Trial Forge Guidance 2: how to decide if a further Study Within A Trial (SWAT) is needed.

The evidence base available to trialists to support trial process decisions-e.g. how best to recruit and retain participants, how to collect data or how to share the results with participants-is thin. One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. These are self-contained research studies embedded within a host trial that aim to evaluate or explore alternative ways of delivering or organising a particular trial process.SWATs are increasingly being supported by funders and considered by trialists, especially in the UK and Ireland. At some point, increasing SWAT evidence will lead funders and trialists to ask: given the current body of evidence for a SWAT, do we need a further evaluation in another host trial? A framework for answering such a question is needed to avoid SWATs themselves contributing to research waste.This paper presents criteria on when enough evidence is available for SWATs that use randomised allocation to compare different interventions.

Trial Forge Guidance 1: what is a Study Within A Trial (SWAT)?

Randomised trials are a central component of all evidence-informed health care systems and the evidence coming from them helps to support health care users, health professionals and others to make more informed decisions about treatment. The evidence available to trialists to support decisions on design, conduct and reporting of randomised trials is, however, sparse. Trial Forge is an initiative that aims to increase the evidence base for trial decision-making and in doing so, to improve trial efficiency.One way to fill gaps in evidence is to run Studies Within A Trial, or SWATs. This guidance document provides a brief definition of SWATs, an explanation of why they are important and some practical 'top tips' that come from existing experience of doing SWATs. We hope the guidance will be useful to trialists, methodologists, funders, approvals agencies and others in making clear what a SWAT is, as well as what is involved in doing one.

Reassessment of the taxonomic position of Burkholderia andropogonis and description of Robbsia andropogonis gen. nov., comb. nov.

The phylogenetic classification of the species Burkholderia andropogonis within the Burkholderia genus was reassessed using 16S rRNA gene phylogenetic analysis and multilocus sequence analysis (MLSA). Both phylogenetic trees revealed two main groups, named A and B, strongly supported by high bootstrap values (100%). Group A encompassed all of the Burkholderia species complex, whi.le Group B only comprised B. andropogonis species, with low percentage similarities with other species of the genus, from 92 to 95% for 16S rRNA gene sequences and 83% for conserved gene sequences. Average nucleotide identity (ANI), tetranucleotide signature frequency, and percentage of conserved proteins POCP analyses were also carried out, and in the three analyses B. andropogonis showed lower values when compared to the other Burkholderia species complex, near 71% for ANI, from 0.484 to 0.724 for tetranucleotide signature frequency, and around 50% for POCP, reinforcing the distance observed in the phylogenetic analyses. Our findings provide an important insight into the taxonomy of B. andropogonis. It is clear from the results that this bacterial species exhibits genotypic differences and represents a new genus described herein as Robbsia andropogonis gen. nov., comb. nov.

Draft Genome Sequence of Burkholderia andropogonis Type Strain ICMP2807, Isolated from Sorghum bicolor.

Here, we report the draft genome sequence of Burkholderia andropogonis ICMP2807, a phytopathogenic bacterium isolated from Sorghum bicolor plants in the United States.

Characterization of human embryonic stem cell lines by the International Stem Cell Initiative.

The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.

A locus for complicated hereditary spastic paraplegia maps to chromosome 1q24-q32.

We updated the clinical features of a consanguineous Arab Israeli family, in which four of seven children were affected by spastic paraplegia complicated by skin pigmentary abnormalities. A genomewide linkage screen performed for the family identified a new locus (SPG23) for this form of hereditary spastic paraplegia, in an approximately 25cM region of chromosome 1q24-q32, with a peak logarithm of odds score of 3.05.

A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10).

We have identified a missense mutation in the motor domain of the neuronal kinesin heavy chain gene KIF5A, in a family with hereditary spastic paraplegia. The mutation occurs in the family in which the SPG10 locus was originally identified, at an invariant asparagine residue that, when mutated in orthologous kinesin heavy chain motor proteins, prevents stimulation of the motor ATPase by microtubule-binding. Mutation of kinesin orthologues in various species leads to phenotypes resembling hereditary spastic paraplegia. The conventional kinesin motor powers intracellular movement of membranous organelles and other macromolecular cargo from the neuronal cell body to the distal tip of the axon. This finding suggests that the underlying pathology of SPG10 and possibly of other forms of hereditary spastic paraplegia may involve perturbation of neuronal anterograde (or retrograde) axoplasmic flow, leading to axonal degeneration, especially in the longest axons of the central nervous system.