Losing the media battle, waging the policy war: The pharmaceutical industry’s response to the access to medicines crisis in the Global South

This article sheds new light on the pharmaceutical industry’s response to the public relations crisis generated by the global civil society campaign for access to HIV/AIDS medicines since the early 2000s – one of the most contentious policy areas of global trade and health governance. Drawing on interviews with industry insiders, the article explores the industry’s communicative agency in both the media sphere and key sites of power, with a focus on the European Union (EU) policy sphere. The analysis shows that the industry has focused primarily on maintaining access to policymakers and sustaining elite consensus around the existing global intellectual property rights regime through political communication activities that largely bypass mediated public arenas – from strategically promoting its corporate social responsibility (CSR) programmes and mobilizing third-party endorsement to direct lobbying. The article concludes by reflecting on the implications of the findings for critical investigations of the interplay between media and political power in relation to global economic governance

3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud

The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of 100 billion electron volts for a deep exposure of 210 hours. Three sources of different types were detected: the pulsar wind nebula of the most energetic pulsar known N 157B, the radio-loud supernova remnant N 132D and the largest non-thermal X-ray shell - the superbubble 30 Dor C. The unique object SN 1987A is, surprisingly, not detected, which constrains the theoretical framework of particle acceleration in very young supernova remnants. These detections reveal the most energetic tip of a gamma-ray source population in an external galaxy, and provide via 30 Dor C the unambiguous detection of gamma-ray emission from a superbubble.Comment: Published in Science Magazine (Jan. 23, 2015). This ArXiv version has the supplementary online material incorporated as an appendix to the main pape

Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World.The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Search for R-parity violating supersymmetry via the LLE couplings lambda_{121}, lambda_{122} or lambda_{133} in ppbar collisions at sqrt(s)=1.96 TeV

A search for gaugino pair production with a trilepton signature in the framework of R-parity violating supersymmetry via the couplings lambda_121, lambda_122, or lambda_133 is presented. The data, corresponding to an integrated luminosity of L~360/pb, were collected from April 2002 to August 2004 with the D0 detector at the Fermilab Tevatron Collider, at a center-of-mass energy of sqrt(s)=1.96 TeV. This analysis considers final states with three charged leptons with the flavor combinations eel, mumul, and eetau (l=e or mu). No evidence for supersymmetry is found and limits at the 95% confidence level are set on the gaugino pair production cross section and lower bounds on the masses of the lightest neutralino and chargino are derived in two supersymmetric models.Comment: 9 pages, 4 figures (fig2 includes 3 subfigures

Measurement of the Bs0B^{0}_{s} Lifetime Using Semileptonic Decays

We report a measurement of the $B^0_{s}$ lifetime in the semileptonic decay channel $B^0_{s}\to D^-_s \mu^{+}\nu X$ (and its charge conjugate), using approximately 0.4 fb$^{-1}$ of data collected with the D0 detector during 2002 -- 2004. We have reconstructed 5176 $D^-_s \mu^{+}$ signal events, where the $D_s^-$ is identified via the decay $D_s^-\to \phi\pi^-$, followed by $\phi\to K^+ K^-$. Using these events, we have measured the $B^0_s$ lifetime to be $\tau(B^0_{s}) = 1.398 \pm 0.044$ $({stat}) ^{+0.028}_{-0.025}$ $({syst}) {ps}$. This is the most precise measurement of the $B_s^0$ lifetime to date.Comment: To appear in Phys. Rev. Lett., 7 pages, 2 figure

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011