Identifying market risk for substandard and falsified medicines

__Introduction:__ Substandard and falsified medicines undermine health systems. We sought to unravel the political and economic factors which drive the production of these products, and to explain how they reach patients. __Methods:__ We conducted in-depth case studies in China, Indonesia, Turkey and Romania. We reviewed academic papers and press reports (n = 840), developing semi-structured questionnaires. We interviewed regulators, policy-makers, pharmaceutical manufacturers, physicians, pharmacists, patients and academics (n=88). We coded data using NVivo software, and developed an analytic framework to assess national risks for substandard and falsified medicines. We tested the framework against cases reported to the World Health Organization, from countries at all income levels. __Results:__ We found that increasing political commitment to provision of universal health coverage has led to public procurement policies aimed at lowering prices of medical products. In response, legitimate, profit-driven pharmaceutical companies protect their margins by cutting costs, or withdrawing from less profitable markets, while distributors engage in arbitrage. Meanwhile, health providers sometimes protect profits by 'upselling' patients to medicines not covered by insurers. Cost-cutting can undermine quality assurance, leading to substandard or degraded medicines. Other responses contribute to shortages, irrational demand and high prices. All of these provide market opportunities for producers of falsified products; they also push consumers outside of the regular supply chain, providing falsifiers with easy access to customers. The analytic framework capturing these interactions explained cases in most high and middle-income settings; additional factors operate in the poorest countries. __Conclusions:__ Most efforts to secure medicine quality currently focus on product regulation. However, our research suggests market mechanisms are key drivers for poor quality medicines, including where political commitments to universal health coverage are under-resourced. We have developed a framework to guide country-specific, system-wide analysis. This can flag risks and pinpoint specific actions to protect medicine quality, and thus health

Updated MiniBooNE Neutrino Oscillation Results with Increased Data and New Background Studies

The MiniBooNE experiment at Fermilab reports a total excess of $638.0 \pm 132.8$ electron-like events ($4.8 \sigma$) from a data sample corresponding to $18.75 \times 10^{20}$ protons-on-target in neutrino mode, which is a 46% increase in the data sample with respect to previously published results, and $11.27 \times 10^{20}$ protons-on-target in antineutrino mode. The additional statistics allow several studies to address questions on the source of the excess. First, we provide two-dimensional plots in visible energy and cosine of the angle of the outgoing lepton, which can provide valuable input to models for the event excess. Second, we test whether the excess may arise from photons that enter the detector from external events or photons exiting the detector from $\pi^0$ decays in two model independent ways. Beam timing information shows that almost all of the excess is in time with neutrinos that interact in the detector. The radius distribution shows that the excess is distributed throughout the volume, while tighter cuts on the fiducal volume increase the significance of the excess. We conclude that models of the event excess based on entering and exiting photons are disfavored.Comment: 22 pages, 18 figure

Measurement of the (π−\pi^-, Ar) total hadronic cross section at the LArIAT experiment

We present the first measurement of the negative pion total hadronic cross section on argon, which we performed at the Liquid Argon In A Testbeam (LArIAT) experiment. All hadronic reaction channels, as well as hadronic elastic interactions with scattering angle greater than 5~degrees are included. The pions have a kinetic energies in the range 100-700~MeV and are produced by a beam of charged particles impinging on a solid target at the Fermilab Test Beam Facility. LArIAT employs a 0.24~ton active mass Liquid Argon Time Projection Chamber (LArTPC) to measure the pion hadronic interactions. For this measurement, LArIAT has developed the ``thin slice method", a new technique to measure cross sections with LArTPCs. While generally higher than the prediction, our measurement of the ($\pi^-$,Ar) total hadronic cross section is in agreement with the prediction of the Geant4 model when considering a model uncertainty of $\sim$5.1\%.Comment: 15 pages, 15 figures, 3 tables, accepted by PR

The Liquid Argon In A Testbeam (LArIAT) Experiment

The LArIAT liquid argon time projection chamber, placed in a tertiary beam of charged particles at the Fermilab Test Beam Facility, has collected large samples of pions, muons, electrons, protons, and kaons in the momentum range 300-1400 MeV/c. This paper describes the main aspects of the detector and beamline, and also reports on calibrations performed for the detector and beamline components

NEXT-CRAB-0: A High Pressure Gaseous Xenon Time Projection Chamber with a Direct VUV Camera Based Readout

The search for neutrinoless double beta decay ($0\nu\beta\beta$) remains one of the most compelling experimental avenues for the discovery in the neutrino sector. Electroluminescent gas-phase time projection chambers are well suited to $0\nu\beta\beta$ searches due to their intrinsically precise energy resolution and topological event identification capabilities. Scalability to ton- and multi-ton masses requires readout of large-area electroluminescent regions with fine spatial resolution, low radiogenic backgrounds, and a scalable data acquisition system. This paper presents a detector prototype that records event topology in an electroluminescent xenon gas TPC via VUV image-intensified cameras. This enables an extendable readout of large tracking planes with commercial devices that reside almost entirely outside of the active medium.Following further development in intermediate scale demonstrators, this technique may represent a novel and enlargeable method for topological event imaging in $0\nu\beta\beta$.Comment: 32 Pages, 22 figure

A Compact Dication Source for Ba2+^{2+} Tagging and Heavy Metal Ion Sensor Development

We present a tunable metal ion beam that delivers controllable ion currents in the picoamp range for testing of dry-phase ion sensors. Ion beams are formed by sequential atomic evaporation and single or multiple electron impact ionization, followed by acceleration into a sensing region. Controllability of the ionic charge state is achieved through tuning of electrode potentials that influence the retention time in the ionization region. Barium, lead, and cobalt samples have been used to test the system, with ion currents identified and quantified using a quadrupole mass analyzer. Realization of a clean $\mathrm{Ba^{2+}}$ ion beam within a bench-top system represents an important technical advance toward the development and characterization of barium tagging systems for neutrinoless double beta decay searches in xenon gas. This system also provides a testbed for investigation of novel ion sensing methodologies for environmental assay applications, with dication beams of Pb$^{2+}$ and Cd$^{2+}$ also demonstrated for this purpose