Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis

BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing.

METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used.

RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles <or=3.3 microm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008).

CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.

Levels of Arsenic and Other Trace Elements in Southern Libyan Agricultural Irrigated Soil and Non-irrigated Soil Projects

The levels of As and various other trace elements found in the irrigated agricultural soil (Tsoil) of southern Libya were compared with non-irrigated soil (Csoil) from the same sampling campaign collected between April and May 2008. The soil samples represented agronomic practice in the southern Libyan regions of Maknwessa (MAK), Aril (ARL) and Taswaa (TAS), and were analyzed by Inductively coupled plasma mass spectrometry (ICP-MS) for Co, Ni, Cu, Se, Mo, Zn, As, Pb, Cd and P. Concentrations of P and As in TAS and MAK were found to be higher in Tsoil compared to Csoil, while the opposite was true for ARL. In general, As concentrations in these areas were 2-3 times lower than the global average. In ARL, the average P concentrations of the Csoil samples were significantly higher than those of Tsoil samples: this site is composed mainly of pasture for animal production, where phosphate fertilizers are used regularly. Distance from the source of irrigation was found to be of an important influence on the heavy metal concentration of the soil, with greater concentrations found closer to the irrigation source. It can be concluded from the results that irrigation water contains elevated levels of As, which finds its way into the soil profile and can lead to accumulation of As in the soil over time.

The Modern Ordinary: Changing culture of living in Egypt’s traditional quarters at the turn of the twentieth Century

Having experienced social and political structures of the 19th century Europe, Western- educated Egyptian elite used public institutions to force legislative structures and procedures that ruled out traditional housing forms and spatial systems. This essay detects direct and indirect impact of these changes that informed the spatial change of modern living in Egypt in the first quarter of the twentieth century. It offers analysis of socio-spatial practices and change in ordinary Cairenes’ modes of everyday living, using social routine and interaction to explain spatial systems and changing house forms during the first quarter of the 20th century. In doing so, the essay utilized archival documents, accounts, formal decrees, and novels of the time as well as conducting survey of house forms and spatial organizations in Old Cairo.

Toluene dioxygenase-catalysed oxidation route to angular cis-monohydrodiols and other bioproducts from bacterial metabolism of 1,2-dihydrobenzocyclobutene and derivatives

A mutant strain (UV4) of the soil bacterium Pseudomonas putida, containing toluene dioxygenase, has been used in the metabolic oxidation of 1,2-dihydrobenzocyclobutene 12 dagger and the related substrates 1,2-dihydrobenzocyclobuten-1-ol 13 and biphenylene 33. Stable angular cis-monohydrodiol metabolites (1R,2S)-bicyclo[4.2.0]octa-3,5-diene-1,2 7, (1S,2S,8S)-bicyclo[4.2.0]octa-3,5-diene-1,2,8-triol 8 and biphenylene-cis-1,8b-diol 9, isolated from each of these substrates, have been structurally and stereochemically assigned. The structure, enantiopurity and absolute configuration of the other cis-diol metabolites, (2R,3S)-bicyclo[4.2.0]octa-1(6),4-diene-2,3-diol 14 and cis-1,2-dihydroxy-1,2-dihydrobenzocyclobutene 16, and the benzylic oxidation bioproducts, 1,2-dihydrobenzocyclobuten-1-ol 13, 1,2-dihydrobenzocyclobuten-1-one 15 and 2-hydroxy-1,2-dihydrobenzocyclobuten-1-one 17, obtained from 1,2-dihydrobenzocyclobutene and 1,2-dihydrobenzocyclobuten-1-ol, have been determined with the aid of chiral stationary-phase HPLC, NMR and CD spectroscopy, and stereochemical correlation. X-Ray crystallographic methods have been used in the determination of absolute configuration of the di-camphanates 27 (from diol 7) and 32 (from diol 9), and the di-MTPA ester 29 (from diol 14) of the corresponding cis-diol metabolites. The metabolic sequence involved in the formation of bioproducts derived from 1,2-dihydrobenzocyclobutene 12 has been investigated.

Late Bronze Age casting debris and other base metal finds from Haughey’s Fort

This paper provides a full overview of base metal finds from the excavations conducted at Haughey's Fort between 1987 and 1995. Most of the assemblage consists of waste metal from casting activities relating to the Late Bronze Age occupation of the site. A small minority of objects are of a later date, mostly Iron Age. Both the latter and the vast majority of Late Bronze metal items were recovered from a specific sector of the inner enclosure. Typological parallels, context and chronology of the finds are discussed, and a tentative interpretation of the evidence proposed.

Striking a Balance:Christianity and the Challenges of Long-Term Human Security in Zimbabwe

African evangelical/Pentecostal/charismatic (EPC) Christians-previously dismissed by scholars as apolitical-are becoming increasingly active socially and politically. This chapter presents a case study of an EPC congregation in Harare. It demonstrates how the congregation provides short-term human security by responding to the needs of the poor, while at the same time creating space where people can develop the "self-expression values" necessary for long-term human security. The case study also demonstrates that even under authoritarian states, religious actors can actively choose to balance the immediate demands of short-term human security with the sometimes competing demands of long-term human security. Policymakers can benefit from a greater understanding of how religious actors strike this balance and from a greater appreciation of the variability, flexibility, and religious resources of EPC Christians in such contexts.

SIMLA: Simulating particle dynamics in intense laser and other electromagnetic fields via classical and quantum electrodynamics

We present the Fortran program SIMLA, which is designed for the study of charged particle dynamics in laser and other background fields. The dynamics can be determined classically via the Lorentz force and Landau–Lifshitz equations or, alternatively, via the simulation of photon emission events determined by strong-field quantum-electrodynamics amplitudes and implemented using Monte-Carlo routines. Multiple background fields can be included in the simulation and, where applicable, the propagation direction, field type (plane wave, focussed paraxial, constant crossed, or constant magnetic), and time envelope of each can be independently specified.

Alien aquatics in Europe: assessing the relative environmental and socio-economic impacts of invasive aquatic macroinvertebrates and other taxa

Invasive alien aquatic species, including marine and freshwater macroinvertebrates, have become increasingly important in terms of both environmental and socio-economic impacts. In order to assess their environmental and economic costs, we applied the Generic Impact Scoring System (GISS) and performed a comparison with other taxa of invaders in Europe. Impacts were scored into six environmental and six socio-economic categories, with each category containing five impact levels. Among 49 aquatic macroinvertebrates, the most impacting species were the Chinese mitten crab, Eriocheir sinensis (Milne-Edwards, 1853) and the zebra mussel, Dreissena polymorpha (Pallas, 1771). The highest impacts found per GISS impact category were, separately; on ecosystems, through predation, as competitors, and on animal production. Eleven species have an impact score > 10 (high impact) and seven reach impact level 5 in at least one impact category (EU blacklist candidates), the maximum score that can be given is 60 impact points. Comparisons were drawn between aquatic macroinvertebrates and vertebrate invaders such as fish, mammals and birds, as well as terrestrial arthropods, revealing invasive freshwater macroinvertebrates to be voracious predators of native prey and damaging to native ecosystems compared with other taxa. GISS can be used to compare these taxa and will aid policy making and targeting of invasive species for management by relevant agencies, or to assist in producing species blacklist candidates.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Solitary and repetitive binding motifs for the AP2 complex alpha-appendage in amphiphysin and other accessory proteins

Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery. This machinery interacts with the appendage domains of APs, which have platform and beta-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the alpha-appendage. The motif domain of amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the alpha-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the alpha-appendage.

Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR).

OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP?

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used.

REVIEW METHODS: Systematic review and economic modelling.

RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO.

LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR.

CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.