Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

Extracellular Matrix in Development and Disease

The extracellular matrix in development and disease deals with the molecular and cellular aspects of development and disease. Cells exist in three-dimensional scaffolding called the extracellular matrix. The matrix holds together the millions of cells that make up our blood vessels, organs, skin, and all tissues of the body. The matrix serves as a reservoir of signaling molecules as well. In bacterial cultures, biofilms form as an extracellular matrix and play essential roles in disease and drug resistance. Topics such as matrix structure and function, cell attachment and cell surface proteins mediating cell-matrix interactions, synthesis, regulation, composition, structure, assembly, remodeling, and function of the matrix are included. A common thread uniting the topics is the essential nature that the matrix plays in normal development and pathophysiology. Providing new knowledge will lead us to improved diagnostics, the preventions of disease progression, and therapeutic strategies for the repair and regeneration of tissues. Topics such as the extracellular matrix in hereditary diseases, reproduction, cancer, muscle, and tissue engineering applications, and diverse roles for integrins, are included in this collection

Imaging studies of peripheral nerve regeneration induced by porous collagen biomaterials

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references.There is urgent need to develop treatments for inducing regeneration in injured organs. Porous collagen-based scaffolds have been utilized clinically to induce regeneration in skin and peripheral nerves, however still there is no complete explanation about the underlying mechanism. This thesis utilizes advanced microscopy to study the expression of contractile cell phenotypes during wound healing, a phenotype believed to affect significantly the final outcome. The first part develops an efficient pipeline for processing challenging spectral fluorescence microscopy images. Images are segmented into regions of objects by refining the outcome of a pixel-wide model selection classifier by an efficient Markov Random Field model. The methods of this part are utilized by the following parts. The second part extends the image informatics methodology in studying signal transduction networks in cells interacting with 3D matrices. The methodology is applied in a pilot study of TGFP signal transduction by the SMAD pathway in fibroblasts seeded in porous collagen scaffolds. Preliminary analysis suggests that the differential effect of TGFP1 and TGFP3 to cells could be attributed to the "non-canonical" SMADI and SMAD5. The third part is an ex vivo imaging study of peripheral nerve regeneration, which focuses on the formation of a capsule of contractile cells around transected rat sciatic nerves grafted with collagen scaffolds, 1 or 2 weeks post-injury. It follows a recent study that highlights an inverse relationship between the quality of the newly formed nerve tissue and the size of the contractile cell capsule 9 weeks post-injury. Results suggest that "active" biomaterials result in significantly thinner capsule already 1 week post-injury. The fourth part describes a novel method for quantifying the surface chemistry of 3D matrices. The method is an in situ binding assay that utilizes fluorescently labeled recombinant proteins that emulate the receptor of , and is applied to quantify the density of ligands for integrins a113, a2p1 on the surface of porous collagen scaffolds. Results provide estimates for the density of ligands on "active" and "inactive" scaffolds and demonstrate that chemical crosslinking can affect the surface chemistry of biomaterials, therefore can affect the way cells sense and respond to the material.by Dimitrios S. Tzeranis.Ph. D

Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes