Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis

Objectives: To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods: We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results: We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions: These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated

A rapid, chromatography-free route to substituted acridine–isoalloxazine conjugates under microwave irradiation

Microwave irradiation was applied to a sequence of condensation reactions from readily available 9-chloroacridines to provide a range of novel acridine–isoalloxazine conjugates. The combination of these two moieties, both of biological interest, was achieved by a chromatography free route

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment

Treatment for CIN is usually undertaken in an outpatient colposcopy clinic to remove the pre-cancerous cells from the cervix. It commonly involves lifting the cells off the cervix with electrically heated wire (diathermy) or laser, or destroying the abnormal cells with freezing methods (cryotherapy). This is potentially a painful procedure. The purpose of this review is to determine which, if any, pain relief should be used during cervical colposcopy treatment. We identified 17 trials and these reported different forms of pain relief before, during and after colposcopy. Evidence from two small trials showed that women having a colposcopy treatment had less pain and blood loss if the cervix was injected with a combination of a local anaesthetic drug and a drug that causes blood vessels to constrict (narrow), compared with placebo. Although taking oral pain-relieving drugs (e.g. ibuprofen) before treatment on the cervix in the colposcopy clinic is recommended by most guidelines, evidence from two small trials did not show that this practice reduced pain during the procedure. Most of the evidence in this field is of a low to moderate quality and further research may change these findings. Additionally, we were unable to obtain evidence with regards to dosage of the local anaesthetic drug or method of administering local anaesthetic into the cervix. There is need for high-quality trials with sufficient numbers of participants in order to provide the data necessary to estimate these effects

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

Peer reviewedPublisher PD

When the carnival is over : Peter Barnes\u27 Red Noses and the theories of Mikhail Bakhtin

Peter Barnes, acknowledged as one of Britain\u27s most important contemporary playwrights, writes plays that are of an enormous scale, both physically and intellectually. Red Noses is one such play. Like Barnes\u27 other works, Red Noses makes great technical demands on directors, designers, actors and audiences. As with all of Barnes\u27 plays, Red Noses is, moreover, informed by a wide variety of theatrical styles. As Bernard Dukore (1990, p. 65) states, actors may be required to quickly switch from intellectual discourse, to period argot, to poetry, to modern slang, to rhetoric, to musical comedy, to ritual, to dance, to opera, to slapstick. .. Furthermore, all of Barnes\u27 plays operate, as Stephen Weeks (1996, p.46) points out, as much through the boldness of their visual imagery as through the inventiveness of their language. All plays in performance are polysemic, with the various systems of signs in dialogical relation. Barnes\u27 play Red Noses foregrounds the polysemic process. The systems of signs that operate within any play in performance may be defined as discrete languages. Some of these languages are non-verbal, such as the use of theatrical space and the movement of bodies within that space, scale of settings and sound and visual effects. This project looks at the verbal and non-verbal polysenic texts in Red Noses in performance. Mikhail Bakhtin\u27s theories are usually applied to verbal and, in particular, printed texts. Indeed, Bakhtin (1981, p.266) himself has stated that the organisation of languages in drama does not allow for the dialogic interpenetration of one language by another. Nevertheless, this project will examine whether the non-verbal language systems of production and performance challenge or extend Bakhtin\u27 s theories of language. Barnes\u27 plays are often referred to as anarchic or carnivalesque. with his theatrical style working as an analogue to his stated aim of seeking to disrupt the social order of contemporary society (Barnes, 1996a, p. viii; Barnes, 1996b, p. x). Some critics have defined Barnes as an iconoclastic writer, but this begs the question as to whether Barnes\u27 iconoclasm is conservative or radical. Is there a reaffirming of the hierarchies of social and political power as a result of the upside-down world created in Red Noses, or is there the promise of a new and ongoing process of change? The object of this project is to explore these questions through the rehearsal and performance processes of a production of Barnes\u27 play Red Noses. The play will be reassessed through Bakhtin\u27s theories of carnival, polyphonic discourse and dialogics, taking particular account of rehearsal and performance processes. In addition to problems of interpretation this project enters the debate about problems of texts in performance. The project can also be expected to generate useful research into performance itself as research

Architecturally diverse proteins converge on an analogous mechanism to inactivate Uracil-DNA glycosylase

Uracil-DNA glycosylase (UDG) compromises the replication strategies of diverse viruses from unrelated lineages. Virally encoded proteins therefore exist to limit, inhibit or target UDG activity for proteolysis. Viral proteins targeting UDG, such as the bacteriophage proteins ugi, and p56, and the HIV-1 protein Vpr, share no sequence similarity, and are not structurally homologous. Such diversity has hindered identification of known or expected UDG-inhibitory activities in other genomes. The structural basis for UDG inhibition by ugi is well characterized; yet, paradoxically, the structure of the unbound p56 protein is enigmatically unrevealing of its mechanism. To resolve this conundrum, we determined the structure of a p56 dimer bound to UDG. A helix from one of the subunits of p56 occupies the UDG DNA-binding cleft, whereas the dimer interface forms a hydrophobic box to trap a mechanistically important UDG residue. Surprisingly, these p56 inhibitory elements are unexpectedly analogous to features used by ugi despite profound architectural disparity. Contacts from B-DNA to UDG are mimicked by residues of the p56 helix, echoing the role of ugi’s inhibitory beta strand. Using mutagenesis, we propose that DNA mimicry by p56 is a targeting and specificity mechanism supporting tight inhibition via hydrophobic sequestration

Carbon fibre composites: integrated electrochemical sensors for wound management

The applicability of employing a carbon fibre mesh as an electrochemical sensing substructure for assessing urate transformations within wound exudates is evaluated. Prototype sensor assemblies have been designed and their response characteristics towards uric acid and other common physiological components are detailed. Modification of the carbon fibre sensor through surface anodisation and the application of cellulose acetate permselective barriers have been shown to lead to optimized responses and much greater sensitivity (1440% increase) and specificity. These could enable the accurate periodic monitoring of uric acid in wound fluid. The performance characteristics of the composite sensors in whole blood, serum and blister fluid have been investigated

Bacillus methanolicus sp. nov., a New Species of Thermotolerant, Methanol-Utilizing, Endospore-Forming Bacteria

The generic position of 14 strains of gram-positive bacteria able to use methanol as a growth substrate was determined. All are obligately aerobic, thermotolerant organisms that are able to grow at temperatures of 35 to 60°C. Nine of the strains produce oval spores at a subterminal-to-central position in slightly swollen rod-shaped cells. DNA-DNA hybridization studies, 5S rRNA sequence analysis, and physiological characteristics revealed that all 14 strains cluster as a well-defined group and form a distinct new genospecies. Analysis of the 16S and 5S rRNA sequences indicated that this new species is distinct from Bacillus brevis but closely related to B. firmus and B. azotoformans. The name proposed for this new species is B. methanolicus. The type strain, PB1, has been deposited in the National Collection of Industrial and Marine Bacteria as NCIMB 13113

Argument for the need of investigation of the relationship between body fatness and experimental pain sensitivity.

In this communication, we argue about the need for an extensive investigation of the relationship between body fatness and fat distribution and experimental pain to explore the factors that might contribute to the increased prevalence of pain conditions in obese individuals

The SCUBA Bright Quasar Survey (SBQS): 850micron observations of the z>4 sample

We present initial results of a new, systematic search for massive star-formation in the host galaxies of the most luminous and probably most massive z>=4 radio-quiet quasars (M(B) 10^13Lsun). A total of 38 z>=4 radio-quiet quasars have been observed at the JCMT using SCUBA at 850microns: 8 were detected (>3sigma) with S(850microns)>~ 10mJy (submillimetre-loud). The new detections almost triple the number of optically selected, submillimetre-loud z>~4 radio-quiet quasars known to date. We include a detailed description of how our quasar sample is defined in terms of radio and optical properties. There is no strong evidence for trends in either detectability or 850microns flux with absolute magnitude, M(B). We find that the weighted mean flux of the undetected sources is 2.0 +/- 0.6mJy, consistent with an earlier estimate of \~3mJy based on more sensitive observations of a sample z>~4 radio-quiet quasars (McMahon et al., 1999). This corresponds to an inferred starformation rate of \~1000Msun/yr, similar to Arp220. The typical starformation timescale for the submillimetre-bright sources is ~1Gyr, 10 times longer than the typical accretion-driven e-folding timescale of ~5x10^7 years. Our 850micron detection of the z=4.4 quasar PSS J1048+4407 when analysed in conjunction with 1.2mm single-dish and interferometric observations suggests that this source is resolved on angular scales of 1-2" (6-12 kpc). In addition, we present a new optical spectrum of this source, identifying it as a broad absorption line (BAL) quasar. The new redshift is outside that covered in a recent CO line search by Guilloteau et al., (1999), highlighting the need for accurate redshifts for the obervation and interpretation of high-redshift line studies.Comment: 16 pages, 11 figures. Accepted by Monthly Notices of the Royal Astronomical Societ