A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1

Costs and cost-effectiveness of malaria control interventions - a systematic review

<p>Abstract</p> <p>Background</p> <p>The control and elimination of malaria requires expanded coverage of and access to effective malaria control interventions such as insecticide-treated nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment (IPT), diagnostic testing and appropriate treatment. Decisions on how to scale up the coverage of these interventions need to be based on evidence of programme effectiveness, equity and cost-effectiveness.</p> <p>Methods</p> <p>A systematic review of the published literature on the costs and cost-effectiveness of malaria interventions was undertaken. All costs and cost-effectiveness ratios were inflated to 2009 USD to allow comparison of the costs and benefits of several different interventions through various delivery channels, across different geographical regions and from varying costing perspectives.</p> <p>Results</p> <p>Fifty-five studies of the costs and forty three studies of the cost-effectiveness of malaria interventions were identified, 78% of which were undertaken in sub-Saharan Africa, 18% in Asia and 4% in South America. The median financial cost of protecting one person for one year was $2.20 (range$0.88-$9.54) for ITNs,$6.70 (range $2.22-$12.85) for IRS, $0.60 (range$0.48-$1.08) for IPT in infants,$4.03 (range $1.25-$11.80) for IPT in children, and $2.06 (range$0.47-$3.36) for IPT in pregnant women. The median financial cost of diagnosing a case of malaria was$4.32 (range $0.34-$9.34). The median financial cost of treating an episode of uncomplicated malaria was $5.84 (range$2.36-$23.65) and the median financial cost of treating an episode of severe malaria was$30.26 (range $15.64-$137.87). Economies of scale were observed in the implementation of ITNs, IRS and IPT, with lower unit costs reported in studies with larger numbers of beneficiaries. From a provider perspective, the median incremental cost effectiveness ratio per disability adjusted life year averted was $27 (range$8.15-$110) for ITNs,$143 (range $135-$150) for IRS, and $24 (range$1.08-$44.24) for IPT.</p> <p>Conclusions</p> <p>A transparent evidence base on the costs and cost-effectiveness of malaria control interventions is provided to inform rational resource allocation by donors and domestic health budgets and the selection of optimal packages of interventions by malaria control programmes.</p

Lack of observational evidence for quantum structure of space-time at Plank scales

It has been noted (Lieu & Hillmann, 2002) that the cumulative affect of Planck-scale phenomenology, or the structure of space-time at extremely small scales, can be lead to the loss of phase of radiation emitted at large distances from the observer. We elaborate on such an approach and demonstrate that such an effect would lead to an apparent blurring of distant point-sources. Evidence of the diffraction pattern from the HST observations of SN 1994D and the unresolved appearance of a Hubble Deep Field galaxy at z=5.34 lead us to put stringent limits on the effects of Planck-scale phenomenology.Comment: 12 pages, 3 figures, accepter for ApJ