Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda: lessons learned and policy implications.

BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons learned and policy implications. RESULTS: Introducing RDTs into drug shops was feasible. To scale-up this intervention however, drug shop practices need to be regulated since the registration process was not clear, supervision was inadequate and record keeping was poor. Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome, but at evaluation this was not found to be a constraint. This presents an important lesson for introducing health management information system into drug shops. Involving stakeholders, especially the district health team, in the design was important for ownership and sustainability. The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions. CONCLUSION: Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy. It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector

The origins of specificity in the microcin-processing protease TldD/E

TldD and TldE proteins are involved in the biosynthesis of microcin B17 (MccB17), an Escherichia coli thiazole/oxazole-modified peptide toxin targeting DNA gyrase. Using a combination of biochemical and crystallographic methods we show that E. coli TldD and TldE interact to form a heterodimeric metalloprotease. TldD/E cleaves the N-terminal leader sequence from the modified MccB17 precursor peptide, to yield mature antibiotic, while it has no effect on the unmodified peptide. Both proteins are essential for the activity; however, only the TldD subunit forms a novel metal-containing active site within the hollow core of the heterodimer. Peptide substrates are bound in a sequence-independent manner through beta sheet interactions with TldD and are likely cleaved via a thermolysin-type mechanism. We suggest that TldD/E acts as a "molecularpencil sharpener'': unfoldedpoly-peptides are fed through a narrow channel into the active site and processively truncated through the cleavage of short peptides from the N-terminal end

Construction of an adult barnacle (Balanus amphitrite) cDNA library and selection of reference genes for quantitative RT-PCR studies

De Gregoris TB, Borra M, Biffali E, et al. Construction of an adult barnacle (Balanus amphitrite) cDNA library and selection of reference genes for quantitative RT-PCR studies. BMC Molecular Biology. 2009;10(1):62.BACKGROUND: Balanus amphitrite is a barnacle commonly used in biofouling research. Although many aspects of its biology have been elucidated, the lack of genetic information is impeding a molecular understanding of its life cycle. As part of a wider multidisciplinary approach to reveal the biogenic cues influencing barnacle settlement and metamorphosis, we have sequenced and annotated the first cDNA library for B. amphitrite. We also present a systematic validation of potential reference genes for normalization of quantitative real-time PCR (qRT-PCR) data obtained from different developmental stages of this animal. RESULTS: We generated a cDNA library containing expressed sequence tags (ESTs) from adult B. amphitrite. A total of 609 unique sequences (comprising 79 assembled clusters and 530 singlets) were derived from 905 reliable unidirectionally sequenced ESTs. Bioinformatics tools such as BLAST, HMMer and InterPro were employed to allow functional annotation of the ESTs. Based on these analyses, we selected 11 genes to study their ability to normalize qRT-PCR data. Total RNA extracted from 7 developmental stages was reverse transcribed and the expression stability of the selected genes was compared using geNorm, BestKeeper and NormFinder. These software programs produced highly comparable results, with the most stable gene being mt-cyb, while tuba, tubb and cp1 were clearly unsuitable for data normalization. CONCLUSION: The collection of B. amphitrite ESTs and their annotation has been made publically available representing an important resource for both basic and applied research on this species. We developed a qRT-PCR assay to determine the most reliable reference genes. Transcripts encoding cytochrome b and NADH dehydrogenase subunit 1 were expressed most stably, although other genes also performed well and could prove useful to normalize gene expression studies

Transformation in a changing climate: a research agenda

The concept of transformation in relation to climate and other global change is increasingly receiving attention. The concept provides important opportunities to help examine how rapid and fundamental change to address contemporary global challenges can be facilitated. This paper contributes to discussions about transformation by providing a social science, arts and humanities perspective to open up discussion and set out a research agenda about what it means to transform and the dimensions, limitations and possibilities for transformation. Key focal areas include: (1) change theories, (2) knowing whether transformation has occurred or is occurring; (3) knowledge production and use; (4), governance; (5) how dimensions of social justice inform transformation; (6) the limits of human nature; (7) the role of the utopian impulse; (8) working with the present to create new futures; and (9) human consciousness. In addition to presenting a set of research questions around these themes the paper highlights that much deeper engagement with complex social processes is required; that there are vast opportunities for social science, humanities and the arts to engage more directly with the climate challenge; that there is a need for a massive upscaling of efforts to understand and shape desired forms of change; and that, in addition to helping answer important questions about how to facilitate change, a key role of the social sciences, humanities and the arts in addressing climate change is to critique current societal patterns and to open up new thinking. Through such critique and by being more explicit about what is meant by transformation, greater opportunities will be provided for opening up a dialogue about change, possible futures and about what it means to re-shape the way in which people live

Frictional drag measurements of large-scale plates in an enhanced plane channel flowcell

This paper describes the design of an enhanced, plane channel, flowcell and its use for testing large-scale coated plates (0.6 m 0.22 m) in fully developed flow, over a wide range of Reynolds numbers, with low uncertainty. Two identical, hydraulically smooth plates were experimentally tested. Uniform biofilms were grown on clean surfaces to test skin friction changes resulting from different biofilm thickness and densities. A velocity survey of the flowcell measurement section, using laser Doppler anemometry, showed a consistent velocity profile and low turbulence intensity in the central flow channel. The skin friction coefficient was experimentally determined using a pressure drop method. Results correlate closely to previously published regression data, particularly at higher speeds. Repeated measurements indicated very low uncertainty. This study demonstrates this flowcell’s applicability for representing consistent frictional drag of ship hull surfaces, enabling comparability of hydrodynamic drag caused by surface roughness to the reference surface measurements