Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation

Domain Dynamics in Piezoresponse Force Microscopy: Quantitative Deconvolution and Hysteresis Loop Fine Structure

Domain dynamics in the Piezoresponse Force Spectroscopy (PFS) experiment is studied using the combination of local hysteresis loop acquisition with simultaneous domain imaging. The analytical theory for PFS signal from domain of arbitrary cross-section is developed and used for the analysis of experimental data on Pb(Zr,Ti)O3 polycrystalline films. The results suggest formation of oblate domain at early stage of the domain nucleation and growth, consistent with efficient screening of depolarization field within the material. The fine structure of the hysteresis loop is shown to be related to the observed jumps in the domain geometry during domain wall propagation (nanoscale Barkhausen jumps), indicative of strong domain-defect interactions.Comment: 17 pages, 3 figures, 2 Appendices, to be submmited to Appl. Phys. Let

The Performance Puzzle: Understanding the Factors Influencing Alternative Dimensions and Views of Performance

There is a large literature on the determinants of organizational performance, and its multidimensional nature is well recognized. However, little research has examined how different organizational and environmental factors influence different stakeholders’ performance assessments of the same service. We address this gap by comparing the factors influencing performance evaluations by different constituencies of child care centers in Ohio. We operationalize performance using (1) regulatory violations documented during state licensing inspections, (2) satisfaction with the center’s quality reported by center directors, (3) satisfaction with the center’s quality reported by teachers, and (4) satisfaction with care quality reported by parents. Our findings suggest that different organizational and environmental factors are associated with the performance assessments of different constituencies. In addition, some of these constituency assessments appear to influence each other

Do Relationships Matter? Assessing the Association Between Relationship Design and Contractor Performance

Contracting relationships vary in the extent to which they are complete and involve formal contract specification as well as the extent to which they are based on strong relationships and rely on cooperation and trust. Where a contracting arrangement falls on these two continuums constitutes what this paper refers to as relationship design and is likely to impact contractor performance. We use data from a survey of child-care centers and Head Start agencies in Ohio to examine the association between the design of contracting relationships and contractor performance. Contractor performance is assessed in two ways: an objective measure of violations identified by government inspectors and a perceptual self-rated measure of performance reported by the contracted service providers. Measures of relationship design are constructed using multiple survey items and are included in multivariate regression analyses while controlling for a variety of organizational characteristics. Findings suggest that contracts involving stronger relationships are positively associated with child-care center performance, and more complete contracts are negatively associated with performance when performance is measured using contractor self-reports

Putting the Pieces Together: A Comprehensive Framework for Understanding the Decision to Contract Out and Contractor Performance

Contracting out is currently one of the most prevalent mechanisms of the privatization movement. Understanding its trends and rigorously analyzing its implications is an increasingly salient issue for public management research. This article builds a multi-stage theoretical framework addressing two broad research questions. The first is to identify the array of economic, political, organizational, and institutional factors that may impact a government agency\u27s decision to contract out. The second is to detail the various organizational and environmental factors influencing contractor performance. Particular attention is paid to effective contract monitoring and its relationship to contractor performance

Faith-Based Assumptions About Performance: Does Church Affiliation Matter for Service Quality and Access?

To date, the common rhetoric and assumptions on the performance of faith-based organizations (FBOs), ironically, appear to be faith based rather than empirically supported: There is a paucity of research evaluating the effectiveness of FBOs that uses sufficiently rigorous methods and multiple measures of organizational performance. This study seeks to inform the debate on the relative effectiveness of FBOs by comparing religiously affiliated and secular nonprofit nursing homes using two distinct but complementary measures of organizational performance: service quality and access for impoverished clients. Using nationally representative panel data on 11,877 church-affiliated and secular nonprofit nursing homes, this study examines the effect of ownership with several regression models. Overall, the findings fail to confirm the assumption that FBOs perform better than secular nonprofit organizations in the context of the nursing home industry. Isomorphic pressures and commercialization trends within the nursing home industry are discussed to help explain these findings

Closer Than “Arms Length”: Understanding the Factors Associated With Collaborative Contracting

This article focuses on collaborative relationships between contractors and government agencies and explores which contract characteristics, contractor traits, and environmental factors are associated with the development of such relationships. The study uses data from the Partnership Impact Research Project, a three-round longitudinal survey of over one hundred child care centers and Head Start agencies in Ohio. Our findings suggest that stronger collaborative contracting relationships are associated with greater contract specificity, better contractor service quality, and contractor affiliation with a larger organization. On the other hand, a contractor’s financial autonomy and nonprofit status are negatively related to collaborative relationship strength. We also find that a contractor’s internal management capacity is positively associated with the development of shared procedures governing contractual relationships