO-aLasso) to estimate the optimal policy which maximizes the expected utility in the mHealth setting. We also derive the convergence rate of the expected outcome of the estimated policy to that of the true optimal policy. The PRO-aLasso estimators are shown to enjoy the same oracle properties as the adaptive Lasso. Simulations and real data application demonstrate that the PRO-aLasso yields simple, more stable policies with better results as compared to the adaptive Lasso and other competing methods. In Chapter 3, we propose a penalized A-learning with a Lasso-type penalty for the construction of optimal DTR and derive generalization error bounds of the estimated DTR. We first examine the relationship between value and the Q-functions, and then we provide a finite sample upper bound on the difference in values between the optimal DTR and the estimated DTR. In practice, we implement a multi-stage PRO-aLasso algorithm to obtain the optimal DTR. Simulation results show advantages of the proposed methods over some existing alternatives. The proposed approach is also demonstrated with the data from a depression clinical trial study. In Chapter 4, we present future work and concluding remarks.

Subjects/Keywords: Biometry; Personalized medicine; Therapeutics

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APA (6^th Edition):

Oh, E. J. (2020). Optimal Treatment Regimes for Personalized Medicine and Mobile Health. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/d8-vvh2-3080

Chicago Manual of Style (16^th Edition):

Oh, Eun Jeong. “Optimal Treatment Regimes for Personalized Medicine and Mobile Health.” 2020. Doctoral Dissertation, Columbia University. Accessed January 22, 2021. https://doi.org/10.7916/d8-vvh2-3080.

MLA Handbook (7^th Edition):

Oh, Eun Jeong. “Optimal Treatment Regimes for Personalized Medicine and Mobile Health.” 2020. Web. 22 Jan 2021.

Vancouver:

Oh EJ. Optimal Treatment Regimes for Personalized Medicine and Mobile Health. [Internet] [Doctoral dissertation]. Columbia University; 2020. [cited 2021 Jan 22]. Available from: https://doi.org/10.7916/d8-vvh2-3080.

Council of Science Editors:

Oh EJ. Optimal Treatment Regimes for Personalized Medicine and Mobile Health. [Doctoral Dissertation]. Columbia University; 2020. Available from: https://doi.org/10.7916/d8-vvh2-3080

University of Ottawa

4. Catley, Christina Anne. Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches .

Degree: 2015, University of Ottawa

URL: http://hdl.handle.net/10393/32054

► Given the emerging importance of personalized medicine (PM) in primary care, now should be the ideal time for engaging with health care professionals (HCPs), both… (more)

Subjects/Keywords: Personalized Medicine; Professional engagement

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APA (6^th Edition):

Catley, C. A. (2015). Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/32054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Catley, Christina Anne. “Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches .” 2015. Thesis, University of Ottawa. Accessed January 22, 2021. http://hdl.handle.net/10393/32054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Catley, Christina Anne. “Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches .” 2015. Web. 22 Jan 2021.

Vancouver:

Catley CA. Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches . [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10393/32054.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Catley CA. Engaging Health Care Professionals in Personalized Medicine: A Pilot Study Comparing Two Professional Engagement Approaches . [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/32054

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

5. Veeramani, Swarna. Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics.

Degree: MS, Medical Sciences, 2017, Boston University

URL: http://hdl.handle.net/2144/20795

► There have been many scientific developments in the last century including the atomic bomb and DNA sequencing. Moreover, when human genome was sequenced in the… (more)

Subjects/Keywords: Molecular biology; Pharmacogenetics; Personalized medicine

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APA (6^th Edition):

Veeramani, S. (2017). Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/20795

Chicago Manual of Style (16^th Edition):

Veeramani, Swarna. “Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics.” 2017. Masters Thesis, Boston University. Accessed January 22, 2021. http://hdl.handle.net/2144/20795.

MLA Handbook (7^th Edition):

Veeramani, Swarna. “Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics.” 2017. Web. 22 Jan 2021.

Vancouver:

Veeramani S. Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics. [Internet] [Masters thesis]. Boston University; 2017. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2144/20795.

Council of Science Editors:

Veeramani S. Personalized medicine: examining the current and future applications of pharmacogenetics and pharmacogenomics. [Masters Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/20795

University of Iowa

6. Papke, Todd Alan. Personalized audio warning alerts in medicine.

Degree: PhD, Informatics, 2014, University of Iowa

URL: https://ir.uiowa.edu/etd/1378

► Modern Electronic Health Record (EHR) systems are now integral to healthcare. Having evolved from hospital billing and laboratory systems in the 80's, EHR systems… (more)

▼ Modern Electronic Health Record (EHR) systems are now integral to healthcare. Having evolved from hospital billing and laboratory systems in the 80's, EHR systems have grown considerably as we learn to represent more and more aspects of patient encounter, diagnosis and treatment digitally. EHR user interfaces, however, lag considerably behind their consumer-electronics counterparts in usability, most notably with respect to customizability. This limitation is especially evident in the implementation of audible alerts that are coupled to sensors or timing devices in intensive-care settings. The most current standard, (ISO/IEC 60601-1-8) has been designed for alerts that are intended to signal situations of varying priorities: however, it is not universally implemented, and has been criticized for the difficulty that healthcare providers have in discriminating between individual alarms, and for the failure to incorporate prior research with respect to "sense of urgency" as it applies to alarm efficacy. In the present work, however, we consider that there are more effective means to allow a user to identify an alarm correctly than "sense of urgency" response. This thesis focuses on the problem of correct identification of alerts: what happens when a human subject is allowed to create or designate (i.e., personalize) one's own alerts? Given the ubiquity, low costs and commoditization of consumer-electronics devices, we believe that it is just a matter of time before such devices become the norm in critical care and replace existing, special-purpose devices for information delivery at the point of patient care. We built a tool, PASA (Personalized Alert Study Application), that would allow us to capture and edit sounds and orchestrate studies that would contrast any two types of sounds. PASA facilitated a study where study participant's responses to "personalized" sounds were contrasted with sounds that meet the ISO/IEC 60601-1-8:2012 standard. We performed two sub-studies that contrasted responses to two banks of 6-alerts and 10-alerts. The 6-alert study was repeated with the same subjects after two weeks without training to measure recall. We observed that accuracy, reaction time, and retention were significantly improved with the personalized sounds. For example, the median errors for the 6-alert baseline study were 4 for personalized vs. 27 for standard alerts. For the 6-alert repeat study it was 7 vs. 43. The median for the 10-alert study was 1 for personalized vs. 55 for standard alerts. Accuracy for recognition, while remaining constant for personalized alerts, degraded considerably for standardized alerts as the number of alerts increased from 6 to 10. We conclude that personalization of alerts may improve information delivery and reduce cognitive overload on the health care provider. This potential positive effect at the point of patient care merits further studies in a clinical or simulated clinical setting. Advisors/Committee Members: Nadkarni, Prakash M. (supervisor).

Subjects/Keywords: Alerts; Critical; Medicine; Personalized; Bioinformatics

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APA (6^th Edition):

Papke, T. A. (2014). Personalized audio warning alerts in medicine. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/1378

Chicago Manual of Style (16^th Edition):

Papke, Todd Alan. “Personalized audio warning alerts in medicine.” 2014. Doctoral Dissertation, University of Iowa. Accessed January 22, 2021. https://ir.uiowa.edu/etd/1378.

MLA Handbook (7^th Edition):

Papke, Todd Alan. “Personalized audio warning alerts in medicine.” 2014. Web. 22 Jan 2021.

Vancouver:

Papke TA. Personalized audio warning alerts in medicine. [Internet] [Doctoral dissertation]. University of Iowa; 2014. [cited 2021 Jan 22]. Available from: https://ir.uiowa.edu/etd/1378.

Council of Science Editors:

Papke TA. Personalized audio warning alerts in medicine. [Doctoral Dissertation]. University of Iowa; 2014. Available from: https://ir.uiowa.edu/etd/1378

Boston University

7. Benson, Adam. Precision medicine in oncology: a complicated idea needs a simple solution.

Degree: MS, Medical Sciences, 2016, Boston University

URL: http://hdl.handle.net/2144/16798

► Cancer therapy has historically been determined by a tumor’s tissue of origin. Now, thanks to advances in genomics technology, scientists are looking further into one’s… (more)

Subjects/Keywords: Genetics; Bioinformatics; Genomics; Personalized medicine; Precision medicine

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APA (6^th Edition):

Benson, A. (2016). Precision medicine in oncology: a complicated idea needs a simple solution. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16798

Chicago Manual of Style (16^th Edition):

Benson, Adam. “Precision medicine in oncology: a complicated idea needs a simple solution.” 2016. Masters Thesis, Boston University. Accessed January 22, 2021. http://hdl.handle.net/2144/16798.

MLA Handbook (7^th Edition):

Benson, Adam. “Precision medicine in oncology: a complicated idea needs a simple solution.” 2016. Web. 22 Jan 2021.

Vancouver:

Benson A. Precision medicine in oncology: a complicated idea needs a simple solution. [Internet] [Masters thesis]. Boston University; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2144/16798.

Council of Science Editors:

Benson A. Precision medicine in oncology: a complicated idea needs a simple solution. [Masters Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16798

University of Exeter

8. Dennis, J. Precision medicine in type 2 diabetes.

Degree: PhD, 2019, University of Exeter

URL: http://hdl.handle.net/10871/37430

► Type 2 diabetes is a progressive disease characterised by raised blood glucose levels. Lowering of blood glucose is required to prevent symptoms of diabetes and… (more)

Subjects/Keywords: Type 2 diabetes; Precision medicine; Personalized medicine

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APA (6^th Edition):

Dennis, J. (2019). Precision medicine in type 2 diabetes. (Doctoral Dissertation). University of Exeter. Retrieved from http://hdl.handle.net/10871/37430

Chicago Manual of Style (16^th Edition):

Dennis, J. “Precision medicine in type 2 diabetes.” 2019. Doctoral Dissertation, University of Exeter. Accessed January 22, 2021. http://hdl.handle.net/10871/37430.

MLA Handbook (7^th Edition):

Dennis, J. “Precision medicine in type 2 diabetes.” 2019. Web. 22 Jan 2021.

Vancouver:

Dennis J. Precision medicine in type 2 diabetes. [Internet] [Doctoral dissertation]. University of Exeter; 2019. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10871/37430.

Council of Science Editors:

Dennis J. Precision medicine in type 2 diabetes. [Doctoral Dissertation]. University of Exeter; 2019. Available from: http://hdl.handle.net/10871/37430

Universiteit Utrecht

9. Taliadourou, V. Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use.

Degree: 2010, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/45172

► It is no secret that the genomic era is upon us. Through the wealth of data generated by the Human Genome Project, in conjunction with… (more)

Subjects/Keywords: Geneeskunde; pharmacogenomics, personal genome, SNPs, personalized medicine

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APA (6^th Edition):

Taliadourou, V. (2010). Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/45172

Chicago Manual of Style (16^th Edition):

Taliadourou, V. “Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use.” 2010. Masters Thesis, Universiteit Utrecht. Accessed January 22, 2021. http://dspace.library.uu.nl:8080/handle/1874/45172.

MLA Handbook (7^th Edition):

Taliadourou, V. “Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use.” 2010. Web. 22 Jan 2021.

Vancouver:

Taliadourou V. Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use. [Internet] [Masters thesis]. Universiteit Utrecht; 2010. [cited 2021 Jan 22]. Available from: http://dspace.library.uu.nl:8080/handle/1874/45172.

Council of Science Editors:

Taliadourou V. Using Whole Genome-Wide Genetic Information for Making Choices in Drug Therapy Use. [Masters Thesis]. Universiteit Utrecht; 2010. Available from: http://dspace.library.uu.nl:8080/handle/1874/45172

Universiteit Utrecht

10. Meddens, C.A. Personalized medicine.

Degree: 2011, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/205090

► There are three different ways in which personalized medicine will likely be used by clinicians and patients; First, the prediction of the way a patient… (more)

Subjects/Keywords: Personalized medicine; SNP analysis; CTC; pharmacogenomics

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APA (6^th Edition):

Meddens, C. A. (2011). Personalized medicine. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/205090

Chicago Manual of Style (16^th Edition):

Meddens, C A. “Personalized medicine.” 2011. Masters Thesis, Universiteit Utrecht. Accessed January 22, 2021. http://dspace.library.uu.nl:8080/handle/1874/205090.

MLA Handbook (7^th Edition):

Meddens, C A. “Personalized medicine.” 2011. Web. 22 Jan 2021.

Vancouver:

Meddens CA. Personalized medicine. [Internet] [Masters thesis]. Universiteit Utrecht; 2011. [cited 2021 Jan 22]. Available from: http://dspace.library.uu.nl:8080/handle/1874/205090.

Council of Science Editors:

Meddens CA. Personalized medicine. [Masters Thesis]. Universiteit Utrecht; 2011. Available from: http://dspace.library.uu.nl:8080/handle/1874/205090

Cornell University

11. Nguyen, Xuanmai. Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.

Degree: PhD, Nutrition, 2014, Cornell University

URL: http://hdl.handle.net/1813/36193

► The overall objective of this research is to examine the joint effect of multiple variants in folate metabolism on CVD outcome. The intermediary outcome, homocysteine,… (more)

Subjects/Keywords: complex systems; personalized medicine; folate metabolism

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APA (6^th Edition):

Nguyen, X. (2014). Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36193

Chicago Manual of Style (16^th Edition):

Nguyen, Xuanmai. “Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.” 2014. Doctoral Dissertation, Cornell University. Accessed January 22, 2021. http://hdl.handle.net/1813/36193.

MLA Handbook (7^th Edition):

Nguyen, Xuanmai. “Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.” 2014. Web. 22 Jan 2021.

Vancouver:

Nguyen X. Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1813/36193.

Council of Science Editors:

Nguyen X. Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36193

Vanderbilt University

12. Malinowski, Jennifer Renee. Women's Health: Genetic Variation in Complex Traits.

Degree: PhD, Human Genetics, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/14371

► Personalized medicine, the individualization of clinical care based, in part, upon an individual’s genetic background, can be thought of as a three step process: scientific… (more)

Subjects/Keywords: personalized medicine; women's health; human genetics

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APA (6^th Edition):

Malinowski, J. R. (2014). Women's Health: Genetic Variation in Complex Traits. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14371

Chicago Manual of Style (16^th Edition):

Malinowski, Jennifer Renee. “Women's Health: Genetic Variation in Complex Traits.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/14371.

MLA Handbook (7^th Edition):

Malinowski, Jennifer Renee. “Women's Health: Genetic Variation in Complex Traits.” 2014. Web. 22 Jan 2021.

Vancouver:

Malinowski JR. Women's Health: Genetic Variation in Complex Traits. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/14371.

Council of Science Editors:

Malinowski JR. Women's Health: Genetic Variation in Complex Traits. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/14371

13. Alyass, Akram. Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine.

Degree: PhD, 2018, McMaster University

URL: http://hdl.handle.net/11375/23291

►

Anticipations of personalized medicine are primarily attributed to the recent advances in computational science and high-throughput technologies that enable the ever-more realistic modeling of complex… (more)

▼

Anticipations of personalized medicine are primarily attributed to the recent advances in computational science and high-throughput technologies that enable the ever-more realistic modeling of complex diseases. These diseases result from the interplay between genes and environment that have limited our ability to predict, prevent, or treat them. While many envision the utility of integrated high-dimensional patient-specific information, basic research towards developing accurate and reliable frameworks for personalized medicine is relatively slow in progress. This thesis provides a state-of-the-art review of current challenges towards personalized medicine. There is a need for global investment in basic research that includes 1) cost-effective generation of high-quality high-throughput data, 2) hybrid education and multidisciplinary teams, 3) data storage and processing, 4) data integration and interpretation, and 5) individual and global economic relevance; to be followed by global investments into public health to adopt routine personalized medicine. This review also highlights that unknown or unadjusted interactions result in true heterogeneity in the effect and relevance of patient data. This limits our ability to integrate and reliably utilize high-dimensional patient-specific data. This thesis further investigates the true heterogeneity in marginal effects of known BMI genetic variants. This involved the development of the novel statistical method, meta-quantile regression (MQR), to identify variants with potential gene-gene / gene-environment interactions. Applying MQR on public and local data (75,230 European adults) showed that FTO, PCSK1, TCF7L2, MC4R, FANCL, GIPR, MAP2K5, and NT5C2 have potential interactions on BMI. In addition, a gene score of 37 BMI variants shows that the genetic architecture of BMI is shaped by gene-gene and gene-environment interactions. The computational cost of fitting MQR models was greatly reduced using unconditional quantile regression. The utility of MQR was further compared to variance heterogeneity tests in identifying variants with potential interactions. MQR tests were found to have a higher power of detecting synergetic and antagonistic interactions for skewed quantitative traits while maintaining nominal Type I error rates compared to variance heterogeneity tests. Overall, MQR is a valuable tool to detect potential interactions without imposing assumptions on the nature of interactions.

Thesis

Doctor of Philosophy (PhD)

The anticipations of personalized medicine are largely due to the recent advances in computational science and our capabilities to rapidly measure and generate biological data. These developments have enhanced our understanding of complex diseases, and should theoretically enable us to predict, prevent and treat such cases in a proactive personalized context. This thesis provides a state-of-the-art review of the challenges and opportunities that explain the relatively slow progress towards personalized medicine. It identifies data integration and…

Advisors/Committee Members: Meyre, David, Computational Engineering and Science.

Subjects/Keywords: personalized medicine; Statistical Genetics; Obesity; BMI

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APA (6^th Edition):

Alyass, A. (2018). Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/23291

Chicago Manual of Style (16^th Edition):

Alyass, Akram. “Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine.” 2018. Doctoral Dissertation, McMaster University. Accessed January 22, 2021. http://hdl.handle.net/11375/23291.

MLA Handbook (7^th Edition):

Alyass, Akram. “Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine.” 2018. Web. 22 Jan 2021.

Vancouver:

Alyass A. Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine. [Internet] [Doctoral dissertation]. McMaster University; 2018. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/11375/23291.

Council of Science Editors:

Alyass A. Leveraging Distribution Quantiles to Detect Gene Interactions in the Pursuit of Personalized Medicine. [Doctoral Dissertation]. McMaster University; 2018. Available from: http://hdl.handle.net/11375/23291

University of Illinois – Chicago

14. Sun, Yan. A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria.

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19777

► Subgroup identification has always been of great interest among the many functions and applications of statistical learning. In the pharmaceutical area, it is desirable to… (more)

Subjects/Keywords: subgroup; personalized medicine; variable selection; quantitative criteria

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APA (6^th Edition):

Sun, Y. (2015). A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19777

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sun, Yan. “A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria.” 2015. Thesis, University of Illinois – Chicago. Accessed January 22, 2021. http://hdl.handle.net/10027/19777.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sun, Yan. “A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria.” 2015. Web. 22 Jan 2021.

Vancouver:

Sun Y. A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10027/19777.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sun Y. A Subgroup Identification Method with Interaction Filtering and Quantitative Criteria. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19777

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

15. Cameron, Kellas Ross. Studies on using data-driven decision support systems to improve personalized medicine processes.

Degree: PhD, Management, 2018, Boston University

URL: http://hdl.handle.net/2144/30452

► This dissertation looks at how new sources of information should be incorporated into medical decision-making processes to improve patient outcomes and reduce costs. There are… (more)

▼ This dissertation looks at how new sources of information should be incorporated into medical decision-making processes to improve patient outcomes and reduce costs. There are three fundamental challenges that must be overcome to effectively use personalized medicine, we need to understand: 1) how best to appropriately designate which patients will receive the greatest value from these processes; 2) how physicians and caregivers interpret additional patient-specific information and how that affects their decision-making processes; and finally, (3) how to account for a patient’s ability to engage in their own healthcare decisions. The first study looks at how we can infer which patients will receive the most value from genomic testing. The difficult statistical problem is how to separate the distribution of patients, based on ex-ante factors, to identify the best candidates for personalized testing. A model was constructed to infer a healthcare provider’s decision on whether this test would provide beneficial information in selecting a patient’s medication. Model analysis shows that healthcare providers’ primary focus is to maximize patient health outcomes while considering the impact the patient’s economic welfare. The second study focuses on understanding how technology-enabled continuity of care (TECC) for Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF) patients can be utilized to improve patient engagement, measured in terms of patient activation. We shed light on the fact that different types of patients garnered different levels of value from the use of TECC. The third study looks at how data-driven decision support systems can allow physicians to more accurately understand which patients are at high-risk of readmission. We look at how we can use available patient-specific information for patients admitted with CHF to more accurately identify which patients are most likely to be readmitted, and also why – whether for condition-related reasons versus for non- related reasons, allowing physicians to suggest different patient-specific readmission prevention strategies. Taken together, these three studies allow us to build a robust theory to tackle these challenges, both operational and policy-related, that need to be addressed for physicians to take advantage of the growing availability of patient-specific information to improve personalized medication processes. Advisors/Committee Members: Joglekar, Nitin R. (advisor).

Subjects/Keywords: Management; Personalized medicine; Predictive analytics; Process improvement

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APA (6^th Edition):

Cameron, K. R. (2018). Studies on using data-driven decision support systems to improve personalized medicine processes. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/30452

Chicago Manual of Style (16^th Edition):

Cameron, Kellas Ross. “Studies on using data-driven decision support systems to improve personalized medicine processes.” 2018. Doctoral Dissertation, Boston University. Accessed January 22, 2021. http://hdl.handle.net/2144/30452.

MLA Handbook (7^th Edition):

Cameron, Kellas Ross. “Studies on using data-driven decision support systems to improve personalized medicine processes.” 2018. Web. 22 Jan 2021.

Vancouver:

Cameron KR. Studies on using data-driven decision support systems to improve personalized medicine processes. [Internet] [Doctoral dissertation]. Boston University; 2018. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2144/30452.

Council of Science Editors:

Cameron KR. Studies on using data-driven decision support systems to improve personalized medicine processes. [Doctoral Dissertation]. Boston University; 2018. Available from: http://hdl.handle.net/2144/30452

Columbia University

16. Zhong, Xiaobo. Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions.

Degree: 2018, Columbia University

URL: https://doi.org/10.7916/D8DJ6Z1K

► The research of my dissertation studies the methods of designing and analyzing sequential multiple assignment randomized trial (SMART) for comparing multiple adaptive interventions. As a… (more)

Subjects/Keywords: Biometry; Public health; Intervention; Personalized medicine; Therapeutics

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APA (6^th Edition):

Zhong, X. (2018). Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8DJ6Z1K

Chicago Manual of Style (16^th Edition):

Zhong, Xiaobo. “Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions.” 2018. Doctoral Dissertation, Columbia University. Accessed January 22, 2021. https://doi.org/10.7916/D8DJ6Z1K.

MLA Handbook (7^th Edition):

Zhong, Xiaobo. “Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions.” 2018. Web. 22 Jan 2021.

Vancouver:

Zhong X. Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions. [Internet] [Doctoral dissertation]. Columbia University; 2018. [cited 2021 Jan 22]. Available from: https://doi.org/10.7916/D8DJ6Z1K.

Council of Science Editors:

Zhong X. Design and Analysis of Sequential Multiple Assignment Randomized Trial for Comparing Multiple Adaptive Interventions. [Doctoral Dissertation]. Columbia University; 2018. Available from: https://doi.org/10.7916/D8DJ6Z1K

Delft University of Technology

17. Shah, Maulik (author). Commercialization Strategy for the Pharmaceutical Industry.

Degree: 2019, Delft University of Technology

URL: http://resolver.tudelft.nl/uuid:075f0b87-636e-4781-a367-3e2d56ad4cc9

► This thesis report is aimed at analysing two phenomena, the first being - the major trends which are shaping the pharmaceutical industry currently. The industry… (more)

▼ This thesis report is aimed at analysing two phenomena, the first being - the major trends which are shaping the pharmaceutical industry currently. The industry is witnessing massive strategic shifts, routine upgrades to new drug technologies in a dynamic regulatory and market environment. The growth rate of the global pharmaceutical industry is projected to exceed 1 trillion dollars by 2022 (Lervolino & Urquhart, 2017). There are increasing expectations from pharmaceutical companies to introduce advanced products and technologies for the welfare of the people. This objective of this descriptive study is to analyse market, technological and strategic trends, the interrelations, and to some extent, the impact of regulatory environment on the pharmaceutical ecosystem. Secondly, this study lays a special emphasis on personalized medicine and assessing its current and future scope amid these changing dynamics. A combination of systematic literature review and expert interviews was undertaken to achieve the above stated objective. The study is qualitative and involves analysis of opinions derived from expert interviews cross verified with scientific literature. The key findings are stated below: Since traditional pharmaceutical companies now face increasing market and regulatory pressures to differentiate their products, they are looking for alternate business models. This pressure is supplemented by a change in payer preferences and healthcare budgets set by governments across the world. High risk of drug failures further adds on to this. Many companies are experimenting with radically different product lines such as biologics and biosimilars. In the recent years, pharmaceutical companies in conjunction with biotechnology companies have identified the potential of technologies such as genetic profiling, advanced diagnostics etc. to understand the effects of drug interactions with the human body. However, the use of such technologies remains largely confined to highly specialized therapeutic areas such as oncology. The main reason is the economic barrier it faces. The costs of most personalized drugs are extremely high, and this affects the market access of a drug. It was also found that, the readiness of the facilitating environment (patient data repositories, Information technology infrastructure) etc. is also essential for commercializing personalized medicine. Healthcare Institutions, service providers are still not equipped to deal with personalized medicine on a mass level. Hence personalized medicine is predicted to remain as a niche offering limited to a select few therapeutic areas such as oncology in the foreseeable future. Two promising avenues for rapidly commercializing personalized medicine were identified: The first relates to develop financing mechanisms for pharmaceutical companies so that they can develop novel drugs for people with serious medical conditions. The second avenue which was identified was designing optimal risk sharing agreements between pharmaceutical companies and the payers. For a… Advisors/Committee Members: Ortt, Roland (mentor), de Bruijne, Mark (graduation committee), Delft University of Technology (degree granting institution).

Subjects/Keywords: Pharmaceutical; personalized medicine; drug; trends; interrelations; strategy

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APA (6^th Edition):

Shah, M. (. (2019). Commercialization Strategy for the Pharmaceutical Industry. (Masters Thesis). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:075f0b87-636e-4781-a367-3e2d56ad4cc9

Chicago Manual of Style (16^th Edition):

Shah, Maulik (author). “Commercialization Strategy for the Pharmaceutical Industry.” 2019. Masters Thesis, Delft University of Technology. Accessed January 22, 2021. http://resolver.tudelft.nl/uuid:075f0b87-636e-4781-a367-3e2d56ad4cc9.

MLA Handbook (7^th Edition):

Shah, Maulik (author). “Commercialization Strategy for the Pharmaceutical Industry.” 2019. Web. 22 Jan 2021.

Vancouver:

Shah M(. Commercialization Strategy for the Pharmaceutical Industry. [Internet] [Masters thesis]. Delft University of Technology; 2019. [cited 2021 Jan 22]. Available from: http://resolver.tudelft.nl/uuid:075f0b87-636e-4781-a367-3e2d56ad4cc9.

Council of Science Editors:

Shah M(. Commercialization Strategy for the Pharmaceutical Industry. [Masters Thesis]. Delft University of Technology; 2019. Available from: http://resolver.tudelft.nl/uuid:075f0b87-636e-4781-a367-3e2d56ad4cc9

Universitat de Valencia

18. Casanova Salas, Irene. Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention .

Degree: 2015, Universitat de Valencia

URL: http://hdl.handle.net/10550/44486

► El cáncer de próstata (CaP) es el segundo tumor más frecuente en hombres y la sexta causa de muerte por cáncer. Así pues, esta enfermedad… (more)

▼ El cáncer de próstata (CaP) es el segundo tumor más frecuente en hombres y la sexta causa de muerte por cáncer. Así pues, esta enfermedad constituye un problema socio-sanitario prioritario para el sistema de Salud Pública. Actualmente, las herramientas para orientar el diagnóstico en CaP (PSA y DRE) no son cáncer específicas y presentan distintas limitaciones tales como el alto número de falsos positivos (aproximadamente un 70% en un rango de PSA de 4-10 ng/ml) que dan lugar a complicaciones asociadas con el proceso de biopsia. Además, un gran número de los CaP diagnosticados son tumores de bajo grado implicando un sobre-diagnóstico y sobre-tratamiento de esta enfermedad. Sin embargo, otros CaP tendrán un comportamiento pronóstico más agresivo que dará lugar a la progresión de la enfermedad y en último término a la muerte del paciente. Estas diferencias en el comportamiento clínico del CaP se explican por una alta heterogeneidad molecular presente en este tumor. En este contexto de heterogeneidad molecular nuestro objetivo se centra en la búsqueda de nuevos biomarcadores identificables mediante procedimientos no invasivos y capaces de clasificar a los pacientes con CaP de acuerdo a biotipos moleculares asociados con diferentes parámetros clínico-patológicos y distinto riesgo de progresión. En este trabajo exploramos el papel que tienen los miRNAs como nueva fuente de biomarcadores en CaP y encontramos que el miR-182 y el miR-187 juegan un papel clave en la patogénesis y el desarrollo del CaP en ambos contextos, el diagnóstico (miR-187) y el pronóstico (miR-182). Además, identificamos ALDH1A3, un gen regulado por andrógenos, como diana del miR-187 y como potencial biomarcador en CaP. En nuestra búsqueda de nuevos biomarcadores estudiamos también el papel que tiene el gen SPOP en CaP confirmando su pérdida de expresión y mutaciones en CaP y siendo el primer grupo en describir la asociación de estas alteraciones moleculares con el pronóstico en CaP. Además en nuestro trabajo también intentamos ofrecer nuevas alternativas terapéuticas para el tratamiento del CaP avanzado de acuerdo con el biotipo molecular. Así, nuestro hallazgo de la asociación directa entre IGF-IR y TMPRSS2-ERG y la mayor sensibilidad de este grupo a los inhibidores de IGF-IR nos llevaron a proponer este subgrupo de pacientes como población diana -biotipo- para la inhibición de IGF-IR. Advisors/Committee Members: López Guerrero, José Antonio (advisor).

Subjects/Keywords: biomarker; personalized medicine; diagnosis; prognosis; prostate cancer

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APA (6^th Edition):

Casanova Salas, I. (2015). Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention . (Doctoral Dissertation). Universitat de Valencia. Retrieved from http://hdl.handle.net/10550/44486

Chicago Manual of Style (16^th Edition):

Casanova Salas, Irene. “Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention .” 2015. Doctoral Dissertation, Universitat de Valencia. Accessed January 22, 2021. http://hdl.handle.net/10550/44486.

MLA Handbook (7^th Edition):

Casanova Salas, Irene. “Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention .” 2015. Web. 22 Jan 2021.

Vancouver:

Casanova Salas I. Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention . [Internet] [Doctoral dissertation]. Universitat de Valencia; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10550/44486.

Council of Science Editors:

Casanova Salas I. Defining new biotypes in Prostate Cancer for diagnosis, prognosis and therapeutic intervention . [Doctoral Dissertation]. Universitat de Valencia; 2015. Available from: http://hdl.handle.net/10550/44486

University of Michigan

19. Li, Pin. Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology.

Degree: PhD, Biostatistics, 2020, University of Michigan

URL: http://hdl.handle.net/2027.42/163037

► The goal of personalized medicine is to give the right treatment to the right patient at the right dose using all we know about the… (more)

▼ The goal of personalized medicine is to give the right treatment to the right patient at the right dose using all we know about the patient. With the increasing availability of biomarkers and prediction models, there is the potential for individualized treatment based on patient specific factors. There are many statistical challenges associated with achieving this goal. One is how to develop and assess good predictions models. Another is how to define a criteria for an optimal treatment when there are multiple outcomes and then how to analyze available data to determine the optimal treatment for each future patient. In Chapter II, we consider the assessment of prediction models using data with missing biomarker values. We propose inverse probability weighted (IPW) and augmented inverse probability weighted (AIPW) estimates of the area under the ROC curve (AUC) and Brier Score to handle the missing data. AIPW is a double-robust method that is robust to the misspecification of either a model for the missingness mechanism or a model for the distribution of the missing variable. We evaluated the performance of IPW and AIPW in comparison with multiple imputation (MI) in simulation studies under missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR) scenarios. We illustrate these methods using an example from prostate cancer. In Chapters III and IV we consider the setting where there is an existing dataset of patients treated with heterogeneous doses and including binary efficacy and toxicity outcomes and patient factors such as clinical features and biomarkers. The goal is to analyze the data to estimate an optimal dose for each (future) patient based on their clinical features and biomarkers. In Chapter III, we propose an optimal individualized dose finding rule by maximizing utility functions for individual patients while limiting the rate of toxicity. The utility is defined as a weighted combination of efficacy and toxicity probabilities. We model the binary efficacy and toxicity outcomes using logistic regression with dose, biomarkers and dose-biomarker interactions. To incorporate the large number of potential biomarkers, we use the LASSO method. We additionally constrain the dose effect to be non-negative for both efficacy and toxicity for all patients. The proposed methods are illustrated using a dataset of patients with lung cancer treated with radiation therapy. In Chapter IV, we extend the approach of Chapter III and propose to use flexible machine learning methods such as random forests and Gaussian processes to build models for efficacy and toxicity depending on the dose and biomarkers. In addition, we allow for dependence between efficacy and toxicity. A copula is used to model the joint distribution of the two outcomes and the estimates are constrained to have non-decreasing dose-efficacy and dose-toxicity relationships. Numerical utilities are assigned to each potential outcome pair, which allow the improvement in the utility due to a change in efficacy to depend… Advisors/Committee Members: Schipper, Matthew Jason (committee member), Taylor, Jeremy Michael George (committee member), Lawrence, Theodore S (committee member), Boonstra, Phil (committee member).

Subjects/Keywords: Personalized Medicine; Public Health; Health Sciences

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APA (6^th Edition):

Li, P. (2020). Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/163037

Chicago Manual of Style (16^th Edition):

Li, Pin. “Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology.” 2020. Doctoral Dissertation, University of Michigan. Accessed January 22, 2021. http://hdl.handle.net/2027.42/163037.

MLA Handbook (7^th Edition):

Li, Pin. “Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology.” 2020. Web. 22 Jan 2021.

Vancouver:

Li P. Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology. [Internet] [Doctoral dissertation]. University of Michigan; 2020. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2027.42/163037.

Council of Science Editors:

Li P. Use and Evaluation of Statistical Methods for Personalized Medicine in Oncology. [Doctoral Dissertation]. University of Michigan; 2020. Available from: http://hdl.handle.net/2027.42/163037

University of California – Irvine

20. Nossair, Fadi. Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care.

Degree: Biomedical and Translational Science, 2018, University of California – Irvine

URL: http://www.escholarship.org/uc/item/6xr3z2zj

► Background: Pediatric hospital-acquired venous thromboembolism (HA-VTE) has increased over the past ten years, with central venous catheters (CVC) being the strongest risk factor. Current tools… (more)

Subjects/Keywords: Medicine; Biomarkers; Central venous catheter; Children; Personalized medicine; Prediction; Venous thromboembolism

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APA (6^th Edition):

Nossair, F. (2018). Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/6xr3z2zj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nossair, Fadi. “Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care.” 2018. Thesis, University of California – Irvine. Accessed January 22, 2021. http://www.escholarship.org/uc/item/6xr3z2zj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nossair, Fadi. “Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care.” 2018. Web. 22 Jan 2021.

Vancouver:

Nossair F. Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care. [Internet] [Thesis]. University of California – Irvine; 2018. [cited 2021 Jan 22]. Available from: http://www.escholarship.org/uc/item/6xr3z2zj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nossair F. Promising Biomarkers for the Prediction of Catheter-related Venous Thromboembolism in Children: An emphasis on prevention and personalized care. [Thesis]. University of California – Irvine; 2018. Available from: http://www.escholarship.org/uc/item/6xr3z2zj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Columbia University

21. Shahn, Zach. Methods for Personalized and Evidence Based Medicine.

Degree: 2016, Columbia University

URL: https://doi.org/10.7916/D8M0458S

► There is broad agreement that medicine ought to be `evidence based' and `personalized' and that data should play a large role in achieving both these… (more)

▼ There is broad agreement that medicine ought to be `evidence based' and `personalized' and that data should play a large role in achieving both these goals. But the path from data to improved medical decision making is not clear. This thesis presents three methods that hopefully help in small ways to clear the path. Personalized medicine depends almost entirely on understanding variation in treatment effect. Chapter 1 describes latent class mixture models for treatment effect heterogeneity that distinguish between continuous and discrete heterogeneity, use hierarchical shrinkage priors to mitigate overfitting and multiple comparisons concerns, and employ flexible error distributions to improve robustness. We apply different versions of these models to reanalyze a clinical trial comparing HIV treatments and a natural experiment on the effect of Medicaid on emergency department utilization. Medical decisions often depend on observational studies performed on large longitudinal health insurance claims databases. These studies usually claim to identify a causal effect, but empirical evaluations have demonstrated that standard methods for causal discovery perform poorly in this context, most likely in large part due to the presence of unobserved confounding. Chapter 2 proposes an algorithm called Ensembles of Granger Graphs (EGG) that does not rely on the assumption that unobserved confounding is absent. In a simulation and experiments on a real claims database, EGG is robust to confounding, has high positive predictive value, and has high power to detect strong causal effects. While decision making inherently involves causal inference, purely predictive models aid many medical decisions in practice. Predictions from health histories are challenging because the space of possible predictors is so vast. Not only are there thousands of health events to consider, but also their temporal interactions. In Chapter 3, we adapt a method originally developed for speech recognition that greedily constructs informative labeled graphs representing temporal relations between multiple health events at the nodes of randomized decision trees. We use this method to predict strokes in patients with atrial fibrillation using data from a Medicaid claims database. I hope the ideas illustrated in these three projects inspire work that someday genuinely improves healthcare. I also include a short `bonus' chapter on an improved estimate of effective sample size in importance sampling. This chapter is not directly related to medicine, but finds a home in this thesis nonetheless.

Subjects/Keywords: Evidence-based medicine; Medical care – Statistics; Personalized medicine; Statistics

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APA (6^th Edition):

Shahn, Z. (2016). Methods for Personalized and Evidence Based Medicine. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8M0458S

Chicago Manual of Style (16^th Edition):

Shahn, Zach. “Methods for Personalized and Evidence Based Medicine.” 2016. Doctoral Dissertation, Columbia University. Accessed January 22, 2021. https://doi.org/10.7916/D8M0458S.

MLA Handbook (7^th Edition):

Shahn, Zach. “Methods for Personalized and Evidence Based Medicine.” 2016. Web. 22 Jan 2021.

Vancouver:

Shahn Z. Methods for Personalized and Evidence Based Medicine. [Internet] [Doctoral dissertation]. Columbia University; 2016. [cited 2021 Jan 22]. Available from: https://doi.org/10.7916/D8M0458S.

Council of Science Editors:

Shahn Z. Methods for Personalized and Evidence Based Medicine. [Doctoral Dissertation]. Columbia University; 2016. Available from: https://doi.org/10.7916/D8M0458S

Columbia University

22. Feldman, Naumi Mira. Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine.

Degree: 2014, Columbia University

URL: https://doi.org/10.7916/D8CG00BR

► OBJECTIVE: Personalized genomic medicine (PGM) has been lauded as the future of medicine, as new human genomic research findings are applied towards the development of… (more)

▼ OBJECTIVE: Personalized genomic medicine (PGM) has been lauded as the future of medicine, as new human genomic research findings are applied towards the development of screenings, diagnostic tools and treatments that are tailored to the genomic profiles of individuals. However, the development of PGM is still in its nascent stages, therefore, some have supported the development of clinical tools and treatments based on population-level characteristics, such as race or ethnicity. Race-based medicine (RBM), has been, and continues to be, promoted as an interim form of PGM, and although an academic debate has flourished over medical, social and ethical concerns related to RBM, to date, there have only been a few small studies that have examined lay beliefs and attitudes regarding RBM. The extent to which the greater American public would believe in the effectiveness of RBM and indicate an intention to use RBM is unclear. Furthermore, it is possible that racial and ethnic groups would differ in their beliefs and attitudes regarding RBM, considering RBM implies the controversial and contested conceptualization of race as having some genetic basis. Therefore, the purpose of this dissertation study was to use, for the first time, a nationally representative sample of adult Americans and examine the importance of race with respect to the following: beliefs and attitudes regarding RBM; the extent to which these beliefs and attitudes can be influenced by mass media messages about the relationship between race and genetics; and how beliefs and attitudes regarding RBM compare with those regarding PGM. METHODS: In order to answer these questions, this dissertation study used a nationally representative sample of self-identified non-Hispanic white, non-Hispanic black and Hispanic U.S. residents who participated in an online survey examining beliefs and attitudes regarding RBM and PGM, and the effect of a vignette experiment using mock news articles that varied in their messages about the relationship between race and genes on these beliefs and attitudes. The survey assessed the following constructs using new measures designed for this dissertation study: RBM's effectiveness at the individual, clinical level; PGM's effectiveness at the individual, clinical level; preferences for using RBM; preferences for using PGM; and RBM's ability to address health inequalities in the U.S. Means, frequencies, mean-difference tests and multiple regression were used to examine the effect of race and/or the vignette experiment on beliefs and attitudes regarding RBM and PGM. RESULTS: The results of this dissertation study show that the majority of white, black and Hispanic Americans equally agreed that RBM would not be clinically effective at the individual level, but the majority of all groups also equally agreed that they would prefer to use RBM if it was available. More than forty percent of all respondents who did not believe RBM would be effective at the individual level, still preferred to use a race-specific treatment if it was…

Subjects/Keywords: Genetics; Race – Social aspects; Personalized medicine; Pharmacogenomics; Social medicine

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APA (6^th Edition):

Feldman, N. M. (2014). Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8CG00BR

Chicago Manual of Style (16^th Edition):

Feldman, Naumi Mira. “Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine.” 2014. Doctoral Dissertation, Columbia University. Accessed January 22, 2021. https://doi.org/10.7916/D8CG00BR.

MLA Handbook (7^th Edition):

Feldman, Naumi Mira. “Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine.” 2014. Web. 22 Jan 2021.

Vancouver:

Feldman NM. Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine. [Internet] [Doctoral dissertation]. Columbia University; 2014. [cited 2021 Jan 22]. Available from: https://doi.org/10.7916/D8CG00BR.

Council of Science Editors:

Feldman NM. Race, Genes and Health: Public Conceptions about the Effectiveness of Race-Based Medicine and Personalized Genomic Medicine. [Doctoral Dissertation]. Columbia University; 2014. Available from: https://doi.org/10.7916/D8CG00BR

University of Washington

23. Wang, Lei. Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES.

Degree: 2018, University of Washington

URL: http://hdl.handle.net/1773/40853

► The complexity of the human genome and variability of individual health histories, living environments, and lifestyles have motivated the development of precision medicine with the… (more)

▼ The complexity of the human genome and variability of individual health histories, living environments, and lifestyles have motivated the development of precision medicine with the goal to enable health care providers to tailor treatments to each patients’ unique characteristics. Targeted delivery of treatments/preventative strategies to subgroups who benefit sufficiently or solely can optimize treatments and improve the benefit/risk ratio for many patients. Therefore, effective methods of identifying subgroups with sufficiently large benefit are highly desired in clinical trials. However, the number of factors under consideration to define subgroups can be large and performing multiple tests to identify subgroups requires appropriate control of the overall Type I error. Here, we focus on investigating the Type I error rate for a new approach, SHAPES, which was recently developed by Prince (2015). SHAPES is an approach to search for the subgroups by directly restricting the type of subgroups that will be accepted. SHAPES subgroups must be convexly or co-convexly connected in the Boolean space. Prince explored the performance of SHAPES in terms of Type I error control and power under various scenarios considering up to four covariates for subgroup definition. We expand the evaluation of Type I error rate and the settings for evaluation as follows: 1) increasing the total number of covariates considered for subgroup definition from 4 up to 50; 2) increasing the maximum number of covariates that can be used in the definition of a subgroup from 4 up to 6; 3) considering both independent and correlated covariates; 4) considering the prevalence of all covariates to be either 0.5 or 0.2. To evaluate the Type I error rate of SHAPES, we simulate data under different scenarios. Briefly, two-arm randomized trials with either binary or continuous outcomes and various number of binary covariates are simulated under the null, i.e. in all simulations it is assumed that in truth there is no treatment benefit for the study population overall or for any subgroup. Qualified SHAPES subgroups are listed, and stratification models (for selected groups) as well as interaction models (for full population) are fitted. We obtain critical values from 5,000 (and up to 15,000 for selected scenarios) simulations under the null hypothesis where all the covariates are generated to be mutually independent. The critical values are then used in another 5,000 (and up to 15,000 for selected scenarios) simulations with independent or correlated covariates to calculate the Type I error rate. The number of covariates under consideration here is limited by the amount of time required for the simulations. When the covariates are independent, the overall Type I error of SHAPES is maintained around the pre-specified α level and appears very robust for the scenarios we simulate. No monotonic trend is observed as the number of covariates considered for subgroup definition increases (up to 50) or the number of covariates for subgroup definition increases (up to… Advisors/Committee Members: May, Susanne (advisor).

Subjects/Keywords: Clinical Trial; Personalized Medicine; Precision Medicine; SHAPES; Subgroup Analysis; Biostatistics; Biostatistics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, L. (2018). Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES. (Thesis). University of Washington. Retrieved from http://hdl.handle.net/1773/40853

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Lei. “Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES.” 2018. Thesis, University of Washington. Accessed January 22, 2021. http://hdl.handle.net/1773/40853.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Lei. “Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES.” 2018. Web. 22 Jan 2021.

Vancouver:

Wang L. Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES. [Internet] [Thesis]. University of Washington; 2018. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1773/40853.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang L. Searching for Predictive Subgroups with Enhanced Treatment Effect in Clinical Trials using SHAPES. [Thesis]. University of Washington; 2018. Available from: http://hdl.handle.net/1773/40853

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universiteit Utrecht

24. Groenendijk, F.H. Cancer Diagnostics: The Future Ain't What It Used to Be.

Degree: 2015, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/304111

► Cancer is a genomic disease. Most cancers contain multiple genetics alterations that drive their unrestrained proliferation, progression and metastatic capacity. For most cancer types, it… (more)

▼ Cancer is a genomic disease. Most cancers contain multiple genetics alterations that drive their unrestrained proliferation, progression and metastatic capacity. For most cancer types, it is known what these alterations are and what their frequency is. Genomics technologies have made it possible to identify these genetic alterations on an individual patient level in a short time frame. This is a major breakthrough, as it allows the clinical implementation of genomics-driven personalized or precision medicine. This means that the genomic data are used for the selection of the best treatment strategy for each patient. Another development that fuels this implementation is the growing repertoire of effective cancer therapies targeted against these drivers or driver signaling pathways. However, we know that targeted therapies are only effective in a subgroup of patients and that observed responses are often not durable. I reviewed the mechanisms of drug resistance to targeted therapies and discussed the lessons that we have learned for future developments. One of these developments is to combine multiple targeted therapies to increase effectiveness and delay or eventually overcome drug resistance. I identified a novel combination of the multikinase inhibitor sorafenib with the antidiabetic drug metformin that can be used in the treatment of lung cancer. I uncovered the mechanism underlying the combinatorial effect of these drugs and found that these compounds synergistically activate the AMP-activate protein kinase (AMPK) and thereby inhibit mTOR signaling. The subsequent chapters focus on the identification of molecular subgroups of breast cancer and bladder cancer. I studied a subgroup of ERα-positive breast cancers that are classified as basal-type instead of luminal-type. I found that those cancer express relatively high levels of the dominant-negative splice variant ERΔ7. The finding that the estrogen receptor signaling in these cancers is inactive, suggests that patients with ERα-positive basal-type breast cancer may not benefit from estrogen receptor antagonists (e.g. tamoxifen). Furthermore, I found that those patients have a high risk of developing disease recurrence. I discovered that activating ERBB2 missense mutations characterize a subgroup of muscle-invasive bladder cancer patients with complete response to neoadjuvant chemotherapy. This is important, as chemotherapy is currently the only approved drug therapy for bladder cancer. ERBB2 missense mutations can be used as a genomic biomarker to select patients who will benefit from neoadjuvant chemotherapy. In addition, I describe the identification of specific DNA copy number alterations that correlate with response to neoadjuvant chemotherapy. Together, the studies described contribute to a better selection of patients that will benefit from the anti-cancer therapy. My thesis is concluded with a general discussion on the clinical applicability of cancer genotyping for personalized medicine. This approach has completely changed the future of cancer diagnostics… Advisors/Committee Members: Bernards, R..

Subjects/Keywords: Targeted therapies; Personalized medicine; ERα; Sorafenib; AMPK; Bladder cancer; ERBB2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Groenendijk, F. H. (2015). Cancer Diagnostics: The Future Ain't What It Used to Be. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/304111

Chicago Manual of Style (16^th Edition):

Groenendijk, F H. “Cancer Diagnostics: The Future Ain't What It Used to Be.” 2015. Doctoral Dissertation, Universiteit Utrecht. Accessed January 22, 2021. http://dspace.library.uu.nl:8080/handle/1874/304111.

MLA Handbook (7^th Edition):

Groenendijk, F H. “Cancer Diagnostics: The Future Ain't What It Used to Be.” 2015. Web. 22 Jan 2021.

Vancouver:

Groenendijk FH. Cancer Diagnostics: The Future Ain't What It Used to Be. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2015. [cited 2021 Jan 22]. Available from: http://dspace.library.uu.nl:8080/handle/1874/304111.

Council of Science Editors:

Groenendijk FH. Cancer Diagnostics: The Future Ain't What It Used to Be. [Doctoral Dissertation]. Universiteit Utrecht; 2015. Available from: http://dspace.library.uu.nl:8080/handle/1874/304111

Universiteit Utrecht

25. Dekkers, J.F. Intestinal organoids as model for cystic fibrosis.

Degree: 2015, Universiteit Utrecht

URL: http://dspace.library.uu.nl:8080/handle/1874/321710

► Recent advances in adult stem cell culture technology have enabled long-term in vitro expansion of intestinal organoids or ‘mini-guts’. In this thesis, we used the… (more)

Subjects/Keywords: Cystic fibrosis; intestinal organoids; CFTR; correctors; potentiators; personalized/precision medicine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dekkers, J. F. (2015). Intestinal organoids as model for cystic fibrosis. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/321710

Chicago Manual of Style (16^th Edition):

Dekkers, J F. “Intestinal organoids as model for cystic fibrosis.” 2015. Doctoral Dissertation, Universiteit Utrecht. Accessed January 22, 2021. http://dspace.library.uu.nl:8080/handle/1874/321710.

MLA Handbook (7^th Edition):

Dekkers, J F. “Intestinal organoids as model for cystic fibrosis.” 2015. Web. 22 Jan 2021.

Vancouver:

Dekkers JF. Intestinal organoids as model for cystic fibrosis. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2015. [cited 2021 Jan 22]. Available from: http://dspace.library.uu.nl:8080/handle/1874/321710.

Council of Science Editors:

Dekkers JF. Intestinal organoids as model for cystic fibrosis. [Doctoral Dissertation]. Universiteit Utrecht; 2015. Available from: http://dspace.library.uu.nl:8080/handle/1874/321710

Vanderbilt University

26. Bersell, Kevin Richard. Genetic variation, pathogenicity, and pathophysiology of human channelopathies.

Degree: PhD, Pharmacology, 2016, Vanderbilt University

URL: http://hdl.handle.net/1803/14389

► The application of genome science to inherited heart disease requires accurate genetic evaluation and understanding of physiologic resulting from genetic variation. Using a Long QT… (more)

Subjects/Keywords: ion channels; personalized medicine; transcription factor; human genetics; inherited arrhythmia syndromes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bersell, K. R. (2016). Genetic variation, pathogenicity, and pathophysiology of human channelopathies. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14389

Chicago Manual of Style (16^th Edition):

Bersell, Kevin Richard. “Genetic variation, pathogenicity, and pathophysiology of human channelopathies.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/14389.

MLA Handbook (7^th Edition):

Bersell, Kevin Richard. “Genetic variation, pathogenicity, and pathophysiology of human channelopathies.” 2016. Web. 22 Jan 2021.

Vancouver:

Bersell KR. Genetic variation, pathogenicity, and pathophysiology of human channelopathies. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/14389.

Council of Science Editors:

Bersell KR. Genetic variation, pathogenicity, and pathophysiology of human channelopathies. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/14389

Penn State University

27. Malys, Tyler. Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine .

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/25153

► This dissertation has two parts: first describes the analysis of microbiomes of the lower respiratory tract of healthy and diseased chickens. The second describes the… (more)

▼ This dissertation has two parts: first describes the analysis of microbiomes of the lower respiratory tract of healthy and diseased chickens. The second describes the epigenetic landscape that determines the gene transcription levels in the erythroid differentiation model. Multicellular animals are complex machines and can no longer be thought of as stand alone organisms. Animals host microbial communities termed microbiomes, which play vital roles in many aspects of an animals life including immune function and nutrient processing. Animal physiology and habits have been shown to affect resident microbiome composition, which in turn affect animal physiology. Understanding host microbe interactions and their ramifications is thus essential in my pursuit to understand human health. Further complicating matters, each microbiome interacts with only a subset of host cell types. Nearly every host cell contains identical DNA yet express radically different phenotypes. These differences in phenotype are brought about by epigenetic effect. Epigenetic factors represent heritable changes, which are not apparent in DNA sequence alone. They include items such as histone modifications, transcription factors and DNAse hypersensitive sites. Epigenetics vary amongst individuals but also amongst cell types within individuals. Understanding epigenetic regulation of gene transcription is essential to understanding human health and has gained much interest in the development of personalized medicine. I conducted fundamental research aimed at advancing both the understanding of resident microbiome and also epigenetic gene regulation. Microbiome studies were conducted in Chickens from Pakistan with the primary goal of identifying potentially novel emerging infectious diseases. I also studied epigenetic gene regulation in an in vitro model system for erythroid maturation. I found that the lower respiratory microbiome of healthy chickens was dominated by relatively few bacterial taxa. Moreover the microbiome of healthy chickens varied with respect to the environment. I was also able to identify differences in microbiome composition between healthy and diseased birds, suggesting the discovery of potential novel pathogens representing emerging infectious disease in the region. In my model system for erythroid maturation I found epigenetic landscape near the transcription start site (TSS) to be sufficient to predict a gene as actively transcribed or silent. Moreover, I was able to relate change in epigenetic landscape with change in gene transcription level in cases of extreme transcription level change. Overall, these results indicated epigenetic landscape near the TSS sets a gene as either permissive or non permissive with respect to transcription. Advisors/Committee Members: Cooduvalli S Shashikant, Dissertation Advisor/Co-Advisor, Ross Cameron Hardison, Committee Member, Michael Mugo Mwangi, Committee Member, Matam Vijay Kumar, Committee Member, Peter John Hudson, Special Member.

Subjects/Keywords: Microbiome; Epigenetics; Personalized Medicine; Agriculture; Pathogen Identification; Erythropoiesis; Pakistan; Gene Expression

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APA (6^th Edition):

Malys, T. (2015). Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/25153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Malys, Tyler. “Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine .” 2015. Thesis, Penn State University. Accessed January 22, 2021. https://submit-etda.libraries.psu.edu/catalog/25153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Malys, Tyler. “Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine .” 2015. Web. 22 Jan 2021.

Vancouver:

Malys T. Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine . [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Jan 22]. Available from: https://submit-etda.libraries.psu.edu/catalog/25153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Malys T. Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine . [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/25153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

28. Hornick, Jacob. Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family.

Degree: 2019, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16283jth5217

► The field of personalized medicine has significantly expanded with the advent of gene sequencing and the decreasing cost and increasing availability of whole genome sequencing… (more)

▼ The field of personalized medicine has significantly expanded with the advent of gene sequencing and the decreasing cost and increasing availability of whole genome sequencing data. This dissertation focused on a family of sphingosine-1-phosphate receptors, members of the G protein-1-coupled receptor (GPCR) superfamily. GPCRs, have been of interest because they are the largest superfamily in the human genome, occur across species, and play a diverse role in signaling and biological function. The sphingosine–1–phosphate receptor (S1PR) family has five members that are broadly expressed throughout human tissues and mediate signaling critical to vascular maturation, hair cell formation and repair, T and natural killer – cell trafficking and function. My goal was to examine how naturally occurring genetic variants affected S1PR function and signaling capabilities. For the analysis, I have developed a yeast model system adapting the yeast, Saccharomyces cerevisiae, pheromone signaling pathway to permit a simple and elegant system to perform single receptor analysis. For example, the S1PR1 variant R13G leads to an increase in potency (EC50) of S1P when compared to the wild type receptor. In S1PR2, the R60Q variant, decreases the potency of S1P compared to the wild type receptor. Most interestingly, the S1PR5 variant L318Q had little effect on S1P signaling mediated by Gαi2–chimeric G protein, yet abolished signaling via Gα12-chimeras. To begin to translate these findings, human cells either transiently or stably transduced with S1PR5 and the L318Q variant were studied. Compared to the wild type S1PR5, the L318Q variant caused decreased f-actin accumulation and less stress fiber and filopodia formation when treated with S1P. This region in S1PR5 was predicted to be post–translationally modified with the addition of a palmitoyl group at two cysteine residues at positions 322 and 323. Acyl–biotin exchange experiments confirmed the S1PR5 L318Q variant, unlike the wild type receptor, is unable to be palmitoylated. To test if the cysteine residues were essential for the Gα12 interaction, the C322A and C323A double mutant was created. This receptor replicated the unusual G protein coupling pattern observed in L318Q receptor. I also performed experiments here where the variant receptors were examined for any dysfunction when treated with current and experimental drugs for relapsing remitting multiple sclerosis (RRMS). I discovered minimal effects caused by the variants compared to the signaling via activation of S1P, however I do observe significant differences between the drugs when comparing potency and efficacy. A major finding from those studies is that the experimental drug RPC1074 displays higher efficacy and potency of S1PR1 signaling when compared to the current standard treatment of fingolimod. Examination of the other drugs ponesimod, siponimod, and MT1303p showed similarities in signaling effects when compared to fingolimod. One important finding of this work was discovered when I examined the allelic… Advisors/Committee Members: James Riley Broach, Dissertation Advisor/Co-Advisor, James Riley Broach, Committee Chair/Co-Chair, Ralph Lauren Keil, Committee Member, Ira Joseph Ropson, Committee Member, Richard Bernard Mailman, Outside Member.

Subjects/Keywords: Personalized medicine; GPCR; S1P; RRMS; G protein; Genetic variation; yeast

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APA (6^th Edition):

Hornick, J. (2019). Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16283jth5217

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hornick, Jacob. “Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family.” 2019. Thesis, Penn State University. Accessed January 22, 2021. https://submit-etda.libraries.psu.edu/catalog/16283jth5217.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hornick, Jacob. “Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family.” 2019. Web. 22 Jan 2021.

Vancouver:

Hornick J. Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family. [Internet] [Thesis]. Penn State University; 2019. [cited 2021 Jan 22]. Available from: https://submit-etda.libraries.psu.edu/catalog/16283jth5217.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hornick J. Analysis of Naturally Occurring Genetic Variants in the Sphingosine-1-Phosphate Receptor Family. [Thesis]. Penn State University; 2019. Available from: https://submit-etda.libraries.psu.edu/catalog/16283jth5217

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Univerzitet u Beogradu

29. Vuković, Marija, 1975- 28980583. Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri.

Degree: Biološki fakultet, 2020, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:20740/bdef:Content/get

►

Biologija - Molekularna biologija / Biology - Molecular biology

amil ija en zi ma u ridin -dif osfat -glu kuronoziltransferaza (U GT ) kat a… (more)

▼

Biologija - Molekularna biologija / Biology - Molecular biology

amil ija en zi ma u ridin -dif osfat -glu kuronoziltransferaza (U GT ) kat a lizuj e glukuronidaciju širokog spektra endobiotika i ksenobiotika. UGT1 familija je kodirana genskim kompleksom UGT1, koji se sastoji od 13 proksimalnih varijabilnih egzona i od 4 zajednička distalna egzona. Alternativnom obradom nastaje više transkripata, među kojima je posebno značajan onaj čiji je produkt UGT1A1 enzim, koji učestvuje u metabolizmu bilirubina i mnogih lekova. Više od 60 varijanti je detektovano u UGT1A1 genu, koje su povezane sa patološkim stanjima. Varijante u TATA boksu promotora UGT1A gena se razlikuje po broju TA ponovaka. Wild type UGT1A1*1 sadrži 6 TA ponovaka (TA6), dok su varijante koje sadrže 5, 7 ili 8 TA ponovaka označene kao UGT1A1*36 (TA5), UGT1A1*28 (TA7) i UGT1A1*37 (TA8). Transkripciona aktivnost promotora je manja što je veći broj ponovaka u odnosu na TA6. Žilberov sindrom (ŽS) je često kliničko stanje koje karakteriše hiperbilirubinemija i ikterus. Uzrokovan je smanjenom aktivnošću UGT1A1 enzima. Najčešće detektovana varijanta koja se nalazi u osnovi ŽS je UGT1A1*28. Njena učestalost varira u različitim populacijama, a kod belaca je prisutna sa 26% do 31%. ŽS je blago oboljenje, ali kao komorbiditet može dovesti do pogrešne dijagnoze bolesti jetre ili hemolitičkih procesa. U tim slučajevima je neophodno potvrditi ili isključiti dijagnozu ŽS molekularnom analizom UGT1A1 gena. Malo se zna o uticaju varijanti promotora UGT1A1 gena na scenario kod oboljenja jetre. Samo u nekoliko slučajeva je kod pacijenata sa hepatitisom C sprovedeno genetičko testiranje na UGT1A1*28, i pošto je dokazana pozitivnost objasnila detektovan nivo bilirubina, pacijenti su lečeni po standardnom protokolu i postigli su kontinuiran virusološki odgovor. Kod hemolitičkih anemija, kao što je talasemija, takođe je pokazano da je nivo bilirubina povezan sa pojavom komplikacija. Stoga se varijante u UGT1A1 genu tretiraju kao tercijarni modifikatori kod beta- talasemijskih sindroma...

Advisors/Committee Members: Zukić, Branka, 1976- 21162343.

Subjects/Keywords: UGT1A1; Gilbert’s syndrome; hyperbilirubinemia; pharmacogenetic marker; population study; personalized medicine

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APA (6^th Edition):

Vuković, Marija, 1. 2. (2020). Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:20740/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vuković, Marija, 1975- 28980583. “Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri.” 2020. Thesis, Univerzitet u Beogradu. Accessed January 22, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:20740/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vuković, Marija, 1975- 28980583. “Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri.” 2020. Web. 22 Jan 2021.

Vancouver:

Vuković, Marija 12. Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri. [Internet] [Thesis]. Univerzitet u Beogradu; 2020. [cited 2021 Jan 22]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:20740/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vuković, Marija 12. Varijante promotora gena za uridin-difosfat-glukuronoziltransferazu 1A1 kao modulatori biohemijskog fenotipa i populaciono farmakogenetički markeri. [Thesis]. Univerzitet u Beogradu; 2020. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:20740/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

30. Chen, Kevin Hui. Looking forward for chimeric antigen receptor therapy.

Degree: MS, Medical Sciences, 2020, Boston University

URL: http://hdl.handle.net/2144/41191

► Chimeric antigen receptors (CAR) are modular genetically modified receptors that consist of an extracellular antigen binding domain fused to intracellular T-cell signaling domains. CAR therapy… (more)

Subjects/Keywords: Therapy; Cancer; CAR; Immunotherapy; Personalized medicine; T-cells

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APA (6^th Edition):

Chen, K. H. (2020). Looking forward for chimeric antigen receptor therapy. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/41191

Chicago Manual of Style (16^th Edition):

Chen, Kevin Hui. “Looking forward for chimeric antigen receptor therapy.” 2020. Masters Thesis, Boston University. Accessed January 22, 2021. http://hdl.handle.net/2144/41191.

MLA Handbook (7^th Edition):

Chen, Kevin Hui. “Looking forward for chimeric antigen receptor therapy.” 2020. Web. 22 Jan 2021.

Vancouver:

Chen KH. Looking forward for chimeric antigen receptor therapy. [Internet] [Masters thesis]. Boston University; 2020. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2144/41191.

Council of Science Editors:

Chen KH. Looking forward for chimeric antigen receptor therapy. [Masters Thesis]. Boston University; 2020. Available from: http://hdl.handle.net/2144/41191

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