146 research outputs found

    POLICY RISK: AN EMPIRICAL ANALYSIS OF A MARKET FOR A GOVERNMENT-CREATED ASSET

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    This paper investigates the California dairy quota. The quota rate of return has been relatively high. The variability of returns is high relative to government bonds but not relative to the S&P500. Most of the returns are from monthly dividends, but most of the variability is from the capital gains.Livestock Production/Industries,

    A STATIC POLICY FOR A DYNAMIC INDUSTRY: THE CALIFORNIA YOUNG ACT OF 1935

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    An economic history of the development of California dairy policies from 1935 to 1965 is used to support the hypothesis that the incompatibility of discrete policy changes for a dynamic industry generates deadweight losses. Combining quantitative industry data with legal and personal narratives provides evidence in support of the hypothesis.dairy policy, quota, agricultural history, Agricultural and Food Policy,

    Explaining Variations in the Price of Dairy Quota: Flow Returns, Liquidity, Quota Characteristics, and Policy Risk

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    An econometric model based on the net present value model is used to examine factors that drive the variation of California dairy quota values over a 29-year period. The results suggest the price of quota is based on expected returns, variations in quota owner liquidity, and the risk of policy default. The dominant influence on the variation of the quota price was the historical variation in monthly flow of net benefits from owning quota. This analysis confirms that the rate of return to quota rises in periods of policy uncertainty.adaptive expectations, capitalization of policy, dairy policy, policy risk, quota, Demand and Price Analysis,

    A Qualitative Metasynthesis of Consultation Process Research: What We Know and Where to Go

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    Qualitative metasynthesis (QM) is a research methodology that permits the meaningful integration and interpretation of qualitative research. This study applies a QM approach combined with constructivist grounded theory methods, bolstered by several features of research credibility, to examine the state of consultee-centered consultation (CCC) and related relational, process-oriented school consultation research. A systematic search and retrieval process including two rounds of appraisal resulted in a final sample of 38 relevant studies from 1995 to 2014. Data analyses included two stages of coding/ theme development. Integrated themes suggest a number of considerations regarding consultation implementation including: system-level factors; consultation structure; consultee voice, social-emotional support, and learning; ecological orientation and cultural responsiveness; and consultation training. Future research priorities stemming from these themes are identified and elaborated upon, as are future applications for QM in educational research

    Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort

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    Tamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds are considered infeasible. Therefore, we aim to validate the association between Z-endoxifen concentration and tamoxifen treatment outcomes, and identify a Z-endoxifen concentration threshold of tamoxifen efficacy, using pharmacometric modeling and simulation. As a first step, the CYP2D6 Endoxifen Percentage Activity Model (CEPAM) cohort was created by pooling data from 28 clinical studies (&gt; 7,000 patients) with measured endoxifen plasma concentrations. After cleaning, data from 6,083 patients were used to develop a nonlinear mixed-effect (NLME) model for tamoxifen and Z-endoxifen pharmacokinetics that includes a conversion factor to allow inclusion of studies that measured total endoxifen but not Z-endoxifen. The final parent-metabolite NLME model confirmed the primary role of CYP2D6, and contributions from body weight, CYP2C9 phenotype, and co-medication with CYP2D6 inhibitors, on Z-endoxifen pharmacokinetics. Future work will use the model to simulate Z-endoxifen concentrations in patients receiving single agent tamoxifen treatment within large prospective clinical trials with long-term survival to identify the Z-endoxifen concentration threshold below which tamoxifen is less efficacious. Identification of this concentration threshold would allow personalized tamoxifen treatment to improve outcomes in patients with hormone receptor-positive breast cancer.</p

    Deep exclusive π+\pi^+ electroproduction off the proton at CLAS

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    The exclusive electroproduction of π+\pi^+ above the resonance region was studied using the CEBAF\rm{CEBAF} Large Acceptance Spectrometer (CLAS\rm{CLAS}) at Jefferson Laboratory by scattering a 6 GeV continuous electron beam off a hydrogen target. The large acceptance and good resolution of CLAS\rm{CLAS}, together with the high luminosity, allowed us to measure the cross section for the γpnπ+\gamma^* p \to n \pi^+ process in 140 (Q2Q^2, xBx_B, tt) bins: 0.16<xB<0.580.16<x_B<0.58, 1.6 GeV2<^2<Q2Q^2<4.5<4.5 GeV2^2 and 0.1 GeV2<^2<t-t<5.3<5.3 GeV2^2. For most bins, the statistical accuracy is on the order of a few percent. Differential cross sections are compared to two theoretical models, based either on hadronic (Regge phenomenology) or on partonic (handbag diagram) degrees of freedom. Both can describe the gross features of the data reasonably well, but differ strongly in their ingredients. If the handbag approach can be validated in this kinematical region, our data contain the interesting potential to experimentally access transversity Generalized Parton Distributions.Comment: 18pages, 21figures,2table

    El Miocè inferior de la conca del Vallès-Penedès : un registre excepcional dels canvis climàtics i faunístics

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    Altres ajuts: CERCA Programme/Generalitat de Catalunya. Les tasques de camp es van poder dur a terme gràcies al suport del Departament de Cultura de la Generalitat de Catalunya (projecte 2014/100584) i la National Geographic Society (beca d'exploració ref. 9640-15).Les intervencions paleontològiques recents han mostrat que el registre de vertebrats continentals del Miocè inferior de la conca del Vallès-Penedès és molt més ric i continu del que es pensava. Avui dia es coneixen una vintena de jaciments que han lliurat tant microvertebrats com macrovertebrats. Els nostres estudis biostratigràfics han permès una datació precisa dels diferents jaciments i també dels principals esdeveniments faunístics i climàtics

    Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

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    Enteroviruses are globally prevalent human pathogens responsible for many diseases. The nonstructural protein 2C is a AAA+ helicase and plays a key role in enterovirus replication. Drug repurposing screens identified 2C-targeting compounds such as fluoxetine and dibucaine, but how they inhibit 2C is unknown. Here, we present a crystal structure of the soluble and monomeric fragment of coxsackievirus B3 2C protein in complex with (S)-fluoxetine (SFX), revealing an allosteric binding site. To study the functional consequences of SFX binding, we engineered an adenosine triphosphatase (ATPase)-competent, hexameric 2C protein. Using this system, we show that SFX, dibucaine, HBB [2-(α-hydroxybenzyl)-benzimidazole], and guanidine hydrochloride inhibit 2C ATPase activity. Moreover, cryo-electron microscopy analysis demonstrated that SFX and dibucaine lock 2C in a defined hexameric state, rationalizing their mode of inhibition. Collectively, these results provide important insights into 2C inhibition and a robust engineering strategy for structural, functional, and drug-screening analysis of 2C proteins

    TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

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    Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit
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