Whole-Genome Sequencing of Brachyspira hyodysenteriae Isolates From England and Wales Reveals Similarities to European Isolates and Mutations Associated With Reduced Sensitivity to Antimicrobials.

Brachyspira hyodysenteriae is the principal cause of swine dysentery, a disease that threatens economic productivity of pigs in many countries as it can spread readily within and between farms, and only a small number of antimicrobials are authorized for treatment of pigs. In this study, we performed whole-genome sequencing (WGS) of 81 B. hyodysenteriae archived at the Animal and Plant Health Agency (APHA) from diagnostic submissions and herd monitoring in England and Wales between 2004 and 2015. The resulting genome sequences were analyzed alongside 34 genomes we previously published. Multi-locus sequence typing (MLST) showed a diverse population with 32 sequence types (STs) among the 115 APHA isolates, 25 of them identified only in England; while also confirming that the dominant European clonal complexes, CC8 and CC52, were common in the United Kingdom. A core-genome SNP tree typically clustered the isolates by ST, with isolates from some STs detected only within a specific region in England, although others were more widespread, suggesting transmission between different regions. Also, some STs were more conserved in their core genome than others, despite these isolates being from different holdings, regions and years. Minimum inhibitory concentrations to commonly used antimicrobials (Tiamulin, Valnemulin, Doxycycline, Lincomycin, Tylosin, Tylvalosin) were determined for 82 of the genome-sequenced isolates; genomic analysis revealed mutations generally correlated well with the corresponding resistance phenotype. There was a major swine dysentery intervention program in 2009-2010, and antimicrobial survival curves showed a significant reduction in sensitivity to tiamulin and valnemulin in isolates collected in and after 2010, compared to earlier isolates. This correlated with a significant increase in post-2009 isolates harboring the pleuromutilin resistance gene tva(A), which if present, may facilitate higher levels of resistance. The reduction in susceptibility of Brachyspira from diagnostic submissions to pleuromutilins, emphasizes the need for prudent treatment, control and eradication strategies.

The real informatics challenges of personalized medicine: not just about the number of central processing units.

Personalized medicine has the potential to revolutionize patient care. In order to do so, it requires a re-engineering of many life sciences and healthcare processes, the most significant being the integration of the complete biomarker lifecycle from discovery to targeted treatment of patients. Individual patient omic profiles have become a reality owing to the diminishing cost of DNA sequencing. However, managing these data has created a bottleneck due to: the limitations in storage, computing power and information access; the lack of biologist-friendly software to replace the user-unfriendly custom scripts, which are crippling collaboration; the urgency for standardizing data across omics and clinical data realms for cross-study comparisons; undermining innovations of enterprise and open-source software, which saps innovations of open-source and reliability and support of enterprise software; and unavailability of a robust, integrative workflow system, which leads to actionable data at the patient care level.

DW4TR: A Data Warehouse for Translational Research.

The linkage between the clinical and laboratory research domains is a key issue in translational research. Integration of clinicopathologic data alone is a major task given the number of data elements involved. For a translational research environment, it is critical to make these data usable at the point-of-need. Individual systems have been developed to meet the needs of particular projects though the need for a generalizable system has been recognized. Increased use of Electronic Medical Record data in translational research will demand generalizing the system for integrating clinical data to support the study of a broad range of human diseases. To ultimately satisfy these needs, we have developed a system to support multiple translational research projects. This system, the Data Warehouse for Translational Research (DW4TR), is based on a light-weight, patient-centric modularly-structured clinical data model and a specimen-centric molecular data model. The temporal relationships of the data are also part of the model. The data are accessed through an interface composed of an Aggregated Biomedical-Information Browser (ABB) and an Individual Subject Information Viewer (ISIV) which target general users. The system was developed to support a breast cancer translational research program and has been extended to support a gynecological disease program. Further extensions of the DW4TR are underway. We believe that the DW4TR will play an important role in translational research across multiple disease types.

Addressing informatics challenges in Translational Research with workflow technology.

Interest in Translational Research has been growing rapidly in recent years. In this collision of different data, technologies and cultures lie tremendous opportunities for the advancement of science and business for organisations that are able to integrate, analyse and deliver this information effectively to users. Workflow-based integration and analysis systems are becoming recognised as a fast and flexible way to build applications that are tailored to scientific areas, yet are built on a common platform. Workflow systems are allowing organisations to meet the key informatics challenges in Translational Research and improve disease understanding and patient care.

Lethal injection for execution: chemical asphyxiation?

BACKGROUND: Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended. METHODS AND FINDINGS: We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest. CONCLUSIONS: We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable.

Inadequate anaesthesia in lethal injection for execution.

Anaesthesia during lethal injection is essential to minimise suffering and to maintain public acceptance of the practice. Lethal injection is usually done by sequential administration of thiopental, pancuronium, and potassium chloride. Protocol information from Texas and Virginia showed that executioners had no anaesthesia training, drugs were administered remotely with no monitoring for anaesthesia, data were not recorded and no peer-review was done. Toxicology reports from Arizona, Georgia, North Carolina, and South Carolina showed that post-mortem concentrations of thiopental in the blood were lower than that required for surgery in 43 of 49 executed inmates (88%); 21 (43%) inmates had concentrations consistent with awareness. Methods of lethal injection anaesthesia are flawed and some inmates might experience awareness and suffering during execution.