225 research outputs found

    Cooperation and Cheating

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    In this article, we extend the variable delivery claim framework (Cross, Buccola, and Thomann, 2006) to examine the option-to-cheat, that is, the option to shift production between contracts ex post. We use this framework to provide a solution to the age-old conflict between enforcement and the cooperative tradition of providing a "home" for member produce. We show that, in contrast to Nourse's competitive yardstick hypothesis, the value of the cooperative-provided option increases as market competition intensifies. When the option-to-cheat is fairly-priced, it is Pareto improving, increasing grower returns, lowering cooperative per-unit costs and reducing contract shortfalls for investor-owned rivals at no additional per-unit cost. Our valuation framework is consistent with replication-based equilibria and is free from parametric specification of individual preference or firm cost structure.Marketing,

    Causal Orthogonalization: Multicollinearity, Economic Interpretability, and the Gram-Schmidt Process

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    This paper considers the problem of interpreting orthogonalization model coefficients. We derive a causal economic interpretation of the Gram-Schmidt orthogonalization process and provide the conditions for its equivalence to total effects from a recursive Directed Acyclic Graph. We extend the Gram-Schmidt process to groups of simultaneous regressors common in economic data sets and derive its finite sample properties, finding its coefficients to be unbiased, stable, and more efficient than those from Ordinary Least Squares. Finally, we apply the estimator to childhood reading comprehension scores, controlling for such highly collinear characteristics as race, education, and income. The model expands Bohren et al.'s decomposition of systemic discrimination into channel-specific effects and improves its coefficient significance levels

    Symplastic solute transport and avocado fruit development : a decline in cytokinin/ABA ratio is related to appearance of the Hass small fruit variant

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    Studies on the effect of fruit size on endogenous ABA and isopentenyladenine (iP) in developing avocado (Persea americana Mill. cv. Hass) fruit revealed that ABA content was negatively correlated with fruit size whilst the iP/ABA ratio showed a linear relationship with increasing size of fruit harvested 226 d after full bloom. The effect of this change in hormone balance on the relationship between symplastic solute transport and appearance of the small fruit variant was examined following manipulation of the endogenous cytokinin (CK)/ABA ratio. Application of ABA caused seed coat senescence and retarded fruit growth but these effects were absent in fruit treated with equal amounts of ABA plus iP. Thus, the underlying physiological mechanisms associated with ABA-induced retardation of Hass avocado fruit growth appeared to be inextricably linked to a decline in CK content and included: diminution of mesocarp and seed coat plasmodesmatal branching, gating of mesocarp and seed coat plasmodesmata by deposition of electron dense material in the neck region, abolishment of the electrochemical gradient between mesocarp and seed coat parenchyma, and arrest of cell-to-cell chemical communication

    Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

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    BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

    Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

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    The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

    Cost-utility analysis of adding abiraterone acetate plus prednisone/prednisolone to long-term hormone therapy in newly diagnosed advanced prostate cancer in England: Lifetime decision model based on STAMPEDE trial data

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    Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011-2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE's £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP's indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup

    Vitamin D pathway gene polymorphisms, diet, and risk of postmenopausal breast cancer: a nested case-control study

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    INTRODUCTION: Vitamin D receptor (VDR) polymorphisms have been inconsistently associated with breast cancer risk. Whether risk is influenced by polymorphisms in other vitamin D metabolism genes and whether calcium or vitamin D intake modifies risk by genotype have not been evaluated. METHODS: We conducted a nested case-control study within the Cancer Prevention Study II Nutrition Cohort of associations between breast cancer and four VDR single-nucleotide polymorphisms (SNPs), Bsm1,Apa1,Taq1, and Fok1, a poly(A) microsatellite, and associated haplotypes (baTL and BAtS). We also examined one SNP in the 24-hydroxylase gene (CYP24A1) and two in the vitamin D-binding protein (group-specific component [GC]) gene. Participants completed a questionnaire on diet and medical history at baseline in 1992. This study includes 500 postmenopausal breast cancer cases and 500 controls matched by age, race/ethnicity, and date of blood collection. RESULTS: Incident breast cancer was not associated with any genotype examined. However, women with the Bsm1 bb SNP who consumed greater than the median intake of total calcium (≥902 mg/day) had lower odds of breast cancer compared to women with the Bb or BB genotype and less than the median calcium intake (odds ratio 0.61, 95% confidence interval 0.38 to 0.96; p(interaction )= 0.01). Similar interactions were observed for Taq1 (T allele) and the poly(A) (LL) repeat. CONCLUSION: We found no overall association between selected vitamin D pathway genes and postmenopausal breast cancer risk. However, certain VDR gene polymorphisms were associated with lower risk in women consuming high levels of calcium, suggesting that dietary factors may modify associations by VDR genotype
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