Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice.

The reinforcing and psychomotor effects of morphine involve opiate stimulation of the dopaminergic system via activation of mu-opioid receptors (muOR). Both mu-opioid and dopamine receptors are members of the G-protein-coupled receptor (GPCR) family of proteins. GPCRs are known to undergo desensitization involving phosphorylation of the receptor and the subsequent binding of beta(arrestins), which prevents further receptor-G-protein coupling. Mice lacking beta(arrestin)-2 (beta(arr2)) display enhanced sensitivity to morphine in tests of pain perception attributable to impaired desensitization of muOR. However, whether abrogating muOR desensitization affects the reinforcing and psychomotor properties of morphine has remained unexplored. In the present study, we examined this question by assessing the effects of morphine and cocaine on locomotor activity, behavioral sensitization, conditioned place preference, and striatal dopamine release in beta(arr2) knock-out (beta(arr2)-KO) mice and their wild-type (WT) controls. Cocaine treatment resulted in very similar neurochemical and behavioral responses between the genotypes. However, in the beta(arr2)-KO mice, morphine induced more pronounced increases in striatal extracellular dopamine than in WT mice. Moreover, the rewarding properties of morphine in the conditioned place preference test were greater in the beta(arr2)-KO mice when compared with the WT mice. Thus, beta(arr2) appears to play a more important role in the dopaminergic effects mediated by morphine than those induced by cocaine.

Olfactory conditioning facilitates diet transition in human infants.

We evaluated whether Pavlovian conditioning methods could be used to increase the ingestion of non-preferred solutions by formula-fed human infants. In baseline measures, 5-7 month old infants sucked less frequently and consumed less water than regular formula. During a 3-day olfactory conditioning period, parents placed a small scented disk, the conditioned stimulus, on the rim of their infants' formula bottle at every feeding. Following this training, infants' responses to water were tested when their water bottles had a disk scented with the training odor, a novel odor, or no odor. Infants tested with the training odor sucked more frequently and consumed significantly more water than they had at baseline. Infants tested with no odor or a novel odor consumed water at or below baseline levels. These data demonstrate that olfactory conditioning can be used to enhance ingestion in infants and suggest that such methods may be useful for infants experiencing difficulty when making transitions from one diet to another.

Poverty and Place in the Context of the American South

In the United States, poverty has been historically higher and disproportionately concentrated in the American South. Despite this fact, much of the conventional poverty literature in the United States has focused on urban poverty in cities, particularly in the Northeast and Midwest. Relatively less American poverty research has focused on the enduring economic distress in the South, which Wimberley (2008:899) calls “a neglected regional crisis of historic and contemporary urgency.” Accordingly, this dissertation contributes to the inequality literature by focusing much needed attention on poverty in the South.

Each empirical chapter focuses on a different aspect of poverty in the South. Chapter 2 examines why poverty is higher in the South relative to the Non-South. Chapter 3 focuses on poverty predictors within the South and whether there are differences in the sub-regions of the Deep South and Peripheral South. These two chapters compare the roles of family demography, economic structure, racial/ethnic composition and heterogeneity, and power resources in shaping poverty. Chapter 4 examines whether poverty in the South has been shaped by historical racial regimes.

The Luxembourg Income Study (LIS) United States datasets (2000, 2004, 2007, 2010, and 2013) (derived from the U.S. Census Current Population Survey (CPS) Annual Social and Economic Supplement) provide all the individual-level data for this study. The LIS sample of 745,135 individuals is nested in rich economic, political, and racial state-level data compiled from multiple sources (e.g. U.S. Census Bureau, U.S. Department of Agriculture, University of Kentucky Center for Poverty Research, etc.). Analyses involve a combination of techniques including linear probability regression models to predict poverty and binary decomposition of poverty differences.

Chapter 2 results suggest that power resources, followed by economic structure, are most important in explaining the higher poverty in the South. This underscores the salience of political and economic contexts in shaping poverty across place. Chapter 3 results indicate that individual-level economic factors are the largest predictors of poverty within the South, and even more so in the Deep South. Moreover, divergent results between the South, Deep South, and Peripheral South illustrate how the impact of poverty predictors can vary in different contexts. Chapter 4 results show significant bivariate associations between historical race regimes and poverty among Southern states, although regression models fail to yield significant effects. Conversely, historical race regimes do have a small, but significant effect in explaining the Black-White poverty gap. Results also suggest that employment and education are key to understanding poverty among Blacks and the Black-White poverty gap. Collectively, these chapters underscore why place is so important for understanding poverty and inequality. They also illustrate the salience of micro and macro characteristics of place for helping create, maintain, and reproduce systems of inequality across place.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.