ClgR regulation of chaperone and protease systems is essential for Mycobacterium tuberculosis parasitism of the macrophage

Chaperone and protease systems play essential roles in cellular homeostasis and have vital functions in controlling the abundance of specific cellular proteins involved in processes such as transcription, replication, metabolism and virulence. Bacteria have evolved accurate regulatory systems to control the expression and function of chaperones and potentially destructive proteases. Here, we have used a combination of transcriptomics, proteomics and targeted mutagenesis to reveal that the clp gene regulator (ClgR) of Mycobacterium tuberculosis activates the transcription of at least ten genes, including four that encode protease systems (ClpP1/C, ClpP2/C, PtrB and HtrA-like protease Rv1043c) and three that encode chaperones (Acr2, ClpB and the chaperonin Rv3269). Thus, M. tuberculosis ClgR controls a larger network of protein homeostatic and regulatory systems than ClgR in any other bacterium studied to date. We demonstrate that ClgR-regulated transcriptional activation of these systems is essential for M. tuberculosis to replicate in macrophages. Furthermore, we observe that this defect is manifest early in infection, as M. tuberculosis lacking ClgR is deficient in the ability to control phagosome pH 1 h post-phagocytosis

Cross-validation of short forms of the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

Background The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item assessment designed to assist in the prediction of aberrant drug-related behavior (ADB) among patients with chronic pain. Recent work has created shorter versions of the SOAPP-R, including a static 12-item short form and two computer-based methods (curtailment and stochastic curtailment) that monitor assessments in progress. The purpose of this study was to cross-validate these shorter versions in two new populations. Methods This retrospective study used data from patients recruited from a hospital-based pain center (n = 84) and pain patients followed and treated at primary care centers (n = 110). Subjects had been administered the SOAPP-R and assessed for ADB. In real-data simulation, the sensitivity, specificity, and area under the curve (AUC) of each form were calculated, as was the mean test length using curtailment and stochastic curtailment. Results Curtailment reduced the number of items administered by 30% to 34% while maintaining sensitivity and specificity identical to those of the full-length SOAPP-R. Stochastic curtailment reduced the number of items administered by 45% to 63% while maintaining sensitivity and specificity within 0.03 of those of the full-length SOAPP-R. The AUC of the 12-item form was equal to that of the 24-item form in both populations. Conclusions Curtailment, stochastic curtailment, and the 12-item short form have potential to enhance the efficiency of the SOAPP-

The validity and reliability of the exposure index as a metric for estimating the radiation dose to the patient

Introduction With the introduction of digital radiography, the feedback between image quality and over-exposure has been partly lost which in some cases has led to a steady increase in dose. Over the years the introduction of exposure index (EI) has been used to resolve this phenomenon referred to as ‘dose creep’. Even though EI is often vendor specific it is always a related of the radiation exposure to the detector. Due to the nature of this relationship EI can also be used as a patient dose indicator, however this is not widely investigated in literature. Methods A total of 420 dose-area-product (DAP) and EI measurements were taken whilst varying kVp, mAs and body habitus on two different anthropomorphic phantoms (pelvis and chest). Using linear regression, the correlation between EI and DAP were examined. Additionally, two separate region of interest (ROI) placements/per phantom where examined in order to research any effect on EI. Results When dividing the data into subsets, a strong correlation between EI and DAP was shown with all R-squared values > 0.987. Comparison between the ROI placements showed a significant difference between EIs for both placements. Conclusion This research shows a clear relationship between EI and radiation dose which is dependent on a wide variety of factors such as ROI placement, body habitus. In addition, pathology and manufacturer specific EI’s are likely to be of influence as well. Implications for practice The combination of DAP and EI might be used as a patient dose indicator. However, the influencing factors as mentioned in the conclusion should be considered and examined before implementation

Development of Short-Form Versions of the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R):A Proof-of-Principle Study

BACKGROUND: The Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) is a 24-item questionnaire designed to assess risk of aberrant medication-related behaviors in chronic pain patients. The introduction of short forms of the SOAPP-R may save time and increase utilization by practitioners. OBJECTIVE: To develop and evaluate candidate SOAPP-R short forms. DESIGN: Retrospective study. SETTING: Pain centers. SUBJECTS: Four hundred and twenty-eight patients with chronic noncancer pain. METHODS: Subjects had previously been administered the full-length version of the SOAPP-R and been categorized as positive or negative for aberrant medication-related behaviors via the Aberrant Drug Behavior Index (ADBI). Short forms of the SOAPP-R were developed using lasso logistic regression. Sensitivity, specificity, and area under the curve (AUC) of all forms were calculated with respect to the ADBI using the complete data set, training-test analysis, and 10-fold cross-validation. The coefficient alpha of each form was also calculated. An external set of 12 pain practitioners reviewed the forms for content. RESULTS: In the complete data set analysis, a form of 12 items exhibited sensitivity, specificity, and AUC greater than or equal to those of the full-length SOAPP-R (which were 0.74, 0.67, and 0.76, respectively). The short form had a coefficient alpha of 0.76. In the training-test analysis and 10-fold cross-validation, it exhibited an AUC value within 0.01 of that of the full-length SOAPP-R. The majority of external practitioners reported a preference for this short form. CONCLUSIONS: The 12-item version of the SOAPP-R has potential as a short risk screener and should be tested prospectively

Performing heritage: the use of live 'actors' in heritage presentations

This paper investigates the phenomenon of 'living history' presentations of heritage, using live 'actors' to portray historical characters. Its aim is to discuss these presentations in the context of what may be understood as 'heritage', and of the nature of 'performance'. Four case studies of heritage sites, each important as a tourist attraction, have been selected for detailed study, together with a number of other examples of heritage performance. It is clear from the empirical work that different performance strategies are employed within the heritage industry and by individual 'actors'. Most of the performers take part as a leisure activity, and many do not consider themselves to be 'performing' at all. The greatest concern of participants lies in the degree of authenticity of the performance. Through 'living history', the 'actors' are drawn into an experience of heritage which has real meaning for them, and which may contribute both to a sense of identity and to an enhanced understanding of society, past and present. The popularity of such presentations with visitors also indicates that similar benefits are perceived by the 'audience'

Effects of sea temperature and stratification changes on seabird breeding success

As apex predators in marine ecosystems, seabirds may primarily experience climate change impacts indirectly, via changes to their food webs. Observed seabird population declines have been linked to climate-driven oceanographic and food web changes. However, relationships have often been derived from relatively few colonies and consider only sea surface temperature (SST), so important drivers, and spatial variation in drivers, could remain undetected. Further, explicit climate change projections have rarely been made, so longer-term risks remain unclear. Here, we use tracking data to estimate foraging areas for eleven black-legged kittiwake (Rissa tridactyla) colonies in the UK and Ireland, thus reducing reliance on single colonies and allowing calculation of colony-specific oceanographic conditions. We use mixed models to consider how SST, the potential energy anomaly (indicating density stratification strength) and the timing of seasonal stratification influence kittiwake productivity. Across all colonies, higher breeding success was associated with weaker stratification before breeding and lower SSTs during the breeding season. Eight colonies with sufficient data were modelled individually: higher productivity was associated with later stratification at three colonies, weaker stratification at two, and lower SSTs at one, whilst two colonies showed no significant relationships. Hence, key drivers of productivity varied among colonies. Climate change projections, made using fitted models, indicated that breeding success could decline by 21 – 43% between 1961-90 and 2070-99. Climate change therefore poses a longer-term threat to kittiwakes, but as this will be mediated via availability of key prey species, other marine apex predators could also face similar threats

Analysis of LIGO data for gravitational waves from binary neutron stars

We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of $\mathcal{R}<$1.7 \times 10^{2}$per year per Milky Way Equivalent Galaxy (MWEG), with 90coalescence rate of binary systems in which each component has a mass in the range 1--3$M_\odot$.Comment: 17 pages, 9 figure

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let