Personalised randomised controlled trial designs—a new paradigm to define optimal treatments for carbapenem-resistant infections

Antimicrobial resistance is impacting treatment decisions for, and patient outcomes from, bacterial infections worldwide, with particular threats from infections with carbapenem-resistant Enterobacteriaceae, Acinetobacter baumanii, or Pseudomonas aeruginosa. Numerous areas of clinical uncertainty surround the treatment of these highly resistant infections, yet substantial obstacles exist to the design and conduct of treatment trials for carbapenem-resistant bacterial infections. These include the lack of a widely acceptable optimised standard of care and control regimens, varying antimicrobial susceptibilities and clinical contraindications making specific intervention regimens infeasible, and diagnostic and recruitment challenges. The current single comparator trials are not designed to answer the urgent public health question, identified as a high priority by WHO, of what are the best regimens out of the available options that will significantly reduce morbidity, costs, and mortality. This scenario has an analogy in network meta-analysis, which compares multiple treatments in an evidence synthesis to rank the best of a set of available treatments. To address these obstacles, we propose extending the network meta-analysis approach to individual randomisation of patients. We refer to this approach as a Personalised RAndomised Controlled Trial (PRACTical) design that compares multiple treatments in an evidence synthesis, to identify, overall, which is the best treatment out of a set of available treatments to recommend, or how these different treatments rank against each other. In this Personal View, we summarise the design principles of personalised randomised controlled trial designs. Specifically, of a network of different potential regimens for life-threatening carbapenem-resistant infections, each patient would be randomly assigned only to regimens considered clinically reasonable for that patient at that time, incorporating antimicrobial susceptibility, toxicity profile, pharmacometric properties, availability, and physician assessment. Analysis can use both direct and indirect comparisons across the network, analogous to network meta-analysis. This new trial design will maximise the relevance of the findings to each individual patient, and enable the top-ranked regimens from any personalised randomisation list to be identified, in terms of both efficacy and safety

Integrable boundary impurities in the t-J model with different gradings

We investigate the generalized supersymmetric $t-J$ model with boundary impurities in different gradings. All three different gradings: fermion, fermion, boson (FFB), boson, fermion, fermion (BFF) and fermion, boson, fermion (FBF), are studied for the generalized supersymmetric $t-J$ model. Boundary K-matrix operators are found for the different gradings. By using the graded algebraic Bethe ansatz method, we obtain the eigenvalues and the corresponding Bethe ansatz equations for the transfer matrix.Comment: Latex file, 20 page

The diagnostic potential of amyloidogenic proteins

Neurodegenerative disorders are a highly prevalent class of diseases, whose pathological mechanisms start before the appearance of any clear symptoms. This fact has prompted scientists to search for biomarkers that could aid early treatment. These currently incurable pathologies share the presence of aberrant aggregates called amyloids in the nervous system, which are composed of specific proteins. In this review, we discuss how these proteins, their conformations and modifications could be exploited as biomarkers for diagnostic purposes. We focus on proteins that are associated with the most prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, and frontotemporal dementia. We also describe current challenges in detection, the most recent techniques with diagnostic potentials and possible future developments in diagnosis

Evaluation of Game-Based Learning in Cybersecurity Education for High School Students

Game based learning is a new game play mechanism that the players explore various aspects of game play in a learning context designed by the instructor or the game designer. Nevertheless, general acceptance of game based learning as a new learning paradigm was deferred by a lack of well-controlled, large sample efficacy studies. To address the increasing need of cybersecurity workforce, this paper introduces a game based learning method for high school cybersecurity education. Purdue University Northwest launched GenCyber high school summer camps to about 200 high school students in Chicago metropolitan area. The survey conducted after the summer camp indicated that the game based learning for cybersecurity education was very effective in cybersecurity awareness training. Further analysis of survey data revealed that there is a gender difference in raising students' interests in cybersecurity and computer science education using game based learning method

The z=5 Quasar Luminosity Function from SDSS Stripe 82

We present a measurement of the Type I quasar luminosity function at z=5 using a large sample of spectroscopically confirmed quasars selected from optical imaging data. We measure the bright end (M_1450<-26) with Sloan Digital Sky Survey (SDSS) data covering ~6000 deg^2, then extend to lower luminosities (M_1450<-24) with newly discovered, faint z~5 quasars selected from 235 deg^2 of deep, coadded imaging in the SDSS Stripe 82 region (the celestial equator in the Southern Galactic Cap). The faint sample includes 14 quasars with spectra obtained as ancillary science targets in the SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), and 59 quasars observed at the MMT and Magellan telescopes. We construct a well-defined sample of 4.7<z<5.1 quasars that is highly complete, with 73 spectroscopic identifications out of 92 candidates. Our color selection method is also highly efficient: of the 73 spectra obtained, 71 are high redshift quasars. These observations reach below the break in the luminosity function (M_1450* ~ -27). The bright end slope is steep (beta <~ -4), with a constraint of beta < -3.1 at 95% confidence. The break luminosity appears to evolve strongly at high redshift, providing an explanation for the flattening of the bright end slope reported previously. We find a factor of ~2 greater decrease in the number density of luminous quasars (M_1450<-26) from z=5 to z=6 than from z=4 to z=5, suggesting a more rapid decline in quasar activity at high redshift than found in previous surveys. Our model for the quasar luminosity function predicts that quasars generate ~30% of the ionizing photons required to keep the universe ionized at z=5.Comment: 29 pages, 22 figures, ApJ accepted (updated to published version

Measuring the Cluster Magnetic Field Power Spectra from Faraday Rotation Maps of Abell 400, Abell 2634 and Hydra A

We apply a novel technique of Faraday Rotation measure (RM) map analysis to three galaxy clusters, Abell 400, Abell 2634 and Hydra A, in order to estimate cluster magnetic field strengths, length scales and power spectra. This analysis is based on the assumption that the magnetic fields are statistically isotropically distributed across the Faraday screen. We investigate the difficulties involved in the application of the analysis to observational data. We derive magnetic power spectra for the three clusters and discuss influences on their shapes. We show that magnetic fluctuations are probed on length scales ranging over at least one order of magnitude. Using this range for the determination of central cluster magnetic field strength yields 3 muG in Abell 2634, 6 muG in Abell 400 and 12 muG in Hydra A. The magnetic field autocorrelation length was determined to be 4.9 kpc for Abell 2634, 3.6 kpc for Abell 400 and 0.9 kpc for Hydra A. We show that the RM autocorrelation length is larger than the magnetic field autocorrelation length. We investigate in a response analysis if it is possible to determine spectral slopes of the power spectra. We find that integrated numbers can be determined from this analysis but differential parameters such as spectral slopes have to be treated differently. Our response analysis results in spectral slopes of the power spectra of spectral indices alpha = 1.6 to 2.0 suggesting that Kolmogorov spectra are possible but flatter spectral slopes than alpha = 1.3 can be excluded.Comment: 14 pages, 9 figures, accepted by A&

Measuring the effect of enhanced cleaning in a UK hospital : a prospective cross-over study

Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at handtouch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both handtouch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30,000 to £70,000.Introducing one extra cleaner produced a measurable effect on the clinical environment, with apparent benefit to patients regarding meticillin-resistant S. aureus infection. Molecular epidemiological methods supported the possibility that patients acquired meticillin-resistant S. aureus from environmental sources. These findings suggest that additional research is warranted to further clarify the environmental, clinical and economic impact of enhanced hygienic cleaning as a component in the control of hospital-acquired infection

Particle acceleration in cooling flow clusters of galaxies: the case of Abell 2626

It has recently been proposed a theoretical model which accounts for the origin of radio mini-halos observed in some cooling flow clusters as related to electron re-acceleration by MHD turbulence (Gitti, Brunetti & Setti 2002). The MHD turbulence is assumed to be frozen into the flow of the thermal ICM and thus amplified in the cooling flow region. Here we present the application of this model to a new mini-halo candidate, the cluster A2626, and compare the results with those obtained for the mini-halo in the Perseus cluster. We present VLA data at 330 MHz and 1.5 GHz of the diffuse radio emission observed in A2626, and we show that its main properties can be explained by the model. We find that the power necessary for the re-acceleration of the relic electron population is only a factor ~ 0.7% of the maximum power that can be extracted by the cooling flow (as estimated on the basis of the standard model). We also discuss the observational properties of known mini-halos in connection with those of host clusters, showing that the radio power of mini--halos increases with the maximum power of cooling flows. This trend is expected in the framework of the model. Possible effects of new Chandra and XMM-Newton estimates of $\dot{M}$ on this trend are considered: we conclude that even if earlier derived cooling rates were overestimated, cooling flow powers are still well above the radio powers emitted by mini-halos.Comment: 12 pages, 11 figures, accepted for publication in Astronomy & Astrophysic