Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor

BACKGROUND: Klebsiella pneumoniae strains are pathogenic to animals and humans, in which they are both a frequent cause of nosocomial infections and a re-emerging cause of severe community-acquired infections. K. pneumoniae isolates of the capsular serotype K2 are among the most virulent. In order to identify novel putative virulence factors that may account for the severity of K2 infections, the genome sequence of the K2 reference strain Kp52.145 was determined and compared to two K1 and K2 strains of low virulence and to the reference strains MGH 78578 and NTUH-K2044.

RESULTS: In addition to diverse functions related to host colonization and virulence encoded in genomic regions common to the four strains, four genomic islands specific for Kp52.145 were identified. These regions encoded genes for the synthesis of colibactin toxin, a putative cytotoxin outer membrane protein, secretion systems, nucleases and eukaryotic-like proteins. In addition, an insertion within a type VI secretion system locus included sel1 domain containing proteins and a phospholipase D family protein (PLD1). The pld1 mutant was avirulent in a pneumonia model in mouse. The pld1 mRNA was expressed in vivo and the pld1 gene was associated with K. pneumoniae isolates from severe infections. Analysis of lipid composition of a defective E. coli strain complemented with pld1 suggests an involvement of PLD1 in cardiolipin metabolism.

CONCLUSIONS: Determination of the complete genome of the K2 reference strain identified several genomic islands comprising putative elements of pathogenicity. The role of PLD1 in pathogenesis was demonstrated for the first time and suggests that lipid metabolism is a novel virulence mechanism of K. pneumoniae.

Recruiting schools, adolescents and parents to a sexual-health trial: experiences, challenges and lessons learned from the Jack Trial

Background
Recruitment to school-based randomised trials is challenging; even more so when the focus of the study is a sensitive issue such as sexual health. The Jack Feasibility Trial aims to determine the facilitators and barriers to recruitment and retention to a school-based sexual health trial and identify optimal multi-level strategies for a full trial.
Method<br/>The Jack Trial is an NIHR-funded feasibility study of a film-based sexual health intervention, recruiting over 800 adolescents from 8 post-primary schools in Northern Ireland. In order to examine the feasibility of piloted recruitment and retention methods and assess acceptability of participation across the range of schools and individuals approached, we analysed qualitative data from triangulated sources including a parents’ survey and semi-structured interviews with principals, vice-principals, teachers and parents recruited to the study.
Results
With reference to Social Learning Theory, we identified a number of individual, behavioural and environmental level factors which influenced recruitment and retention. Commonly identified facilitators included the perceived relevance and potential benefit of the intervention to adolescents, the credibility of the organisation running the study, support offered by trial staff, and financial incentives. Key barriers were prior commitment to other research, lack of time and resources, and perceptions that the intervention was incompatible with adolescent needs or school ethos.
Conclusion
This study highlights pertinent general and trial-specific facilitators and barriers to recruitment to a sexual health trial in a school setting, which will prove useful for successful conduct of future trials with schools, adolescents and parents.

Nuclear disasters and health: lessons learned, challenges, and proposals

Past nuclear disasters, such as the atomic bombings in 1945 and major accidents at nuclear power plants, have highlighted similarities in potential public health effects of radiation in both circumstances, including health issues unrelated to radiation exposure. Although the rarity of nuclear disasters limits opportunities to undertake rigorous research of evidence-based interventions and strategies, identification of lessons learned and development of an effective plan to protect the public, minimise negative effects, and protect emergency workers from exposure to high-dose radiation is important. Additionally, research is needed to help decision makers to avoid premature deaths among patients already in hospitals and other vulnerable groups during evacuation. Since nuclear disasters can affect hundreds of thousands of people, a substantial number of people are at risk of physical and mental harm in each disaster. During the recovery period after a nuclear disaster, physicians might need to screen for psychological burdens and provide general physical and mental health care for many affected residents who might experience long-term displacement. Reliable communication of personalised risks has emerged as a challenge for health-care professionals beyond the need to explain radiation protection. To overcome difficulties of risk communication and provide decision aids to protect workers, vulnerable people, and residents after a nuclear disaster, physicians should receive training in nuclear disaster response. This training should include evidence-based interventions, support decisions to balance potential harms and benefits, and take account of scientific uncertainty in provision of community health care. An open and joint learning process is essential to prepare for, and minimise the effects of, future nuclear disasters.

Supervisor Continuity or Co-Location: Which Matters in Residency Education? Findings From a Qualitative Study of Remote Supervisor Family Physicians in Australia and Canada

Purpose: Changes to health care systems andworking hours have fragmentedresidents’ clinical experiences withpotentially negative effects ontheir development as professionals.Investigation of off-site supervision,which has been implemented in isolatedrural practice, could reveal importantbut less overt components of residencyeducation. 

Method: Insights from sociocultural learningtheory and work-based learning provideda theoretical framework. In 2011–2012,16 family physicians in Australia andCanada were asked in-depth how theyremotely supervised residents’ workand learning, and for their reflectionson this experience. The verbatiminterview transcripts and researchers’memos formed the data set. Templateanalysis produced a description andinterpretation of remote supervision. 

Results: Thirteen Australian family physiciansfrom five states and one territory, andthree Canadians from one province,participated. The main themes werehow remoteness changed the dynamicsof care and supervision; the importanceof ongoing, holistic, nonhierarchical,supportive supervisory relationships; andthat residents learned “clinical courage”through responsibility for patients’ careover time. Distance required supervisorsto articulate and pass on their expertiseto residents but made monitoringdifficult. Supervisory continuityencouraged residents to build on pastexperiences and confront deficiencies. 

Conclusions: Remote supervision enabled residents todevelop as clinicians and professionals.This questions the supremacy of co-locationas an organizing principle forresidency education. Future specialists maybenefit from programs that give themongoing and increasing responsibilityfor a group of patients and supportive.

What Have We Learned...

Presentation on the outworkings of the selective system of secondary education in Northern Ireland and a commentary on themes emerging on the conference held to mark the 50th anniversary of comprehensive schooling in Scotland. The two main challenges identified were: (1) how to deal with the consequence that not all children arrive in school with the same experiences or support, that is, dealing with the consequences of social disadvantage; and (2) not all post-school outcomes are seen to have the same value, so post-compulsory schooling risks becoming a selective mechanism for entry to more desirable outcomes

Handbook of Disabled Children's Childhoods: Building Understandings: Child, Youth, Family and Disability. Palgrave Macmillan:Disabled Children in Out-of-Home Care: Issues and Challenges for Practice Kelly, B., Sandra, D. & Winter, K. 2016

This chapter provides an overview of some of the key findings from a large mixed methods study regarding disabled children in care in Northern Ireland