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Description
Introduction: There are 350 to 400 pediatric heart transplants annually according to the Pediatric Heart Transplant Database (Dipchand et al. 2014). Finding appropriate donors can be challenging especially for the pediatric population. The current standard of care is a donor-to-recipient weight ratio. This ratio is not necessarily

Introduction: There are 350 to 400 pediatric heart transplants annually according to the Pediatric Heart Transplant Database (Dipchand et al. 2014). Finding appropriate donors can be challenging especially for the pediatric population. The current standard of care is a donor-to-recipient weight ratio. This ratio is not necessarily a parameter directly indicative of the size of a heart, potentially leading to ill-fitting allografts (Tang et al. 2010). In this paper, a regression model is presented - developed by correlating total cardiac volume to non-invasive imaging parameters and patient characteristics – for use in determining ideal allograft fit with respect to total cardiac volume.
Methods: A virtual, 3D library of clinically-defined normal hearts was compiled from reconstructed CT and MR scans. Non-invasive imaging parameters and patient characteristics were collected and subjected to backward elimination linear regression to define a model relating patient parameters to the total cardiac volume. This regression model was then used to retrospectively accept or reject an ‘ideal’ donor graft from the library for 3 patients that had undergone heart transplantation. Oversized and undersized grafts were also transplanted to qualitatively analyze virtual transplantation specificity.
Results: The backward elimination approach of the data for the 20 patients rejected the factors of BMI, BSA, sex and both end-systolic and end-diastolic left ventricular measurements from echocardiography. Height and weight were included in the linear regression model yielding an adjusted R-squared of 82.5%. Height and weight showed statistical significance with p-values of 0.005 and 0.02 respectively. The final equation for the linear regression model was TCV = -169.320+ 2.874h + 3.578w ± 73 (h=height, w=weight, TCV= total cardiac volume).
Discussion: With the current regression model, height and weight significantly correlate to total cardiac volume. This regression model and virtual normal heart library provide for the possibility of virtual transplant and size-matching for transplantation. The study and regression model is, however, limited due to a small sample size. Additionally, the lack of volumetric resolution from the MR datasets is a potentially limiting factor. Despite these limitations the virtual library has the potential to be a critical tool for clinical care that will continue to grow as normal hearts are added to the virtual library.
ContributorsSajadi, Susan (Co-author) / Lindquist, Jacob (Co-author) / Frakes, David (Thesis director) / Ryan, Justin (Committee member) / Harrington Bioengineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
E-commerce has rapidly become a mainstay in today's economy, and many websites have built themselves around providing a platform for independent sellers. Sites such as Etsy, Storenvy, Redbubble, and Society6 are increasingly popular options for anyone looking to open their own online store. With this project, I attempted to examine

E-commerce has rapidly become a mainstay in today's economy, and many websites have built themselves around providing a platform for independent sellers. Sites such as Etsy, Storenvy, Redbubble, and Society6 are increasingly popular options for anyone looking to open their own online store. With this project, I attempted to examine the effects of four different marketing techniques on sales in an online store. I opened a shop on Etsy and tracked sales in connection with promotion through social media, selling products in-person at a convention, holding a holiday tie-in sale, and using price anchoring. Social media accounts were opened on Facebook, Tumblr, and Instagram to promote the shop over the course of the project period, and Etsy's web analytics were used to track which sites directed the most traffic to the shop. I attended a convention in mid-January 2016 where I sold my products and distributed business cards with a discount code to track sales resulting from being at the convention. A holiday sale was held in conjunction with Valentine's Day to look at whether holidays influenced purchases. Lastly, a significantly more expensive product was temporarily put in the shop to see whether it produced a price anchoring effect \u2014 that is, encouraged sales of the less expensive products by making them seem affordable in comparison. While the volume of sales data was too small to draw statistically significant conclusions, the project was a highly instructive experience in the process of opening a small online store. The decision-making steps outlined may be helpful to other students looking to open their own online shop.
ContributorsChen, Candice Elizabeth (Author) / Moore, James (Thesis director) / Sanford, Adriana (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane

Abstract
The aim of the research performed was to increase research potential in the field of cell stimulation by developing a method to adhere human neural progenitor cells (hNPC’s) to a sterilized stretchable microelectrode array (SMEA). The two primary objectives of our research were to develop methods of sterilizing the polydimethylsiloxane (PDMS) substrate being used for the SMEA, and to derive a functional procedure for adhering hNPC’s to the PDMS. The proven method of sterilization was to plasma treat the sample and then soak it in 70% ethanol for one hour. The most successful method for cell adhesion was plasma treating the PDMS, followed by treating the surface of the PDMS with 0.01 mg/mL poly-l-lysine (PLL) and 3 µg/cm2 laminin. The development of these methods was an iterative process; as the methods were tested, any problems found with the method were corrected for the next round of testing until a final method was confirmed. Moving forward, the findings will allow for cell behavior to be researched in a unique fashion to better understand the response of adherent cells to physical stimulation by measuring changes in their electrical activity.
ContributorsBridgers, Carson (Co-author) / Peterson, Mara (Co-author) / Stabenfeldt, Sarah (Thesis director) / Graudejus, Oliver (Committee member) / Harrington Bioengineering Program (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
In the medical industry, there have been promising advances in the increase of new types of healthcare to the public. As of 2015, there was a 98% Premarket Approval rate, a 38% increase since 2010. In addition, there were 41 new novel drugs approved for clinical usage in 2014 where

In the medical industry, there have been promising advances in the increase of new types of healthcare to the public. As of 2015, there was a 98% Premarket Approval rate, a 38% increase since 2010. In addition, there were 41 new novel drugs approved for clinical usage in 2014 where the average in the previous years from 2005-2013 was 25. However, the research process towards creating and delivering new healthcare to the public remains remarkably inefficient. It takes on average 15 years, over $900 million by one estimate, for a less than 12% success rate of discovering a novel drug for clinical usage. Medical devices do not fare much better. Between 2005-2009, there were over 700 recalls per year. In addition, it takes at minimum 3.25 years for a 510(k) exempt premarket approval. Plus, a time lag exists where it takes 17 years for only 14% of medical discoveries to be implemented clinically. Coupled with these inefficiencies, government funding for medical research has been decreasing since 2002 (2.5% of Gross Domestic Product) and is predicted to be 1.5% of Gross Domestic Product by 2019. Translational research, the conversion of bench-side discoveries to clinical usage for a simplistic definition, has been on the rise since the 1990s. This may be driving the increased premarket approvals and new novel drug approvals. At the very least, it is worth considering as translational research is directly related towards healthcare practices. In this paper, I propose to improve the outcomes of translational research in order to better deliver advancing healthcare to the public. I suggest Best Value Performance Information Procurement System (BV PIPS) should be adapted in the selection process of translational research projects to fund. BV PIPS has been shown to increase the efficiency and success rate of delivering projects and services. There has been over 17 years of research with $6.3 billion of projects and services delivered showing that BV PIPS has a 98% customer satisfaction, 90% minimized management effort, and utilizes 50% less manpower and effort. Using University of Michigan \u2014 Coulter Foundation Program's funding process as a baseline and standard in the current selection of translational research projects to fund, I offer changes to this process based on BV PIPS that may ameliorate it. As concepts implemented in this process are congruent with literature on successful translational research, it may suggest that this new model for selecting translational research projects to fund will reduce costs, increase efficiency, and increase success. This may then lead to more Premarket Approvals, more new novel drug approvals, quicker delivery time to the market, and lower recalls.
ContributorsDel Rosario, Joseph Paul (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define

Breast and other solid tumors exhibit high and varying degrees of intra-tumor heterogeneity resulting in targeted therapy resistance and other challenges that make the management and treatment of these diseases rather difficult. Due to the presence of admixtures of non-neoplastic cells with polyclonal cell populations, it is difficult to define cancer genomes in patient samples. By isolating tumor cells from normal cells, and enriching distinct clonal populations, clinically relevant genomic aberrations that drive disease can be identified in patients in vivo. An in-depth analysis of clonal architecture and tumor heterogeneity was performed in a stage II chemoradiation-naïve breast cancer from a sixty-five year old patient. DAPI-based DNA content measurements and DNA content-based flow sorting was used to to isolate nuclei from distinct clonal populations of diploid and aneuploid tumor cells in surgical tumor samples. We combined DNA content-based flow cytometry and ploidy analysis with high-definition array comparative genomic hybridization (aCGH) and next-generation sequencing technologies to interrogate the genomes of multiple biopsies from the breast cancer. The detailed profiles of ploidy, copy number aberrations and mutations were used to recreate and map the lineages present within the tumor. The clonal analysis revealed driver events for tumor progression (a heterozygous germline BRCA2 mutation converted to homozygosity within the tumor by a copy number event and the constitutive activation of Notch and Akt signaling pathways. The highlighted approach has broad implications in the study of tumor heterogeneity by providing a unique ultra-high resolution of polyclonal tumors that can advance effective therapies and clinical management of patients with this disease.
ContributorsLaughlin, Brady Scott (Author) / Ankeny, Casey (Thesis director) / Barrett, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2015-05
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DescriptionMy main goal for my thesis is in conjunction with the research I started in the summer of 2010 regarding the creation of a TBI continuous-time sensor. Such goals include: characterizing the proteins in sensing targets while immobilized, while free in solution, and while in free solution in the blood.
ContributorsHaselwood, Brittney (Author) / LaBelle, Jeffrey (Thesis director) / Pizziconi, Vincent (Committee member) / Cook, Curtiss (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2011-12
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Description
The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be

The purpose of this project was to examine the viability of protein biomarkers in pre-symptomatic detection of lung cancer. Regular screening has been shown to vastly improve patient survival outcome. Lung cancer currently has the highest occurrence and mortality of all cancers and so a means of screening would be highly beneficial. In this research, the biomarker neuron-specific enolase (Enolase-2, eno2), a marker of small-cell lung cancer, was detected at varying concentrations using electrochemical impedance spectroscopy in order to develop a mathematical model of predicting protein expression based on a measured impedance value at a determined optimum frequency. The extent of protein expression would indicate the possibility of the patient having small-cell lung cancer. The optimum frequency was found to be 459 Hz, and the mathematical model to determine eno2 concentration based on impedance was found to be y = 40.246x + 719.5 with an R2 value of 0.82237. These results suggest that this approach could provide an option for the development of small-cell lung cancer screening utilizing electrochemical technology.
ContributorsEvans, William Ian (Author) / LaBelle, Jeffrey (Thesis director) / Spano, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Batman is one of the most iconic characters in the history of popular culture. Ever since his creation in 1939, the character and his stories have gone through several changes. In my thesis, I explore and analyze the character within the nearly 20-year period in which he went through the

Batman is one of the most iconic characters in the history of popular culture. Ever since his creation in 1939, the character and his stories have gone through several changes. In my thesis, I explore and analyze the character within the nearly 20-year period in which he went through the most significant changes (1968-1986). Overall, these changes can be summarized as a shift from a lighthearted superhero consistently placed in campy situations to a dark and brooding vigilante who brutally dispatches his enemies. While analyzing the different versions of this character in this period of time, I reference the conclusions of two scholars: Travis Langley and Chuck Tate. Langley wrote a general psychological analysis of Batman by considering the essential characteristics of the character found in all forms of media. Tate concluded that Batman only uses hostile aggression for the sake of deriving pleasure form the pain he causes to criminals. After analyzing the comics as my primary sources, I have concluded that the general findings of Tate and Langley actually ignore the subtle details of changes in the humanity and self-awareness of the character through time. The lighthearted version of Batman in the late 60's is actually a self-obsessed narcissist, but as time passes, the darker mood of the character can be attributed to an increased acknowledgment of the destructive nature of his unique lifestyle. As the character grows more accepting of himself and his own reasons for continuing this lifestyle, his motivations become less self-centered. Overall, the central change of the character throughout time can be traced back to the status of his inner conflict between normal, human desires and the pure desire for constant vengeance.
ContributorsRivera-Passapera, Hiram Alfonso (Author) / Martin, Thomas (Thesis director) / Miller, April (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
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Description
Humans rely on a complex interworking of visual, tactile and proprioceptive feedback to accomplish even the most simple of daily tasks. These senses work together to provide information about the size, weight, shape, density, and texture of objects being interacted with. While vision is highly relied upon for many tasks,

Humans rely on a complex interworking of visual, tactile and proprioceptive feedback to accomplish even the most simple of daily tasks. These senses work together to provide information about the size, weight, shape, density, and texture of objects being interacted with. While vision is highly relied upon for many tasks, especially those involving accurate reaches, people can typically accomplish common daily skills without constant visual feedback, instead relying on tactile and proprioceptive cues. Amputees using prosthetic hands, however, do not currently have access to such cues, making these tasks impossible. This experiment was designed to test whether vibratory haptic cues could be used in replacement of tactile feedback to signal contact for a size discrimination task. Two experiments were run in which subjects were asked to identify changes in block size between consecutive trials using wither physical or virtual blocks to test the accuracy of size discrimination using tactile and haptic feedback, respectively. Blocks randomly increased or decreased in size in increments of 2 to 12 mm between trials for both experiments. This experiment showed that subjects were significantly better at determining size changes using tactile feedback than vibratory haptic cues. This suggests that, while haptic feedback can technically be used to grasp and discriminate between objects of different sizes, it does not lend the same level of input as tactile cues.
ContributorsOlson, Markey Cierra (Author) / Helms-Tilley, Stephen (Thesis director) / Buneo, Christopher (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05