A phase I clinical study of inhaled nitric oxide in healthy adults

AbstractBackgroundNitric oxide (NO) is an approved pulmonary vasodilator for neonates and full term infants up to a dose of 80ppm. At 100ppm to 200ppm, NO has potent antimicrobial activities in vitro and in animal studies which suggest its therapeutic use for infectious diseases in humans. However, whether inhaled NO is safe at 160ppm in healthy human adults is unknown. The aim of the phase I study was to assess the safety of delivery and the physiologic effects of intermittent 160ppm NO in healthy human adults.MethodsTen healthy adult volunteers (5 males, 5 females; 20–62years) were recruited and inhaled 163.3ppm (SD: 4.0) NO for 30min, 5 times daily, for 5 consecutive days. Lung function and blood levels of methemoglobin, nitrites/nitrates, prothrombin, pro-inflammatory cytokines and chemokines were determined before and during treatment.ResultsAll individuals tolerated the NO treatment courses well. No significant adverse events occurred and three minor adverse events, not attributable to NO, were reported. Forced expiratory volume in 1sec % predicted and other lung function parameters, serum nitrites/nitrates, prothrombin, pro-inflammatory cytokine and chemokine levels did not differ between baseline and day 5, while methemoglobin increased significantly during the study period to a level of 0.9% (SD: 0.08) (p<0.001).ConclusionThese data suggest that inhalation of 160ppm NO for 30min, 5 times daily, for 5 consecutive days, is safe and well tolerated in healthy individuals

Associations between perioperative fluid management and patient outcomes: a multicentre retrospective study

BACKGROUND: Postoperative complications increase hospital length of stay and patient mortality. Optimal perioperative fluid management should decrease patient complications. This study examined associations between fluid volume and noncardiac surgery patient outcomes within a large multicentre US surgical cohort. METHODS: Adults undergoing noncardiac procedures from January 1, 2012 to December 31, 2017, with a postoperative length of stay ≥24 h, were extracted from a large US electronic health record database. Patients were segmented into quintiles based on recorded perioperative fluid volumes with Quintile 3 (Q3) serving as the reference. The primary outcome was defined as a composite of any complications during the surgical admission and a postoperative length of stay ≥7 days. Secondary outcomes included in-hospital mortality, respiratory complications, and acute kidney injury. RESULTS: A total of 35 736 patients met the study criteria. There was a U-shaped pattern with highest (Q5) and lowest (Q1) quintiles of fluid volumes having increased odds of complications and a postoperative length of stay ≥7 days (Q5: odds ratio [OR] 1.51 [95% confidence interval {CI}: 1.30-1.74], P<0.001; Q1: OR 1.20 [95% CI: 1.04-1.38], P=0.011) compared with Q3. Patients in Q5 had greater odds of more severe acute kidney injury compared with Q3 (OR 1.52 [95% CI: 1.22-1.90]; P<0.001) and respiratory complications (OR 1.44 [95% CI: 1.17-1.77]; P<0.001). CONCLUSIONS: Both very high and very low perioperative fluid volumes were associated with an increase in complications after noncardiac surgery

A new high: Cannabis as a budding source of carbon-based materials for electrochemical power sources

Cannabis sativa L., a low-cost, fast-growing herbaceous plant, is seeing a resurgence in widespread cultivation as a result of new policies and product drive. Its biodegradable and environmentally benign nature coupled with its high specific surface area and three-dimensional hierarchal structure makes it an excellent candidate for use as a biomass-derived carbon material for electrochemical power sources. It is proposed that this ‘wonder crop’ could have an important role in the energy transition by providing high-functioning carbon-based materials for electrochemistry. In this article, all instances of C. sativa usage in batteries, fuel cells and supercapacitors are discussed with a focus on highlighting the high capacity, rate capability, capacitance, current density and half-wave potential that can be achieved with its utilisation in the field

Towards the Formalization of Fractional Calculus in Higher-Order Logic

Fractional calculus is a generalization of classical theories of integration and differentiation to arbitrary order (i.e., real or complex numbers). In the last two decades, this new mathematical modeling approach has been widely used to analyze a wide class of physical systems in various fields of science and engineering. In this paper, we describe an ongoing project which aims at formalizing the basic theories of fractional calculus in the HOL Light theorem prover. Mainly, we present the motivation and application of such formalization efforts, a roadmap to achieve our goals, current status of the project and future milestones.Comment: 9 page

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Rating neighborhoods for older adult health: results from the African American Health study

<p>Abstract</p> <p>Background</p> <p>Social theories suggest that neighborhood quality affects health. Observer ratings of neighborhoods should be subjected to psychometric tests.</p> <p>Methods</p> <p>African American Health (AAH) study subjects were selected from two diverse St. Louis metropolitan catchment areas. Interviewers rated streets and block faces for 816 households. Items and a summary scale were compared across catchment areas and to the resident respondents' global neighborhood assessments.</p> <p>Results</p> <p>Individual items and the scale were strongly associated with both the catchment area and respondent assessments. Ratings based on both block faces did not improve those based on a single block face. Substantial interviewer effects were observed despite strong discriminant and concurrent validity.</p> <p>Conclusion</p> <p>Observer ratings show promise in understanding the effect of neighborhood on health outcomes. The AAH Neighborhood Assessment Scale and other rating systems should be tested further in diverse settings.</p

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio

Inferring introduction routes of invasive species using approximate Bayesian computation on microsatellite data

Determining the routes of introduction provides not only information about the history of an invasion process, but also information about the origin and construction of the genetic composition of the invading population. It remains difficult, however, to infer introduction routes from molecular data because of a lack of appropriate methods. We evaluate here the use of an approximate Bayesian computation (ABC) method for estimating the probabilities of introduction routes of invasive populations based on microsatellite data. We considered the crucial case of a single source population from which two invasive populations originated either serially from a single introduction event or from two independent introduction events. Using simulated datasets, we found that the method gave correct inferences and was robust to many erroneous beliefs. The method was also more efficient than traditional methods based on raw values of statistics such as assignment likelihood or pairwise F(ST). We illustrate some of the features of our ABC method, using real microsatellite datasets obtained for invasive populations of the western corn rootworm, Diabrotica virgifera virgifera. Most computations were performed with the DIYABC program (http://www1.montpellier.inra.fr/CBGP/diyabc/)