A randomised trial and economic evaluation of the effect of response mode on response rate, response bias, and item non-response in a survey of doctors

<p>Abstract</p> <p>Background</p> <p>Surveys of doctors are an important data collection method in health services research. Ways to improve response rates, minimise survey response bias and item non-response, within a given budget, have not previously been addressed in the same study. The aim of this paper is to compare the effects and costs of three different modes of survey administration in a national survey of doctors.</p> <p>Methods</p> <p>A stratified random sample of 4.9% (2,702/54,160) of doctors undertaking clinical practice was drawn from a national directory of all doctors in Australia. Stratification was by four doctor types: general practitioners, specialists, specialists-in-training, and hospital non-specialists, and by six rural/remote categories. A three-arm parallel trial design with equal randomisation across arms was used. Doctors were randomly allocated to: online questionnaire (902); simultaneous mixed mode (a paper questionnaire and login details sent together) (900); or, sequential mixed mode (online followed by a paper questionnaire with the reminder) (900). Analysis was by intention to treat, as within each primary mode, doctors could choose either paper or online. Primary outcome measures were response rate, survey response bias, item non-response, and cost.</p> <p>Results</p> <p>The online mode had a response rate 12.95%, followed by the simultaneous mixed mode with 19.7%, and the sequential mixed mode with 20.7%. After adjusting for observed differences between the groups, the online mode had a 7 percentage point lower response rate compared to the simultaneous mixed mode, and a 7.7 percentage point lower response rate compared to sequential mixed mode. The difference in response rate between the sequential and simultaneous modes was not statistically significant. Both mixed modes showed evidence of response bias, whilst the characteristics of online respondents were similar to the population. However, the online mode had a higher rate of item non-response compared to both mixed modes. The total cost of the online survey was 38% lower than simultaneous mixed mode and 22% lower than sequential mixed mode. The cost of the sequential mixed mode was 14% lower than simultaneous mixed mode. Compared to the online mode, the sequential mixed mode was the most cost-effective, although exhibiting some evidence of response bias.</p> <p>Conclusions</p> <p>Decisions on which survey mode to use depend on response rates, response bias, item non-response and costs. The sequential mixed mode appears to be the most cost-effective mode of survey administration for surveys of the population of doctors, if one is prepared to accept a degree of response bias. Online surveys are not yet suitable to be used exclusively for surveys of the doctor population.</p

Divergence in transcriptional and regulatory responses to mating in male and female fruitflies

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involving de novo gene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and female Drosophila to mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness

Kicking against the PRCs - a domesticated transposase antagonises silencing mediated by polycomb group proteins and is an accessory component of polycomb repressive complex 2

The Polycomb group (PcG) and trithorax group (trxG) genes play crucial roles in development by regulating expression of homeotic and other genes controlling cell fate. Both groups catalyse modifications of chromatin, particularly histone methylation, leading to epigenetic changes that affect gene activity. The trxG antagonizes the function of PcG genes by activating PcG target genes, and consequently trxG mutants suppress PcG mutant phenotypes. We previously identified the ANTAGONIST OF LIKE HETEROCHROMATIN PROTEIN1 (ALP1) gene as a genetic suppressor of mutants in the Arabidopsis PcG gene LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Here, we show that ALP1 interacts genetically with several other PcG and trxG components and that it antagonizes PcG silencing. Transcriptional profiling reveals that when PcG activity is compromised numerous target genes are hyper-activated in seedlings and that in most cases this requires ALP1. Furthermore, when PcG activity is present ALP1 is needed for full activation of several floral homeotic genes that are repressed by the PcG. Strikingly, ALP1 does not encode a known chromatin protein but rather a protein related to PIF/Harbinger class transposases. Phylogenetic analysis indicates that ALP1 is broadly conserved in land plants and likely lost transposase activity and acquired a novel function during angiosperm evolution. Consistent with this, immunoprecipitation and mass spectrometry (IP-MS) show that ALP1 associates, in vivo, with core components of POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a widely conserved PcG protein complex which functions as a H3K27me3 histone methyltransferase. Furthermore, in reciprocal pulldowns using the histone methyltransferase CURLY LEAF (CLF), we identify not only ALP1 and the core PRC2 components but also plant-specific accessory components including EMBRYONIC FLOWER 1 (EMF1), a transcriptional repressor previously associated with PRC1-like complexes. Taken together our data suggest that ALP1 inhibits PcG silencing by blocking the interaction of the core PRC2 with accessory components that promote its HMTase activity or its role in inhibiting transcription. ALP1 is the first example of a domesticated transposase acquiring a novel function as a PcG component. The antagonistic interaction of a modified transposase with the PcG machinery is novel and may have arisen as a means for the cognate transposon to evade host surveillance or for the host to exploit features of the transposition machinery beneficial for epigenetic regulation of gene activity.Fil: Liang, Shih Chieh. University of Edinburgh; Reino UnidoFil: Hartwig, Ben. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Perera, Pumi. University of Edinburgh; Reino UnidoFil: Mora Garcia, Santiago. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: de Leau, Erica. University of Edinburgh; Reino UnidoFil: Thornton, Harry. University of Edinburgh; Reino UnidoFil: Lima de Alves, Flavia. University of Edinburgh; Reino UnidoFil: Rapsilber, Juri. University of Edinburgh; Reino UnidoFil: Yang, Suxin. University of Edinburgh; Reino UnidoFil: James, Geo Velikkakam. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Schneeberger, Korbinian. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Finnegan, E. Jean. University of Edinburgh; Reino UnidoFil: Turck, Franziska. Max Planck Institute for Plant Breeding Research; AlemaniaFil: Goodrich, Justin. Mc Gill University; Canad