Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Boron neutron capture therapy for the treatment of prostate cancer using a boron-containing cholesteryl ester compound
    (2013) Gifford, Ian; Al-Sheikhly, Mohamad; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Boron neutron capture therapy (BNCT) for the treatment of prostate cancer using a boron-containing cholesteryl ester compound (BCH) was investigated. BNCT is a binary radiation therapy that relies on targeted delivery of 10B to cancer cells followed by irradiation with thermal neutrons. High-linear energy transfer (LET) α particles and 7Li nuclei released from the 10B neutron capture event result in lethal double-strand DNA breaks within a 9 μm range. Given the high density energy deposition and short range, neighboring cells without 10B remain unharmed. To evaluate the efficacy of BCH as a BNCT compound, a sample chamber within the thermal column experimental facility of the Maryland University Training Reactor (MUTR) was designed to provide a means of irradiating samples in vitro in a thermal neutron field. The thermal neutron fluence rate at 250 kW within the sample chamber is 8.7 x108 n/cm2/s with the < 3 eV neutron energy region representing 94.6% of the total neutron field. The hydrophobic BCH compound was embedded in the lipid bilayer of DPPC:cholesterol liposomes for delivery to PC-3 prostate cancer cells. Liposomes were synthesized by the thin film layer technique with high-pressure homogenization size reduction. Dynamic light scattering analysis of the liposomes yielded a mean diameter of 111.5 nm and 0.113 relative variance. Cytotoxicity of the BCH-containing liposomes was evaluated by neutral red, MTS, LDH, and colony formation assays. Boron uptake by PC-3 cells was analyzed with high-performance liquid chromatography (HPLC) and inductively coupled plasma-mass spectrometry (ICP-MS). Drug delivery conditions that minimized cytotoxic effects yielded a boron uptake of 35.2 + 4.3 μg/g cell. PC-3 cells were irradiated in the MUTR thermal column sample chamber to quantify the enhanced cell killing of the high-LET thermal neutron capture 10B reactions. PC-3 cells treated with BCH and exposed to a 9.4 x 1011 n/cm2/s thermal neutron fluence yielded a 20-25% increase in cell death compared to the untreated control.
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    An EM Algorithm for Mixed-Type Multiple Outcome Regressions With Applications to a Prostate Cancer Study
    (2008-06-05) Rudd, JoAnn M.; Smith, Paul J.; Mathematical Statistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    We propose a joint model for binary and continuous responses using a latent variable for the binary response. The observed continuous response and the latent response are treated as correlated normals obeying a bivariate regression model. We develop an EM algorithm to find maximum likelihood estimates for the parameters. We perform the E-step analytically and use an iterative algorithm for the M-step. The algorithm is applied to a prostate cancer clinical trial whose goal was to assess therapeutic effects of diethylstilbestrol (DES) in advanced cancer patients and to assess possible excess cardiovascular mortality. Therapeutic effects were measured as prostatic acid phosphatase (PAP) levels follow-up and whether the patient progressed to stage IV or died of cancer. The treatment reduced PAP levels but not the incidence of cancer mortality within a six-month time frame. Higher doses of DES were associated with increased risk of cardiovascular-related death.