Zoonotic potential of Salmonella enterica carried by pet tortoises

The prevalence of Salmonella in chelonians is not known in the UK and it is not clear whether such Salmonella strains would be pathogenic for human beings. Some strains, such as members of the Arizonae subgroup, may be unable to cause anything more than very mild disease. To determine the carriage of Salmonella in pet tortoises, cloacal swabs were taken for culture. Salmonella enterica Group D was isolated from 5 of the 89 samples. All five were from the same household of seven tortoises. Salmonella isolates were shown by PCR to carry the invA and spiC genes associated with pathogenicity islands 1 and 2. Each isolate carried both genes indicating they had the genetic basis for disease and enterocyte invasion in human beings. The study indicates a low rate of asymptomatic carriage among the general population of pet tortoises. However, it does suggest that those Salmonella strains colonising the tortoise can carry Salmonella pathogenicity island (SPI)-1 and SPI-2 conferring the potential to cause disease in human beings and other animals

Stereospecific four-bond phosphorus-phosphorus spin couplings in phosphazenyl-phosphazenes

Four-bond phosphorus-phosphorus coupling constants have been measured from the 31P NMR spectra of phosphazenylcyclophosphazenes. Their magnitude appears to be related to the conformation adopted by the phosphazenyl-group relative to the phosphazene ring

A case study evaluation of implementation of a care pathway to support normal birth in one English birth centre: anticipated benefits and unintended consequences

Background: The policy drive for the UK National Health Service (NHS) has focused on the need for high quality services informed by evidence of best practice. The introduction of care pathways and protocols to standardise care and support implementation of evidence into practice has taken place across the NHS with limited evaluation of their impact. A multi-site case study evaluation was undertaken to assess the impact of use of care pathways and protocols on clinicians, service users and service delivery. One of the five sites was a midwifery-led Birth Centre, where an adapted version of the All Wales Clinical Pathway for Normal Birth had been implemented. Methods: The overarching framework was realistic evaluation. A case study design enabled the capture of data on use of the pathway in the clinical setting, use of multiple methods of data collection and opportunity to study and understand the experiences of clinicians and service users whose care was informed by the pathway. Women attending the Birth Centre were recruited at their 36 week antenatal visit. Episodes of care during labour were observed, following which the woman and the midwife who cared for her were interviewed about use of the pathway. Interviews were also held with other key stakeholders from the study site. Qualitative data were content analysed. Results: Observations were undertaken of four women during labour. Eighteen interviews were conducted with clinicians and women, including the women whose care was observed and the midwives who cared for them, senior midwifery managers and obstetricians. The implementation of the pathway resulted in a number of anticipated benefits, including increased midwifery confidence in skills to support normal birth and promotion of team working. There were also unintended consequences, including concerns about a lack of documentation of labour care and negative impact on working relationships with obstetric and other midwifery colleagues. Women were unaware their care was informed by a care pathway. Conclusion: Care pathways are complex interventions which generate a number of consequences for practice. Those considering introduction of pathways need to ensure all relevant stakeholders are engaged with this and develop robust evaluation strategies to accompany implementation

An extension to VORO++ for multithreaded computation of Voronoi cells

VORO++ is a software library written in C++ for computing the Voronoi tessellation, a technique in computational geometry that is widely used for analyzing systems of particles. VORO++ was released in 2009 and is based on computing the Voronoi cell for each particle individually. Here, we take advantage of modern computer hardware, and extend the original serial version to allow for multithreaded computation of Voronoi cells via the OpenMP application programming interface. We test the performance of the code, and demonstrate that we can achieve parallel efficiencies greater than 95% in many cases. The multithreaded extension follows standard OpenMP programming paradigms, allowing it to be incorporated into other programs. We provide an example of this using the VoroTop software library, performing a multithreaded Voronoi cell topology analysis of up to 102.4 million particles.Comment: Fix typo and section number

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

Collaboration and co-production knowledge in healthcare: opportunities and challenges

Over time there has been a shift, at least in the rhetoric, from a pipeline conceptualisation of knowledge implementation, to one that recognises the potential of more collaboration, co-productive approaches to knowledge production and use. In this editorial, which is grounded in our research and collective experience, we highlight both the potential and challenge with collaboration and co-production. This includes issues about stakeholder engagement, governance arrangements, and capacity and capability for working in a coproductive way. Finally, we reflect on the fact that this approach is not a panacea, but is accompanied by some philosophical and practical challenges

Recent advances in global electric circuit coupling between the space environment and the troposphere

The global atmospheric electric circuit is driven by thunderstorms and electrified rain/shower clouds and is also influenced by energetic charged particles from space. The global circuit maintains the ionosphere as an equipotential at∼+250 kV with respect to the good conducting Earth (both land and oceans). Its “load” is the fair weather atmosphere and semi-fair weather atmosphere at large distances from the disturbed weather “generator” regions. The main solar-terrestrial (or space weather) influence on the global circuit arises from spatially and temporally varying fluxes of galactic cosmic rays (GCRs) and energetic electrons precipitating from the magnetosphere. All components of the circuit exhibit much variability in both space and time. Global circuit variations between solar maximum and solar minimum are considered together with Forbush decrease and solar flare effects. The variability in ion concentration and vertical current flow are considered in terms of radiative effects in the troposphere, through infra-red absorption, and cloud effects, in particular possible cloud microphysical effects from charging at layer cloud edges. The paper identifies future research areas in relation to Task Group 4 of the Climate and Weather of the Sun-Earth System (CAWSES-II) programme

Mycoplasma hyopneumoniae evades phagocytic uptake by porcine alveolar macrophages in vitro

Mycoplasma hyopneumoniae, the agent of porcine enzootic pneumonia (EP), is able to persist in the lung tissue and evade destruction by the host for several weeks. To understand the mechanism of pathogen survival, phagocytic uptake of M. hyopneumoniae by primary porcine alveolar macrophages was investigated. Intracellular location and survival of the pathogen were explored using gentamicin survival assays, flow cytometry and confocal microscopy of M. hyopneumoniae 232 labelled with green fluorescent protein (GFP). Following 1 h and 16 h of co-incubation, few viable M. hyopneumoniae were recovered from inside macrophages. Flow cytometric analysis of macrophages incubated with M. hyopneumoniae expressing GFP indicated that the mycoplasmas became associated with macrophages, but were shown to be extracellular when actin-dependent phagocytosis was blocked with cytochalasin D. Confocal microscopy detected GFP-labelled M. hyopneumoniae inside macrophages and the numbers increased modestly with time of incubation. Neither the addition of porcine serum complement or convalescent serum from EP-recovered pigs was able to enhance engulfment of M. hyopneumoniae. This investigation suggests that M. hyopneumoniae evades significant uptake by porcine alveolar macrophages and this may be a mechanism of immune escape by M. hyopneumoniae in the porcine respiratory tract

Opioid-related (ORL1) receptors are enriched in a subpopulation of sensory neurons and prolonged activation produces no functional loss of surface N-type calcium channels.

The opioid-related receptor, ORL1, is activated by the neuropeptide nociceptin/orphanin FQ (N/OFQ) and inhibits high-voltage-activated (HVA) calcium channel currents (I(Ca)) via a G-protein-coupled mechanism. Endocytosis of ORL1 receptor during prolonged N/OFQ exposure was proposed to cause N-type voltage-gated calcium channel (VGCC) internalization via physical interaction between ORL1 and the N-type channel. However, there is no direct electrophysiological evidence for this mechanism in dorsal root ganglion (DRG) neurons or their central nerve terminals. The present study tested this using whole-cell patch-clamp recordings of HVA I(Ca) in rat DRG neurons and primary afferent excitatory synaptic currents (eEPSCs) in spinal cord slices. DRG neurons were classified on the basis of diameter, isolectin-B4 (IB4) binding and responses to capsaicin, N/OFQ and a μ-opioid agonist, DAMGO. IB4-negative neurons less than 20 μm diameter were selectively responsive to N/OFQ as well as DAMGO. In these neurons, ORL1 desensitization by a supramaximal concentration of N/OFQ was not followed by a decrease in HVA I(Ca) current density or proportion of whole-cell HVA I(Ca) contributed by N-type VGCC as determined using the N-type channel selective blocker, ω-conotoxin CVID. There was also no decrease in the proportion of N-type I(Ca) when neurons were incubated at 37°C with N/OFQ for 30 min prior to recording. In spinal cord slices, N/OFQ consistently inhibited eEPSCs onto dorsal horn neurons. As observed in DRG neurons, preincubation of slices in N/OFQ for 30 min produced no decrease in the proportion of eEPSCs inhibited by CVID. In conclusion, no internalization of the N-type VGCC occurs in either the soma or central nerve terminals of DRG neurons following prolonged exposure to high, desensitizing concentrations of N/OFQ.NHMRC Grant: 056992