Rapid fine mapping of causative mutations from sets of unordered, contig-sized fragments of genome sequence

Background Traditional Map based Cloning approaches, used for the identification of desirable alleles, are extremely labour intensive and years can elapse between the mutagenesis and the detection of the polymorphism. High throughput sequencing based Mapping-by-sequencing approach requires an ordered genome assembly and cannot be used with fragmented, un-scaffolded draft genomes, limiting its application to model species and precluding many important organisms. Results We addressed this gap in resource and presented a computational method and software implementations called CHERIPIC (Computing Homozygosity Enriched Regions In genomes to Prioritise Identification of Candidate variants). We have successfully validated implementation of CHERIPIC using three different types of bulk segregant sequence data from Arabidopsis, maize and barley, respectively. Conclusions CHERIPIC allows users to rapidly analyse bulk segregant sequence data and we have made it available as a pre-packaged binary with all dependencies for Linux and MacOS and as Galaxy tool

SATRE: Standardised Architecture for Trusted Research Environments

The SATRE DARE UK-funded Driver Project was challenged to create a trusted research environment (TRE) architecture supporting the research community's need to have suitable data analytics and research environments for working with sensitive data. The project developed an inclusive and transparent way of working to ensure that what was created was representative of the TRE community in the UK. We have created, for the first time, an open specification for TRE operators by which to evaluate themselves against a set of capabilities. It is a thorough specification, perhaps definition, for TREs informed not only by the experience of the project team who have been running a TRE and supporting sensitive data projects for a combined 15 years but also the expansive knowledge of the wider UK research community. The public has also been involved throughout the development of the specification to ensure their voices are heard and reflected in the specification. The specification has been informed through one survey completed by 105 individuals representing approximately 60 organisations, 14 Collaboration Cafés with up to 75 participants, 26 individuals contributing directly, 44 issues raised and six public engagement sessions online and in-person. Despite the breadth and diversity of the individuals included, we have been able to create a single specification encompassing four architectural principles, four pillars, 29 capabilities and 160 statements. The 75 mandatory statements are what is considered the minimum required to be a SATRE-compliant TRE. Now, with a stable version 1.0 release, the specification is ready for use by the UK TRE community. We are and will continue to work with all organisations to evaluate themselves against the specification and also identify what works and what doesn't, which will be captured in future versions of the specification. The specification has been developed with the long-term in mind and can be a basis for a common understanding between operators, data controllers, accreditors, researchers, industry and government organisations for how TREs can federate and interoperate better.This work was funded by UK Research & Innovation [Grant Number MC_PC_23008] as part of Phase 1 of the DARE UK (Data and Analytics Research Environments UK) programme, delivered in partnership with Health Data Research UK (HDR UK) and Administrative Data Research UK (ADR UK)

Working Collaboratively: Outcomes of Geriatrician Input in Older Patients Undergoing Emergency Laparotomy in a District General Hospital

With the increasing median age of survival in the UK, there is an increased burden on the provision of medical and surgical care to the population. The 2010 National Confidential Enquiry into Patient Outcome and Death report, “An Age Old Problem,” emphasizes the early involvement of surgical and geriatric consultant input to improve perioperative care in older patients. This study describes the development of a Geriatric Surgical Liaison Service aimed at providing consultant-led geriatrician support to improve the outcomes of older patients undergoing Emergency Laparotomy (EL). The primary outcome is the reduction in length of stay (LOS) compared to baseline data prior to geriatrician involvement. The service was designed to include one clinical session involving a consultant geriatrician and two and a half days with a junior doctor in a week. Data was collected prospectively from February 2018 till July 2018 for surgical patients aged ≥ 70 years, who underwent EL, had an inpatient stay of more than seven days, and who were diagnosed with delirium or incurred inpatient falls (intervention group). Baseline data, prior to geriatrician involvement, were collected retrospectively for EL patients aged ≥ 70 years from December 2015 until May 2016. Length of stay and 30-day mortality were also compared between the two cohorts undergoing EL. A total of 69 patients were included in the intervention group; 45 patients underwent EL and their mean LOS was 17.5 days, which was reduced from 22.5 days prior to geriatrician involvement (n=57). There was no difference in median length of stay and 30-day mortality between the retrospective baseline group and the intervention groups. In the intervention group, 8.5% of patients had a new medical diagnosis and 26.8% of patients were offered follow-ups. Although statistically not significant (p=0.40), a shorter stay in hospital by five days can potentially have a positive impact on patient outcomes by reducing psychosocial, cognitive, and functional deconditioning. This would also improve patient flow, release capacity, and waiting times and would be of benefit to the financially strained National Health Service (NHS). Overall, our study suggests that a collaborative, consultant-led geriatric service can improve the management of older surgical patients by potentially reducing length of stay, identifying high-risk patients, and facilitating early and appropriate specialty input alongside adequate and required outpatient follow-up

Brain abscess in Korean children: A 15-year single center study

PurposeA brain abscess is a serious disease of the central nerve system. We conducted this study to summarize the clinical manifestations and outcomes of brain abscesses.MethodsA retrospective chart review of pediatric patients diagnosed with brain abscesses from November 1994 to June 2009 was performed at Samsung Medical Center, Seoul, Korea.ResultsTwenty-five patients were included in this study. On average, 1.67 cases per year were identified and the median age was 4.3 years. The common presenting clinical manifestations were fever (18/25, 72%), seizure (12/25, 48%), altered mental status (11/25, 44%), and signs of increased intracranial pressure (9/25, 36%). A total of 14 (56%) patients had underlying illnesses, with congenital heart disease (8/25, 32%) as the most common cause. Predisposing factors were identified in 15 patients (60%). The common predisposing factors were otogenic infection (3/25, 12%) and penetrating head trauma (3/25, 12%). Causative organisms were identified in 64% of patients (16/25). The causative agents were S. intermedius (n=3), S. aureus (n=3), S. pneumoniae (n=1), Group B streptococcus (n=2), E. coli (n=1), P. aeruginosa (n=1), and suspected fungal infection (n=5). Seven patients received medical treatment only while the other 18 patients also required surgical intervention. The overall fatality rate was 16% and 20% of patients had neurologic sequelae. There was no statistical association between outcomes and the factors studied.ConclusionAlthough uncommon, a brain abscess is a serious disease. A high level of suspicion is very important for early diagnosis and to prevent serious consequences