Manin products, Koszul duality, Loday algebras and Deligne conjecture

In this article we give a conceptual definition of Manin products in any category endowed with two coherent monoidal products. This construction can be applied to associative algebras, non-symmetric operads, operads, colored operads, and properads presented by generators and relations. These two products, called black and white, are dual to each other under Koszul duality functor. We study their properties and compute several examples of black and white products for operads. These products allow us to define natural operations on the chain complex defining cohomology theories. With these operations, we are able to prove that Deligne's conjecture holds for a general class of operads and is not specific to the case of associative algebras. Finally, we prove generalized versions of a few conjectures raised by M. Aguiar and J.-L. Loday related to the Koszul property of operads defined by black products. These operads provide infinitely many examples for this generalized Deligne's conjecture.Comment: Final version, a few references adde

Cost-Effectiveness of Web-Based Patient-Reported Outcome Surveillance in Patients With Lung Cancer

INTRODUCTION: A multicenter randomized clinical trial in France found an overall survival benefit of web-based patient-reported outcome (PRO)-based surveillance after initial treatment for lung cancer compared with conventional surveillance. The aim of this study was to assess the cost-effectiveness of this PRO-based surveillance in lung cancer patients. METHODS: This medico-economic analysis used data from the clinical trial, augmented by abstracted chart data and costs of consultations, imaging, transportations, information technology, and treatments. Costs were calculated based on actual reimbursement rates in France, and health utilities were estimated based on scientific literature review. Willingness-to-pay thresholds of €30,000 per quality-adjusted life year (QALY) and €90,000 per QALY were used to define a very cost-effective and cost-effective strategy, respectively. Average annual costs of experimental and control surveillance approaches were calculated. The incremental cost-effectiveness ratio was expressed as cost per life-year gained and QALY gained, from the health insurance payer perspective. One-way and multivariate probabilistic sensitivity analyses were performed. RESULTS: Average annual cost of surveillance follow-up was €362 lower per patient in the PRO arm (€941/year/patient) compared to control (€1,304/year/patient). The PRO approach presented an incremental cost-effectiveness ratio of €12,127 per life-year gained and €20,912 per QALY gained. The probabilities that the experimental strategy is very cost-effective and cost-effective were 97% and 100%, respectively. CONCLUSIONS: Surveillance of lung cancer patients using web-based PRO reduced the follow-up costs. Compared to conventional monitoring, this surveillance modality represents a cost-effective strategy and should be considered in cancer care delivery

Rapid Publication Prostaglandin E2 and Collagenase Production by Fibroblasts and Synovial Cells Is Regulated by Urine-derived Human Interleukin 1 and Inhibitor(s)

Abstract Interleukin 1 (IL-1) possesses multiple biological activities that may be blocked selectively by different inhibitors. Some known inhibitors block the lymphocyte activating factor (LAF/IL-1) but not the mononuclear cell factor (MCF/IL-1) measured by its capacity to stimulate prostaglandin E2 (PGE2) and colingenase production. The presence of IL-1 in vivo may be difficult to detect due to the presence of inhibitor(s) and the level of the inhibitor(s) may vary depending upon pathological conditions. We have found that urine from three patients with monocytic leukemia (M5) contained high levels of inhibitor(s) of MCF/II-1, whereas urine of normal subjects did not contain significant amounts. Urine from two patients with other blood neoplasic diseases also contained little inhibitory activity. The MCF/IL-1 inhibitor(s), which also acts on human recombinant IL-1 ft, is -25-35 kD, is not retained on concanavalin A-Sepharose column and can be partially destroyed with urea and boiling. At this stage of the purification the fraction containing the MCF/IL-1 inhibitor(s) also inhibits the LAF/IL-1 assay. However, this inhibitor(s) is probably distinct from other inhibitors already described

Cost-Effectiveness of Web-Based Patient-Reported Outcome Surveillance in Patients With Lung Cancer

Introduction: A multicenter randomized clinical trial in France found an overall survival benefit of web-based patient-reported outcome (PRO)–based surveillance after initial treatment for lung cancer compared with conventional surveillance. The aim of this study was to assess the cost-effectiveness of this PRO-based surveillance in lung cancer patients. Methods: This medico-economic analysis used data from the clinical trial, augmented by abstracted chart data and costs of consultations, imaging, transportations, information technology, and treatments. Costs were calculated based on actual reimbursement rates in France, and health utilities were estimated based on scientific literature review. Willingness-to-pay thresholds of €30,000 per quality-adjusted life year (QALY) and €90,000 per QALY were used to define a very cost-effective and cost-effective strategy, respectively. Average annual costs of experimental and control surveillance approaches were calculated. The incremental cost-effectiveness ratio was expressed as cost per life-year gained and QALY gained, from the health insurance payer perspective. One-way and multivariate probabilistic sensitivity analyses were performed. Results: Average annual cost of surveillance follow-up was €362 lower per patient in the PRO arm (€941/year/patient) compared to control (€1,304/year/patient). The PRO approach presented an incremental cost-effectiveness ratio of €12,127 per life-year gained and €20,912 per QALY gained. The probabilities that the experimental strategy is very cost-effective and cost-effective were 97% and 100%, respectively. Conclusions: Surveillance of lung cancer patients using web-based PRO reduced the follow-up costs. Compared to conventional monitoring, this surveillance modality represents a cost-effective strategy and should be considered in cancer care delivery

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Genomic Organization and Expression Demonstrate Spatial and Temporal Hox Gene Colinearity in the Lophotrochozoan Capitella sp. I

Hox genes define regional identities along the anterior–posterior axis in many animals. In a number of species, Hox genes are clustered in the genome, and the relative order of genes corresponds with position of expression in the body. Previous Hox gene studies in lophotrochozoans have reported expression for only a subset of the Hox gene complement and/or lack detailed genomic organization information, limiting interpretations of spatial and temporal colinearity in this diverse animal clade. We studied expression and genomic organization of the single Hox gene complement in the segmented polychaete annelid Capitella sp. I. Total genome searches identified 11 Hox genes in Capitella, representing 11 distinct paralog groups thought to represent the ancestral lophotrochozoan complement. At least 8 of the 11 Capitella Hox genes are genomically linked in a single cluster, have the same transcriptional orientation, and lack interspersed non-Hox genes. Studying their expression by situ hybridization, we find that the 11 Capitella Hox genes generally exhibit spatial and temporal colinearity. With the exception of CapI-Post1, Capitella Hox genes are all expressed in broad ectodermal domains during larval development, consistent with providing positional information along the anterior–posterior axis. The anterior genes CapI-lab, CapI-pb, and CapI-Hox3 initiate expression prior to the appearance of segments, while more posterior genes appear at or soon after segments appear. Many of the Capitella Hox genes have either an anterior or posterior expression boundary coinciding with the thoracic–abdomen transition, a major body tagma boundary. Following metamorphosis, several expression patterns change, including appearance of distinct posterior boundaries and restriction to the central nervous system. Capitella Hox genes have maintained a clustered organization, are expressed in the canonical anterior–posterior order found in other metazoans, and exhibit spatial and temporal colinearity, reflecting Hox gene characteristics that likely existed in the protostome–deuterostome ancestor

A pharmacological organization of G protein–coupled receptors

Protein classification typically uses structural, sequence, or functional similarity. Here we introduce an orthogonal method that organizes proteins by ligand similarity, focusing here on the class A G protein-coupled receptor (GPCR) protein family. Comparing a ligand-based dendogram to a sequence-based one, we sought examples of GPCRs that were distantly linked by sequence but neighbors by ligand similarity. Experimental testing of compounds predicted to link three of these new pairs confirmed the predicted association, with potencies ranging from the low-nanomolar to low-micromolar. We then identified hundreds of non-GPCRs closely related to GPCRs by ligand similarity, including the CXCR2 chemokine receptor to Casein kinase I, the cannabinoid receptors to epoxide hydrolase 2, and the α2 adrenergic receptor to phospholipase D. These, too, were confirmed experimentally. Ligand similarities among these targets may reflect a chemical integration in the time domain of molecular signaling