Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>Community acquired (CA) methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear.</p> <p>Results</p> <p>We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from <it>S. epidermidis</it>. The USA300 sequence was aligned with other sequenced <it>S. aureus </it>genomes and regions unique to USA300 MRSA were identified.</p> <p>Conclusion</p> <p>USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The relationship between novel word learning and anomia treatment success in adults with chronic aphasia

Introduction: Learning capacity may influence an individual's response to aphasia rehabilitation. However, investigations into the relationship between novel word learning ability and response to anomia therapy are lacking. The aim of the present study was to evaluate the novel word learning ability in post stroke aphasia and to establish the relationship between learning ability and anomia treatment outcomes. We also explored the influence of locus of language breakdown on novel word learning ability and anomia treatment response

Spherical White with Diamond

Site-specific public work, commissioned by NATUR North Atlantic Tales/Curated Place in collaboration with National Trust Formby. The work includes three sound installations: 'Spherical White with Diamond', stereo work (voice: Jez Dolan). 'Þytur', 9 mono-channels (voices: Maja Jantar, Angela Rawlings, Halla Steinunn Stefánsdóttir). 'The Shadowy Space Beneath', a stereo work, which builds on texts from Jane Sprackland’s Strands (2013) (voices: David Dolan Martin, Ellie Paskall and Alicia Prowse)

Combined Use of Airborne Lidar and DBInSAR Data to Estimate LAI in Temperate Mixed Forests

The objective of this study was to determine whether leaf area index (LAI) in temperate mixed forests is best estimated using multiple-return airborne laser scanning (lidar) data or dual-band, single-pass interferometric synthetic aperture radar data (from GeoSAR) alone, or both in combination. &lt;em&gt;In situ&lt;/em&gt; measurements of LAI were made using the LiCor LAI-2000 Plant Canopy Analyzer on 61 plots (21 hardwood, 36 pine, 4 mixed pine hardwood; stand age ranging from 12-164 years; mean height ranging from 0.4 to 41.2 m) in the Appomattox-Buckingham State Forest, Virginia, USA. Lidar distributional metrics were calculated for all returns and for ten one meter deep crown density slices (a new metric), five above and five below the mode of the vegetation returns for each plot. GeoSAR metrics were calculated from the X-band backscatter coefficients (four looks) as well as both X- and P-band interferometric heights and magnitudes for each plot. Lidar metrics alone explained 69% of the variability in LAI, while GeoSAR metrics alone explained 52%. However, combining the lidar and GeoSAR metrics increased the &lt;em&gt;R&lt;sup&gt;2&lt;/sup&gt;&lt;/em&gt; to 0.77 with a CV-RMSE of 0.42. This study indicates the clear potential for X-band backscatter and interferometric height (both now available from spaceborne sensors), when combined with small-footprint lidar data, to improve LAI estimation in temperate mixed forests