Clinico-epidemiological features of infections caused by CTX-M type extended spectrum beta lactamase-producing Escherichia coli in hospitalised patients

A review of medical records of 45 of 53 hospitalised patients with positive cultures for CTX-M type ESBL-producing Escherichia coli between 01 January and 31 May 2004 was conducted. The mean age of the population studied was 73.1 (+/-14.6) years and the majority (55.6%) had been under the care of the internal medicine or elderly care service. In the majority (77.8%) of instances the isolate was attributed to a clinical infection rather than colonisation and the commonest clinical specimen to yield the organism was urine, which was positive in 57.8% of patients. Acquisition of the organism was categorised as nosocomial in 68.9% of patients; in this subgroup, the median duration of inpatient stay prior to recovery of the organism was 24 (range 3-240) days. Haemodialysis-dependence was the most common of the comorbidities evaluated. The mean number of antibiotics prescribed per patient in the 30 days prior to first isolation of the organism was 1.7 (range 0-4). Furthermore, the mean number of antibiotic-days exposure per patient during this period was 13.9 (range 0-48). The most frequently received class of antibiotic was beta-lactam/beta-lactamase inhibitor combinations. Of 35 infections, 26 (74.2%) were successfully treated. Overall 12 patients with infection died (34.3%); attributable mortality was presumed in seven (20%).

Evaluation of the VITEK 2 AST N-054 test card for the detection of extended-spectrum beta-lactamase production in Escherichia coli with CTX-M phenotypes

A new VITEK 2 antibiotic susceptibility testing (AST) card, AST N-054, was introduced for aerobic gram-negative bacilli in 2007 and has been widely adopted for routine use in the UK. We evaluated its performance for detecting extended-spectrum beta-lactamase (ESBL) production in Escherichia coli.

The impact of antibiotic use on the incidence and resistance pattern of extended-spectrum beta-lactamase-producing bacteria in primary and secondary healthcare settings

Aims: The objective of the present study was to study the relationship between hospital antibiotic use, community antibiotic use and the incidence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in hospitals, while assessing the impact of a fluoroquinolone restriction policy on ESBL-producing bacteria incidence rates. METHODS: The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate antibiotic use to ESB-producing bacteria incidence rates and resistance patterns over a 5 year period (January 2005-December 2009). Results: Analysis showed that the hospital incidence of ESBLs had a positive relationship with the use of fluoroquinolones in the hospital (coefficient = 0.174, P= 0.02), amoxicillin-clavulanic acid in the community (coefficient = 1.03, P= 0.03) and mean co-morbidity scores for hospitalized patients (coefficient = 2.15, P= 0.03) with various time lags. The fluoroquinolone restriction policy was implemented successfully with the mean use of fluoroquinolones (mainly ciprofloxacin) being reduced from 133 to 17 defined daily doses (DDDs)/1000 bed days (P <0.001) and from 0.65 to 0.54 DDDs/1000 inhabitants/day (P= 0.0007), in both the hospital and its surrounding community, respectively. This was associated with an improved ciprofloxacin susceptibility in both settings [ciprofloxacin susceptibility being improved from 16% to 28% in the community (P <0.001)] and with a statistically significant reduction in ESBL-producing bacteria incidence rates. Discussion: This study supports the value of restricting the use of certain antimicrobial classes to control ESBL, and demonstrates the feasibility of reversing resistance patterns post successful antibiotic restriction. The study also highlights the potential value of the time-series analysis in designing efficient antibiotic stewardship. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

flp-32 Ligand/Receptor Silencing Phenocopy Faster Plant Pathogenic Nematodes

Restrictions on nematicide usage underscore the need for novel control strategies for plant pathogenic nematodes such as Globodera pallida (potato cyst nematode) that impose a significant economic burden on plant cultivation activities. The nematode neuropeptide signalling system is an attractive resource for novel control targets as it plays a critical role in sensory and motor functions. The FMRFamide-like peptides (FLPs) form the largest and most diverse family of neuropeptides in invertebrates, and are structurally conserved across nematode species, highlighting the utility of the FLPergic system as a broad-spectrum control target. flp-32 is expressed widely across nematode species. This study investigates the role of flp-32 in G. pallida and shows that: (i) Gp-flp-32 encodes the peptide AMRNALVRFamide; (ii) Gp-flp-32 is expressed in the brain and ventral nerve cord of G. pallida; (iii) migration rate increases in Gp-flp-32-silenced worms; (iv) the ability of G. pallida to infect potato plant root systems is enhanced in Gp-flp-32-silenced worms; (v) a novel putative Gp-flp-32 receptor (Gp-flp-32R) is expressed in G. pallida; and, (vi) Gp-flp-32R silenced worms also display an increase in migration rate. This work demonstrates that Gp30 flp-32 plays an intrinsic role in the modulation of locomotory behaviour in G. pallida, and putatively interacts with at least one novel G-protein coupled receptor (Gp-flp-32R). This is the first functional characterisation of a parasitic nematode FLP-GPCR. © 2013 Atkinson et al.

Amplitude-modulation characteristics of power-combining Class-E amplifier with finite choke

Power back-off performances of a new variant power-combining Class-E amplifier under different amplitude-modulation schemes such as continuous wave (CW), envelope elimination and restoration (EER), envelope tracking (ET) and outphasing are for the first time investigated in this study. Finite DC-feed inductances rather than massive RF chokes as used in the classic single-ended Class-E power amplifier (PA) resulted from the approximate yet effective frequency-domain circuit analysis provide the wherewithal to increase modulation bandwidth up to 80% higher than the classic single-ended Class-E PA. This increased modulation bandwidth is required for the linearity improvement in the EER/ET transmitters. The modified output load network of the power-combining Class-E amplifier adopting three-harmonic terminations technique relaxes the design specifications for the additional filtering block typically required at the output stage of the transmitter chain. Qualitative agreements between simulation and measurement results for all four schemes were achieved where the ET technique was proven superior to the other schemes. When the PA is used within the ET scheme, an increase of average drain efficiency of as high as 40% with respect to the CW excitation was obtained for a multi-carrier input signal with 12 dB peak-to-average power ratio. © 2011 The Institution of Engineering and Technology.

Entanglement Spectrum, Critical Exponents and Order Parameters in Quantum Spin Chains

We investigate the entanglement spectrum near criticality in finite quantum spin chains. Using finite size scaling we show that when approaching a quantum phase transition, the Schmidt gap, i.e., the difference between the two largest eigenvalues of the reduced density matrix ?1, ?2, signals the critical point and scales with universal critical exponents related to the relevant operators of the corresponding perturbed conformal field theory describing the critical point. Such scaling behavior allows us to identify explicitly the Schmidt gap as a local order parameter.

Immunotoxicity of aflatoxin B1: Impairment of the cell-mediated response to vaccine antigen and modulation of cytokine expression

Aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus or A. parasiticus, is a frequent contaminant of food and feed. This toxin is hepatotoxic and immunotoxic. The present study analyzed in pigs the influence of AFB1 on humoral and cellular responses, and investigated whether the immunomodulation observed is produced through interference with cytokine expression. For 28 days, pigs were fed a control diet or a diet contaminated with 385, 867 or 1807 mu g pure AFB1/kg feed. At days 4 and 15, pigs were vaccinated with ovalbumin. AFB1 exposure, confirmed by an observed dose-response in blood aflatoxin-albumin adduct, had no major effect on humoral immunity as measured by plasma concentrations of total IgA, IgG and IgM and of anti-ovalbumin IgG. Toxin exposure did not impair the mitogenic response of lymphocytes but delayed and decreased their specific proliferation in response to the vaccine antigen, suggesting impaired lymphocyte activation in pigs exposed to AFB1. The expression level of pro-inflammatory (TNF-alpha, IL-1 beta, IL-6, IFN-gamma) and regulatory (IL-10) cytokines was assessed by real-time PCR in spleen. A significant up-regulation of all 5 cytokines was observed in spleen from pigs exposed to the highest dose of AFB1. In pigs exposed to the medium dose, IL-6 expression was increased and a trend towards increased IFN-gamma and IL-10 was observed. In addition we demonstrate that IL-6 impaired in vitro the antigenic- but not the mitogenic-induced proliferation of lymphocytes from control pigs vaccinated with ovalbumin. These results indicate that AFB1 dietary exposure decreases cell-mediated immunity while inducing an inflammatory response. These impairments in the immune response could participate in failure of vaccination protocols and increased susceptibility to infections described in pigs exposed to AFB1. (C) 2008 Elsevier Inc. All rights reserved.

Aldo goes to Primary School: Experiencing school through the lens of the autistic spectrum.

The document draws largely on the results of research carried out by Hugh McNally and Dominic Morris of McNally Morris Architects and Keith McAllister of Queen’s University Belfast between 2012 and 2013. The objective of the study was to obtain a greater understanding of the impact that architecture and the built environment can have on people with autism spectrum disorder (ASD). The investigation into the subject centred on parents of young children with ASD in the belief that they are most likely to have an intimate knowledge of the issues that affect their children and are relatively well positioned to communicate those issues.

The study comprised a number of components.

- Focus Group Discussions with parents of children with ASD
- A Postal Questionnaire completed by parents of children with ASD
- A Comprehensive Desktop study of contemporary research into the relationship between ASD and aspects of the built environment.

Social stories are then used to help illustrate the world of a child with ASD to the reader and identify a series of potential difficulties for the pupil with ASD in a primary school setting. Design considerations and mitigating measures are then proposed for each difficulty.

The intention is that the document will raise awareness of some of the issues affecting primary school children with ASD and generate discourse among those whose task it is to provide an appropriate learning environment for all children. This includes teachers, health professionals, architects, parents, carers, school boards, government bodies and those with ASD themselves.

While this document uses the primary school as a lens through which to view some of the issues associated with ASD, it is the authors’ contention that the school can be seen as a “microcosm” for the wider world and that lessons taken from the learning environment can be applied elsewhere. The authors therefore hope that the document will help raise awareness of the myriad of issues for those with ASD that are embedded in the vast landscape of urban configurations and building types making up the spatial framework of our society.

Detection of magnetic dipole lines of Fe XII in the ultraviolet spectrum of the dwarf star ε Eri

We report observations of the dwarf star e Eri (K2V) made with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope. The high sensitivity of the STIS instrument has allowed us to detect the magnetic dipole transitions of Fe XII at 1242.00 and 1349 38 Å for the first time in a star other than the Sun. The width of the stronger line at 1242.00 Å has also been measured; such measurements are not possible for the permitted lines of Fe XII in the extreme-ultraviolet. To within the accuracy of the measurements the N v and the Fe XII lines occur at their rest wavelengths. Electron densities and linewidths have been measured from other transition region lines. Together, these can be used to investigate the non-thermal energy flux in the lower and upper transition regions, which is useful in constraining possible heating processes. The Fe XII lines are also present in archival STIS spectra of other G/K-type dwarfs.

Evidence for relativistic features in the X-ray spectrum of Mrk 335

We present an analysis of hard X-ray features in the spectrum of the bright Sy 1 galaxy Mrk 335 observed by the XMM-Newton satellite. Our analysis confirms the presence of a broad, ionized Fe Ka emission line in the spectrum, first found by Gondoin et al. The broad line can be modelled successfully by relativistic accretion disc reflection models. This interpretation is unusually robust in the case of Mrk 335 because of the lack of any ionized ('warm') absorber and the absence a clear narrow core to the line. Partial covering by neutral gas cannot, however, be ruled out statistically as the origin of the broad residuals. Regardless of the underlying continuum we report, for the first time in this source, the detection of a narrow absorption feature at the rest frame energy of ~5.9 keV. If the feature is identified with a resonance absorption line of iron in a highly ionized medium, the redshift of the line corresponds to an inflow velocity of ~0.11-0.15c. We present a simple model for the inflow, accounting approximately for relativistic and radiation pressure effects, and use Monte Carlo methods to compute synthetic spectra for qualitative comparison with the data. This modelling shows that the absorption feature can plausibly be reproduced by infalling gas providing that the feature is identified with Fe xxvi. We require the inflowing gas to extend over a limited range of radii at a few tens of r to match the observed feature. The mass accretion rate in the flow corresponds to 60 per cent of the Eddington limit, in remarkable agreement with the observed rate. The narrowness of the absorption line tends to argue against a purely gravitational origin for the redshift of the line, but given the current data quality we stress that such an interpretation cannot be ruled out. © 2006 The Authors.

Time-dependent three-dimensional spectrum synthesis for Type Ia supernovae

A Monte Carlo code (artis) for modelling time-dependent three-dimensional spectral synthesis in chemically inhomogeneous models of Type Ia supernova ejecta is presented. Following the propagation of ?-ray photons, emitted by the radioactive decay of the nucleosynthesis products, energy is deposited in the supernova ejecta and the radiative transfer problem is solved self-consistently, enforcing the constraint of energy conservation in the comoving frame. Assuming a photoionization-dominated plasma, the equations of ionization equilibrium are solved together with the thermal balance equation adopting an approximate treatment of excitation. Since we implement a fully general treatment of line formation, there are no free parameters to adjust. Thus, a direct comparison between synthetic spectra and light curves, calculated from hydrodynamic explosion models, and observations is feasible. The code is applied to the well-known W7 explosion model and the results tested against other studies. Finally, the effect of asymmetric ejecta on broad-band light curves and spectra is illustrated using an elliptical toy model. © 2009 RAS.

Histone deacetylase 7 controls endothelial cell growth through modulation of beta-catenin

Rationale: Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role in endothelial function.

Objective: This study aimed to investigate the role of HDAC7 in endothelial cell (EC) proliferation and growth and the underlying mechanism.

Methods and Results: Overexpression of HDAC7 by adenoviral gene transfer suppressed human umbilical vein endothelial cell (HUVEC) proliferation by preventing nuclear translocation of ß-catenin and downregulation of T-cell factor-1/Id2 (inhibitor of DNA binding 2) and cyclin D1, leading to G1 phase elongation. Further assays with the TOPFLASH reporter and quantitative RT-PCR for other ß-catenin target genes such as Axin2 confirmed that overexpression of HDAC7 decreased ß-catenin activity. Knockdown of HDAC7 by lentiviral short hairpin RNA transfer induced ß-catenin nuclear translocation but downregulated cyclin D1, cyclin E1 and E2F2, causing HUVEC hypertrophy. Immunoprecipitation assay and mass spectrometry analysis revealed that HDAC7 directly binds to ß-catenin and forms a complex with 14-3-3 e, ?, and ? proteins. Vascular endothelial growth factor treatment induced HDAC7 degradation via PLC?-IP3K (phospholipase C?–inositol-1,4,5-trisphosphate kinase) signal pathway and partially rescued HDAC7-mediated suppression of proliferation. Moreover, vascular endothelial growth factor stimulation suppressed the binding of HDAC7 with ß-catenin, disrupting the complex and releasing ß-catenin to translocate into the nucleus.

Conclusions: These findings demonstrate that HDAC7 interacts with ß-catenin keeping ECs in a low proliferation stage and provides a novel insight into the mechanism of HDAC7-mediated signal pathways leading to endothelial growth

The role of sexual steroids in the modulation of growth hormone (GH) secretion in humans

Sex steroids contribute to modulate GH secretion in man. However, both the exact locus and mechanism by which their actions are exerted still remain not clearly understood. We undertook a number of studies designed to ascertain: (1) whether or not sudden or chronic changes in circulating gonadal steroids may affect GH secretion in normal adults; and (2) the reason(s) for gender-related dimorphic pattern of GH release. The pituitary reserve of GH, as evaluated by means of a GHRH challenge, was similar in women with anorexia nervosa and in normally menstruating women. Estrogenic receptor blockade with tamoxifen (TMX) did not significantly change GHRH-induced GH response in these normal women. Therefore, acute or chronic hypoestrogenism apparently had no important effects at level of somatotrophs. In another group of normal women we tested the possibility that changes in circulating estrogens might induce changes in the hypothalamic-somatotroph rhythm (HSR). GHRH challenges were performed throughout a menstrual cycle, and again after having achieved functional ovarian blockade with a GnRH agonist treatment. Short-term ovarian blockade did not significantly affect the parameters of GH response to GHRH, although it was accompanied by an increase in the number of women ina refractory HSR phase at testing. This suggested a low potentiating effect on the basic pattern of somatostatin (SS) release occurring as a consequence of the decrease in circulating estrogens. In normal men, neither the GH response to GHRH nor the HSR were affected by functional testicular blockade (after GnRH agonist treatment). However, the administration of testosterone enanthate (250 mg) to another group of men increased both the GHRH-induced GH release and the number of subjects in a spontaneous secretory HSR phase at testing; these were reversed by estrogenic receptor blockade with TMS. In another group of normal men, the fraction of GH secreted in pulses (FGHP) during a nocturnal sampling period was significantly decreased by testicular blockade. Other parameters of GH secretion, such as the number of GH pulses and their mean amplitude (A), and the mean plasma GH concentration (MCGH), showed a slight, although not significant, decrease following the lack of androgens. The administration of testosterone enanthate (500 mg) reversed these parameters to values similar to those in the basal study. Interestingly, when tamoxifen was given after testosterone enanthate, A, MCGH and FGHP increased to values significantly higher than in any other experimental condition in that study. In all, these data suggest that 17ß-estradiol may participate in GH modulation by inhibiting the hypothalamic release of somatostatin, while testosterone stimulates it. The results obtained after estrogenic receptor blockade appear to indicate that the effect of testosterone in such a modulation is dependent on its aromatization to 17ß-estradiol. The differential levels of this steroid in both sexes might account for the sexual dimorphic pattern of GH secretion. From other data in the literature, obtained in rats, and our preliminary data in children with constitutional delay of growth and puberty, it is tempting to speculate that the effect of 17ß-estradiol may be exerted by modifying the functional activity of a-2 adrenergic pathways involved in the negative modulation of SS release.

Interceptive skills in children aged 9-11 years, diagnosed with Autism Spectrum Disorder

Growing evidence suggests that significant motor problems are associated with a diagnosis of Autism Spectrum Disorders (ASD), particularly in catching tasks. Catching is a complex, dynamic skill that involves the ability to synchronise one's own movement to that of a moving target. To successfully complete the task, the participant must pick up and use perceptual information about the moving target to arrive at the catching place at the right time. This study looks at catching ability in children diagnosed with ASD (mean age 10.16 ± 0.9 years) and age-matched non-verbal (9.72 ± 0.79 years) and receptive language (9.51 ± 0.46) control groups. Participants were asked to "catch" a ball as it rolled down a fixed ramp. Two ramp heights provided two levels of task difficulty, whilst the sensory information (audio and visual) specifying ball arrival time was varied. Results showed children with ASD performed significantly worse than both the receptive language (p =.02) and non-verbal (p =.02) control groups in terms of total number of balls caught. A detailed analysis of the movement kinematics showed that difficulties with picking up and using the sensory information to guide the action may be the source of the problem. © 2013 Elsevier Ltd.