An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network

Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism–environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bacillus subtilis and two transcriptomics datasets (including one with 38 separate experiments collected specifically for this study), we use a new combination of network component analysis and model selection to simultaneously estimate transcription factor activities and learn a substantially expanded transcriptional regulatory network for this bacterium. In total, we predict 2,258 novel regulatory interactions and recall 74% of the previously known interactions. We obtained experimental support for 391 (out of 635 evaluated) novel regulatory edges (62% accuracy), thus significantly increasing our understanding of various cell processes, such as spore formation

Weight-bearing in ankle fractures: An audit of UK practice.

INTRODUCTION: The purpose of this national study was to audit the weight-bearing practice of orthopaedic services in the National Health Service (NHS) in the treatment of operatively and non-operatively treated ankle fractures. METHODS: A multicentre prospective two-week audit of all adult ankle fractures was conducted between July 3rd 2017 and July 17th 2017. Fractures were classified using the AO/OTA classification. Fractures fixed with syndesmosis screws or unstable fractures (>1 malleolus fractured or talar shift present) treated conservatively were excluded. No outcome data were collected. In line with NICE (The National Institute for Health and Care Excellence) criteria, "early" weight-bearing was defined as unrestricted weight-bearing on the affected leg within 3 weeks of injury or surgery and "delayed" weight-bearing as unrestricted weight-bearing permitted after 3 weeks. RESULTS: 251 collaborators from 81 NHS hospitals collected data: 531 patients were managed non-operatively and 276 operatively. The mean age was 52.6 years and 50.5 respectively. 81% of non-operatively managed patients were instructed for early weight-bearing as recommended by NICE. In contrast, only 21% of operatively managed patients were instructed for early weight-bearing. DISCUSSION: The majority of patients with uni-malleolar ankle fractures which are managed non-operatively are treated in accordance with NICE guidance. There is notable variability amongst and within NHS hospitals in the weight-bearing instructions given to patients with operatively managed ankle fractures. CONCLUSION: This study demonstrates community equipoise and suggests that the randomized study to determine the most effective strategy for postoperative weight-bearing in ankle fractures described in the NICE research recommendation is feasible