Economic evaluation of propofol and lorazepam for critically ill patients undergoing mechanical ventilation*

The economic implications of sedative choice in the management of patients receiving mechanical ventilation are unclear because of differences in costs and clinical outcomes associated with specific sedatives. Therefore, we aimed to determine the cost-effectiveness of the most commonly used sedatives prescribed for mechanically ventilated critically ill patients

COSMIC: An Ethernet-based Commensal, Multimode Digital Backend on the Karl G. Jansky Very Large Array for the Search for Extraterrestrial Intelligence

The primary goal of the search for extraterrestrial intelligence (SETI) is to gain an understanding of the prevalence of technologically advanced beings (organic or inorganic) in the Galaxy. One way to approach this is to look for technosignatures: remotely detectable indicators of technology, such as temporal or spectral electromagnetic emissions consistent with an artificial source. With the new Commensal Open-Source Multimode Interferometer Cluster (COSMIC) digital backend on the Karl G. Jansky Very Large Array (VLA), we aim to conduct a search for technosignatures that is significantly more comprehensive, more sensitive, and more efficient than previously attempted. The COSMIC system is currently operational on the VLA, recording data, and designed with the flexibility to provide user-requested modes. This paper describes the hardware system design, the current software pipeline, and plans for future development.Comment: 30 pages, 17 figures. Accepted for publication in A

Outbreak of Antiviral Drug–Resistant Influenza A in Long-Term Care Facility, Illinois, USA, 2008

An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

BACKGROUND: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. METHODS AND FINDINGS: Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. CONCLUSIONS: The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans

From 'trading zones' to 'buffer zones': Art and metaphor in the communication of psychiatric genetics to publics

Psychiatric genetics has a difficult relationship with the public given its unshakeable connection to eugenics. Drawing from a five-year public engagement programme that emerged from an internationally renowned psychiatric genetics centre, we propose the concept of the Buffer Zone to consider how an exchange of viewpoints between groups of people – including psychiatric geneticists and lay publics - who are often uneasy in one another’s company can be facilitated through the use of art and metaphor. The artwork at the exhibitions provided the necessary socio-cultural context for scientific endeavours, whilst also enabled public groups to be part of, and remain in, the conversation. Crucial to stress is that this mitigation was not to protect the science; it was to protect the discussion

Centering inclusivity in the design of online conferences: An OHBM-Open Science perspective

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume

Detection of Dysplasia in Barrett's Esophagus With In Vivo Depth-Resolved Nuclear Morphology Measurements

Patients with Barrett’s esophagus (BE) show increased risk for developing esophageal adenocarcinoma and are routinely examined using upper endoscopy with biopsy to search for neoplastic changes. Angle-resolved low coherence interferometry (a/LCI) uses in vivo depth-resolved nuclear morphology measurements to detect dysplasia. We assessed the clinical utility of a/LCI in the endoscopic surveillance of BE patients

Thousands of Rab GTPases for the Cell Biologist

Rab proteins are small GTPases that act as essential regulators of vesicular trafficking. 44 subfamilies are known in humans, performing specific sets of functions at distinct subcellular localisations and tissues. Rab function is conserved even amongst distant orthologs. Hence, the annotation of Rabs yields functional predictions about the cell biology of trafficking. So far, annotating Rabs has been a laborious manual task not feasible for current and future genomic output of deep sequencing technologies. We developed, validated and benchmarked the Rabifier, an automated bioinformatic pipeline for the identification and classification of Rabs, which achieves up to 90% classification accuracy. We cataloged roughly 8.000 Rabs from 247 genomes covering the entire eukaryotic tree. The full Rab database and a web tool implementing the pipeline are publicly available at www.RabDB.org. For the first time, we describe and analyse the evolution of Rabs in a dataset covering the whole eukaryotic phylogeny. We found a highly dynamic family undergoing frequent taxon-specific expansions and losses. We dated the origin of human subfamilies using phylogenetic profiling, which enlarged the Rab repertoire of the Last Eukaryotic Common Ancestor with Rab14, 32 and RabL4. Furthermore, a detailed analysis of the Choanoflagellate Monosiga brevicollis Rab family pinpointed the changes that accompanied the emergence of Metazoan multicellularity, mainly an important expansion and specialisation of the secretory pathway. Lastly, we experimentally establish tissue specificity in expression of mouse Rabs and show that neo-functionalisation best explains the emergence of new human Rab subfamilies. With the Rabifier and RabDB, we provide tools that easily allows non-bioinformaticians to integrate thousands of Rabs in their analyses. RabDB is designed to enable the cell biology community to keep pace with the increasing number of fully-sequenced genomes and change the scale at which we perform comparative analysis in cell biology