Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial

Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic agent to prevent delirium in the critically ill population. This study will also provide one of the largest series of polysomnographic testing done in ICU. Trial registration: Australian New Zealand Clinical Trial Registry (ANZCTR) number: ACTRN12616000436471. Registered on 20 December 2015

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Fusarium: more than a node or a foot-shaped basal cell

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org)

Further support for a role for Th2-like cytokines in blister formation of pemphigus

Pemphigus vulgaris and pemphigus foliaceus are commonly known as antibody-mediated bullous diseases. However, recently a role for infiltrating cells as contributors to the pathogenesis of these diseases has been suggested. The aims of our study were to characterize the immunophenotype of the cellular infiltrate of pemphigus lesional skin and to study the cytokines secreted. We have therefore performed an immunohistochemical study with a large panel of monoclonal antibodies (to CD3, CD4, CD8, CD25, CD30, myeloperoxidase, eosinophil cationic protein EG2, tryptase, human interleukin (IL)-2, human IL-4, human IL-5, human IL-6, human IL-8, and interferon (IFN)-γ using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and uninvolved skin of six patients with clinical, histological, and immunofluorescent proven pemphigus. We also performed RT-PCR in order to demonstrate mRNA expression of the cytokines of interest. Our results suggest the presence of a T cell population with a prevalent Th2-like cytokine pattern in lesional skin. In addition, we demonstrate a consistent number of granulocytes and mast cells that show clear signs of activation. These data suggest the involvement of an inflammatory infiltrate in the production of pemphigus lesions. In particular, we assume that Th2 cells may be implicated in the very early stages of autoimmune response, concluding that they exert broad activity in blister formation. © 2000 Academic Press

Kinetics of Fibrinopeptide Release by Thrombin as a Function of CaCl 2 Concentration: Different Susceptibility of FPA and FPB and Evidence for a Fibrinogen Isoform-Specific Effect at Physiological Ca 2+ Concentration

The kinetics of release of fibrinopeptide A (FPA) and B (FPB) by thrombin were investigated on unfractionated fibrinogen samples as a function of CaCl2 concentration. A 50 mM Tris, 104 mM NaCl, pH 7.4 (TBS) buffer, to which 1 mM EDTA-Na2 (TBE) or 2.5 (TBC2.5), 14 (TBC14), and 30 mM CaCl2 (TBC30) was alternatively added, was employed. The % FPA versus time curves were fitted with single stretched-exponential growth functions, where the stretch parameter \u3b2 likely reflects substrate polydispersity (\u3b2 = 1, monodisperse). For TBE, TBS, TBC14, and TBC30, we found \u3b2 48 1, with corresponding normalized rate constants (K a) of 3.8, 4.2, 2.7, and 1.9 7 10-5 [(NIHu/L)s] -1. Surprisingly, in TBC2.5 we found \u3b2 = 0.69, with an "average" Ka of 3.5 7 10-5 [(NIHu/L)s]-1. This effect disappeared {\u3b2 = 0.97, Ka = 2.7 7 10-5 [(NIHu/L)s]-1} with an increase in the ionic strength I to that of TBC30 with 186 mM NaCl (TBCaNa buffer). FPB releases were instead consistent with a nonstretched consecutive exponential growth function, except in TBC30 where some FPB appeared to be cleaved independently. Log-log plots of Ka versus Ca2+ concentration, Cl- concentration, or I showed a strong linear correlation with only the latter two except in TBCaNa, again suggesting specific effects of the physiological Ca2+ concentration and I on FPA release. The corresponding Kb plots showed instead that both total depletion and high Ca2+ hampered FPB release. To further investigate the TBC2.5 \u3b2 = 0.69 effect, FG polydispersity was assessed by Western blot analyses. The thrombin-binding \u3b3\u2032-chain isoform was 3c4%, resulting in a bound:free thrombin ratio of 3c25:75. With regard to the C-terminal ends of the A\u3b1-chains, 3c45% were either intact or lightly degraded, while the remaining 3c55% were more degraded. Fitting the % FPA release data in TBC2.5 with a sum of two exponentials resulted in a faster component and a slower component (Ka1/Ka2 48 6), with a ratio of 3c48:52. While a role for the \u3b3\u2032-chain isoform cannot be excluded, this good correlation with the C-terminal degradation of the A\u3b1-chains suggests their calcium-dependent involvement in FPA release

Technical Design Report for the: PANDA Straw Tube Tracker

This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM-stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy-loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole \Panda scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described

Overview of the JET ITER-like wall divertor

The work presented draws on new analysis of components removed following the second JET ITER-like wall campaign 2013–14 concentrating on the upper inner divertor, inner and outer divertor corners, lifetime issues relating to tungsten coatings on JET carbon fibre composite divertor tiles and dust/particulate generation. The results show that the upper inner divertor remains the region of highest deposition in the JET-ILW. Variations in plasma configurations between the first and second campaign have altered material migration to the corners of the inner and outer divertor. Net deposition is shown to be beneficial in the sense that it reduces W coating erosion, covers small areas of exposed carbon surfaces and even encapsulates particles