Essay: Poets in the Ninth Circle. Host Publication: 'Poetry Ireland Review (Issue 113): A Seamus Heaney Special Issue'

No abstract available

Patient safety and communication: A new assessment for doctors trained in countries where language differs from that of the host country: Results of a pilot using a domain-based assessment

Objective

Global migration of healthcare workers places responsibility on employers to comply with legal employment rights whilst ensuring patient safety remains the central goal. We describe the pilot of a communication assessment designed for doctors who trained and communicated with patients and colleagues in a different language from that of the host country. It is unique in assessing clinical communication without assessing knowledge.

A 14-station OSCE was developed using a domain-based marking scheme, covering professional communication and English language skills (speaking, listening, reading and writing) in routine, acute and emotionally challenging contexts, with patients, carers and healthcare teams. Candidates (n = 43), non-UK trained volunteers applying to the UK Foundation Programme, were provided with relevant station information prior to the exam.

The criteria for passing the test included achieving the pass score and passing 10 or more of the 14 stations. Of the 43 candidates, nine failed on the station criteria. Two failed the pass score and also the station criteria. The Cronbach's alpha coefficient was 0.866.

This pilot tested ‘proof of concept’ of a new domain-based communication assessment for non-UK trained doctors.

The test would enable employers and regulators to verify communication competence and safety in clinical contexts, independent of clinical knowledge, for doctors who trained in a language different from that of the host country.

Within-host evolution of Burkholderia pseudomallei over a twelve-year chronic carriage infection

UNLABELLED: Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is generally accepted that B. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. Over a 23-year study of melioidosis cases in Darwin, Australia, just one patient from 707 survivors has developed persistent asymptomatic B. pseudomallei carriage. To better understand the mechanisms behind this unique scenario, we performed whole-genome analysis of two strains isolated 139 months apart. During this period, B. pseudomallei underwent several adaptive changes. Of 23 point mutations, 78% were nonsynonymous and 43% were predicted to be deleterious to gene function, demonstrating a strong propensity for positive selection. Notably, a nonsense mutation inactivated the universal stress response sigma factor RpoS, with pleiotropic implications. The genome underwent substantial reduction, with four deletions in chromosome 2 resulting in the loss of 221 genes. The deleted loci included genes involved in secondary metabolism, environmental survival, and pathogenesis. Of 14 indels, 11 occurred in coding regions and 9 resulted in frameshift mutations that dramatically affected predicted gene products. Disproportionately, four indels affected lipopolysaccharide biosynthesis and modification. Finally, we identified a frameshift mutation in both P314 isolates within wcbR, an important component of the capsular polysaccharide I locus, suggesting virulence attenuation early in infection. Our study illustrates a unique clinical case that contrasts a high-consequence infectious agent with a long-term commensal infection and provides further insights into bacterial evolution within the human host.

IMPORTANCE: Some bacterial pathogens establish long-term infections that are difficult or impossible to eradicate with current treatments. Rapid advances in genome sequencing technologies provide a powerful tool for understanding bacterial persistence within the human host. Burkholderia pseudomallei is considered a highly pathogenic bacterium because infection is commonly fatal. Here, we document within-host evolution of B. pseudomallei in a unique case of human infection with ongoing chronic carriage. Genomic comparison of isolates obtained 139 months (11.5 years) apart showed a strong signal of adaptation within the human host, including inactivation of virulence and immunogenic factors, and deletion of pathways involved in environmental survival. Two global regulatory genes were mutated in the 139-month isolate, indicating extensive regulatory changes favoring bacterial persistence. Our study provides insights into B. pseudomallei pathogenesis and, more broadly, identifies parallel evolutionary mechanisms that underlie chronic persistence of all bacterial pathogens.

The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds. 

Complete nucleotide sequence of φCHU: A Luz24likevirus infecting Pseudomonas aeruginosa and displaying a unique host range

A complete nucleotide sequence of the new Pseudomonas aeruginosa Luz24likevirus phiCHU was obtained. This virus was shown to have a unique host range whereby it grew poorly on the standard laboratory strain PAO1, but infected 26 of 46 clinical isolates screened, and strains harboring IncP2 plasmid pMG53. It was demonstrated that phiCHU has single strand interruptions in its genome. Analysis of the phiCHU genome also suggested that recombination event(s) participated in the evolution of the leftmost portion of the genome, presumably encoding early genes.

Environmental forensic investigations: The potential use of a novel heavy metal sensor and novel taggants

This chapter presents a novel hand-held instrument capable of real-time in situ detection and identification of heavy metals, along with the potential use of novel taggants in environmental forensic investigations. The proposed system provides the facilities found in a traditional laboratory-based instrument but in a hand held design, without the need for an associated computer. The electrochemical instrument uses anodic stripping voltammetry, which is a precise and sensitive analytical method with excellent limits of detection. The sensors comprise a small disposable plastic strip of screen-printed electrodes rather than the more common glassy carbon disc and gold electrodes. The system is designed for use by a surveyor on site, allowing them to locate hotspots, thus avoiding the expense and time delay of prior laboratory analysis. This is particularly important in environmental forensic analysis when a site may have been released back to the owner and samples could be compromised on return visits. The system can be used in a variety of situations in environmental assessments, the data acquired from which provide a metals fingerprint suitable for input to a database. The proposed novel taggant tracers, based on narrow-band atomic fluorescence, are under development for potential deployment as forensic environmental tracers. The use of discrete fluorescent species in an environmentally stable host has been investigated to replace existing toxic, broadband molecular dye tracers. The narrow band emission signals offer the potential for tracing a large number of signals in the same environment. This will give increased data accuracy and allow multiple source environmental monitoring of environmental parameters.

Fasciola hepatica vaccine: We may not be there yet but we're on the right road

Major advances have been made in identifying potential vaccine molecules for the control of fasciolosis in livestock but we have yet to reach the level of efficacy required for commercialisation. The pathogenesis of fasciolosis is associated with liver damage that is inflicted by migrating and feeding immature flukes as well as host inflammatory immune responses to parasite-secreted molecules and tissue damage alarm signals. Immune suppression/modulation by the parasites prevents the development of protective immune responses as evidenced by the lack of immunity observed in naturally and experimentally infected animals. In our opinion, future efforts need to focus on understanding how parasites invade and penetrate the tissues of their hosts and how they potentiate and control the ensuing immune responses, particularly in the first days of infection. Emerging 'omics' data employed in an unbiased approach are helping us understand liver fluke biology and, in parallel with new immunological data, to identify molecules that are essential to parasite development and accessible to vaccine-induced immune responses.