Biology subjects

Walker, D.

Publications and source records attributed to Walker, D..

3 recordsLinked to original sources

bioRxiv2018

Adherence to the iDSI reference case among published cost-per-DALY averted studies

BackgroundThe iDSI reference case, originally published in 2014, aims to improve the quality and comparability of cost-effectiveness analyses (CEAs). This study assesses whether the development of the guideline has improved the reporting and methodology for CEAs using disability-adjusted life-years (DALYs).\n\nMethodsWe analyzed the Tufts Medical Center Global Health CEA Registry to identify cost-per-DALY averted studies published from 2011 to 2017. Among each of 11 principles in the iDSI reference case, we translated all reporting standards and methodological specifications into quantifiable yes/no questions and awarded articles one point for each item satisfied. We then separately calculated reporting and methods scores, measured as percent adherence (0%=no adherence, 100%=full adherence). Using the year 2014 as the dissemination period, we conducted a pre-post analysis. Additionally, we conducted an analysis stratified by the 11 principles and examined different scoring strategies and dissemination periods in sensitivity analyses.\n\nResultsArticles averaged 74% adherence to reporting standards and 60% adherence to methodological specifications. Adherence to reporting standards increased slightly over time (72% pre-2014 vs. 75% post-2014, p<0.01), but methodological adherence did not significantly improve (59% pre-2014 vs. 60% post-2014, p=0.53). Overall, reporting adherence scores exceeded methodology adherence scores (74% vs. 60%, p<0.001). Articles seldom addressed budget impact (9% reporting, 10% methodology) or equity (7% reporting, 7% methodology).\n\nConclusionsThe iDSI reference case has substantial potential to serve as a useful resource for researchers and policy-makers in global health settings, but greater effort to promote adherence and awareness is needed to achieve its potential.

scientific communication and education↗

bioRxiv2018

Galleria mellonella as an infection model for the multi-host pathogen Streptococcus agalactiae reflects hypervirulence of ST283

Streptococcus agalactiae, or group B streptococcus (GBS), infects diverse hosts including humans, economically important livestock and fishes. In the context of human health, GBS is a major cause of neonatal infections and an emerging cause of invasive disease in adults. Here we show that GBS is able to establish a systemic infection in G. mellonella larvae that is associated with extensive bacterial replication and dose dependent larval survival. This infection model is suitable for use with GBS isolates from both homeothermic and poikilothermic hosts and a hypervirulent sequence type (ST) associated with invasive human disease, ST283, shows increased virulence in this model, indicating it may be useful in studying GBS virulence determinants. In addition, we demonstrate that larval survival can be afforded by antibiotic treatment and so the model may also be useful in the development of novel anti-GBS strategies. The use of G. mellonella in GBS research has the potential to provide a low cost infection model that could reduce the number of vertebrates used in the study of GBS infection.

microbiology↗

bioRxiv2018

Genomic inversion drives small colony variant formation and increased virulence in P. aeruginosa

Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, well-characterised phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoid P. aeruginosa strain NH57388A. Here we show, using a combination of singlemolecule real-time (PacBio) and Illumina sequencing that the genetic switch for conversion to the SCV phenotype is a large genomic inversion through recombination between homologous regions of two rRNA operons. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance since the appearance of SCVs during chronic infection is associated with declining lung function.

microbiology↗