IU Indianapolis ScholarWorks :: Browsing by Subject "Mathematical modeling"

Browsing by Subject "Mathematical modeling"

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Artificial Intelligence to Aid Glaucoma Diagnosis and Monitoring: State of the Art and New Directions
(MDPI, 2022) Nunez, Roberto; Harris, Alon; Ibrahim, Omar; Keller, James; Wikle, Christopher K.; Robinson, Erin; Zukerman, Ryan; Siesky, Brent; Verticchio, Alice; Rowe, Lucas; Guidoboni, Giovanna; Ophthalmology, School of Medicine
Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians.
CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre
(Wiley, 2014-08-14) Kiragga, Agnes N.; Lok, Judith J.; Musick, Beverly S.; Bosch, Ronald J.; Mwangi, Ann; Wools-Kaloustian, Kara K.; Yiannoutsos, Constantin T.; East Africa IeDEA Regional Consortium; Medicine, School of Medicine
Objective: Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design: We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods: We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be "had everyone starting ART remained on observation?" and "were everyone starting ART maintained on treatment?" Results: Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6-14% from the naïve estimates depending on assumptions about access to care among lost patients. Conclusions: Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it.
Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents
(American Scientific, 2013) Guidoboni, Giovanna; Harris, Alon; Arciero, Julia C.; Siesky, Brent A.; Amireskandari, Annahita; Gerber, Austin L.; Huck, Andrew H.; Kim, Nathaniel J.; Cassani, Simone; Carichino, Lucia; Mathematical Sciences, School of Science
Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.
Mathematical modeling of the effects of Wnt-10b on bone metabolism
(Wiley, 2022) Cook, Carley V.; Islam, Mohammad Aminul; Smith, Brenda J.; Ford Versypt, Ashlee N.; Obstetrics and Gynecology, School of Medicine
Bone health is determined by factors including bone metabolism or remodeling. Wnt-10b alters osteoblastogenesis through pre-osteoblast proliferation and differentiation and osteoblast apoptosis rate, which collectively lead to the increase of bone density. To model this, we adapted a previously published model of bone remodeling. The resulting model for the bone compartment includes differential equations for active osteoclasts, pre-osteoblasts, osteoblasts, osteocytes, and the amount of bone present at the remodeling site. Our alterations to the original model consist of extending it past a single remodeling cycle and implementing a direct relationship to Wnt-10b. Four new parameters were estimated and validated using normalized data from mice. The model connects Wnt-10b to bone metabolism and predicts the change in trabecular bone volume caused by a change in Wnt-10b input. We find that this model predicts the expected increase in pre-osteoblasts and osteoblasts while also pointing to a decrease in osteoclasts when Wnt-10b is increased.
A physical basis for quantitative ChIP-sequencing
(Elsevier, 2020-11-20) Dickson, Bradley M.; Tiedemann, Rochelle L.; Chomiak, Alison A.; Cornett, Evan M.; Vaughan, Robert M.; Rothbart, Scott B.; Biochemistry and Molecular Biology, School of Medicine
ChIP followed by next-generation sequencing (ChIP-Seq) is a key technique for mapping the distribution of histone posttranslational modifications (PTMs) and chromatin-associated factors across genomes. There is a perceived challenge to define a quantitative scale for ChIP-Seq data, and as such, several approaches making use of exogenous additives, or "spike-ins," have recently been developed. Herein, we report on the development of a quantitative, physical model defining ChIP-Seq. The quantitative scale on which ChIP-Seq results should be compared emerges from the model. To test the model and demonstrate the quantitative scale, we examine the impacts of an EZH2 inhibitor through the lens of ChIP-Seq. We report a significant increase in immunoprecipitation of presumed off-target histone PTMs after inhibitor treatment, a trend predicted by the model but contrary to spike-in-based indications. Our work also identifies a sensitivity issue in spike-in normalization that has not been considered in the literature, placing limitations on its utility and trustworthiness. We call our new approach the sans-spike-in method for quantitative ChIP-sequencing (siQ-ChIP). A number of changes in community practice of ChIP-Seq, data reporting, and analysis are motivated by this work.
Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics
(MDPI, 2022) Verticchio Vercellin, Alice; Harris, Alon; Belamkar, Aditya; Zukerman, Ryan; Carichino, Lucia; Szopos, Marcela; Siesky, Brent; Quaranta, Luciano; Bruttini, Carlo; Oddone, Francesco; Riva, Ivano; Guidoboni, Giovanna; Ophthalmology, School of Medicine
Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.
Sizing it up: The mechanical feedback hypothesis of organ growth regulation
(Elsevier, 2014) Buchmann, Amy; Alber, Mark; Zartman, Jeremiah J.; Medicine, School of Medicine
The question of how the physical dimensions of animal organs are specified has long fascinated both experimentalists and computational scientists working in the field of developmental biology. Research over the last few decades has identified many of the genes and signaling pathways involved in organizing the emergent multi-scale features of growth and homeostasis. However, an integrated model of organ growth regulation is still unrealized due to the numerous feedback control loops found within and between intercellular signaling pathways as well as a lack of understanding of the exact role of mechanotransduction. Here, we review several computational and experimental studies that have investigated the mechanical feedback hypothesis of organ growth control, which postulates that mechanical forces are important for regulating the termination of growth and hence the final physical dimensions of organs. In particular, we highlight selected computational studies that have focused on the regulation of growth of the Drosophila wing imaginal disc. In many ways, these computational and theoretical approaches continue to guide experimental inquiry. We demonstrate using several examples how future progress in dissecting the crosstalk between the genetic and biophysical mechanisms controlling organ growth might depend on the close coupling between computational and experimental approaches, as well as comparison of growth control mechanisms in other systems.
Underlying Neurobiological and Neurocognitive Mechanisms of Impulsivity in Risk-Taking Behaviors
(MDPI, 2020-03-25) Cyders, Melissa A.; Psychology, School of Science
Impulsivity has been widely implicated in many maladaptive risk-taking and clinical disorders associated with such behaviors [1,2], and may be the most frequently noted criteria in the Diagnostic Statistical Manual for Mental Disorders [3] across a wide variety of disorder classes [4] [...].
Using a Theoretical Model to Assess the Impact of Vascular Risk Factors on Autoregulation in the Retina
(Association for Research in Vision and Ophthalmology, 2025) Fry, Brendan C.; Arciero, Julia C.; Gyurek, Croix; Albright, Amanda; Siesky, Brent; Verticchio, Alice; Harris, Alon; Mathematical Sciences, School of Science
Purpose: Vascular impairments, including reduced capillary density (CD), impaired autoregulation capacity (Reg), and elevated intraocular pressure (IOP), have been identified as significant contributors to glaucomatous disease. This study implemented a theoretical model to quantify the impact of these impairments on retinal blood flow and oxygenation as intraluminal pressure (Pa) is varied. Methods: A theoretical model of the retinal vasculature was used to simulate reductions in CD by 10% (early glaucoma) and 30% to 50% (advanced glaucoma), a range in autoregulation capacity from 0% (totally impaired) to 100% (totally functional), and normal (15 mm Hg) and elevated (25 mm Hg) levels of IOP. Results: Under baseline conditions of CD = 500 mm-2, Reg = 100%, and IOP = 15 mm Hg, an autoregulation plateau was predicted for Pa = 28 to 44 mm Hg. Decreased CD, impaired flow regulation mechanisms, and increased IOP all cause a loss of the autoregulation plateau and a corresponding decrease in tissue oxygenation in this pressure range. Although the detrimental effects of small decreases in CD or elevations in IOP are mostly offset by functional flow regulation, larger changes and/or combinations of vascular impairments lead to a significant drop in retinal oxygenation. Conclusions: Model predictions indicate that isolated or combined vascular impairments in CD, flow regulation, and IOP contribute to poor retinal tissue oxygenation, which could lead to vision loss in advanced glaucoma patients. This study motivates early identification of vascular changes to prevent a substantially worse effect of these factors on retinal oxygenation during the progression of glaucoma.

Browsing by Subject "Mathematical modeling"

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