Overcoming the false-minima problem in direct methods: Structure determination of the packaging enzyme P4 from bacteriophage φ13

The problems encountered during the phasing and structure determination of the packaging enzyme P4 from bacteriophage φ13 using the anomalous signal from selenium in a single-wavelength anomalous dispersion experiment (SAD) are described. The oligomeric state of P4 in the virus is a hexamer (with sixfold rotational symmetry) and it crystallizes in space group C2, with four hexamers in the crystallographic asymmetric unit. Current state-of-the-art ab initio phasing software yielded solutions consisting of 96 atoms arranged as sixfold symmetric clusters of Se atoms. However, although these solutions showed high correlation coefficients indicative that the substructure had been solved, the resulting phases produced uninterpretable electron-density maps. Only after further analysis were correct solutions found (also of 96 atoms), leading to the eventual identification of the positions of 120 Se atoms. Here, it is demonstrated how the difficulties in finding a correct phase solution arise from an intricate false-minima problem. © 2005 International Union of Crystallography - all rights reserved

The development of a theory-based intervention to promote appropriate disclosure of a diagnosis of dementia

Background: The development and description of interventions to change professional practice are often limited by the lack of an explicit theoretical and empirical basis. We set out to develop an intervention to promote appropriate disclosure of a diagnosis of dementia based on theoretical and empirical work. Methods: We identified three key disclosure behaviours: finding out what the patient already knows or suspects about their diagnosis; using the actual words 'dementia' or 'Alzheimer's disease' when talking to the patient; and exploring what the diagnosis means to the patient. We conducted a questionnaire survey of older peoples' mental health teams (MHTs) based upon theoretical constructs from the Theory of Planned Behaviour (TPB) and Social Cognitive Theory (SCT) and used the findings to identify factors that predicted mental health professionals' intentions to perform each behaviour. We selected behaviour change techniques likely to alter these factors. Results: The change techniques selected were: persuasive communication to target subjective norm; behavioural modelling and graded tasks to target self-efficacy; persuasive communication to target attitude towards the use of explicit terminology when talking to the patient; and behavioural modelling by MHTs to target perceived behavioural control for finding out what the patient already knows or suspects and exploring what the diagnosis means to the patient. We operationalised these behaviour change techniques using an interactive 'pen and paper' intervention designed to increase intentions to perform the three target behaviours. Conclusion : It is feasible to develop an intervention to change professional behaviour based upon theoretical models, empirical data and evidence based behaviour change techniques. The next step is to evaluate the effect of such an intervention on behavioural intention. We argue that this approach to development and reporting of interventions will contribute to the science of implementation by providing replicable interventions that illuminate the principles and processes underlying change.This project is funded by UK Medical Research Council, Grant reference number G0300999. Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. Jill Francis is funded by the Chief Scientist Office of the Scottish Government Health Directorate. The views expressed in this study are those of the authors

Surveillance and comparison of antimicrobial susceptibility patterns of ESKAPE organisms isolated from patients with bacteraemia in South Africa, 2016 - 2017

Background. In South Africa (SA), the National Department of Health has developed an Antimicrobial Resistance National Strategy Framework document to manage antimicrobial resistance (AMR). One of the strategic objectives is to optimise surveillance and early detection of AMR. At the National Institute for Communicable Diseases (NICD), an analysis of selected organisms and antimicrobial agents from both the public and the private sectors was conducted.Objectives. The relevance of surveillance for AMR is increasingly recognised in the light of global action plans to combat resistance. In this report, we present an overview of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) organisms and Escherichia coli reported from public and private sector laboratories in SA for the period 2016 - 2017.Methods. Antimicrobial susceptibility testing (AST) profiles on selected ESKAPE organisms and E. coli isolated from blood cultures from the public and private sectors in 2016 and 2017 were analysed. AST data were extracted from a web-based electronic platform created by the NICD. Drug-bug combinations following the World Health Organization’s Global Antimicrobial Surveillance System guidelines were included in the analysis.Results. A total of 28 920 ESKAPE organisms and E. coli were reported in 2016 and 32 293 in 2017 across the two health sectors. Proportions of some organisms differed between the two health sectors, such as E. coli (19% in the public sector and 36% in the private sector), A. baumannii (14% public and 4% private), P. aeruginosa (7% public and 11% private) and S. aureus (27% public and 17% private). Susceptibility data indicated changing patterns in both sectors towards an increase in non-susceptibility to carbapenems in K. pneumoniae (p<0.01). However, we demonstrated an increase in susceptibility to cloxacillin in S. aureus (p<0.01) in both sectors.Conclusions. The key clinically important finding is the rapidly decreasing carbapenem susceptibility among Enterobacteriaceae reported in SA, irrespective of sector. In addition, the analysis provides information that could be used to monitor the effectiveness of interventions implemented at a national level under the guidance and direction of the national AMR framework.

Repetitive arm functional tasks after stroke (RAFTAS): a pilot randomised controlled trial

Background Repetitive functional task practise (RFTP) is a promising treatment to improve upper limb recovery following stroke. We report the findings of a study to determine the feasibility of a multi-centre randomised controlled trial to evaluate this intervention. Methods A pilot randomised controlled trial was conducted. Patients with new reduced upper limb function were recruited within 14 days of acute stroke from three stroke units in North East England. Participants were randomised to receive a four week upper limb RFTP therapy programme consisting of goal setting, independent activity practise, and twice weekly therapy reviews in addition to usual post stroke rehabilitation, or usual post stroke rehabilitation. The recruitment rate; adherence to the RFTP therapy programme; usual post stroke rehabilitation received; attrition rate; data quality; success of outcome assessor blinding; adverse events; and the views of study participants and therapists about the intervention were recorded. Results Fifty five eligible patients were identified, 4-6% of patients screened at each site. Twenty four patients participated in the pilot study. Two of the three study sites met the recruitment target of 1-2 participants per month. The median number of face to face therapy sessions received was 6 [IQR 3-8]. The median number of daily repetitions of activities recorded was 80 [IQR 39-80]. Data about usual post stroke rehabilitation were available for 18/24 (75%). Outcome data were available for 22/24 (92%) at one month and 20/24 (83%) at three months. Outcome assessors were unblinded to participant group allocation for 11/22 (50%) at one month and 6/20 (30%) at three months. Four adverse events were considered serious as they resulted in hospitalisation. None were related to study treatment. Feedback from patients and local NHS therapists about the RFTP programme was mainly positive. Conclusions A multi-centre randomised controlled trial to evaluate an upper limb RFTP therapy programme provided early after stroke is feasible and acceptable to patients and therapists, but there are issues which needed to be addressed when designing a Phase III study. A Phase III study will need to monitor and report not only recruitment and attrition but also adherence to the intervention, usual post stroke rehabilitation received, and outcome assessor blinding

Registration evaluation of dynamic breast MR images

The interpretation of dynamic contrast-enhanced breast MR images is predicated on the assumption of minimal voxel movement during the time course of the image acquisition. Misalignment of the dynamic image sequence as a result of movement during image acquisition can lead to potentially misleading diagnostic conclusions. In this paper a new methodology is presented for assessing the degree of in-plane (intra-slice) movement in a dynamic image sequence. The method is demonstrated on data from six subjects. The conclusion is that the method makes it possible to quantitatively qualify the accuracy of computed enhancement curves and more importantly to identify unacceptably poor registration

N-{3-[2-(4-Fluoro­phen­oxy)eth­yl]-2,4-dioxo-1,3-diaza­spiro­[4.5]decan-7-yl}-4-methyl­benzamide

In the title compound, C24H26FN3O4, the two aromatic rings form a dihedral angle of 88.81 (15)°. The cyclo­hexane ring adopts a chair conformation and the five-membered ring is essentially planar, with a maximum deviation from planarity of 0.041 (2) Å. The crystal structure displays inter­molecular C—H⋯O and N—H⋯O hydrogen bonds

Irradiation-induced Ag nanocluster nucleation in silicate glasses: analogy with photography

The synthesis of Ag nanoclusters in sodalime silicate glasses and silica was studied by optical absorption (OA) and electron spin resonance (ESR) experiments under both low (gamma-ray) and high (MeV ion) deposited energy density irradiation conditions. Both types of irradiation create electrons and holes whose density and thermal evolution - notably via their interaction with defects - are shown to determine the clustering and growth rates of Ag nanocrystals. We thus establish the influence of redox interactions of defects and silver (poly)ions. The mechanisms are similar to the latent image formation in photography: irradiation-induced photoelectrons are trapped within the glass matrix, notably on dissolved noble metal ions and defects, which are thus neutralized (reverse oxidation reactions are also shown to exist). Annealing promotes metal atom diffusion, which in turn leads to cluster nuclei formation. The cluster density depends not only on the irradiation fluence, but also - and primarily - on the density of deposited energy and the redox properties of the glass. Ion irradiation (i.e., large deposited energy density) is far more effective in cluster formation, despite its lower neutralization efficiency (from Ag+ to Ag0) as compared to gamma photon irradiation.Comment: 48 pages, 18 figures, revised version publ. in Phys. Rev. B, pdf fil

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Galaxy And Mass Assembly (GAMA)

The GAMA survey aims to deliver 250,000 optical spectra (3--7Ang resolution) over 250 sq. degrees to spectroscopic limits of r_{AB} <19.8 and K_{AB}<17.0 mag. Complementary imaging will be provided by GALEX, VST, UKIRT, VISTA, HERSCHEL and ASKAP to comparable flux levels leading to a definitive multi-wavelength galaxy database. The data will be used to study all aspects of cosmic structures on 1kpc to 1Mpc scales spanning all environments and out to a redshift limit of z ~ 0.4. Key science drivers include the measurement of: the halo mass function via group velocity dispersions; the stellar, HI, and baryonic mass functions; galaxy component mass-size relations; the recent merger and star-formation rates by mass, types and environment. Detailed modeling of the spectra, broad SEDs, and spatial distributions should provide individual star formation histories, ages, bulge-disc decompositions and stellar bulge, stellar disc, dust disc, neutral HI gas and total dynamical masses for a significant subset of the sample (~100k) spanning both the giant and dwarf galaxy populations. The survey commenced March 2008 with 50k spectra obtained in 21 clear nights using the Anglo Australian Observatory's new multi-fibre-fed bench-mounted dual-beam spectroscopic system (AAOmega).Comment: Invited talk at IAU 254 (The Galaxy Disk in Cosmological Context, Copenhagen), 6 pages, 5 figures, high quality PDF version available at http://www.eso.org/~jliske/gama

Galaxy And Mass Assembly (GAMA): the 0.013 < z < 0.1 cosmic spectral energy distribution from 0.1 m to 1 mm

We use the Galaxy And Mass Assembly survey (GAMA) I data set combined with GALEX, Sloan Digital Sky Survey (SDSS) and UKIRT Infrared Deep Sky Survey (UKIDSS) imaging to construct the low-redshift (z < 0.1) galaxy luminosity functions in FUV, NUV, ugriz and YJHK bands from within a single well-constrained volume of 3.4 × 105 (Mpc h−1)3. The derived luminosity distributions are normalized to the SDSS data release 7 (DR7) main survey to reduce the estimated cosmic variance to the 5 per cent level. The data are used to construct the cosmic spectral energy distribution (CSED) from 0.1 to 2.1 μm free from any wavelength-dependent cosmic variance for both the elliptical and non-elliptical populations. The two populations exhibit dramatically different CSEDs as expected for a predominantly old and young population, respectively. Using the Driver et al. prescription for the azimuthally averaged photon escape fraction, the non-ellipticals are corrected for the impact of dust attenuation and the combined CSED constructed. The final results show that the Universe is currently generating (1.8 ± 0.3) × 1035 h W Mpc−3 of which (1.2 ± 0.1) × 1035 h W Mpc−3 is directly released into the inter-galactic medium and (0.6 ± 0.1) × 1035 h W Mpc−3 is reprocessed and reradiated by dust in the far-IR. Using the GAMA data and our dust model we predict the mid- and far-IR emission which agrees remarkably well with available data. We therefore provide a robust description of the pre- and post-dust attenuated energy output of the nearby Universe from 0.1 μm to 0.6 mm. The largest uncertainty in this measurement lies in the mid- and far-IR bands stemming from the dust attenuation correction and its currently poorly constrained dependence on environment, stellar mass and morphology