DETERMINANTS OF FERTILIZER ADOPTION BY AFRICAN FARMERS: POLICY ANALYSIS FRAMEWORK, ILLUSTRATIVE EVIDENCE, AND IMPLICATIONS

Crop Production/Industries,

Incentives for Fertilizer Use in Sub-Saharan Africa: A Review of Empirical Evidence on Fertilizer Response and Profitability

This research addresses two questions: Why is fertilizer not yet fulfilling its potential as a major stimulus to agricultural productivity in SSA? What can be done to improve the situation? Our answers are based on an extensive review of fertilizer response, profitability, and policy literature as well as some analysis of crop budgets and aggregate national statistics on fertilizer consumption. Much of the debate about fertilizer use in SSA focuses on two issues: whether the profit incentive is adequate and, if so, whether farmers have the capacity to access and use it.food security, food policy, fertilizer use, sub-Saharan Africa, Crop Production/Industries, Downloads May 2008-July 2009: 153, Q18,

Progression-free survival as a surrogate endpoint for overall survival in glioblastoma: a literature-based meta-analysis from 91 trials

Background: The aim of this study was to determine correlations between progression-free survival (PFS) and the objective response rate (ORR) with overall survival (OS) in glioblastoma and to evaluate their potential use as surrogates for OS. Method Published glioblastoma trials reporting OS and ORR and/or PFS with sufficient detail were included in correlative analyses using weighted linear regression. Results: Of 274 published unique glioblastoma trials, 91 were included. PFS and OS hazard ratios were strongly correlated; R2 = 0.92 (95% confidence interval [CI], 0.71–0.99). Linear regression determined that a 10% PFS risk reduction would yield an 8.1% ± 0.8% OS risk reduction. R2 between median PFS and median OS was 0.70 (95% CI, 0.59–0.79), with a higher value in trials using Response Assessment in Neuro-Oncology (RANO; R2 = 0.96, n = 8) versus Macdonald criteria (R2 = 0.70; n = 83). No significant differences were demonstrated between temozolomide- and bevacizumab-containing regimens (P = .10) or between trials using RANO and Macdonald criteria (P = .49). The regression line slope between median PFS and OS was significantly higher in newly diagnosed versus recurrent disease (0.58 vs 0.35, P = .04). R2 for 6-month PFS with 1-year OS and median OS were 0.60 (95% CI, 0.37–0.77) and 0.64 (95% CI, 0.42–0.77), respectively. Objective response rate and OS were poorly correlated (R2 = 0.22). Conclusion: In glioblastoma, PFS and OS are strongly correlated, indicating that PFS may be an appropriate surrogate for OS. Compared with OS, PFS offers earlier assessment and higher statistical power at the time of analysis

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Exploring the biochemistry at the extracellular redox frontier of bacterial mineral Fe(III) respiration

Many species of the bacterial Shewanella genus are notable for their ability to respire in anoxic environments utilizing insoluble minerals of Fe(III) and Mn(IV) as extracellular electron acceptors. In Shewanella oneidensis, the process is dependent on the decahaem electron-transport proteins that lie at the extracellular face of the outer membrane where they can contact the insoluble mineral substrates. These extracellular proteins are charged with electrons provided by an inter-membrane electron-transfer pathway that links the extracellular face of the outer membrane with the inner cytoplasmic membrane and thereby intracellular electron sources. In the present paper, we consider the common structural features of two of these outer-membrane decahaem cytochromes, MtrC and MtrF, and bring this together with biochemical, spectroscopic and voltammetric data to identify common and distinct properties of these prototypical members of different clades of the outer-membrane decahaem cytochrome superfamily

Characterization of an electron conduit between bacteria and the extracellular environment

A number of species of Gram-negative bacteria can use insoluble minerals of Fe(III) and Mn(IV) as extracellular respiratory electron acceptors. In some species of Shewanella, deca-heme electron transfer proteins lie at the extracellular face of the outer membrane (OM), where they can interact with insoluble substrates. To reduce extracellular substrates, these redox proteins must be charged by the inner membrane/periplasmic electron transfer system. Here, we present a spectro-potentiometric characterization of a trans-OM icosa-heme complex, MtrCAB, and demonstrate its capacity to move electrons across a lipid bilayer after incorporation into proteoliposomes. We also show that a stable MtrAB subcomplex can assemble in the absence of MtrC; an MtrBC subcomplex is not assembled in the absence of MtrA; and MtrA is only associated to the membrane in cells when MtrB is present. We propose a model for the modular organization of the MtrCAB complex in which MtrC is an extracellular element that mediates electron transfer to extracellular substrates and MtrB is a trans-OM spanning ß-barrel protein that serves as a sheath, within which MtrA and MtrC exchange electrons. We have identified the MtrAB module in a range of bacterial phyla, suggesting that it is widely used in electron exchange with the extracellular environment