Community frailty response service: the ED at your front door.

We describe the expansion and adaptation of a frailty response team to assess older people in their usual place of residence. The team had commenced a weekend service to a limited area in February 2020. As a consequence of demand related to the COVID-19 pandemic, we expanded it and adapted the model of care to provide a 7-day service to our entire catchment area. Five hundred and ninety two patient reviews have been completed in the first 105 days of operation with 43 patients transferred to hospital for further investigation or management following assessment.

The efficacy of Euler diagrams and linear diagrams for visualizing set cardinality using proportions and numbers.

This paper presents the first empirical investigation that compares Euler and linear diagrams when they are used to represent set cardinality. A common approach is to use area-proportional Euler diagrams but linear diagrams can exploit length-proportional straight-lines for the same purpose. Another common approach is to use numerical annotations. We first conducted two empirical studies, one on Euler diagrams and the other on linear diagrams. These suggest that area-proportional Euler diagrams with numerical annotations and length-proportional linear diagrams without numerical annotations support significantly better task performance. We then conducted a third study to investigate which of these two notations should be used in practice. This suggests that area-proportional Euler diagrams with numerical annotations most effectively supports task performance and so should be used to visualize set cardinalities. However, these studies focused on data that can be visualized reasonably accurately using circles and the results should be taken as valid within that context. Future work needs to determine whether the results generalize both to when circles cannot be used and for other ways of encoding cardinality information.

Theory of signs and statistical approach to big data in assessing the relevance of clinical biomarkers of inflammation and oxidative stress.

Biomarkers are widely used not only as prognostic or diagnostic indicators, or as surrogate markers of disease in clinical trials, but also to formulate theories of pathogenesis. We identify two problems in the use of biomarkers in mechanistic studies. The first problem arises in the case of multifactorial diseases, where different combinations of multiple causes result in patient heterogeneity. The second problem arises when a pathogenic mediator is difficult to measure. This is the case of the oxidative stress (OS) theory of disease, where the causal components are reactive oxygen species (ROS) that have very short half-lives. In this case, it is usual to measure the traces left by the reaction of ROS with biological molecules, rather than the ROS themselves. Borrowing from the philosophical theories of signs, we look at the different facets of biomarkers and discuss their different value and meaning in multifactorial diseases and system medicine to inform their use in patient stratification in personalized medicine.

SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments.

Rapidly decreasing genome sequencing costs have led to a proportionate increase in the number of samples used in prokaryotic population studies. Extracting single nucleotide polymorphisms (SNPs) from a large whole genome alignment is now a routine task, but existing tools have failed to scale efficiently with the increased size of studies. These tools are slow, memory inefficient and are installed through non-standard procedures. We present SNP-sites which can rapidly extract SNPs from a multi-FASTA alignment using modest resources and can output results in multiple formats for downstream analysis. SNPs can be extracted from a 8.3 GB alignment file (1842 taxa, 22 618 sites) in 267 seconds using 59 MB of RAM and 1 CPU core, making it feasible to run on modest computers. It is easy to install through the Debian and Homebrew package managers, and has been successfully tested on more than 20 operating systems. SNP-sites is implemented in C and is available under the open source license GNU GPL version 3.

Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins.

The emergence of new sequencing technologies has facilitated the use of bacterial whole genome alignments for evolutionary studies and outbreak analyses. These datasets, of increasing size, often include examples of multiple different mechanisms of horizontal sequence transfer resulting in substantial alterations to prokaryotic chromosomes. The impact of these processes demands rapid and flexible approaches able to account for recombination when reconstructing isolates' recent diversification. Gubbins is an iterative algorithm that uses spatial scanning statistics to identify loci containing elevated densities of base substitutions suggestive of horizontal sequence transfer while concurrently constructing a maximum likelihood phylogeny based on the putative point mutations outside these regions of high sequence diversity. Simulations demonstrate the algorithm generates highly accurate reconstructions under realistically parameterized models of bacterial evolution, and achieves convergence in only a few hours on alignments of hundreds of bacterial genome sequences. Gubbins is appropriate for reconstructing the recent evolutionary history of a variety of haploid genotype alignments, as it makes no assumptions about the underlying mechanism of recombination. The software is freely available for download at github.com/sanger-pathogens/Gubbins, implemented in Python and C and supported on Linux and Mac OS X.