Pseudomonas aeruginosa infection in augmented care: the molecular ecology and transmission dynamics in four large UK hospitals.

BACKGROUND: Pseudomonas aeruginosa is a common opportunistic pathogen and molecular typing in outbreaks has linked patient acquisition to contaminated hospital water systems. AIM: To elucidate the role of P. aeruginosa transmission rates in non-outbreak augmented care settings in the UK. METHODS: Over a 16-week period, all water outlets in augmented care units of four hospitals were sampled for P. aeruginosa and clinical isolates were collected. Outlet and clinical P. aeruginosa isolates underwent whole-genome sequencing (WGS), which with epidemiological data identified acquisition from water as definite (level 1), probable (level 2), possible (level 3), and no evidence (level 4). FINDINGS: Outlets were positive in each hospital on all three occasions: W (16%), X (2.5%), Y (0.9%) and Z (2%); and there were 51 persistently positive outlets in total. WGS identified likely transmission (at levels 1, 2 and 3) from outlets to patients in three hospitals for P. aeruginosa positive patients: W (63%), X (54.5%) and Z (26%). According to the criteria (intimate epidemiological link and no phylogenetic distance), approximately 5% of patients in the study 'definitely' acquired their P. aeruginosa from their water outlets in the intensive care unit. This study found extensive evidence of transmission from the outlet to the patients particularly in the newest hospital (W), which had the highest rate of positive outlets. CONCLUSIONS: The overall findings suggest that water outlets are the most likely source of P. aeruginosa nosocomial infections in some settings, and that widespread introduction of control measures would have a substantial impact on infections.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

First Complete Genome Sequences of Zika Virus Isolated from Febrile Patient Sera in Ecuador.

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, EcEs062_16 and EcEs089_16, isolated from the sera of febrile patients in Esmeraldas City, in the northern coastal province of Esmeraldas, Ecuador, in April 2016. These are the first complete ZIKV genomes to be reported from Ecuador.

The AUSTRAL VLBI observing program.

The AUSTRAL observing program was started in 2011, performing geodetic and astrometric very long baseline interferometry (VLBI) sessions using the new Australian AuScope VLBI antennas at Hobart, Katherine, and Yarragadee, with contribution from the Warkworth (New Zealand) 12 m and Hartebeesthoek (South Africa) 15 m antennas to make a southern hemisphere array of telescopes with similar design and capability. Designed in the style of the next-generation VLBI system, these small and fast antennas allow for a new way of observing, comprising higher data rates and more observations than the standard observing sessions coordinated by the International VLBI Service for Geodesy and Astrometry (IVS). In this contribution, the continuous development of the AUSTRAL sessions is described, leading to an improvement of the results in terms of baseline length repeatabilities by a factor of two since the start of this program. The focus is on the scheduling strategy and increased number of observations, aspects of automated operation, and data logistics, as well as results of the 151 AUSTRAL sessions performed so far. The high number of the AUSTRAL sessions makes them an important contributor to VLBI end-products, such as the terrestrial and celestial reference frames and Earth orientation parameters. We compare AUSTRAL results with other IVS sessions and discuss their suitability for the determination of baselines, station coordinates, source coordinates, and Earth orientation parameters.

Are you prepared to take the risk: Extending governance for perioperative roles.

In the 25 years since the Oxford Heart Centre in England appointed the first British nurse to be formally trained as a non-medically qualified surgical assistant, the number of nurses and allied health professionals (AHPs) undertaking advancing surgical roles has increased in order to backfill the deficit of a surgical workforce (Quick and Hall 2014). Despite initial concerns over nurses and AHPs undertaking roles and responsibilities which were previously performed solely by doctors, the role of non-medical surgical assistants has been shown to maintain surgical services, provide an additional career route for nurses, and enhance patient care (Abraham 2011, Quick 2013, Jones et al 2012). In the early days however, a lack of role specific regulation, practice guidelines and a variety of educational standards led to variances in job titles and role responsibilities for nurses and AHPs performing surgical assistance (Box 1).

Part two: Qualitative research.

This second article in the series Spotlight on Research focuses on qualitative research, its applications, principles and methodologies. It provides an insight into how this approach can be used within the perioperative setting and gives advice for practitioners looking to undertake a qualitative research study.

Part four: The research dissertation: planning, producing and writing a thesis.

Dissertations have become common inclusions to postgraduate degrees in healthcare. To the novice researcher, undertaking an extensive project of this kind can appear daunting. In this final article in the series 'Spotlight on Research', Julie Quick and Susan Hall advise perioperative practitioners on how to plan, produce and write a research dissertation. Guidance is also given on disseminating the results from research studies.

The surgical first assistant: are you compliant?

It is over a century now since the importance of the knowledge and skills of the surgeon's assistant were first considered (Brickner 1907). More recently both the Royal College of Surgeons of England (RCSE 1999, 2011) and the Perioperative Care Collaborative (PCC 2007) have reviewed the role of the non-medically qualified surgical assistant. In 2012, the PCC published their review of the surgical first assistant (SFA) role in response to a call by the RCSE for greater clarity in relation to the plethora of titles afforded to non-medical surgical assistants (RCSE 2011).

Molecular cytogenetic and agronomic characterization of advanced generations of wheat x triticale hybrids resistant to Diuraphis noxia (Mordvilko): application of GISH and microsatellite markers.

The PI 386148 triticale from Russia is among the highest resistant line to the Russian wheat aphid (RWA) (Diuraphis noxia (Mordvilko)). This triticale line was used as the male parent in crosses with Lamar wheat (Triticum aestivum L.). The F1 plants were backcrossed to Lamar wheat. The progenies were tested for RWA biotype 1 reaction for at least eight backcross and selfing generations. Five lines from these selections were identified for their resistance to the RWA and their seeds were increased for agronomic and other characterizations. Molecular and cytological analyses of these lines were performed using genomic in situ hybridization and rye chromosome-specific microsatellites markers. Three lines were cytologically stable and carried a pair of rye (Secale strictum (C. Presl) C. Presl) chromosomes as disomic addition lines of 1R. One line was unstable and showed a moderate level of mixoploidy with monosomic additions of 1R. Duplication of rye chromosome 1R was also identified. No wheat-rye chromosome interchange was detected, suggesting little homology between S. strictum and T. aestivum chromosomes. Specific microsatellite primers were used to identify the rye chromosomes present in each line. One rye chromosome, 1R, from the donor species contains genes for RWA resistance. Grain yield and test weight of three of the lines were similar to some adapted released wheat varieties under stress conditions.

The tumour microenvironment: a novel target for cancer therapy.

Cancer therapy is in the midst of a major paradigm shift. Traditionally, cancer treatments have focused on tumour cells. However, studies over the past few decades have demonstrated that cancer is a vastly complex entity with multiple components affecting a tumour's growth, invasion and metastasis. These components, collectively termed the 'tumour microenvironment', include endothelial cells, pericytes, fibroblasts, inflammatory cells, leucocytes and elements of the extracellular matrix (ECM). Biological agents that target components of the tumour microenvironment may provide an interesting alternative to traditional tumour cell-directed therapy. Because of the complexity of the tumour milieu, the most beneficial therapy will likely involve the combination of one or more agents directed at this new target. This review highlights recent preclinical and clinical studies involving agents that target tumour vasculature, leucocytes, pericytes, cancer-associated fibroblasts and ECM components. We pay particular attention to combination therapies targeting multiple components of the tumour microenvironment, and aim to demonstrate that this strategy holds promise for the future of cancer treatment.

Identification, preparation, and characterization of several polymorphs and solvates of terazosin hydrochloride.

The phenomenon of polymorphism is prevalent in pharmaceuticals, yet it is unusual to identify more than three or four forms for any particular drug. Terazosin hydrochloride has been found to exist at room temperature in four solvent-free forms that can be isolated directly, one solvent-free form that can be prepared by desolvation of a methanolate, a methanol solvate, and a dihydrate. This study presents characterization and methods for preparation of each of these forms. Data are also presented demonstrating the relative stability of these forms.

Cortical bone geometry in asthmatic children.

At the mid-radius, pre-pubertal asthmatic children had smaller periosteal and endosteal circumferences and thicker cortical shells compared to controls, when assessed by peripheral quantitative computed tomography. Asthmatics had diminished periosteal expansion for muscle size, suggesting that asthma, its treatment, or its effects on physical activity had resulted in impaired adaptation of bone to muscle loading. Alterations in cortical bone geometry might explain the increased fracture risk in asthmatic children.

Case-control study of the muscular compartments and osseous strength in neurofibromatosis type 1 using peripheral quantitative computed tomography.

Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the pathogenesis is unknown. Given that muscle mass is important in the development of the strength of bone, peripheral quantitative computed tomography (pQCT) was utilized to compare measurements of muscle compartments between NF1 individuals and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross-sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT-2000, Stratec) and variables were compared to controls without NF1 ((age 5-18 years, N=380) using analysis-of-covariance controlling for age, height, Tanner stage, and gender. The NF1 cohort showed decreased total cross-sectional area [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased muscle cross-sectional area [p<0.001], and decreased Stress Strain Index [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross-sectional area and decreased bone strength than individuals without NF1.

The outer membrane localization of the Neisseria gonorrhoeae MsrA/B is involved in survival against reactive oxygen species.

The PilB protein of Neisseria gonorrhoeae has been reported to be involved in the regulation of pilin gene transcription, but it also possesses significant homology to the peptide methionine sulfoxide reductase family of enzymes, specifically MsrA and MsrB from Escherichia coli. MsrA and MsrB in E. coli are able to reduce methionine sulfoxide residues in proteins to methionines. In addition, the gonococcal PilB protein encodes for both MsrA and MsrB activity associated with the repair of oxidative damage to proteins. In this work, we demonstrate that the PilB protein of Neisseria gonorrhoeae is not involved in pilus expression. Additionally, we show that wild-type N. gonorrhoeae produces two forms of this polypeptide, one of which contains a signal sequence and is secreted from the bacterial cytoplasm to the outer membrane; the other lacks a signal sequence and is cytoplasmic. Furthermore, we show that the secreted form of the PilB protein is involved in survival in the presence of oxidative damage.

Ritonavir: an extraordinary example of conformational polymorphism.

PURPOSE: In the summer of 1998, Norvir semi-solid capsules supplies were threatened as a result of a new much less soluble crystal form of ritonavir. This report provides characterization of the two polymorphs and the structures and hydrogen bonding network for each form. METHODS: Ritonavir polymorphism was investigated using solid state spectroscopy and microscopy techniques including solid state NMR, Near Infrared Spectroscopy, powder X-ray Diffraction and Single crystal X-ray. A sensitive seed detection test was developed. RESULTS: Ritonavir polymorphs were thoroughly characterized and the structures determined. An unusual conformation was found for form II that results in a strong hydrogen bonding network A possible mechanism for heterogeneous nucleation of form II was investigated. CONCLUSIONS: Ritonavir was found to exhibit conformational polymorphism with two unique crystal lattices having significantly different solubility properties. Although the polymorph (form II) corresponding to the "cis" conformation is a more stable packing arrangement, nucleation, even in the presence of form II seeds, is energetically unfavored except in highly supersaturated solutions. The coincidence of a highly supersaturated solution and a probable heterogeneous nucleation by a degradation product resulted in the sudden appearance of the more stable form II polymorph.

The use of near-infrared spectroscopy to monitor the mobility of water within the sarafloxacin crystal lattice.

Near-infrared spectroscopy (NIRS) is proposed as a technique to study the mobility of water within the sarafloxacin crystal lattice. An investigation of two samples of sarafloxacin revealed that NIRS can distinguish between acceptable and unacceptable batches for formulation purposes. X-ray powder diffraction (XRPD), mid-infrared (mid-IR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) could not detect any differences between the two samples. NIRS detected differences in the location or orientation of the water molecules within the crystal lattices.

Role of an isomorphic desolvate in dissolution failures of an erythromycin tablet formulation.

The investigation of dissolution failures for erythromycin dihydrate tablet formulation over a 12-month period using a near-infrared spectroscopy technique revealed the role of a desolvated dihydrate in the retardation of dissolution. Near infrared spectroscopy (NIR) indicated a dehydrated dihydrate of erythromycin is produced during formulation and gradually binds with Mg(OH)2. The binding delays the process of dissolution. NIR was used to successfully predict that humidifying the tablets would reverse the binding and increase the dissolution rate.