High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669]

INTRODUCTION: To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted. METHODS: Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up. RESULTS: The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22–2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43–3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI. CONCLUSION: No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI

Electrophoretic field gradient focusing with on-column detection by fluorescence quenching

Native, uncoloured, proteins can be focused in a column containing a fluorescent packing material, using hydrodynamic flow and a counteracting non-linear electric field, and imaged along the length of the channel by fluorescence quenching

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system

Aeciospore ejection in the rust pathogen Puccinia graminis is driven by moisture ingress

Fungi have evolved an array of spore discharge and dispersal processes. Here, we developed a theoretical model that explains the ejection mechanics of aeciospore liberation in the stem rust pathogen Puccinia graminis. Aeciospores are released from cluster cups formed on its Berberis host, spreading early-season inoculum into neighboring small-grain crops. Our model illustrates that during dew or rainfall, changes in aeciospore turgidity exerts substantial force on neighboring aeciospores in cluster cups whilst gaps between spores become perfused with water. This perfusion coats aeciospores with a lubrication film that facilitates expulsion, with single aeciospores reaching speeds of 0.053 to 0.754 m·s−1. We also used aeciospore source strength estimates to simulate the aeciospore dispersal gradient and incorporated this into a publicly available web interface. This aids farmers and legislators to assess current local risk of dispersal and facilitates development of sophisticated epidemiological models to potentially curtail stem rust epidemics originating on Berberis

An Inhaled Galectin-3 Inhibitor in COVID-19 Pneumonitis (DEFINE):A Phase Ib/IIa Randomised Controlled Trial

RATIONALE: High circulating galectin-3 is associated with poor outcomes in patients with coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with antiinflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. OBJECTIVES: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalized with COVID-19 pneumonitis. METHODS: We present the findings of two arms of a phase Ib/IIa randomized controlled platform trial in hospitalized patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. MEASUREMENTS AND MAIN RESULTS: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. Primary outcomes: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139 + SoC vs. 35 with SoC). Secondary outcomes: plasma GB0139 was measurable in all patients after inhaled exposure and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc analysis of covariance [ANCOVA] over days 2–7; P = 0.0099 vs. SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy, and major organ function were evaluated. CONCLUSIONS: In COVID-19 pneumonitis, inhaled GB0139 was well-tolerated and achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registered with ClinicalTrials.gov (NCT04473053) and EudraCT (2020–002230–32)

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

BRIGHT [C ii] AND DUST EMISSION IN THREE z > 6.6 QUASAR HOST GALAXIES OBSERVED BY ALMA

journal_title: The Astrophysical Journal article_type: paper copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2015-06-16 date_accepted: 2015-11-23 date_epub: 2015-12-29journal_title: The Astrophysical Journal article_type: paper copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2015-06-16 date_accepted: 2015-11-23 date_epub: 2015-12-29journal_title: The Astrophysical Journal article_type: paper copyright_information: © 2016. The American Astronomical Society. All rights reserved. date_received: 2015-06-16 date_accepted: 2015-11-23 date_epub: 2015-12-2

Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1:A multicentre cohort follow-up study

Objective: High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1). Methods: 117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months. Results: Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Conclusions: Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting

An Experimental Analysis Of the Demand For Payday Loans

The payday loan industry is one of the fastest growing segments of the consumer financial services market in the United States. We design an environment similar to the one that payday loan customers face and then conduct a laboratory experiment to examine what effect, if any, the existence of payday loans has on individuals\u27 abilities to manage and to survive financial setbacks. Our primary objective is to examine whether access to payday loans improves or worsens the likelihood of financial survival in our experiment. We also test the degree to which people\u27s use of payday loans affects their ability to survive financially. We find that payday loans help the subjects to absorb expenditure shocks and therefore survive financially. However, subjects whose demand for payday loans exceeds a certain threshold level are at a greater risk than a corresponding subject in the treatment in which payday loans do not exist

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 452 (2008): 202-205, doi:10.1038/nature06686.Worldwide, anthropogenic addition of bioavailable nitrogen (N) to the biosphere is increasing and terrestrial ecosystems are becoming increasingly N saturated, causing more bioavailable N to enter groundwater and surface waters. Large-scale N budgets show that an average of about 20-25% of the N added to the biosphere is exported from rivers to the ocean or inland basins, indicating substantial sinks for N must exist in the landscape. Streams and rivers may be important sinks for bioavailable N owing to their hydrologic connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favor microbial denitrification. Here, using data from 15N tracer experiments replicated across 72 streams and 8 regions representing several biomes, we show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of instream nitrate that is removed from transport. Total uptake of nitrate was related to ecosystem photosynthesis and denitrification was related to ecosystem respiration. Additionally, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.Funding for this research was provided by the National Science Foundation