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The Virginia School's economics of natural equals makes consent critical for policy. Democracy is understood as government by discussion, not majority rule. The claim of efficiency unsupported by consent, as common in orthodox economics, appeals to social hierarchy. Politics becomes an act of exchange among equals where the economist is only entitled to offer advice to citizens, not to dictators. The foundation of natural equality and consent explains the common themes of James Buchanan and John Rawls as well as Ronald Coase and the Fabian socialists. What orthodox economics treats as efficient racial discrimination violates the fair chance entitlement to which people consent in a market economy. The importance of replication stressed by Gordon Tullock, developing themes from Karl Popper, is another expression of natural equality since the foresight of replication induces care into research. The publication of previously unpublished correspondence and documentation allows the reader to judge recent controversy.
OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.
Deutetrabenazine is approved for treating Huntington disease (HD) chorea and is being evaluated for tardive dyskinesia (TD).
To assess the effect of deutetrabenazine on cardiac repolarization.
A QT interval study was performed to evaluate effects of deutetrabenazine 12 and 24 mg on cardiac repolarization, as assessed by time-matched change from baseline, placebo-adjusted, in Fridericia-corrected QT interval (ΔΔQTcF). Moxifloxacin (400 mg) and tetrabenazine (50 mg) were the positive control and comparator, respectively. An exposure–response analysis was developed from this study to predict maximal effects on QTcF at maximum recommended dosing based on CYP2D6 status, an approach consistent with regulatory guidance at predicting QT interval effects.
Maximal ΔΔQTcF between the least-squares mean (90% two-sided confidence interval) of deutetrabenazine 12 and 24 mg (n=45 in each group) were 2.8 (0.7–4.8) ms and 4.5 (2.4–6.5) ms, respectively. The ΔΔQTcF increase with tetrabenazine (n=45) was 7.6 (5.6–9.5) ms. Assay sensitivity was verified with moxifloxacin (n=47), which produced a maximal effect on ΔΔQTcF of 14.0 (11.9–16.0) ms. A linear model was developed that described a correlation between plasma concentrations from pivotal HD andTD trials (n=101) and QT interval prolongation. Using that model and the individual predicted Cmax for HD and TD patients, the placebo-adjusted change from baseline inQTcF for deutetrabenazine at maximal recommended daily doses was found to be 5.4 (2.5–9.5) ms.
Patients receiving the maximal recommended doses of deutetrabenazine are predicted to have a QTcF increase below the level of regulatory concern.
Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel
The lesser date moth (LDM) Batrachedra amydraula is a significant pest of date palm fruits. Previously, detection and monitoring of the pest was inaccurate due to high costs of sampling with lifting machines. We report a practical system for detection and monitoring of LDM based on pheromone traps and relevant models. Dose–response experiments with LDM pheromone traps indicated a 1 mg lure is optimal for monitoring. Delta traps with adhesive covering their entire inner surface gave the highest captures while trap colour was unimportant. Sampling pheromone traps throughout the night indicated male flight began at 1:00–2:00 and reached a peak 2 h before sunrise. Monitoring traps exposed all year long in Israel revealed three generations with different abundance. Trapping transects in a date plantation indicated interference from a monitoring trap became minimal at distances >27 m away. Inter-trap distances closer than this may lower efficiency of monitoring and mass trapping in control programs. Our estimate of the circular effective attraction radius (EARc) of a 1 mg delta trap for LDM (3.43 m) shows this bait is among the most attractive compared with baits for other insects. We developed encounter-rate equations with the pheromone trap EARc to model the interplay between population levels, trap density and captures that are useful for detection of invasive LDM and its control by mass trapping. The integrated methodologies are applicable to many pest species.
The fragmentation and international dispersion of production has given rise to complex global production networks (GPNs), also termed global value chains (GVCs), transforming structures and processes of international production. This phenomenon, which has attracted considerable attention in geography (Dicken et al., 2001; Henderson et al., 2002), sociology (Gereffi and Korzeniewicz, 1994; Bair, 2005) and political science (Berger, 2005), represents a new phase in the organization of the global political economy (Neilson and Pritchard, 2009) and bears significant implications for the role, and even the meaning, of the corporation. New economic and institutional forms are shifting and blurring the traditional boundaries of firms, industries and countries, while altering the economic and governance relationships among business, labour, governmental agencies and non-governmental organizations (NGOs).
Despite the growing research on GPNs and GVCs, large corporations are still frequently portrayed as self-contained entities evolving in increasingly global markets. This misleading premise of a unified corporate entity is dominant not just in the international business literature but also in policy circles where discourses are elaborated and decisions are made to promote economic growth, competitiveness, development, sustainability and social welfare. As a consequence, a number of core issues arising from the transnational disintegration of economic activity remain poorly understood in assessing the impacts of globalizing processes. For example, the expansion of GPNs can be viewed as global Taylorism, as outsourced activities are routinized and commoditized despite their growing sophistication. The implications for labour and for development are not as rosy as free-trade advocates would contend.
The management literature has generally embraced the vertical disintegration of firms and the formation of ‘strategic networks’ (Sydow, 1992) as a positive development in which corporations become more agile and dynamic, focusing on their core competencies while leveraging complementary capabilities held by network partners that remain indispensable to the overall productive enterprise. Governance in these networks is often viewed as less hierarchical and more democratic than in production systems dominated by large multinational corporations (MNCs); indeed, the fragmentation of production has been associated with the demise of the era of large, powerful integrated corporations (Davis, 2013).
Late Neogene Sirius Group strata from Tillite Spur and Quartz Hills in the Reedy Glacier area, Antarctica, demonstrate the variability in Sirius Group facies and contrasts Sirius Group strata deposited at high and low paleo-elevation, respectively. The Tillite Spur and Quartz Hills Formations (Pliocene) are formally defined here.The Tillite Spur Formation type section crops out on the edge of the Wisconsin Plateau overlooking Tillite Spur. It comprises 32m of alternating coarse gray conglomerate and muddy olive-brown diamictites. The Quartz Hills Formation type section crops out above the western margin of Reedy Glacier in a pre-existing cirque towards the southern end of the Quartz Hills. It comprises c.100m of alternating massive diamictites and rhythmically interbedded sandstone and laminated mudstones which were deposited close to sea level and subsequently rapidly uplifted (>500 m Myr−1) to their present elevation at c. 1500 m. Three orders of paleoclimatic variability are recorded in the Sirius Group strata from Reedy Valley: (1) recycled marine microfloras in glacial diamictites indicate intervals of marine incursion into the Antarctic cratonic interior co-occurring with reductions in the East Antarctic ice sheet; (2) an advancing and retreating paleo-Reedy Glacier deposited a glacial/interglacial sequence alternating on a 10-100 kyr scale; 3) Centimeter and millimeter stratification in strata of the Quartz Hills Formation record annual kyr scale variability.
The orthodox view of economic policy holds that public deliberation sets the goals or ends, and then experts select the means to implement these goals. This assumes that experts are no more than trustworthy servants of the public interest. David M. Levy and Sandra J. Peart examine the historical record to consider cases in which experts were trusted with disastrous results, such as eugenics, the regulatory use of security ratings, and central economic planning. This history suggests that experts have not only the public interest but also their own interests to consider. The authors then recover and extend an alternative view of economic policy that subjects experts' proposals to further discussion, resulting in transparency and ensuring that the public obtains the best insights of experts in economics while avoiding pitfalls such as expert bias.