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<title>Open Access Dissertations</title>
<copyright>Copyright (c) 2013 University of Rhode Island All rights reserved.</copyright>
<link>http://digitalcommons.uri.edu/oa_diss</link>
<description>Recent documents in Open Access Dissertations</description>
<language>en-us</language>
<lastBuildDate>Sat, 18 May 2013 01:31:19 PDT</lastBuildDate>
<ttl>3600</ttl>


	
		
	







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<title>Using Structural Equation Modeling</title>
<link>http://digitalcommons.uri.edu/oa_diss/51</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/51</guid>
<pubDate>Fri, 17 May 2013 12:55:45 PDT</pubDate>
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	<p>The present study aimed to further explore the established relationship between acculturative stress and diminished pediatric asthma outcomes in Latino populations. Three psychosocial variables related to pediatric asthma outcomes were predicted to mediate this relationship. Secondary data on pediatric asthma outcomes were analyzed using Structural Equation Modeling path analyses. Study results did not support the hypothesized mediating effect of the psychosocial variables. Rather, post hoc analyses indicated that the psychosocial variables moderated the relationship between acculturative stress and pediatric asthma outcomes. The significance of these findings in relation to pediatric asthma vulnerability and pediatric asthma interventions is discussed, and methodological recommendations are suggested for future research.</p>

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<author>Lara Jane Kaplan Goodrich</author>


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<title>Multicultural Training of Clinical and Counseling Psychology Doctoral Students: Ideals vs. Practice</title>
<link>http://digitalcommons.uri.edu/oa_diss/50</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/50</guid>
<pubDate>Tue, 07 May 2013 06:45:52 PDT</pubDate>
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	<p>The American Psychological Association (APA), which is the advocating body for the field of psychology, emphasizes the importance of multicultural competencies for researchers and clinicians (APA, 2003; 2010). Graduate students are the field’s future professionals. The multicultural training of doctoral level clinical and counseling psychology graduate students is integral to efforts to improve clinical services and the research that provides the foundation for those services. While the literature addresses issues of multicultural competence and training in a general way, few specifics regarding the methods employed by graduate programs to aid their students in the process of developing those competencies are explored.</p>
<p>This study is a survey of doctoral programs. It was hypothesized that many training programs acknowledge the importance of multicultural training but fall far short in their efforts to provide students with sufficient training. Additionally, it was hypothesized that doctoral students who identified their programs as highlighting multicultural competence would have greater multicultural self-­‐efficacy. Graduate students’ self-­‐perceived multicultural competence was associated with a number of program training methods. Although analyses yielded clear differences in guidelines and standards adherence between program types, all participating training directors reported that multicultural issues are incorporated into their program training methods. As anticipated, many programs did not directly address multiculturalism and diversity in their training materials. Descriptive information about multicultural training methods, reflection on exemplary training methods, and recommendations for training initiatives are provided.</p>

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<author>Bryana F. C. White</author>


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<title>Alcohol Cognitions and College Student Drinking: The Moderate Effect of Executive Abilities</title>
<link>http://digitalcommons.uri.edu/oa_diss/49</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/49</guid>
<pubDate>Mon, 29 Apr 2013 13:35:31 PDT</pubDate>
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	<p>Research informed by dual process models of addictions has clearly demonstrated an association between automatic and controlled alcohol-related cognitions and alcohol use. However, the literature is limited with respect to examination of the cognitive abilities that may moderate these associations across populations. This study examined executive abilities, automatic and controlled alcohol-related cognitions, and alcohol use and problems in sample of college students. It was hypothesized that the executive abilities of working memory and response inhibition would moderate relations between alcohol-related cognitions and involvement. Specifically, it was anticipated that individuals with weaker abilities in these areas would demonstrate stronger relations between automatic cognitions and use, while individuals with stronger abilities in these areas would demonstrate more robust relations between controlled cognitions and use. Research participants completed two Implicit Association Tasks measuring alcohol-related arousal and relaxation associations. In addition, participants completed questionnaires regarding alcohol expectancies, alcohol consumption and problems, and various measures of neuropsychological functioning. We tested study hypotheses using structural equation modeling and probed significant interactions using simple slope analyses. Support for a moderating effect of inhibition abilities on relations between implicit relaxation associations and alcohol involvement was observed. Findings from this study contribute to our understanding of cognitive and neuropsychological factors that contribute to alcohol misuse with important implications for preventive interventions and treatment.</p>

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<author>Andrea M. Lavine</author>


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<title>Video Steganalysis for Digital Forensics Investigation</title>
<link>http://digitalcommons.uri.edu/oa_diss/48</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/48</guid>
<pubDate>Mon, 29 Apr 2013 13:35:30 PDT</pubDate>
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	<p>Increasing use of steganography in espionage and exfiltration of company secrets means that it is important to find ways to detect such activity. Because the amount of data being transferred is also growing, channels that can hide larger amounts of data are going to become increasingly attractive. This research will focus on detecting hidden data in one such medium, namely MPEG video.</p>

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<author>Kevin Bryan</author>


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<title>Physical Properties of Marine Sediments and their Application Toward Climate Change Studies</title>
<link>http://digitalcommons.uri.edu/oa_diss/47</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/47</guid>
<pubDate>Mon, 29 Apr 2013 13:35:29 PDT</pubDate>
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	<p>The Integrated Ocean Drilling Program (IODP) is the world’s largest collaborative research initiative for the study of the ocean seafloor, subseafloor, and their application to earth system science. The processing of recovered cores from the subseafloor by IODP has been standardized to maintain constant, reproducible results and to make the measurements available to the scientific community using a worldwide- web based database. The study of physical properties is a basic requirement for the study of marine sediments as they form a foundation data set for most of earth system dynamic studies.</p>
<p>This thesis focuses on solving four different scientific problems using analyses and modeling of marine sediments based on physical properties among other IODP data. The four manuscripts presented here are applied cases that use marine sediment physical properties to understand various aspects of past and future climate change. The main objectives of this dissertation are: validation of the design and development steps of a new seafloor observatory that will measure physical properties over time in IODP boreholes; dimensioning of this system based on the physical properties previously measured at the deployment site; development of a classification system for the major types of carbonate sediments used to reconstruct past sea level rise; and reconstructing past Pacific Ocean maximum bottom water salinities during the Last Glaciation Maximum (LGM) based on physical properties of marine sediments. These objectives were addressed by using multivariate statistics, machine learning techniques and a one dimensional diffusion model.</p>
<p>A new modular borehole observatory, named SCIMPI (Simple Cabled Instrument for Measuring Parameters<em> In situ</em>) was successfully developed and tested for deployment. This system is equipped to take time series measurements of temperature, pressure and electrical resistivity in the geological formation where it is emplaced. The characteristics of the system and the testing process are presented in Chapter 1.</p>
<p>In Chapter 2, the modular design of the first SCIMPI prototype is dimensioned using a clustering approach based on physical properties from the deployment site. The multivariate statistics applied show direct relation with the geological formation and gas hydrate dynamics at the site.</p>
<p>In the third Chapter of this dissertation, physical properties are related to characteristics of marine carbonates that, in turn, are indicative of their lithological type. Three different models were tested: Linear Discriminant Analysis, Random Forest and, Support Vector Machines. This study demonstrates a strong nonlinear relationship between physical properties and carbonate lithotypes. The results show that machine learning models can help identify lithologies, thus aiding the selection of sample locations, core-log correlations, and processing of these rare core materials.</p>
<p>Finally, pore fluid chloride concentration profiles from six Pacific Ocean deep sea sites were used to reconstruct past salinities. This study expands the spatial coverage of salinity reconstructions during the Last Glacial Maximum (LGM) to the equatorial Pacific and North and South Pacific Gyres. These reconstructed LGM chloride concentrations of deep Pacific bottom water are ~4% greater than today’s values. This is consistent with the view that the deep ocean density structure was primarily controlled by salinity variations during the LGM.</p>

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<author>Tania Lado Insua</author>


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<title>Compounds from A. Platanoides Bark, V. Corymbosum Roots &amp; Topical Formulations using Maple Syrup</title>
<link>http://digitalcommons.uri.edu/oa_diss/46</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/46</guid>
<pubDate>Mon, 29 Apr 2013 13:30:40 PDT</pubDate>
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	<p>The United States is the world’s largest producer of blueberries and the world’s second largest producer of maple syrup. Maine is the nation’s leading producer of wild blueberries, harvesting 82.6 million pounds of wild blueberries. Similarly, the New England region represents roughly 75% of the total U.S. production of maple syrup. These plants play a vital role in New England’s economy and are commonly consumed; however, these plants benefit more than the economy. The secondary metabolites of these plants are both antioxidants, and also anti-inflammatory, antibacterial and anti-viral agents. Blueberries are commonly consumed and have been investigated exhaustively. On the other hand, the roots and stems of the blueberry bush have not been investigated for their phytochemicals. Similarly, our laboratory has investigated two of the most common species tapped for their sap of the maple (<em>Acer</em>) genus. Another species of the maple family that produces sap is the Norway maple tree (<em>Acer platanoides</em>). Investigating the phytochemicals from these plants can revolutionize many industries.</p>

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<author>Raed Omar</author>


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<title>Some Results on Graph Representations and Graph Colorings</title>
<link>http://digitalcommons.uri.edu/oa_diss/45</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/45</guid>
<pubDate>Fri, 26 Apr 2013 06:45:45 PDT</pubDate>
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	<p>A graph <em>G(V,E)</em> is a structure used to model pairwise relations between a set of objects. In this context, a graph is a collection of <em>vertices</em> (representing the objects) and a collection of <em>edges</em> (representing the relation) that connect pairs of vertices. It is possible to represent a graph using an adjacency matrix, but often this is not the most efficient representation of the relation. In studying graph representation, the object is to capture the structure of the graph more efficient using a variety of other discrete structures.</p>
<p>This work considers path representations of graphs. Consider a host graph,<em> H</em>. A path representation <em>[H</em> : <em>r</em> : <em>q</em>] of a target graph <em>G</em> is a labeling in which each vertex is assigned a unique path of length <em>r</em> found in <em>H</em> in such a way that if <em>uv</em> <em>∈ E(G)</em>, then the<em> P<sub>r</sub></em> assigned to <em>u</em> and the <em>P<sub>r</sub></em> assigned to v have at least a <em>P<sub>q</sub></em> in common. This study considers representations in which the host tree is the com- plete graph on n vertices, [<em>K<sub>n</sub></em>, <em>r</em>,<em> q</em>] which will be referred to as P<sub><em>r</em></sub>,<sub><em>q</em></sub>-representations.</p>
<p>This work also considers the area in graph theory known as vertex-coloring, specifically coloring planar graphs, and explores a special class of planar graphs called "coils".</p>

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<author>Arlene Mia Heissan</author>


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<title>The Effects of N-Butonol on the Model and Reconstituted Membrane of Clostridium Pasteurianum</title>
<link>http://digitalcommons.uri.edu/oa_diss/44</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/44</guid>
<pubDate>Fri, 26 Apr 2013 06:45:43 PDT</pubDate>
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	<p>During n-butanol fermentation, n-butanol partitions into microbial membranes result in destabilizing cellular lipid membranes by altering their lipid composition (generally the ratio of saturated to unsaturated lipids) whereas adapted microorganisms respond by altering the ratio of unsaturated to saturated lipids. The mechanism of how microbes achieve a high adaptation in response to n-butanol is barely known. This dissertation describes the role of unsaturated lipids and charged lipid composition in modulating n-butanol partition into membrane using model bacteria (i.e. lipid bilayer vesicles or liposomes and Langmuir monolayers) and those studies were compared with reconstituted membranes (<em>Clostridium pasteurianum</em>) that represented an original sample which was collected during batch fermentation as a function of different fermentation conditions.</p>
<p>Calorimetric, spectroscopic, Langmuir balance and chromatographic techniques were used to examine the effects of unsaturated lipid, charged lipid and n-butanol on membrane phase behavior, membrane packing, and membrane structure. The effects of n-butanol on heterogeneous membrane phase behavior was dependent on n-butanol concentration and which phase was continuous (saturated or unsaturated lipids). An increase of unsaturated lipid ratios increased n-butanol partitioning into the membranes due to "binding pocket" on acyl chain of unsaturated lipid and increased area per molecule resulting in enhancing membrane elasticity.</p>
<p>Heterogenous monolayer membrane of DPPC/DOPC with n-butanol was also examined using Langmuir balance trough and fluorescence microscope. Lipid phase behavior, lipid packing, and monolayer elasticity were evaluated by surface pressure-area <em>(<strong>Π</strong>-A)</em> analysis. This study shows that n-butanol partitioning in DPPC, DOPC domain and at DPPC/DOPC interface. n-Butanol partitioning into DPPC monolayers led to lipid expansion and decreased elasticity. Lipid expansion became greater when DOPC content increased. n-Butanol accumulation at equimolar DPPC/DOPC was amplified at the interface between coexisting liquid expanded (<em>LE</em>, DOPC-rich) phases and liquid condensed (<em>LC</em>, DPPC-rich) domains. The accumulation of n-butanol also reduced<em> LE-LC</em> line tension and changed the domain size and morphology of <em>LC</em> domains.</p>
<p>The integrity of charged lipid membrane was driven by electrostatic interactions between cations and negatively charged lipid headgroups and hydrophobic effects on lipid tails. However, above interdigitation concentration (0.13 M) of n-butanol, n-butanol partitioning into membrane transformed the gel phase to the interdigitated phase disregarding DPPG content and salt concentration. Increasing DPPG content in the DPPC/DPPG membrane and salts above 0.13 M of n-butanol concentration, aggregation/ fusion could be prevented and the transformation of LUV-SUVs could be observed. Increasing salt and DPPG concentration, screening electrostatic repulsion between PG headgroups was apparent to promote more rigid bilayer structures and reduced butanol partition.</p>
<p>Reconstituted membrane of<em> C. pasteurianum</em> have been examined to determine membrane composition, membrane phase behavior, and membrane fluidization using different techniques such as chromatographic, spectroscopic, and Langmuir balance. n-Butanol adaptated membrane was the result of lipid modification by increasing longer fatty acids and decreasing the amount of unsaturation and protein improvement that increased membrane rigidity that counter-acted the fluidizing effect of butanol.</p>
<p>Model and reconstituted membrane studies revealed that membrane rigidity and stability were promoted by decreasing unsaturated lipids, increasing the length of lipid tails and increasing charged lipid ratios in the electrolyte solution. The accumulation of n-butanol within membrane influenced membrane fluidity and membrane packing. These results demonstrate a fundamental link of the disordering effects of butanol and lipid compositions on cell membranes.</p>

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<author>Yogi Kurniawan</author>


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<title>Cognitive-Behavioral Treatment of Childhood Anxiety: Examining a Parent Consultation Model</title>
<link>http://digitalcommons.uri.edu/oa_diss/43</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/43</guid>
<pubDate>Wed, 24 Apr 2013 13:40:34 PDT</pubDate>
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	<p>Strong evidence supports the use of cognitive-behavioral therapy (CBT) for the treatment of clinical anxiety in children. As parents may play an etiological role in the development, progression, and maintenance of childhood anxiety, researchers have noted that including parents in child treatment confers some benefit upon child outcomes. Conducting CBT solely with the parents of anxious children may be equally beneficial and potentially more cost-effective than treatment modalities with only the child. The present study examined the efficacy of a ten-session parent-only CBT intervention delivered individually to parents of anxious children (ICBT) in comparison to a ten week wait-list control condition (WL). Conditions were compared at three time-points, with regard to the child’s anxiety symptoms (by child, parent, and teacher reports) and diagnostic status (by structured interview with parents), as well as parents' self-reported anxiety, protective parenting behaviors, parenting satisfaction, and parenting self-efficacy. The ICBT intervention was more effective than the WL condition in reducing total number of anxiety disorder diagnoses, the total parent-rated interference of those diagnoses, and the total clinician-rated severity of those diagnoses (via structured diagnostic interview), as well as reducing maternal protective parenting behaviors. These changes were maintained at 3-month follow-up in the ICBT group. There were no significant differences between conditions in father-report of any variables, in child self-report or teacher-report of child anxiety, or mother-report on maternal anxiety, satisfaction, or self-efficacy. These findings suggest that treatment with the parents of anxious children can be an effective treatment modality. They also suggest that the influence of parenting factors such as protective behaviors should be a fundamental consideration for practitioners when planning childhood anxiety treatment in any modality. Future research is warranted with larger, more diverse samples and long-term follow-up in order to elucidate the mechanisms through which individual CBT with the parents of anxious children results in symptom reduction for the child and whether these gains are maintained over time.</p>

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<author>Allison M. Smith</author>


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<title>Response of Materials to Various Shock Loading Conditions Generated by Plate Impact Experiments</title>
<link>http://digitalcommons.uri.edu/oa_diss/42</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/42</guid>
<pubDate>Wed, 24 Apr 2013 13:40:31 PDT</pubDate>
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	<p>The response of materials to shock loading has been investigated through use of a plate impact experimental technique. A single stage gas gun was utilized to drive projectiles to velocities between 50-500 m/s, facilitating investigations into low to moderate shock loading conditions. Temporal records of the dynamic events were captured with the use of commercial manganin stress gauges that were embedded within layers of test material.</p>
<p>Within this thesis, there is a bimodal theme. The first portion of this thesis investigated the spall fracture of cast irons with varying microstructure. Although the study of the spall fracture of materials is a common theme in literature, there exists a noteworthy scarcity of research specific to cast iron. Given that cast iron is one of the most widely utilized materials in engineering structures, this research was pursued in an effort to characterize its strength and identify the fracture mechanisms and kinetics associated with its failure process. The second portion of this thesis involved the development of a new technique that could be utilized to generate multiple Hugoniot states in a single experiment. Generation of a material’s Hugoniot is a fundamental theme in shock wave studies because it allows researchers to determine all mechanical and thermodynamic properties associated with dynamic loading conditions. Traditionally, the locus of points necessary to construct a material’s Hugoniot is obtained through a rigorous series of experiments, where each test produces a single data set. By considering the shock wave processes associated with layered plates, a new method was developed that will significantly reduce the process of obtaining material Hugoniots.</p>
<p>Within the study of the spall fracture of cast iron, experiments were designed to induce an extreme tensile state within test samples from the interaction of decompression waves. The dynamic fracture strength, known as spall strength, was determined from temporal records of the stress evolution inside the samples. In order to encompass a vast majority of castings typical to industry, five separate cast irons were tested. Four of these castings consisted of gray cast iron with graphite in flake form, where three were classified as Type VII <em>A</em>2 and the other contained a bimodal distribution of Type VII <em>A</em>4 and VII <em>D</em>8. The fifth casting consisted of ductile cast iron with graphite in nodular form, classified as Type I with an average of 200 nodules per square millimeter of size class 5. The spall strength for the Type VII <em>A</em>2 gray cast irons was found to vary 40-370 MPa, and the additional gray cast iron was found to vary between 410-490 MPa. The spall strength of the ductile cast iron was found to fall within the range of 0.94-1.2 GPa. It was shown that the spall strength is linked to the damage level at the spall plane, where an increased amount of tensile stress is required to generate higher levels of damage. Post mortem analysis was performed on recovered samples in order to establish a relationship between microstructure and the fracture mechanisms of the failure process. This study has identified the graphite phase as the primary factor governing the spall fracture of cast irons, where crack nucleation is directly correlated to the debonding of graphite from the metal matrix. It has been noted that the average length of graphite found within a casting is linked to the material’s strength, where strength has been shown to increase as a function of decreasing length. The morphology, and mean free path of graphite precipitates, has been shown to further govern the subsequent coalescence of initiated cracks to form a complete fracture plane. In cases where graphite spacing is large, an increased amount of energy is required to complete the fracture process. A secondary factor governing the spall fracture of cast irons has been linked to the microstructure of the metal matrix. It has been noted that pearlite will yield higher spall strengths in cast irons than free ferrite.</p>
<p>Within the second portion of this thesis, an experimental approach was developed to induce shock reflections in a low impedance inner-layer embedded within a high impedance bulk structure. By capturing temporal records of the stress evolution at each side of the inner-layer, step-like loading profiles were obtained that allowed for the capture of multiple Hugoniot states. The mathematical framework employed in this technique utilized the classical Rankine-Hugoniot equations in the method of impedance matching, where either the bulk material (case 1) or inner-layer (case 2) was required to have a known Hugoniot. Validation of the new technique was performed by testing well classified materials in order to facilitate comparison of the Hugoniots generated from the method with published data found in literature. For the first case, where the Hugoniot of the bulk material is known, the Hugoniot Ring-Up Method (HRUM) was shown to accurately generate states along the Hugoniot of the inner-layer, where the number of states acquired is directly linked to the experimental design. Factors including the wave velocities in the materials, input pulse duration (controlled by the thickness and wave velocity of the impactor), thickness of the innerlayer, and diameter of the test samples (arrival of the radial release) affect the number</p>
<p>of states that can be generated from a single experiment. Experiments employing 6061 aluminum and polycarbonate, respectively, as the bulk material and inner-layer, accurately generated six Hugoniot states for polycarbonate. Additionally, experiments employing A572 grade 50 structural steel as the bulk material were able to accurately generate ten Hugoniot states of the polycarbonate inner-layer. In these experiments, the method was extended to generate a Hugoniot equation defining the material response of the inner-layer within the domain encompassed by the specific test. Through comparison of these experimentally determined equations to the real Hugoniot of polycarbonate, it has been shown that a single HRUM experiment can yield an accurate Hugoniot for the inner-layer. For the second case, when the Hugoniot of the inner-layer is known, the HRUM failed to accurately generate states along the Hugoniot of the bulk material. Thus, the HRUM requires significant improvements before it can be used in this application. In light of these shortcomings, a procedure utilizing over-deterministic methodology has been proposed, that may allow future researchers to extend application of the HRUM to the case of determining the Hugoniot of the bulk material.</p>

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<author>Gifford W. Plume IV</author>


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<title>Effect of Manufacturing Methods Used in the Stability of Amorphous Solid Solutions and Predictions to Test them</title>
<link>http://digitalcommons.uri.edu/oa_diss/41</link>
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<pubDate>Wed, 24 Apr 2013 13:35:30 PDT</pubDate>
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	<p>With the advent of combinatorial chemistry and high throughput screening of drug molecules, poorly water soluble molecules have been entering the development stage as new drug candidates. The poor aqueous solubility of these molecules is one of the limiting factors for them to succeed as a new drug product. This had led to converting these drugs in most cases are crystalline to amorphous solid dispersion with use of amorphous polymers to improve the solubility. Although amorphous solid dispersion of a poorly water drug can improve the solubility, careful selection of polymer is a necessity in order to stabilize the high energy nature of the amorphous solid dispersion. Miscibility of a drug and a polymer is important. With specific interaction between the drug and the polymer, the dispersion can remain miscible much longer. Another factor that needs to be considered when formulating an amorphous solid dispersion is the amount of drug that is incorporated into the polymer. Over saturating the polymer with the drug can cause instability of the dispersion and crystallization may occur which will lead to reduced solubility.</p>
<p>In this work, effects of processing method, polymer selection and the drug concentrations for the preparation of amorphous solid dispersion as well as prediction of drug-polymer miscibility have been studied. Hot melt extrusion (HME), rotary evaporation (Rot) and spray drying (SD) processing methods used in the study with Eudragit E 100 (EPO), HPMCAS LF and PVPVA 64 polymers. Drug concentration was another factor that was explored.</p>
<p>The objective of this dissertation were: (1) to prepare amorphous solid dispersion of nifedipine with polymers (2) to characterize the solid dispersions (3) to determine the factors which contributes to successful amorphous solid dispersion (4) to evaluate prediction methods used to study drug and polymer miscibility and solubility (5) to use a thermodynamic prediction model to determine solubility of nifedipine at room temperature.</p>
<p>In the first manuscript, amorphous solid dispersions of nifedipine and polymers were prepared. Physical and chemical characterizations of the solid dispersions indicated solid dispersions prepared with EPO polymer were unstable although intrinsic dissolution rates (IDR) of those samples had higher rates than those prepared with HPMCAS LF or PVPVA 64 polymers. The instability was explained by the lack of specific hydrogen bond interaction while the high IDR was explained by the low glass transition temperature (T<sub>g</sub>) of the polymer. With lower T<sub>g</sub>, molecular mobility would be higher and therefore the drug could dissolve at a faster rate. ANOVA analysis of factorial design showed all factors (process, polymer and drug concentration) affected the IDR. Further optimization of experiments may be necessary to determine the dominant factor for improving IDR.</p>
<p>In the second manuscript, we have calculated three different ways to calculate the Flory-Huggins interaction parameter, χ. Although using melting point depression approach and solubility parameter of a drug and a polymer are common to estimate the miscibility of the two, there were assumptions that needed to be addressed. We have modified the melting point depression approach by calculating a better estimate of volume fractions needed to calculate the interaction parameter.</p>
<p>In the third manuscript, we have taken a recently published thermodynamic prediction model, which can estimate the stable drug concentration that can be incorporated into an amorphous solid dispersion at room temperature, to predict the solubility of nifedipine with EPO, HPMCAS LF and PVPVA 64 polymers in amorphous solid dispersions prepared by HME, Rot and SD processes. The predictions showed less stable nifedipine concentration could be incorporated into HME processed solid dispersions than samples prepared by Rot or SD processes. Overall, nifedipine-PVPVA 64 solid dispersion prepared by SD method was predicted to incorporate nifedipine concentration up to 30 % w/w.</p>

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<author>Kaoru Tominaga</author>


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<title>Positive Nurse-Resident Relationships a Focused Ethnography in a Nursing Home</title>
<link>http://digitalcommons.uri.edu/oa_diss/40</link>
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<pubDate>Wed, 24 Apr 2013 13:35:28 PDT</pubDate>
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	<p>More than 1.4 million Americans reside in long term care facilities across the United States. Social and professional relationships are an integral component of everyday life within these environments. Few studies have systematically examined positive relationships that exist between residents and nursing assistants in long term care. A focused ethnography of a nursing home, one known for the quality of life experienced by its residents and located in the northeastern United States, was used to examine the nature of (1) interactions (2) positive relationships (their development and maintenance) between residents and nursing assistants, and (3) supportive environmental factors. Peace House (a pseudonym) was one of 30 nonprofit, continuing care facilities operated in the US by an order of Catholic Nuns committed to the care of the elderly poor. Participant observation took place primarily in public spaces over a four-week period. Interviews were conducted with ten Caucasian, English speaking and cognitively alert residents, including 9 women, 1 man and ranging in age from 74 to 103 and residing on a skilled nursing unit. Schatzman and Strauss’s fieldwork notation system was used to record and analyze data. Semi-structured taped interviews were transcribed, read and re-read and analyzed in relation to general themes. Credibility and trustworthiness were enhanced by member check and expert review of transcripts and findings.</p>
<p>Overall, interactions in public spaces were resident-to-resident, social in nature, and initiated primarily by residents. On skilled units interactions were primarily initiated by staff to resident but controlled by the resident. Residents interviewed had at least one positive relationship with a direct caregiver, but differentiated as, specific, non-specific, or distant. The presence, or lack, of close familial relationships did not influence the forming of close personal relationships between residents and nursing assistants. Most of the residents were unable to describe how these relationships developed and were maintained over time due to memory lapses surrounding the initial period of transition. A number of public spaces and social and work opportunities existed that facilitated social interaction. The sisters and staff members supported positive relationships by allowing the residents to be themselves. Knowledge of individual resident preferences was communicated effectively among the staff, enabling residents to decide with whom and how they wished to establish a relationship. Implications from this study include expanding Kim’s (2000) conception of the nurse-client domain to encompass interactions that are prolonged and sustained over time, increasing research on transition periods into long term care and the importance of acknowledged individuality.</p>

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<author>Rosemary A. Costigan</author>


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<title>Effect of Metabolic Disease and Xenobiotic Exposure on Hepatic ATP-Binding Cassette (ABC) Drug Transporter Expression</title>
<link>http://digitalcommons.uri.edu/oa_diss/39</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/39</guid>
<pubDate>Wed, 24 Apr 2013 13:35:27 PDT</pubDate>
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	<p>Drug transporters are membrane bound proteins, which are involved in facilitating both uptake and efflux of xenobiotics, endogenous compounds and their metabolites in various tissues such as liver, kidney, testis, and brain. Alteration in drug transporters may cause imbalances in endogenous compounds such as bile acids, hormones, and bilirubin. Xenobiotic metabolism is inefficient without drug transporters, and drug transporters are recognized as vital mediators for moving polar compounds across membranes. ATP binding cassette (Abc) transporters are a kind of drug transporters, which are ATP-dependent membrane bound proteins involved in transport of wide variety of compounds. Multiple hepatic conditions can alter drug transporter expression such as obesity, oxidative stress, cytokines, druginduced liver injury and environmental toxicants. Specifically, drug transporter expression is known to alter during several metabolic conditions. For example, both genetically modified and diet-induced obesity models of rodents displayed altered hepatic drug transporter expression. Previous studies shown not only during metabolic syndrome, but also exposure to xenobiotics such as estradiol and polybrominated diphenyls (PBDs), which are endocrine disrupting chemicals, alter drug transporter expression. The objective of this study is to determine whether certain liver conditions, such as development of fatty liver (i.e. steatosis) and developmental exposure to an environmental endocrine disruptor (i.e. Bisphenol A) alter hepatic Abc drug transporter expression in conjunction with nuclear receptor expression. This study also aims to show, changes in hepatic Phase II and Abc drug transporter expression during metabolic syndrome alters metabolism and disposition of endocrine disruptor such as Bisphenol A (BPA) This research will provide novel observation and mechanisms by which expression of drug transporters will be affected and regulated. To delineate these aspects whole thesis research was divided into three specific sub studies:</p>
<p>In the first study, which is presented as <strong>Manuscript I</strong> shows changes in hepatic Abc drug transporters, uptake transporters, Phase I enzyme expression, and factor involved in regulation of hepatic Abc transporter expression during development of obesity. This study also shows possible physiological and transcription factors role in regulation of hepatic Abc transporter expression during development of obesity. In this study, hepatic gene expression and physiological factors were analyzed in both C57BL/6 and ob/ob mice at different time points such as week-1, 3, 4 and 8 age to capture physiological and gene expression changes that occur during development of obesity. Correlation between physiological changes and gene expression was performed using canonical correlations. Significant correlations were observed between physiological changes, hormones, and gene expression changes during development of obesity. Correlation between metabolismrelated hormones and hepatic gene expression are sex-dependent. Correlation between physiological changes and gene expression indicated metabolism-related hormones might have a role in regulation of hepatic genes involved in drug metabolism and transport.</p>
<p>In second study, which is presented as <strong>Manuscript II</strong> shows changes in hepatic Abc transporter expression with developmental exposure to endocrine disruptor BPA and identifies mechanistic pathways by which BPA exposure causes these effects. In this study, female mice are exposed to either control or BPA or ethinyl estradiol (EE) or phytoestrogen enriched diet. Studies were performed in male pups to analyze gene expression and functional activities of respective genes. Developmental exposure to BPA and EE downregulated hepatic drug transporters and Phase II enzyme expression and activity that are involved in BPA metabolism and excretion, whereas genistein co-administration reversed these changes. Changes observed with developmental exposure of BPA were persistently observed even after cessation of BPA exposure to male pups. Decrease in nuclear factors mRNA expression and binding activity could be partially responsible for downregulation of hepatic Phase II enzymes and drug transporter expression. Further, increase in expression of histone deactylases (Hdac’s) upon BPA exposure could be responsible for decreased transcription factor expression and activity. Our data suggest that developmental BPA and EE exposure may work via similar pathways, and greatly affect the expression of key hepatic genes involved in BPA and hormone metabolism and clearance.</p>
<p>In third study, presented as <strong>Manuscript III</strong> shows changes in hepatic drug metabolism gene expression observed during obesity alters BPA, an endocrine disruptor disposition. This study aim to identify whether changes in Phase II and drug transporter expression alters BPA disposition, as increase in urinary total BPA levels and BPA exposure in humans are correlated to occurrence of obesity. BPA (10 mg/kg, i.v.) was administered; parent and its metabolites were analyzed in bile, plasma and urine sample of lean and obese rats. Along with in vivo BPA disposition studies, hepatic glucuronidation and sulfation enzymatic assays were performed to identify whether obesity altered hepatic metabolic processes. Changes in hepatic Phase II and III protein expression in obese rats resulted in altered BPA metabolism and disposition. In obese rats, BPA metabolites specifically BPA-glucuronide levels were increased in urine and decreased in bile compared to lean rats. This altered BPA metabolism and disposition during obesity suggests, in humans detailed evaluation of urinary BPA levels such as ratio of metabolite to parent compound, are needed to correlate BPA exposure to occurrence of obesity.</p>

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<author>Ajay Chowdary Donepudi</author>


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<item>
<title>Pathological Effects of Soybean Anti-Nutritional Factors on Summer Flounder (Paralichthys Dentatus) Tissues</title>
<link>http://digitalcommons.uri.edu/oa_diss/38</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/38</guid>
<pubDate>Wed, 24 Apr 2013 13:30:40 PDT</pubDate>
<description>
	<![CDATA[
	<p>Summer flounder (<em>Paralichthys dentatus</em>), a popular carnivorous fish in New England, is an important candidate for aquaculture development. The inclusion of plant proteins as a replacement for fish meal in the diets of marine carnivorous fish may lead to economical advantages and increased sustainability. Anti-nutritional factors, organic molecules that cannot be digested and may inhibit digestion of other molecules present in soybean meal, but not in soy protein concentrate, may limit the inclusion of soybean meal into carnivorous fish diets by impacting fish growth rates or immune function. In order to determine the mechanisms by which soybean meal impacts growth or immune function, it is important to analyze the effect of anti-nutritional factors on the morphology of important digestive and immune organs: liver, spleen, and intestine. The goal of this project was to determine: 1) If pathological change was occurring in selected summer flounder organs when fish were fed diets in which a portion of fish meal was replaced with soy protein concentrate and varying amounts of anti-nutritional factors; and 2) Which fractions of soybeans (either as saponin-containing or oligosaccharide-rich), led to pathological changes. Feeding of summer flounder for eight weeks with diets in which 60% of fish meal was replaced with soy protein concentrate supplemented with increasing amounts of a fraction of soybean flakes containing anti-nutritional factors (corresponding to the amounts present in a 5%, 14%, and 27% soybean meal replacement diet) led to a significant decrease in growth in all diets compared to that with a fish meal control diet. Fish fed diets containing anti-nutritional factors at levels as low as those present in a 5% soybean meal replacement diet showed significant pathological changes in liver, spleen, and anterior intestinal morphology as early as two weeks into the trial. These changes included: a decrease in the storage of nutrients in liver, a relative increase in the amount of white pulp versus red pulp and the presence of fibrosis in the spleen, and a decrease in the amount of goblet cells in the anterior intestine, accompanied by an increase in the thickness of the lamina propria and fusion and shortening of the mucosal folds. Fish fed the 27% diet had the worst overall growth and the most apparent change in tissue morphology, suggesting that anti-nutritional factors in soybean meal have a dose-dependent impact on the liver, spleen, and anterior intestine of summer flounder. A second six-week feeding trial was conducted in order to determine the impact of soy saponins and oligosaccharides on fish growth and tissue morphology. There were no statistically significant changes in morphology in all parameters evaluated except in the thickness of the lamina propria in the anterior intestine. Therefore, low levels of soy saponins and oligosaccharides may not significantly impact the morphology of summer flounder spleen, liver and anterior intestinal tissue. Pathological changes observed in fish fed the soybean meal equivalent replacement diets may be due to higher amounts of anti-nutritional factors in these diets or to additive or synergistic impacts of several anti-nutritional factors.</p>

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<author>Rachel Michelle Bone</author>


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<title>Pharmacodynamic Mechanisms of Tolfenamic Acid Induced SP1 Degradation Relative to Alzheimer&apos;s Disease Pathology</title>
<link>http://digitalcommons.uri.edu/oa_diss/37</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/37</guid>
<pubDate>Wed, 24 Apr 2013 13:30:39 PDT</pubDate>
<description>
	<![CDATA[
	<p>Alzheimer’s disease (AD) continues to disrupt the lives of millions of patients and caregivers around the world. The few drugs currently used for AD have modest effects on the symptoms and do not prevent the progression of the disease into total memory loss and death. With the increase in the number of AD cases and the high social and economical costs of the disease, there is a great need to find disease-modifying therapeutics that target the core pathology of the disease as well as improve the symptoms and the patients’ everyday quality of life. Two types of pathological aggregates are found in AD. The senile plaques are composed of amyloid beta (Aβ), which is cleaved off the amyloid precursor protein (APP) by beta-site APP cleaving enzyme (BACE) and γ-secretase. The other deposits are the neurofibrillary tangles (NFTs), which are mainly composed of hyperphosphorylated tau. These aggregates and factors involved in the production or clearance of Aβ, as well as the phosphorylation of tau are being investigated for potential AD treatments but so far no successful drug candidate has been found. The transcription factor specificity protein 1 (Sp1) has been linked to pathological intermediates in AD. Sp1 regulates the transcription of APP, BACE1, tau and its cyclin dependent kinase-5 (CDK5) activators p39 and p35. Previous experiments from our lab have shown that AD like pathology develops later in vitro and in vivo following early lead (Pb) exposure including elevated levels of SP1, APP, Aβ, tau and CDK5 as well as cognitive decline in mice. Studies from our lab demonstrated that decreasing Sp1 protein (SP1) levels following oral administration of tolfenamic acid to mice was able to reduce APP and Aβ levels and improve cognition. In this dissertation, we first provided an introduction to AD with a review on the role of epigenetics in the disease and the various means by which transcriptional pathways can provide therapeutic alternatives for AD. We then examined the ability of tolfenamic acid to affect the expression of AD targets that are regulated by Sp1 including tau, phosphorylated tau, CDK5 and BACE1 in mice by using Western blot, real time PCR and enzyme activity assays. In addition, we studied the ability of tolfenamic acid to prevent the increase in SP1, APP and Aβ in differentiated neuroblastoma cells that was triggered by prior exposure to Pb. After treatment of cells with Pb, tolfenamic acid or both, we used real time PCR, ELISA and Western blot analyses to examine the effects of both agents on AD related intermediates compared to control. In addition to providing a summary of the current knowledge on epigenetic therapeutic targets for AD, the major findings of this dissertation provide proof that tolfenamic acid was able to decrease the transcription and translation of proteins involved in AD like tau, BACE1 and CDK5 as well as the phosphorylation of tau in mice. Moreover, in differentiated neuroblastoma cells, tolfenamic acid decreased the expression of SP1, APP gene and Aβ which was previously upregulated by Pb. Hence, tolfenamic acid represents a novel oral drug candidate that can be beneficial for AD by affecting both the amyloid and tangle pathology of the disease through a unique transcription driven mechanism.</p>

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<author>Lina I. Adwan</author>


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<title>Assessment of Mammal Biodiversity in Coffee-Dominated Landscapes of India and Costa Rica</title>
<link>http://digitalcommons.uri.edu/oa_diss/36</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/36</guid>
<pubDate>Wed, 24 Apr 2013 10:30:45 PDT</pubDate>
<description>
	<![CDATA[
	<p>The fate of many tropical wildlife species depends on the way in which human-dominated landscapes are managed. Conservation strategies that incorporate agricultural landscapes are imperative for the survival of native fauna. Coffee is a major cash crop worldwide and is grown in tropical regions of the world that are often designated as biodiversity hotspots. Shade coffee, an agroforestry system in which coffee is grown under the shade of intentionally managed and/or native tree cover, has shown promise to provide habitat and support the diversity of bird, bat, and insect communities, but few studies have focused on non-volant mammals living in and around coffee farms. Further research is needed to understand ecosystem dynamics within coffee-dominated landscapes and to evaluate the value of this landscape as habitat for wildlife. The objectives of my research were to assess the mammal diversity within coffee-dominated landscapes, quantify the habitat parameters that are important for mammals, and based on my findings, develop guidance and suggested management practices for ways to enhance mammal diversity on coffee farms.</p>
<p>I hypothesize that increased vegetation diversity within coffee farms leads to an increase in mammalian diversity. Additionally, I hypothesize that native forests support the highest amount of mammal abundance and diversity and that as vegetation complexity decreases within the coffee farms, the abundance and diversity of mammals also decrease.</p>
<p>I assessed mammal diversity within coffee landscapes in Kodagu, India and Turriabla, Costa Rica. In India, I investigated the effects of native and non-native shade trees on mammal diversity and vegetation structure within coffee farms. Twenty farms, each with two 50- x 50-m trap grids, were sampled for five nights throughout the three rainfall zones in the region. Each farm also contained a grid with indirect sampling methods: track plates, hair traps, and camera traps.</p>
<p>In Costa Rica, I surveyed diversity and habitat preference of non-volant mammals across a broader coffee-forest landscape. Three 25-ha sites were selected that contained forest, shade coffee, and sun coffee habitats; and in two of the sites, a mix of other agricultural land uses were present. Each site was set with a 500- x 500-m trap grid, four camera traps, and four track plates. The sites were sampled in four sessions, each approximately two weeks in duration, totaling 46 sampling nights per site.</p>
<p>During the four-month study period in India, I captured 146 small mammals (129 individuals). Eleven species of mammals were detected, six species captured in small mammal traps and five detected from the track plates and camera traps. I found that neither abundance nor richness of small mammals was influenced by the composition of native or non-native trees within the site. On the plot level, small mammal abundances were higher at farms with higher amounts of low vegetation cover and basal area of shade trees, and lower numbers of shade trees within the farm; and species richness was positively associated with low vegetation cover. On a landscape level, the small mammal abundance increased as the distance to forest decreased. Although the amount of non-native trees was not related to mammal diversity, it was significantly related to vegetation structure and composition within the coffee farms. Overall, the coffee farms surveyed in India had relatively high levels of tree species richness and diversity but did not support a high diversity of mammals.</p>
<p>For the study in Costa Rica, I found that small mammals used a variety of agricultural habitats. I captured 1,258 mammals (597 individuals) during the seven-month study period. Sixteen species of mammals were found, thirteen were captured in the traps and camera trap yielded an additional three species. In general, I found the forest habitats had greater species richness and abundance of mammals than shade coffee, which in turn had more species and higher abundances than sun coffee habitats. Habitat type was significantly associated with mammal abundance and richness, but the distance to forest was not. Increased amounts of shade canopy and herbaceous ground cover within the habitats were shown to significantly increase the mammal abundance and richness for the study sites in Costa Rica. While there is no substitute for native forest, the abundance and richness of small mammals within shade coffee rivaled that of forest, whereas abundance and richness within sun coffee was much lower than both shade coffee and forest.</p>
<p>In the habitat preference analysis of five focal species found within the coffee-forest landscapes of Costa Rica, I found that all of the focal species preferred forest habitat over coffee habitats, except one species that had an equal preference for shade coffee and forest. Three species preferred shade coffee over sun coffee, while the remaining two species had no preference between the two coffee habitats.</p>
<p>My findings suggest that, although small mammals may be present in coffee habitats, most do not use shade coffee exclusively and may rely primarily upon forest habitat for survival. Small mammals may require forest tracts surrounding or intersecting coffee agriculture in addition to shade trees within the coffee farm. These habitat requirements should be included in conservation strategies for the promotion of biodiversity and sustainable agriculture. Our conservation strategies may need to be expanded to a broader-landscape scale that incorporates not only the management of shade trees and vegetation complexity within coffee farms, but also that includes forest habitats in the surrounding landscape.</p>

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<author>Stephanie Amanda Caudill</author>


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<title>Asleep Behind the Wheel: Experiences of Night Shift Nurses on the Commute Home</title>
<link>http://digitalcommons.uri.edu/oa_diss/35</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/35</guid>
<pubDate>Wed, 24 Apr 2013 10:30:44 PDT</pubDate>
<description>
	<![CDATA[
	<p><strong>Aim:</strong> The aim of this study was to obtain descriptions of nurses’ perceptions and experiences of falling asleep behind the wheel on the drive home after a worked night shift.</p>
<p><strong>Background:</strong> While the evidence suggests that the problem of drowsy driving and fall asleep driving is a strong contributor to vehicular accidents, little is known about nursing perceptions of the issue.</p>
<p><strong>Methods:</strong> The design of the study is qualitative and descriptive. Face-to-face interviews were conducted with 12 registered nurses who had experienced falling asleep behind the wheel on the drive home from work after a worked night shift. The interviews were transcribed verbatim and analyzed using content analysis.</p>
<p><strong>Results:</strong> The eight themes which emerged from the data evolved from factors identified by the participants during the interviews. They were: (1.) night shifts better for new grads, (2.) auto-pilot, (3.) struggling to stay awake, (4.) it’s scary, (5.) just need to get home, (6.) not a night person, (7.) feeling awful, and (8.) don’t know how to fix it.</p>
<p><strong>Conclusion:</strong>This study strongly suggests the need for additional research. Because we know that drowsy and fall asleep driving after a worked night shift is a ubiquitous phenomenon among night nurses, the need to develop interventions to mitigate the risks of the phenomenon was confirmed. The findings emphasize the importance of open dialogue and heightened awareness of the dangers faced by the nurses when they have finished their shift and are driving home. Understanding the context of nurses’ experiences with falling asleep behind the wheel may elicit stronger communications between nurses and their nursing leaders. Targeted education on sleep hygiene, drowsy driving, and fall asleep driving for nurses, nursing leaders, and hospital administrators may serve to open the dialogue. Negative physiologic and psychological influences of night shift centered around poor quality and quantity of sleep. These negative influences were consistently presented by all participants. The nurses’ beliefs that they are physically unable to adapt to shiftwork warrants further research into screening for physiological and psychological ability to engage in shiftwork. Further studies are needed to explore the efficacy of restorative napping, and other interventions to prevent drowsy and fall asleep driving. Many participants expressed the fact that they had little to no choice but to work the night shift as new graduates. We need to closely examine why the newest members of the nursing profession are placed on the shift with the least amount of resources. The phenomenon of fall asleep driving after a worked night shift environment in nursing is poorly understood. The goal of this qualitative descriptive study was to elicit a description of the experience of night shift nurses with the goal of obtaining information that would serve to find ways to eliminate the occurrence of drowsy/fall asleep driving in nurse shiftworkers. Nursing and hospital administrators may be able to utilize the information gleaned from this study to optimize the nurse scheduling, implement evidence based interventions, and subsequently, keep the nurses safe.</p>

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<author>Shirley A. Sargent</author>


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<title>Exploring Nurse Case Managers&apos; Language Describing Health Needs and Interventions with Populations</title>
<link>http://digitalcommons.uri.edu/oa_diss/34</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/34</guid>
<pubDate>Wed, 24 Apr 2013 10:30:42 PDT</pubDate>
<description>
	<![CDATA[
	<p>Major advances in health information technologies, safety and quality initiatives, and health policy changes have fueled the development and implementation of the Electronic Health Record (EHR). Any discipline’s work and contribution to patient care exist in the EHR only as they are coded. Thus, coding nursing’s knowledge, work and contribution to patient care in meaningful ways requires nurses to have a language that defines nursing concepts and works consistently and reliably. Currently the American Nurses Association (ANA) recognizes twelve (12) nursing languages being used in the EHR. Over the last forty years many research efforts have validated these nursing languages and mapped the languages to each other and to other clinical terminologies. Although these nursing languages exist and are in use, they were developed and are used primarily for describing nursing care to individual clients and occasionally extended to families and groups. Nursing languages describing the care of populations has not been well researched. Thus, the purpose of this study was to identify the descriptors and names nurse case managers used to refer to subpopulations, the data elements they used to assess subpopulations, the descriptors and names did nurse case managers use to refer to interventions for the subpopulation, and the descriptors and names used to refer to outcomes of the interventions.</p>
<p>The study was designed to investigate language used by nurses doing population based care. Participants were nurse case managers who were members of the Case Management Society of New England. A questionnaire was distributed in both online and written formats; 19 participants answered questions based on a case study about subscribers of an insurance company with diabetes mellitus. A tentative folk taxonomy was generated from responses to the questionnaire. Although the tentative folk taxonomy requires further investigation, it identified ten categories labeled utilization, cost, disease-related, treatment-related, people factors, living factors, education, support/coach/care coordination, and type of interactions. Thirty-nine subcategories were associated with the five categories and gave more specificity to the language in the categories. Further investigation of the folk taxonomy with different samples is needed to validate the categories and subcategories followed by additional research with different diseases and conditions.</p>

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<author>Kathleen I. Gremel</author>


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<title>Role of Nuclear Factor E2 Related Factor 2 (NRF2) in Development of Steatosis and Drug Transporter Alterations</title>
<link>http://digitalcommons.uri.edu/oa_diss/33</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/33</guid>
<pubDate>Wed, 24 Apr 2013 10:30:41 PDT</pubDate>
<description>
	<![CDATA[
	<p>Steatosis is fat deposition in liver arising from conditions like obesity, diabetes, and/or alcohol consumption. It is a benign condition with normal liver function, and can often be reversed. Both alcoholic and non-alcoholic liver steatosis can further progress to irreversible steatohepatitis to cirrhosis and substantial loss of liver function. Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor known to combat oxidative stress in the cell. The contribution of Nrf2 to other cellular functions, such as lipid homeostasis is emerging. The work herein assessed how enhanced Nrf2 activity impacts progression of hepatic steatosis with long-term high fat diet (HFD) feeding. C57BL/6 and Keap1- Knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight, liver weight and higher hepatic fat deposition. Lipogenic gene expression was also higher in livers of Keap1-KD mice fed HFD. Next, the work herein studied effect of steatosis and cirrhosis on Nrf2 and drug transporter expression in human livers. Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals, and can be determinants of drug-induced liver injury. Alcohol cirrhosis increased efflux transporter mRNA and protein expression in human livers as compared to normal non-steatotic livers. It was observed that transporter expression alterations with steatosis were much less severe as compared to cirrhosis. In order to demonstrate the effects of these drug transporter and metabolizing enzyme alterations on pharmacokinetics, we conducted oral Bisphenol A (BPA) disposition study in diet-induced obese mice. The mice were administered deuterated BPA orally and blood levels were detected for BPA and BPA metabolites at times after BPA administration. Increased BPA clearance was observed in DIO mice, as compared to lean controls, attributed to increased phase II conjugation enzyme Ugt and biliary efflux transporter Abcc2 expression. In conclusion, constitutive activity of Nrf2 increases susceptibility to mice to develop liver steatosis; and human livers with steatosis and alcohol cirrhosis have altered expression of drug transporters, which may result in xenobiotic disposition alterations.</p>

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<author>Vijay R. More</author>


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<item>
<title>An In Vitro Study on the Non-Enzymatic Glycation of Melamine and Serum Albumin by Reducing Sugars</title>
<link>http://digitalcommons.uri.edu/oa_diss/32</link>
<guid isPermaLink="true">http://digitalcommons.uri.edu/oa_diss/32</guid>
<pubDate>Tue, 23 Apr 2013 13:25:47 PDT</pubDate>
<description>
	<![CDATA[
	<p>Glycation is a non-enzymatic reaction with reactants including a reducing sugar and a free amino containing molecule such as protein, amino acids, DNA, RNA and lipids. In the initial phase of glycation, the carbonyl group of the reducing carbohydrate condenses with the free amino groups on the target biomolecule to form reversible glycosylamines, which are then converted to more stable Amadori products. Once formed, these Amadori products can with time undergo dehydration, cyclization, oxidation, and rearrangement to form a polymorphic group of compounds collectively referred to as Advanced Glycation Endproducts (AGEs). The accumulation of AGEs in vivo has been implicated as a major pathogenic process in diabetic complications including diabetic cataract formation, retinopathy and neurological diseases, as well as other health disorders, such as Alzheimer's disease (AD). Chapter one reviewed the chemistry of glycation and the formation of AGEs in a mechanical perspective. The role of AGEs in the pathogenesis of diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and Alzheimer's disease were considered. Here we also reviewed the potential inhibitors against glycation published to date, focusing on some novel potential AGE inhibitors such as zinc and gold nanoparticles. The purpose of the study described in chapter two was to investigate the susceptibility of the amine groups of melamine to glycation by milk</p>
<p>sugars and sugar metabolites. Dairy products adulterated with melamine have been recently blamed for the death of at least several infants and the sickening of countless children in China. The presented study described the non-enzymatic glycation of melamine with milk sugar D-galactose and several sugar metabolites including methylglyoxal, glyoxal and DL-glyceraldehyde. The chemical structures of melamine AGEs were characterized by electrospray mass spectrometry. The factors influencing the rate and extent of melamine's glycation were also evaluated. The third part of the dissertation described a study on anti-glycation effect of gold nanoparticles (GNPs). In this study we showed that certain sizes of spherical GNPs exhibit an inhibitory effect on the formation of AGEs when Bovine Serum Albumin (BSA) was glycated by D-ribose. A combination of UV spectrometry, HPLC and circular dichroism showed that only GNPs with size ranging from 2nm to 20nm inhibited the formation of BSA AGEs. The inhibition effect of GNPs was correlated to the overall surface area of nanoparticles in the solution. GNPs with higher surface areas were found to be better inhibitors of glycation, whereas those with low surface areas were less effective inhibitors. The inhibitory effect of GNPs on non-enzymatic glycation reactions may be due to the covalent bonding between gold atoms on the surface of GNP and E. amino groups of L-lysine residue on protein. In chapter four, we evaluated the effect of UVC radiation on glycation of</p>
<p>Human Serum Albumin (HSA). In this study, we found that exposure to UVC radiation accelerated the glycation level of HSA and promoted the formation of AGEs, which may be stimulated by the generation of ROS by UVC radiation. A combination of several analytical methods including UV spectrometry, HPLC, and MALDI-TOF were used to evaluate the glycation level of HSA at 37 °C under neutral pH in the presence of D-glucose in vitro. This study warrants further investigation as there have been few reports on the correlation between the UVC radiation of proteins and their enhanced glycation by a reducing sugar.</p>

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</description>

<author>Weixi Liu</author>


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