pH-Dependent Drug Delivery Systems

Gastric carcinoma, or stomach cancer, is a major disease in the world today. Although it only accounts for about 2% of all cancer cases in the United States, it is much more prevalent in nations such as Korea, Japan, Great Britain, South America, and Iceland. While the most common treatment for gastric carcinoma is surgery, there are chemotherapeutic alternatives including the application of doxorubicin, also known as Adriamycin?. However, as with nearly all chemotherapy drugs, doxorubicin causes dose-dependent toxicity that results in severe biological side effects and, potentially, death. Many of the adverse effects of doxorubicin may be attributed to the fact that it is normally administered intravenously; thus, although the drug?s target is the stomach, the doxorubicin is systemically rampant. Hence, we have developed a delivery system for doxorubicin that we hope will limit the drug?s action to the stomach alone. We begin with a means for encasing the doxorubicin inside two types of hydrogels whose diffusive properties vary depending on temperature and pH levels, such that diffusion may be maximized in the stomach and minimized at all other locations inside the gastrointestinal tract. This original design was modeled as a 1-D radial line to represent the spherical shape of the pill. After investigation, another design involving a hollowed out hemisphere was modeled and tested. Results comparison shows that the second design scheme is superior to the first both in outward drug flux and in the amount of drug able to be delivered. Ultimately, results of the study showed that pH-dependent drug release can be attained at a steady and reliable rate, with significantly greater rates of release inside the stomach. However, we were unable to attain a clinically adequate amount of total doxorubicin release with our model designs. Still, it may be possible to achieve medically useful results with pH-dependent drug delivery systems given certain technological improvements in the future

Early Patterns of Change in Parent-Child Interaction Therapy

Early intervention for young children with behavior problems is important for promoting healthy social/emotional development and reducing the risk of persistent and worsening conduct problems (DuPaul, McGoey, Eckert, & VanBrakle, 2001; Lahey et al., 1995; Shaw, 2013). Parent-Child Interaction Therapy (PCIT) is an evidence-based treatment for young children exhibiting behavior problems (Eyberg, Nelson, & Boggs, 2008). PCIT aims to promote parents’ use of positive attention and effective discipline skills with their children (Zisser & Eyberg, 2010). Although substantial research has demonstrated the efficacy of PCIT in research settings, far fewer studies have tested its effectiveness with clinically referred samples in community settings. Pilot and case studies have shown promise that PCIT can be implemented effectively in community settings and produce clinically meaningful results (Budd, Hella, Bae, Meyerson, & Watkin, 2011; Lyon & Budd, 2010; McCabe & Yeh, 2009; Phillips, Morgan, Cawthorn, & Barnett, 2008). However, attrition tends to be higher and treatment often takes longer in community settings (Budd, Danko, & Legato, 2012; Lanier, et al., 2011). The early stage of treatment in PCIT is particularly important, as most attrition occurs in the first stage as compared to the later stage of treatment (Lanier et al., 2011). Learning more about parents’ trajectories across the early phase of treatment and the associated effects on child behavior change has implications for improving the effectiveness of PCIT and reducing treatment attrition with clinically referred and diverse ethnic, racial, and socio-economic populations. The current study examined data from 48 young children and their families who were referred to a PCIT program in a university-affiliated, community mental health center. Through use of longitudinal multilevel modeling, this dissertation study is the first to describe trajectories of parental skill acquisition using session-by-session observational data in the early stage of PCIT with a clinically referred sample. As hypothesized, all parents showed significant linear increases in the targeted positive skills (i.e., praise, reflections, and behavioral descriptions) taught during the early stage of treatment, and linear decreases in behaviors to avoid (i.e., negative talk, asking questions, giving commands). Parents’ session-by-session ratings of their child’s behavior problems also showed a significant linear decrease across the first phase of treatment. Importantly, the analyses demonstrated that parents’ increases in positive skill use mediated the decreases in child behavior ratings, whereas parents’ decreases in negative skills use did not show a mediating effect. Several treatment engagement and demographic factors predicted parental skill acquisition. Specifically, parents who attended weekly sessions gained positive skills and decreased negative behaviors faster than parents with more days elapsed between sessions. Single parents showed slower acquisition of positive skills than parents from two-parent households; however, single parents decreased their negative behaviors at a faster rate. Household income, parents’ racial/ethnic minority status, and initial child severity did not predict differing rates of skill acquisition or child behavior ratings across time. Homework completion also did not emerge as a clear predictor of skill gains. Although completers of the first phase of treatment showed faster progress with decreasing negative behaviors than dropouts, they did not differ in positive skill acquisition rates. In summary, the current study demonstrated a mediating effect of parents\u27 session-by-session trajectory of positive skill acquisition on child behavior ratings across the early phase of PCIT, identified several variables related to parents’ rates of target skill gains, and failed to confirm other variables as predictors of change. Implications for treatment and future research directions are discussed

From Gender to Genomics: Achievements and Challenges in Sex-Specific Science

Dr. Legato\u27s keynote speech, delivered at the Journal\u27s Symposium, covered the evolution of gendered approaches to medical examination and research from the early 1900s up to today. This issue features a transcribed version of that address. In the early 1900s, doctors and medical researchers focused solely on men as normative subjects representative of the population at large. Since then, the focus has shifted; first, to a dual approach, considering both sexes, and then, to a greater emphasis on women, to the detriment of the male community. The classic debate of nature versus nurter has been a recurring theme throughout these shifts of focus. What is biologically hardwired and what is a consequence of social forces? Perhaps the response need not be dualistic; nature and nurture may be complimentary considerations, not mutually exclusive forces. Exciting scientific revelations further probe this debate. The Human Genome Project in 2000 sparked questions regarding how prevention and cure of disease may differ for male and female patients. Today, in 2011, the advent of synthetic biology begs the question, does sex matter? With synthetic biology, scientists are working toward creating living organisms with the ablity to reproduce from inert chemicals. Dr. Legato hypothesizes that evolution may no longer be based in natural selection in the Darwinian sense, as genetic engineering is changing the very nature of created life

Effects of teacher factors on expectations of students with ADHD

The current study sought to inform the literature on teacher variables related to expectations for students with ADHD. The study examined the relationships among teachers’ knowledge about ADHD, self-efficacy, and their expectations about how ADHD behaviors affect the child, the classroom environment, and the teacher’s own well-being. Results indicated self-efficacy was positively related to teachers\u27 knowledge of ADHD. Teachers with higher knowledge also tended to have higher self-efficacy; however, it remains unknown whether one is causally related to the other. No significant relationships were found among teachers\u27 knowledge of ADHD or their self-efficacy and expectations for problems. Finally, unlike previous studies, the current study did not find that experience teaching students with ADHD was significantly related to ADHD knowledge. Possible reasons for these findings, study limitations, and implications for future research are discussed

“It doesn’t hit the scorecard”: the corporate (un)accountability and legal crisis accounting of Chiquita Brands’ crimes in Colombia

El presente proyecto de investigación tuvo por objetivo comprender el recorrido hasta la fecha de Chiquita Brands, empresa bananera anteriormente denominada United Fruit, a través de jurisdicciones civiles y penales en Estados Unidos y Colombia después de la admisión de la empresa en el 2007 de haber financiado a sabiendas a grupos guerrilleros y, sobre todo, paramilitares involucrados en el conflicto armado colombiano. Se presta especial atención a la economía política de la “rendición de cuentas corporativas”, el movimiento orientado a cerrar la brecha creada por la omisión del sujeto corporativo del derecho penal internacional (DPI). Tomando en consideración documentos filtrados de la empresa (los denominados “Chiquita Papers”), documentos judiciales de Estados Unidos y archivos del Estado colombiano, esta investigación cuestiona el papel que juega el derecho en el manejo de la crisis generalizada de impunidad corporativa, el desplazamiento de los deberes tradicionales del sistema de justicia a burocracias de control y auditoría, y el propósito de revelar estos "secretos a voces" en el orden mundial neoliberal.Ejecutivos corporativos estadounidensesEjecutivos corporativos colombianosThe purpose of this investigation was to understand the journey of Chiquita Brands, the banana company previously known as United Fruit, through civil and criminal jurisdictions in the United States and Colombia to date following the company’s 2007 admission to having knowingly financed guerrilla and, above all, paramilitary groups involved in the Colombian armed conflict. Special attention is paid to the political economy of “corporate accountability”, the movement to close the gap created by the omission of the corporate subject from international criminal law (ICL). Referring to leaked company documents (the “Chiquita Papers”), U.S court documents, and Colombian state archives, this thesis questions the role played by the law in managing the crisis of widespread corporate impunity, the displacement of the traditional duties of the justice system onto compliance officers and bureaucracies, and the purpose of transparent secrets in the neoliberal world order.Magíster en Estudios CulturalesMaestrí

Stereoselective handling of perhexiline:Implications regarding accumulation within the human myocardium

Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (−) perhexiline may selectively modulate heart rate reduction

Empresas, universidad y mercado: un trípode institucional como factor de competitividad de empresas y desarrollo de comunidades

El desarrollo, como expresión del bienestar de la comunidad y, consecuentemente, de las metas de los gobiernos y del management de las organizaciones empresarias, compromete el efecto sinérgico del funcionamiento eficiente de tres pilares: empresas, universidad, y la organización-coordinación de la actividad económica basada en el mercado. Se demuestra, investigación mediante, que la existencia y desarrollo de empresas implica una demanda incremental de conocimiento formal en función de algunos aspectos clave de su evolución. Seguidamente queda expuesta la necesidad de optimizar el proceso de creación, difusión y aplicación del conocimiento a cargo de las universidades y de un contexto que, en lo fundamental, debiera estar dado por una economía de mercado sujeta a efectiva regulación. Ello implica, para el management público, un compromiso fundamental referido a la competitividad global y a la efectividad de las asignaciones destinadas a finalidades cruciales para el desarrollo y la superación de desigualdades básicas