Development and characterization of promoterless helper RNAs for the production of alphavirus replicon particle

Alphavirus-based replicon systems are frequently used as preclinical vectors and as antigen discovery tools, and they have recently been assessed in clinical vaccine trials. Typically, alphavirus replicon RNAs are delivered within virus-like replicon particles (VRP) that are produced following transfection of replicon RNA and two helper RNAs into permissive cells in vitro. The non-structural proteins expressed from the replicon RNA amplify the replicon RNA in cis and the helper RNAs in trans, the latter providing the viral structural proteins necessary to package the replicon RNA into VRP. Current helper RNA designs incorporate the alphavirus 26S promoter to direct the transcription of high levels of structural gene mRNAs. We demonstrate here that the 26S promoter is not required on helper RNAs to produce VRP and propose that such promoterless helper RNAs, by design, reduce the probability of generating replication-competent virus that may otherwise result from RNA recombination

Using targeted vouchers and health equity funds to improve access to skilled birth attendants for poor women: a case study in three rural health districts in Cambodia

<p>Abstract</p> <p>Background</p> <p>In many developing countries, the maternal mortality ratio remains high with huge poor-rich inequalities. Programmes aimed at improving maternal health and preventing maternal mortality often fail to reach poor women. Vouchers in health and Health Equity Funds (HEFs) constitute a financial mechanism to improve access to priority health services for the poor. We assess their effectiveness in improving access to skilled birth attendants for poor women in three rural health districts in Cambodia and draw lessons for further improvement and scaling-up.</p> <p>Methods</p> <p>Data on utilisation of voucher and HEF schemes and on deliveries in public health facilities between 2006 and 2008 were extracted from the available database, reports and the routine health information system. Qualitative data were collected through focus group discussions and key informant interviews. We examined the trend of facility deliveries between 2006 and 2008 in the three health districts and compared this with the situation in other rural districts without voucher and HEF schemes. An operational analysis of the voucher scheme was carried out to assess its effectiveness at different stages of operation.</p> <p>Results</p> <p>Facility deliveries increased sharply from 16.3% of the expected number of births in 2006 to 44.9% in 2008 after the introduction of voucher and HEF schemes, not only for voucher and HEF beneficiaries, but also for self-paid deliveries. The increase was much more substantial than in comparable districts lacking voucher and HEF schemes. In 2008, voucher and HEF beneficiaries accounted for 40.6% of the expected number of births among the poor. We also outline several limitations of the voucher scheme.</p> <p>Conclusions</p> <p>Vouchers plus HEFs, if carefully designed and implemented, have a strong potential for reducing financial barriers and hence improving access to skilled birth attendants for poor women. To achieve their full potential, vouchers and HEFs require other interventions to ensure the supply of sufficient quality maternity services and to address other non-financial barriers to demand. If these conditions are met, voucher and HEF schemes can be further scaled up under close monitoring and evaluation.</p

Effects of Working Memory Load on Oscillatory Power in Human Intracranial EEG

Studies of working memory load effects on human EEG power have indicated divergent effects in different frequency bands. Although gamma power typically increases with load, the load dependency of the lower frequency theta and alpha bands is uncertain. We obtained intracranial electroencephalography measurements from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in order to characterize the anatomical distribution of load-related changes across the frequency spectrum. Gamma power increases occurred throughout the brain, but were most common in the occipital lobe. In the theta and alpha bands, both increases and decreases were observed, but with different anatomical distributions. Increases in theta and alpha power were most prevalent in frontal midline cortex. Decreases were most commonly observed in occipital cortex, colocalized with increases in the gamma range, but were also detected in lateral frontal and parietal regions. Spatial overlap with group functional magnetic resonance imaging results was minimal except in the precentral gyrus. These findings suggest that power in any given frequency band is not a unitary phenomenon; rather, reactivity in the same frequency band varies in different brain regions, and may relate to the engagement or inhibition of a given area in a cognitive task

DOI: 10.1111/j.1471-0528.2009.02209.x

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Low upper limits on the O2 abundance from the Odin satellite

NRC publication: Ye