A modeling platform to predict cancer survival and therapy outcomes using tumor tissue derived metabolomics data.

Cancer is a complex and broad disease that is challenging to treat, partially due to the vast molecular heterogeneity among patients even within the same subtype. Currently, no reliable method exists to determine which potential first-line therapy would be most effective for a specific patient, as randomized clinical trials have concluded that no single regimen may be significantly more effective than others. One ongoing challenge in the field of oncology is the search for personalization of cancer treatment based on patient data. With an interdisciplinary approach, we show that tumor-tissue derived metabolomics data is capable of predicting clinical response to systemic therapy classified as disease control vs. progressive disease and pathological stage classified as stage I/II/III vs. stage IV via data analysis with machine-learning techniques (AUROC = 0.970; AUROC=0.902). Patient survival was also analyzed via statistical methods and machine-learning, both of which show that tumor-tissue derived metabolomics data is capable of risk stratifying patients in terms of long vs. short survival (OS AUROC = 0.940TEST; PFS AUROC = 0.875TEST). A set of key metabolites as potential biomarkers and associated metabolic pathways were also found for each outcome, which may lead to insight into biological mechanisms. Additionally, we developed a methodology to calibrate tumor growth related parameters in a well-established mathematical model of cancer to help predict the potential nuances of chemotherapeutic response. The proposed methodology shows results consistent with clinical observations in predicting individual patient response to systemic therapy and helps lay the foundation for further investigation into the calibration of mathematical models of cancer with patient-tissue derived molecular data. Chapters 6 and 8 were published in the Annals of Biomedical Engineering. Chapters 2, 3, and 7 were published in Metabolomics, Lung Cancer, and Pharmaceutical Research, respectively. Chapters 4 has been accepted for publication at the journal Metabolomics (in press) and Chapter 5 is in review at the journal Metabolomics. Chapter 9 is currently undergoing preparation for submission

Evaluation of drug-loaded gold nanoparticle cytotoxicity as a function of tumor tissue heterogeneity.

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug strength affects the proportion of proliferating, hypoxic, and necrotic tissue fractions, which in turn dynamically affect and are affected by the vascular density. This study establishes a first step towards a more systematic methodology to assess the effect of vascular-induced tumor tissue heterogeneity on the response to nanotherapy

The Contribution of a Layman to the Restoration Movement

The name of Tomas Wharton Phillips, (1835-1912), occurs quite frequently in the history of the Disciples of Christ. Probably his family name is best known by its association with Phillips University, Enid, Oklahoma. There has also been a renewed interest in him through the recent completion of the T.W. Phillips Memorial Library in Nashville, Tennessee, now the headquarters of the Disciples of Christ Historical Society. This general interst generated into a special interst, when, during the lectures on the history of the Disciples of Christ, a remark was made to the effect that there was a need for a more adequte understanding of the place of T.W. Phillips in the Brotherhood of Disciples of Christ. This promoted the undertaking of a study of this layman

A Regulatory Comparison of Hydraulic Fracturing Fluid Disclosure Regimes in the United States, Canada, and Australia

Numerous state, provincial, and federal governments in the United States, Canada, and Australia have created guidelines, legislation, and/or regulations (or are in the process of doing so) in response to public concerns about water contamination from hydraulic fracturing. This article will compare and analyze three national regimes in the leading states and provinces in which laws have been amended, proposed, or adopted to address public concerns about the chemicals and additives in hydraulic fracturing fluids used to produce unconventional hydrocarbons. New regulations, recent legislative amendments, and, in some cases, new statutes have been proposed or adopted in the past few years. Most of the state and provincial laws require public disclosure of some information about the contents of hydraulic fracturing fluids. At the same time, governments interested in attracting investment capital to develop their shale oil and gas resources recognize the importance of protecting the intellectual property rights (trade secrets) of those parties that have developed hydraulic fracturing fluids

Reduction of Myopia Burden and Progression

Myopia is a significant worldwide public health concern, and its prevalence is drastically increasing in recent years. It was once viewed as a benign refractive error, but is now one of the leading causes of blindness and is associated with numerous ocular diseases, which makes it crucial to develop viable treatment options to adequately correct the refractive error and to halt the disease progression. The treatment of myopia can be classified into three groups: optical, pharmacological, and surgical management, which are aimed at adjusting to the refractive error and reducing the axial elongation. The conventional treatment modalities for myopia, such as single vision glasses, correct the refractive error and improve visual quality of life, but do not affect myopia progression or axial elongation. The newer and various myopic interventions including spectacle corrections, contact lens corrections, pharmacological treatments and surgical corrections, hold great potential for adequate disease control to improve the quality of life, reduce myopia burden, and preserve the ocular health

I mārama te rironga ko a te Kuīni : the Waipukurau purchase and the subsequent consequences on Central Hawke's Bay Māori to 1900 : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in History at Massey University, Manawatū, New Zealand

Permission for the re-use of nine Figures in this thesis was obtained from the Alexander Turnbull Library.In 1820s and 1830s Māori from Central Hawke’s Bay came into contact with Pākehā for the first time and they began to trade. From this contact they began to see the benefits of Pākehā. So they requested the government to establish a Pākehā settlement and offered land for sale. Land was purchased at Waipukurau on 4 November 1851. Donald McLean made sweeping promises of benefits and riches when the deed was signed however these benefits and riches would never come to the Māori of Central Hawke’s Bay. The Waipukurau purchase opened the door for more purchases. The Māori of Central Hawke’s Bay began alienating their land. First through direct purchasing with Donald McLean then through the Native Land Court. Māori would soon find themselves in debt which would lead to the Hawke’s Bay Native Lands Alienation Commission 1873. Central Hawke’s Bay Māori emerged as leaders of the Repudiation Movement of the 1870s and then the Kotahitanga Māori Parliament of the 1890s in order to fight for their lost lands. In 2015 Māori of Central Hawke’s Bay along with Heretaunga Māori settled their Treaty of Waitangi claim with the Crown. However, because they went straight to negotiations, a full report by the Waitangi Tribunal was never completed. This thesis demonstrates a long term and irrevocable effect of the Waipukurau purchase for the iwi and hapū concerned

A geospatial tool for assessing potential wildland fire risk in central Texas.

Wildland fires in the United States are not always confined to wilderness areas. The growth of population centers and housing developments in wilderness areas has blurred the boundaries between rural and urban. This merger of human development and natural landscape is known in the wildland fire community as the wildland urban interface or WUI, and it is within this interface that many wildland fires increasingly occur. As wildland fire intrusions in the WUI increase so too does the need for tools to assess potential impact to valuable assets contained within the interface. This study presents a methodology that combines real-time weather data, a wildland fire behavior model, satellite remote sensing and geospatial data in a geographic information system to assess potential risk to human developments and natural resources within the Austin metropolitan area and surrounding ten counties of central, Texas. The methodology uses readily available digital databases and satellite images within Texas, in combination with an industry standard fire behavior model to assist emergency and natural resource managers assess potential impacts from wildland fire. Results of the study will promote prevention of WUI fire disasters, facilitate watershed and habitat protection, and help direct efforts in post wildland fire mitigation and restoration

A study of selected factors influencing the reproductive performance of the common tern (Sterna hirundo) at Port Colborne, Ontario in 1973 and 1974

Several study areas were investigated at two Port Colborne terneries during the summers of 1973 and 1974 in an attempt to determine the influence of clutch size, time of clutch initiation, position in the colony, proximity to Ring-billed Gulls, vegetation and nesting substrate on the reproductive performance of the Common Tern. Hatching success and reproductive success (the number of chicks fledged per egg laid) were generally higher for 3-egg than 2-egg clutches but fledging (the number of chicks fledged per egg hatched) success was usually independant of clutch size. Hatching, fledging and reproductive success declined as a function of time of clutch initiation. Mean clutch sizes also generally declined as a function of time. Nests located in the center of the colony exhibited higher fledging success than those on the periphery. Rock-based clutches had a lower hatching success than clutches initiated on sand or dried vegetation. Reproductive performance did not appear to be related to proximity to Ring-billed Gulls or vegetation within the study area

A Comparison of Universal Soil Loss Equation Results Using a Remote Sensing/GIS Technique to Results Obtained Using a Field Survey Technique

Digital satellite remote sensing and Geographic Information Systems (GIS) have been used in conjunction with the Universal Soil Loss Equation (USLE) to model soil erosion potential within watersheds. This study compared erosion estimates calculated by the remote sensing method to results obtained in the field by soil conservationists using conventional methods