Nebulized heparin in burn patients with inhalation trauma : safety and feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients

Uniqueness Typing for Resource Management in Message-Passing Concurrency

We view channels as the main form of resources in a message-passing programming paradigm. These channels need to be carefully managed in settings where resources are scarce. To study this problem, we extend the pi-calculus with primitives for channel allocation and deallocation and allow channels to be reused to communicate values of different types. Inevitably, the added expressiveness increases the possibilities for runtime errors. We define a substructural type system which combines uniqueness typing and affine typing to reject these ill-behaved programs

Climate response to increasing Antarctic iceberg and ice shelf melt

Mass loss from the Antarctic continent is increasing; however, climate models either assume a constant mass loss rate or return snowfall over land to the ocean to maintain equilibrium. Numerous studies have investigated sea ice and ocean sensitivity to this assumption and reached different conclusions, possibly due to different representations of melt fluxes. The coupled atmosphere-land-ocean-sea ice model, HadGEM3-GC3.1, includes a realistic spatial distribution of coastal melt fluxes, a new ice shelf cavity parameterization, and explicit representation of icebergs. This configuration makes it appropriate to revisit how increasing melt fluxes influence ocean and sea ice and to assess whether responses to melt from ice shelves and icebergs are distinguishable. We present results from simulated scenarios of increasing meltwater fluxes and show that these drive sea ice increases and, for increasing ice shelf melt, a decline in Antarctic Bottom Water formation. In our experiments, the mixed layer around the Antarctic coast deepens in response to rising ice shelf meltwater and shallows in response to stratification driven by iceberg melt. We find similar surface temperature and salinity responses to increasing meltwater fluxes from ice shelves and icebergs, but midlayer waters warm to greater depths and farther north when ice shelf melt is present. We show that as meltwater fluxes increase, snowfall becomes more likely at lower latitudes and Antarctic Circumpolar Current transport declines. These insights are helpful for interpretation of climate simulations that assume constant mass loss rates and demonstrate the importance of representing increasing melt rates for both ice shelves and icebergs

Interactions between increasing CO2 and Antarctic melt rates

Meltwater from the Antarctic ice sheet is expected to increase the sea ice extent. However, such an expansion may be moderated by sea ice decline associated with global warming. Here we investigate the relative balance of these two processes through experiments using HadGEM3-GC3.1 and compare these to two standard idealized CMIP6 experiments. Our results show that the decline in sea ice projected under scenarios of increasing CO 2 may be inhibited by simultaneously increasing melt fluxes. We find that Antarctic Bottom Water formation, projected to decline as CO 2 increases, is likely to decline further with an increasing meltwater flux. In our simulations, the response of the westerly wind jet to increasing CO 2 is enhanced when the meltwater flux increases, resulting in a stronger peak wind stress than is found when either CO 2 or melt rates increase exclusively. We find that the sensitivity of the Antarctic Circumpolar Current to increasing melt fluxes in the Southern Ocean is countered by increasing CO 2, removing or reducing a feedback mechanism that may otherwise allow more heat to be transported to the polar regions and drive increasing ice shelf melt rates. The insights presented here and in a companion paper (which focuses on the effect of increasing melt fluxes under preindustrial forcings) provide insights helpful to the interpretation of both future climate projections and sensitivity studies into the effect of increasing melt fluxes from the Antarctic ice sheet when different forcing scenarios are used

Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation. suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obtained on the day of inhalation trauma and on alternate days thereafter until patients were completely weaned from the mechanical ventilator. Mechanically ventilated patients without burns and without pulmonary disease served as controls. Systemic levels of suPAR in burn patients with inhalation trauma were not different from those in control patients. On admission and follow up, pulmonary levels of suPAR in patients with inhalation trauma were significantly higher compared with controls. Pulmonary levels of suPAR highly correlated with pulmonary levels of interleukin 6, a marker of inflammation, and thrombin-antithrombin complexes, markers of coagulation, but not plasminogen activator activity, a marker of fibrinolysis. Systemic levels of suPAR were predictive of the duration of mechanical ventilation and length of intensive care unit (ICU) stay. Duration of mechanical ventilation and length of ICU stay were significantly longer in burn-injury patients with systemic suPAR levels > 9.5 ng/ml. Pulmonary levels of suPAR are elevated in burn patients with inhalation trauma, and they correlate with pulmonary inflammation and coagulation. Although pulmonary levels of suPAR may have diagnostic value in burn-injury patients, systemic levels of suPAR have prognostic valu

Genomic insight and physiological characterization of thermoacidophilic Alicyclobacillus isolated from Yellowstone National Park

IntroductionAlicyclobacillus has been isolated from extreme environments such as hot springs, volcanoes, as well as pasteurized acidic beverages, because it can tolerate extreme temperatures and acidity. In our previous study, Alicyclobacillus was isolated during the enrichment of methane oxidizing bacteria from Yellowstone Hot Spring samples.MethodsPhysiological characterization and genomic exploration of two new Alicyclobacillus isolates, AL01A and AL05G, are the main focus of this study to identify their potential relationships with a thermoacidophilic methanotroph (Methylacidiphilum) isolated from the same hot spring sediments.Results and discussionIn the present study, both Alicyclobacillus isolates showed optimal growth at pH 3.5 and 55°C, and contain ω-alicyclic fatty acids as a major lipid (ca. 60%) in the bacterial membrane. Genomic analysis of these strains revealed specific genes and pathways that the methanotroph genome does not have in the intermediary carbon metabolism pathway such as serC (phosphoserine aminotransferase), comA (phosphosulfolactate synthase), and DAK (glycerone kinase). Both Alicyclobacillus strains were also found to contain transporter systems for extracellular sulfate (ABC transporter), suggesting that they could play an important role in sulfur metabolism in this extreme environment. Genomic analysis of vitamin metabolism revealed Alicyclobacillus and Methylacidiphilum are able to complement each other’s nutritional deficiencies, resulting in a mutually beneficial relationship, especially in vitamin B1(thiamin), B3 (niacin), and B7 (biotin) metabolism. These findings provide insights into the role of Alicyclobacillus isolates in geothermal environments and their unique metabolic adaptations to these environments

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Understanding Business Travel Time and Its Place in the Working Day

This article argues that there is a need to understand business travel time in the context of the wider organization of work time. It considers why travel time use is potentially changing with the use of mobile technologies by the increasing number of individuals engaged in ‘knowledge work’, and examines existing evidence that indicates that travel time use is part of a wider work-related ‘taskscape’. However, it not only considers material productive output, but suggests that travel time as ‘time out’ from work-related activities also plays a vital role for employees. It also suggests that business travel time use that is not of benefit to the employer may not be at the employer's expense. This is contrasted with the assumptions used in UK transport appraisal. Data gathered from the autumn 2004 wave of the National Rail Passenger Survey (GB) is used to illustrate some key issues concerning productivity and ‘anti-activity’. A case study of an individual business traveller then points towards the need for a new approach to exploring the role played by travel time in the organization of work practices to be considered. © 2008, Sage Publications. All rights reserved

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Reduction of PG:1115+080 Images

The data are three exposures in PC6 through F785LP obtained on March 3, 1991. The exposure times are 120, 400, and 400 seconds. The data are reduced with the "standard" WFPC reduction scheme: A-to-D correction, DC bias subtraction, AC bias subtraction, dark current subtraction, preflash subtraction, and flat field normalization, using the best available calibration data. The exposures are combined into a weighted average normalized to 400 seconds exposure time, so one DN (data number) is about 17.25 electrons. At this step, cosmic rays are removed by intercomparison of the three images