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BACKGROUND Computerised provider order entry (CPOE) systems are widely used in clinical settings for the electronic ordering of medications, laboratory tests and radiological therapies. However, evidence regarding effects of CPOE-based medication ordering on clinical and safety outcomes is mixed. We conducted an overview of systematic reviews (SRs) to characterise the cumulative effects of CPOE use for medication ordering in clinical settings. METHODS MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched to identify published SRs from inception to 12 February 2018. SRs investigating the effects of the use of CPOE for medication ordering were included. Two reviewers independently extracted data and assessed the methodological quality of included SRs. RESULTS Seven SRs covering 118 primary studies were included for review. Pooled studies from the SRs in inpatient settings showed that CPOE use resulted in statistically significant decreases in medication errors and adverse drug events (ADEs); however, there was considerable variation in the magnitude of their relative risk reduction (54%-92% for errors, 35%-53% for ADEs). There was no significant relative risk reduction on hospital mortality or length of stay. Bibliographic analysis showed limited overlap (24%) among studies included across all SRs. CONCLUSION SRs on CPOEs included predominantly non-randomised controlled trials and observational studies with varying foci. SRs predominantly focused on inpatient settings and often lacked comparison groups; SRs used inconsistent definitions of outcomes, lacked descriptions regarding the effects on patient harm and did not differentiate among the levels of available decision support. With five of the seven SRs having low to moderate quality, findings from the SRs must be interpreted with caution. We discuss potential directions for future primary studies and SRs of CPOE. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA 3D structure prediction. With agreement from crystallographers, the RNA structures are predicted by various groups before the publication of the crystal structures. We now report the prediction of six RNA sequences four structures of nucleolytic ribozymes and two of riboswitches. Repertaxin Systematic protocols for comparing models and crystal structures are described and analyzed. In these six puzzles, we discuss a) the comparison between the automated web server and human experts; b) the prediction of coaxial stacking; c) the prediction of structural details and ligand binding; d) the development of novel prediction methods; and e) the potential improvements to be made. It is illustrated that correct coaxial stacking and tertiary contacts are key for the prediction of RNA architecture, while ligand binding modes can be only predicted with low resolution and accurate ligand binding prediction still remains out of reach. All the predicted models are available for the future development of force field parameters and the improvement of comparison and assessment tools. Published by Cold Spring Harbor Laboratory Press for the RNA Society.Nop9 is an essential factor in the processing of pre-ribosomal RNA. Its absence in yeast is lethal, and defects in the human ortholog are associated with breast cancer, autoimmunity, and learning/language impairment. PUF family RNA-binding proteins are best known for sequence-specific RNA recognition, and most contain eight α-helical repeats that bind to the RNA bases of single-stranded RNA. Nop9 is an unusual member of this family in that it contains eleven repeats and recognizes both RNA structure and sequence. Here we report a crystal structure of Saccharomyces cerevisiae Nop9 in complex with its target RNA within the 20S pre-ribosomal RNA. This structure reveals that Nop9 brings together a C-terminal module recognizing the 5' single-stranded region of the RNA and a bifunctional N-terminal module recognizing the central double-stranded stem region. We further show that the 3' single-stranded region of the 20S target RNA adds sequence-independent binding energy to the RNA-Nop9 interaction. Both the N- and C-terminal modules retain the characteristic sequence-specific recognition of PUF proteins but the N-terminal module has also evolved a distinct interface, which allows Nop9 to recognize either single-stranded RNA sequences or RNAs with a combination of single-stranded and structured elements. Published by Cold Spring Harbor Laboratory Press for the RNA Society.The use of haplotypes may improve the accuracy of genomic prediction over single SNPs because haplotypes can better capture linkage disequilibrium and genomic similarity in different lines and may capture local high-order allelic interactions. Additionally, prediction accuracy could be improved by portraying population structure in the calibration set. A set of 383 advanced lines and cultivars that represent the diversity of the University of Minnesota wheat breeding program was phenotyped for yield, test weight, and protein content and genotyped using the Illumina 90K SNP Assay. Population structure was confirmed using single SNPs. Haplotype blocks of 5, 10, 15, and 20 adjacent markers were constructed for all chromosomes. A multi-allelic haplotype prediction algorithm was implemented and compared with single SNPs using both k-fold cross validation and stratified sampling optimization. After confirming population structure, the stratified sampling improved the predictive ability compared with k-fold cross validation for yield and protein content, but reduced the predictive ability for test weight. In all cases, haplotype predictions outperformed single SNPs. Haplotypes of 15 adjacent markers showed the best improvement in accuracy for all traits; however, this was more pronounced in yield and protein content. The combined use of haplotypes of 15 adjacent markers and training population optimization significantly improved the predictive ability for yield and protein content by 14.3 (four percentage points) and 16.8% (seven percentage points), respectively, compared with using single SNPs and k-fold cross validation. These results emphasize the effectiveness of using haplotypes in genomic selection to increase genetic gain in self-fertilized crops. Copyright © The Author(s) 2020. Published by the Genetics Society of America.

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