Intellectual Property Management Strategies to Accelerate the Development and Access of Vaccines and Diagnostics: Case Studies on Pandemic Influenza, Malaria and SARS

Achieving global access to vaccines, diagnostics, and pharmaceuticals remains a challenge. Throughout the developing world, intellectual property (IP) constraints complicate access to critically essential medical technologies and products. Vaccines for malaria and pandemic strains of influenza, as well as diagnostic and vaccine technologies for SARS, are not only relevant to global public health but are particularly critical to the needs of developing countries. A global access solution is urgently needed. This article offers a timely case‐by‐case analysis of preliminary patent landscape surveys and formulates options via patent pools and other forms of creative IP management to accelerate development and access. The analysis of the feasibility of patent pools reveals several impediments to patent pools: these include antitrust considerations, bargaining difficulties caused by asymmetric interests and asymmetric rights among IP holders (e.g. improvement vs. foundational patents), and the difficulties of securing financial support given the significant transaction costs associated with pools. Because of the above conceptual and operational hurdles, patent pools do not appear to be a feasible way to accelerate development. Other mechanisms, however, can ameliorate IP constraints. For example, a key IP constraint related to pandemic influenza vaccines R&D appears to have been resolved when Medimmune secured the assembly of all relevant reverse genetics IP and pledged broad access. Clearly, the landscape is complex and multidimensional. Licensing systems are not the only issue. Measures must also be taken to limit regulatory hurdles and enable the swift, legal production of pandemic influenza vaccines to meet the needs of developing countries. This is why a comprehensive analysis is so necessary. From a strictly legal perspective, IP systems work through the power to exclude. However, as this study’s exploration and formulation of creative licensing strategies reveals, it is also true that IP can be structured and managed to work through the “power to include.

Studies in the completeness and efficiency of theorem-proving by resolution

Inference systems Τ and search strategies E for T are distinguished from proof procedures β = (T,E) The completeness of procedures is studied by studying separately the completeness of inference systems and of search strategies. Completeness proofs for resolution systems are obtained by the construction of semantic trees. These systems include minimal α-restricted binary resolution, minimal α-restricted M-clash resolution and maximal pseudo-clash resolution. Certain refinements of hyper-resolution systems with equality axioms are shown to be complete and equivalent to refinements of the pararmodulation method for dealing with equality. The completeness and efficiency of search strategies for theorem-proving problems is studied in sufficient generality to include the case of search strategies for path-search problems in graphs. The notion of theorem-proving problem is defined abstractly so as to be dual to that of and" or tree. Special attention is given to resolution problems and to search strategies which generate simpler before more complex proofs. For efficiency, a proof procedure (T,E) requires an efficient search strategy E as well as an inference system T which admits both simple proofs and relatively few redundant and irrelevant derivations. The theory of efficient proof procedures outlined here is applied to proving the increased efficiency of the usual method for deleting tautologies and subsumed clauses. Counter-examples are exhibited for both the completeness and efficiency of alternative methods for deleting subsumed clauses. The efficiency of resolution procedures is improved by replacing the single operation of resolving a clash by the two operations of generating factors of clauses and of resolving a clash of factors. Several factoring methods are investigated for completeness. Of these the m-factoring method is shown to be always more efficient than the Wos-Robinson method

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

State Control and the Effects of Foreign Relations on Bilateral Trade

Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy

Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.info:eu-repo/semantics/publishedVersio

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe