Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD

Background Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk strati fi cation to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. Methods The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identi fi ed by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. Results In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV 1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. Conclusions DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0 – 1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3 – 6) for escalation planning or appropriate early palliation. Trial registration number UKCRN ID 14214

Linear stability analysis of transverse dunes

Sand-moving winds blowing from a constant direction in an area of high sand availability form transverse dunes, which have a fixed profile in the direction orthogonal to the wind. Here we show, by means of a linear stability analysis, that transverse dunes are intrinsically unstable. Any along-axis perturbation on a transverse dune amplify in the course of dune migration due to the combined effect of two main factors, namely: the lateral transport through avalanches along the dune's slip-face, and the scaling of dune migration velocity with the inverse of the dune height. Our calculations provide a quantitative explanation for recent observations from experiments and numerical simulations, which showed that transverse dunes moving on the bedrock cannot exist in a stable form and decay into a chain of crescent-shaped barchans.Comment: 8 pages, 4 figure

In the name of the rose: a roadmap for rose research in the genome era

The recent completion of the rose genome sequence is not the end of a process, but rather a starting point that opens up a whole set of new and exciting activities. Next to a high-quality genome sequence other genomic tools have also become available for rose, including transcriptomics data, a high-density single-nucleotide polymorphism array and software to perform linkage and quantitative trait locus mapping in polyploids. Rose cultivars are highly heterogeneous and diverse. This vast diversity in cultivated roses can be explained through the genetic potential of the genus, introgressions from wild species into commercial tetraploid germplasm and the inimitable efforts of historical breeders. We can now investigate how this diversity can best be exploited and refined in future breeding work, given the rich molecular toolbox now available to the rose breeding community. This paper presents possible lines of research now that rose has entered the genomics era, and attempts to partially answer the question that arises after the completion of any draft genome sequence: ‘Now that we have “the” genome, what’s next?’. Having access to a genome sequence will allow both (fundamental) scientific and (applied) breeding-orientated questions to be addressed. We outline possible approaches for a number of these questions

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Multi-allelic QTL analysis of protein content in a biparental population of cultivated tetraploid potato

Protein content is a key quality trait for thepotato starch industry. The objective of this study wasto identify allele-specific quantitative trait loci (QTLs)for tuber protein content in cultivated potato (Solanumtuberosum L.) at the tetraploid level

Tools for Genetic Studies in Experimental Populations of Polyploids

Polyploid organisms carry more than two copies of each chromosome, a condition rarely tolerated in animals but which occurs relatively frequently in the plant kingdom. One of the principal challenges faced by polyploid organisms is to evolve stable meiotic mechanisms to faithfully transmit genetic information to the next generation upon which the study of inheritance is based. In this review we look at the tools available to the research community to better understand polyploid inheritance, many of which have only recently been developed. Most of these tools are intended for experimental populations (rather than natural populations), facilitating genomics-assisted crop improvement and plant breeding. This is hardly surprising given that a large proportion of domesticatedplant species are polyploid. We focus on three main areas: (1) polyploid genotyping; (2) genetic and physical mapping; and (3) quantitative trait analysis and genomic selection. We also briefly review some miscellaneous topics such as the mode of inheritance and the availability of polyploid simulation software. The current polyploid analytic toolbox includes software for assigning marker genotypes (and in particular, estimating the dosage of marker alleles in the heterozygous condition), establishing chromosome-scale linkage phase among marker alleles, constructing (short-range) haplotypes, generating linkage maps, performing genome-wide association studies (GWAS) and quantitative trait locus (QTL) analyses, and simulating polyploid populations. These tools can alsohelp elucidate the mode of inheritance (disomic, polysomic or a mixture of bothas in segmental allopolyploids) or reveal whether double reduction and multivalent chromosomal pairing occur. An increasing number of polyploids (or associated diploids) are being sequenced, leading to publicly available reference genome assemblies. Much work remains in order to keep pace with developments in genomic technologies. However, such technologies also offer the promise of understanding polyploid genomes at a level which hitherto has remained elusive

Cytogenetics of structural rearrangements in Musa hybrids and cultivars

Edible bananas are diploid or triploid Musa acuminata, or hybrids of M. acuminata x M. balbisi-ana, producing nutritious seedless fruit of different taste and structure. Breeding for high yield and host plant resistance to pathogens and pests as well as adaptation to abiotic stress of im-portant cultivars is challenging because of seedless and parthenocarpic fruit. In addition, cross-ings and selections of diploid cultivars and wild relatives are severely hampered by transloca-tions and inversions that are widespread in the M. acuminata populations. In this study we pre-sent an overview of cytogenetics, genetics and genomics research carried out to elucidate the meiotic chromosome behaviour in the hybrids and the mapping of genes, and to analyse the dif-ferent classes of DNA sequences in the banana genomes. Finally, we illustrate cytogenetic and linkage mapping of a diploid M. acuminata ssp. malaccensis using the diploid M. acuminata ‘Pa-hang’ as a genome reference and focus on the occurrence of structural rearrangements

Using molecular markers in breeding: ornamentals catch up

Thanks to advances in next generation sequencing it is now straightforward to develop tens or even hundreds of thousands of SNP markers. Advances in genotyping technology have made it feasible to genotype progenies of crosses, panels of genotypes, or even a complete breeding program, by using arrays with tens of thousands of SNPs, or by random or targeted sequencing technologies. Recently software has been developed for dosage scoring and linkage mapping in polyploid crops. This means that advanced genetic analyses can now also be performed in many polyploid ornamentals. A DNA marker, such as a single nucleotide polymorphism (SNP), linked to a trait enables following a gene or allele during crosses and in a breeding program. Association of a SNP marker to a trait or a component of a trait may be done through QTL analysis in segregating populations, by genome-wide association analysis (GWAS) in a set of accessions, or through an analysis across a pedigree. In these analyses, a dense linkage map is a very important tool, to delineate and possibly narrow down the QTL interval and to filter away false positive SNPs. New developments in linkage mapping include paying attention to even marker coverage, and new ways to use markers to infer haplotypes. The latter is especially important in polyploids, in populations with multiple parents, or in wide panels used for association studies. In such cases multiple functional alleles may segregate simultaneously, that cannot all be tagged uniquely by single biallelic SNP markers.</p

Some thoughts on how to use markers in tetraploid rose breeding

Thanks to recent advances in high-throughput genotyping tools and software for genetic analyses, it is now possible to perform QTL mapping and genome-wide association analysis in tetraploid roses and to establish the effect of favorable SNP marker haplotype(s) (“plus-alleles”). The challenge is how to use these tools and technologies for rose breeding in a cost-effective way. At least four points need to be addressed: (1) which steps of the breeding process may benefit from marker information; (2) what is the value of the identified plus-alleles for the trait; (3) where in the breeding germplasm do these plus-alleles occur, and (4) how can plants carrying these plus-alleles be selected efficiently. Here we discuss for which purposes markers may be applied.</p