Inequalities, Agency, and Well-being: Conceptual Linkages and Measurement Challenges in Development

development, inequality, gender, well-being, agency, capability, distribution, Sen

Leadership and Global Justice

What does global justice look like, and how can leadership help get us there? The contributors to Leadership and Global Justice confront the conceptual and practical challenges associated with pursuing justice beyond national boundaries. Essays analyze the roles and responsibilities of institutions - states, corporations, international financial institutions, UN bodies, nongovernmental organizations - in making collaborative progress towards international justice. They explore justice in various spheres: citizenship, the marketplace, health, education, and the environment. And they provide creative and constructive moral approaches for evaluating and promoting global justice, including human rights, capabilities, and solidarity of people across boundaries.https://scholarship.richmond.edu/bookshelf/1025/thumbnail.jp

The International Library of Leadership

The International Library of Leadership brings together in one place the most significant writings on leadership, the process by which groups, organizations, and societies seek to satisfy their needs and achieve their objectives. Volume 1 focuses on classic discussions of perennial leadership issues including the moral purpose of leadership, the nature of legitimate authority, and the role of followers. Volume 2 turns to investigations of leadership in the modern era and makes available the seminal social scientific works that inaugurated the modern theories of leadership. Volume 3 builds upon the analyses of power, culture, and gender in the first two volumes to address current ethical, democratic, and international challenges of leadership.https://scholarship.richmond.edu/bookshelf/1002/thumbnail.jp

The expression of TRMT2A, a novel cell cycle regulated protein, identifies a subset of breast cancer patients with HER2 over-expression that are at an increased risk of recurrence

<p>Abstract</p> <p>Background</p> <p>Over-expression of <it>HER2 </it>in a subset of breast cancers (<it>HER2</it>+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of <it>HER2</it>+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients.</p> <p>Methods</p> <p>A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in <it>HER2</it>+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in <it>HER2</it>+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI).</p> <p>Results</p> <p>TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 <it>HER2</it>+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 <it>HER2</it>+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts.</p> <p>Conclusions</p> <p>Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in <it>HER2+ </it>breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with <it>HER2 </it>targeted therapy.</p

Can the Marginal Productivity Theory of Distribution be Tested?

This paper shows why attempts to test the neoclassical aggregate marginal productivity theory of distribution are inherently flawed. The use of constant-price value data and an underlying accounting identity mean that the close correspondence often found between the “output elasticities” of a putative aggregate production function and the relevant factor shares is a mere statistical artefact. Likewise, the results of estimating neoclassical labor demand functions must, for the same reason, always give spurious results. The authors received no financial support for the research, authorship and/or publication of this article.This is the accepted manuscript. The final version is available from Sage at http://rrp.sagepub.com/content/47/2/274.abstrac

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

GMOs: Non-Health Issues

The controversy over genetically modified [GM] organisms is often framed in terms of possible hazards for human health. Articles in a previous volume of this *Encyclopedia* give a general overview of GM crops [@Mulvaney2014] and specifically examine human health [@Nordgard2014] and labeling [@Bruton2014] issues surrounding GM organisms. This article explores several other aspects of the controversy: environmental concerns, political and legal disputes, and the aim of "feeding the world" and promoting food security. Rather than discussing abstract, hypothetical GM organisms, this article explores the consequences of the GM organisms that have actually been deployed in the particular contexts that they have been deployed, on the belief that there is little point in discussing GM organisms in an idealized or context-independent way

Hepatic profile analyses of tipranavir in Phase II and III clinical trials

<p>Abstract</p> <p>Background</p> <p>The risk and course of serum transaminase elevations (TEs) and clinical hepatic serious adverse event (SAE) development in ritonavir-boosted tipranavir (TPV/r) 500/200 mg BID recipients, who also received additional combination antiretroviral treatment agents in clinical trials (TPV/r-based cART), was determined.</p> <p>Methods</p> <p>Aggregated transaminase and hepatic SAE data through 96 weeks of TPV/r-based cART from five Phase IIb/III trials were analyzed. Patients were categorized by the presence or absence of underlying liver disease (+LD or -LD). Kaplan-Meier (K-M) probability estimates for time-to-first US National Institutes of Health, Division of AIDS (DAIDS) Grade 3/4 TE and clinical hepatic SAE were determined and clinical actions/outcomes evaluated. Risk factors for DAIDS Grade 3/4 TE were identified through multivariate Cox regression statistical modeling.</p> <p>Results</p> <p>Grade 3/4 TEs occurred in 144/1299 (11.1%) patients; 123/144 (85%) of these were asymptomatic; 84% of these patients only temporarily interrupted treatment or continued, with transaminase levels returning to Grade ≤ 2. At 96 weeks of study treatment, the incidence of Grade 3/4 TEs was higher among the +LD (16.8%) than among the -LD (10.1%) patients. K-M analysis revealed an incremental risk for developing DAIDS Grade 3/4 TEs; risk was greatest through 24 weeks (6.1%), and decreasing thereafter (>24-48 weeks: 3.4%, >48 weeks-72 weeks: 2.0%, >72-96 weeks: 2.2%), and higher in +LD than -LD patients at each 24-week interval. Treatment with TPV/r, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline were found to be independent risk factors for development of DAIDS Grade 3/4 TE; the hazard ratios (HR) were 2.8, 2.0, 2.1 and 1.5, respectively. Four of the 144 (2.7%) patients with Grade 3/4 TEs developed hepatic SAEs; overall, 14/1299 (1.1%) patients had hepatic SAEs including six with hepatic failure (0.5%). The K-M risk of developing hepatic SAEs through 96 weeks was 1.4%; highest risk was observed during the first 24 weeks and decreased thereafter; the risk was similar between +LD and -LD patients for the first 24 weeks (0.6% and 0.5%, respectively) and was higher for +LD patients, thereafter.</p> <p>Conclusion</p> <p>Through 96 weeks of TPV/r-based cART, DAIDS Grade 3/4 TEs and hepatic SAEs occurred in approximately 11% and 1% of TPV/r patients, respectively; most (84%) had no significant clinical implications and were managed without permanent treatment discontinuation. Among the 14 patients with hepatic SAE, 6 experienced hepatic failure (0.5%); these patients had profound immunosuppression and the rate appears higher among hepatitis co-infected patients. The overall probability of experiencing a hepatic SAE in this patient cohort was 1.4% through 96 weeks of treatment. Independent risk factors for DAIDS Grade 3/4 TEs include TPV/r treatment, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline.</p> <p>Trial registration</p> <p>US-NIH Trial registration number: NCT00144170</p

Communications Biophysics

Contains reports on four research projects.National Institutes of Health (Grant 5 P01 NS13126-02)National Institutes of Health (Grant 5 K04 NS00113-03)National Institutes of Health (Grant 2 ROI NS11153-02A1)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 RO1 NS10916-03)National Institutes of Health (Fellowship 1 F32 NS05327)National Institutes of Health (Grant 5 ROI NS12846-02)National Institutes of Health (Fellowship 1 F32 NS05266)Edith E. Sturgis FoundationNational Institutes of Health (Grant 1 R01 NS11680-01)National Institutes of Health (Grant 2 RO1 NS11080-04)National Institutes of Health (Grant 5 T32 GIM107301-03)National Institutes of Health (Grant 5 TOI GM01555-10