Cost-Effectiveness of Malaria Diagnosis in Sub-Saharan Africa: The Role of Rapid Diagnostic Tests. Report submitted to WHO

Objective To evaluate the relative cost-effectiveness in different sub-Saharan African settings of presumptive treatment, field-standard microscopy and rapid diagnostic tests (RDTs) to diagnose malaria. Methods We used a decision tree model and probabilistic sensitivity analysis applied to outpatients presenting at rural health facilities with suspected malaria. Costs and effects encompassed those for both patients positive on RDT (assuming artemisinin-based combination therapy) and febrile patients negative on RDT (assuming antibiotic treatment). Interventions were defined as cost-effective if they were less costly and more effective or had an incremental cost per disability-adjusted life year averted of less than US$ 150. Data were drawn from published and unpublished sources, supplemented with expert opinion. Findings RDTs were cost-effective compared with presumptive treatment up to high prevalences of Plasmodium falciparum parasitaemia. Decision-makers can be at least 50% confident of this result below 81% malaria prevalence, and 95% confident below 62% prevalence, a level seldom exceeded in practice. RDTs were more than 50% likely to be cost-saving below 58% prevalence. Relative to microscopy, RDTs were more than 85% likely to be cost-effective across all prevalence levels, reflecting their expected better accuracy under real-life conditions. Results were robust to extensive sensitivity analysis. The cost-effectiveness of RDTs mainly reflected improved treatment and health outcomes for non-malarial febrile illness, plus savings in antimalarial drug costs. Results were dependent on the assumption that prescribers used test results to guide treatment decisions. Conclusion RDTs have the potential to be cost-effective in most parts of sub-Saharan Africa. Appropriate management of malaria and non-malarial febrile illnesses is required to reap the full benefits of these tests

Fake CPT Violation in Disappearance Neutrino Oscillations

We make an analysis of the fake CPT-violating asymmetries between the survival probabilities of neutrinos and antineutrinos, induced by the terrestrial matter effects, in three different scenarios of long-baseline neutrino oscillation experiments with L=730 km, L=2100 km and L=3200 km. In particular, the dependence of those asymmetries on the Dirac-type CP-violating phase of the lepton flavor mixing matrix is examined.Comment: RevTex 8 pages (including 3 PS figures). To be publishe

Structure activity relationships of αv integrin antagonists for pulmonary fibrosis by variation in aryl substituents

Antagonism of alphav beta6 is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an alphav beta3 antagonist lead and through simple variation in the nature and position of aryl substituent, the discovery of compounds with improved alphav beta6 activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery programme. Compounds 33S and 43E1 are pan alphav antagonists having ca 100 nM potency against alphav beta3, alphav beta5, alphav beta6 and alphav beta8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC50 values between the integrins in question) for alphav beta3 and alphav beta5

Newtonian Hydrodynamics of the Coalescence of Black Holes with Neutron Stars I: Tidally locked binaries with a stiff equation of state

We present a detailed study of the hydrodynamical interactions in a Newtonian black hole-neutron star binary during the last stages of inspiral. We consider close binaries which are tidally locked, use a stiff equation of state (with an adiabatic index Gamma=3) throughout, and explore the effect of different initial mass ratios on the evolution of the system. We calculate the gravitational radiation signal in the quadrupole approximation. Our calculations are carried out using a Smooth Particle Hydrodynamics (SPH) code.Comment: Replaces previous version which had figures separate from the text of the paper. Now 47 pages long with 19 embedded figures (the figures are the same, they were renumbered) Uses aaspp4.st

Risk measures for direct real estate investments with non-normal or unknown return distributions

The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate. We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification

Measurement of the Neutrino Mass Splitting and Flavor Mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10^(20) protons on target. A fit to neutrino oscillations yields values of |Δm^2|=(2.32_(-0.08)^(+0.12))×10^(-3)  eV^2 for the atmospheric mass splitting and sin^2(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×10^(20) protons on target in which neutrinos of energies between ∼500  MeV and 120 GeV are produced predominantly as ν_μ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ν_μ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles θ_(24) and θ_(34) are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime τ_3/m_3>2.1×10^(-12) s/eV at 90% C.L

Measurement of the neutrino mass splitting and flavor mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of $7.25 imes 10^{20}$ protons on target. A fit to neutrino oscillations yields values of $|Delta m^2| = (2.32^{+0.12}_{-0.08}) imes10^{-3}$,eV$^2$ for the atmospheric mass splitting and m sin^2!(2 heta) > 0.90 (90%,C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

First Direct Observation of Muon Antineutrino Disappearance

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν̅ _μ production, accumulating an exposure of 1.71×10^(20) protons on target. In the Far Detector, 97 charged current ν̅ _μ events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm̅ 2|= [3.36=_(-0.40)^(+0.46)(stat)±0.06(syst)]x10^(-3)eV^2,sin^2(2θ̅)=0.86 _(-0.12)^(+0.11)(stat)±0.01(syst). The MINOS ν̅ _μ and ν̅ _μ measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters

New constraints on muon-neutrino to electron-neutrino transitions in MINOS

This paper reports results from a search for ν_μ → ν_e transitions by the MINOS experiment based on a 7×10^(20) protons-on-target exposure. Our observation of 54 candidate ν_e events in the far detector with a background of 49.1±7.0(stat)±2.7(syst) events predicted by the measurements in the near detector requires 2sin^2(2θ_(13))sin^2θ_(23)<0.12(0.20) at the 90% C.L. for the normal (inverted) mass hierarchy at δ_(CP)=0. The experiment sets the tightest limits to date on the value of θ_(13) for nearly all values of δ_(CP) for the normal neutrino mass hierarchy and maximal sin^2(2θ_(23))