text:
SUGAR LAND, Texas, Feb. 21, 2019 /PRNewswire/ -- Researched by Industrial Info Resources (Sugar Land, Texas)--This year is set to be a strong one for the U.S. liquefied natural gas (LNG) sector. Earlier in February, Exxon Mobil Corporation (Irving, Texas) and Qatar Petroleum reached a positive final investment decision to proceed with construction of the Golden Pass LNG project in Sabine Pass, Texas. Construction is expected to begin this quarter, with the plant entering operation in 2024. Perhaps even more exciting is the completion of several LNG projects, many of which have been in construction for several years. Industrial Info is tracking $26 billion in planned 2019 LNG project completions in the U.S.
To read the full article, check out the latest edition of Industrial Info's NavigatIIR online newsletter.
Industrial Info Resources (IIR), with global headquarters in Sugar Land, Texas, six offices in North America and 12 international offices, is the leading provider of global market intelligence specializing in the industrial process, heavy manufacturing and energy markets. Industrial Info's quality-assurance philosophy, the Living Forward Reporting Principle™, provides up-to-the-minute intelligence on what's happening now, while constantly keeping track of future opportunities. To contact an office in your area, visit the www.industrialinfo.com "Contact Us" page.


text:
Easy vision correction through ACCELERATED Orthokeratology!
ORTHO-K is a NON-SURGICAL, FDA approved procedure for children as young as 6 yrs old.
ORTHO-K WILL stop MYOPIA FROM PROGRESSING THE VERY FIRST NIGHT the lenses are worn!
NIGHT THERAPY ORTHO-K LENSES, are worn ONLY while the patient sleeps, and are removed upon awakening ....
That's right !!! ....NO EYE GLASSES, or contacts are worn during the day with good functional vision, all day long!!!
Not only does ORTHO-K stop the nearsightedness from progressing, but in addition, the patients vision continues to improve continually every day, with MANY patients achieving 20/20 in several days. In addition, Dr. Garber PERSONALLY custom designs EVERY patient's lenses individually... Every patient's eyes are UNIQUE, and must be treated that way..... And last, but not least, Dr. Jerome Martin Garber is the MOST CARING and experienced ORTHO-K doc in current practice, having SUCCESSFULLY treated thousands of patients at a fair and professional fee.
HELP STOP YOUR CHILDREN'S NEARSIGHTEDNESS(myopia) from progressing NOW, .... and have them experience the real joy of healthy, clear vision. THAT'S RIGHT ...NO GLASSES OR CONTACTS... ALL DAY LONG!
Learn more about your options as you travel through our website. Let us know if we can answer any questions or get you set up in one of our Orthokeratology programs in New York!
Contact Dr. Garber today to make an appointment or learn more about the future of vision correction.

domain: medical


North Wales Police have took to social media to ask the public to be vigilant following a spate of vehicle related crimes in the Prestatyn area.
Since the start of 2020 there has been an increase in the number of thefts from and damage to vehicles across Prestatyn.
Denbighshire and Abergele Coastal Sgt Kevin Smith said: “We want to thank members of the public and residents who have assisted the policing team with reports of a suspicious male trying car door handles in the early hours.”
“A dedicated policing operation is being run to target those responsible and we ask for the public’s help in identifying any potential suspects.”
“We are urging owners to ensure their vehicles and homes are locked and secure and that any valuable items are removed from vehicles to reduce the temptation for thieves.”
If you have any information relating to car crime please contact North Wales Police on 101 or contact the control room direct via https://www.north-wales.police.uk/contact/live-chat-support. Alternatively call Crimestoppers anonymously on 0800 555111.


text:
How to use Mahan in a sentence
Fresh from government sniffing school, Bill Mahan describes the odd odors protecting the public health.
Dr. Asa Mahan told me of an experience of this kind which he had in a very dangerous sickness.When the Holy Ghost is Come | S. L. Brengle
It was one of Prof. Mahan's maxims that the spade was as useful in war as the musket, and to this I will add the axe.The Memoirs of General W. T. Sherman, Complete | William T. Sherman
While the Doctor was upon the road he was called to prescribe for another sick man by the name of Mahan, from Missouri.How Marcus Whitman Saved Oregon | Oliver W. Nixon
Gradually a slight change for the better occurred, the writings of Captain Mahan playing no small part therein.Theodore Roosevelt | Theodore Roosevelt
I see that Captain Mahan has been getting out a new book on the subject, just at the right time.The Life and Letters of Lafcadio Hearn, Volume 2 | Elizabeth Bisland

domain: library


text:
This two-level, underground station has an island platform. It is located beneath the intersection of Minquan West Rd. and Linsen North Rd. and opened on 3 November 2010 with the opening of the Luzhou Branch Line and the Taipei City section of the Xinzhuang Line.
Excavation depth for this station is around 19 meters. It is 160 meters in length and 23 meters wide. It has four entrances, one accessible elevator, and two vent shafts. It is equipped with platform screen doors.

domain: geography


With the tendency to increase the size of cement equipment and in turn the increased reliability requirement, the dynamic analysis shouted be considered without exception. The author discusses system atically the computation method of on dynamic behaviour of ball mill and rotary kiln and its application in design and maintanance.
Dynamic analysis design for ball mill SAXUM Efficient Procedure for Computational Dynamic mill gap during the dynamic performance allow verifying both the dynamic stability and the appropriateness of the SAG and BALL Mill Sys-tems regarding the expected seismic excitations at Quellaveco.
Aug 09, 2015 the scope of works for seismic analysis consultant for the SAG and Ball Mill dynamic analysis being executed by xxx The structural section of the company continued to work on the calculations and designs for the grinding area, the foundations, and the steel works.
Two methods can be used to carry out the dynamic analysis for ball mill foundations, the free vibration analysis and the forced vibration analysis. 5.1. Free Vibration Analysis For small ball mill,.
Ball Mill Design and Failure Analysis. Our customer asked us to redesign their 60” Ball Mill to overcome the shortcomings from their existing Ball Mill. Also, we delivered a complete failure analysis report of their critical parts. Download the case study to .
Design and Analysis of Ball Mill For Paint Industries Mayur H Patel1 Mr. Vishal A Pandya 2 1ME-Machine Design- pursuing2Asst. Prof 12 B.V.M Engineering College, VallabhVidyanagar. Abstract—The work present in this paper focuseson the ball mill used in paint industries for optimizing the parameter like i) Selecting optimum thickness of mill.
Mar 01, 2014 With a view to developing a sound basis for the design and scale-up of ball mills, a large amount of data available in the literature were analyzed for variation of the two key mill performance parameters power specific values of the ‘absolute breakage rate of the coarsest size fraction’, S , and ‘absolute rate of production of fines’, F , with some of the important operating and.
A ball screw feed drive system is extensively used in machine tools. Reliable theoretical modeling and dynamic characteristic analysis of such a system are vital for the performance research and subsequent design of machine tools [1, 2]. The precise modeling and dynamic analysis of feed drive systems are becoming increasingly important.
Design Construction and Performance Analysis of a 5 . circulating load of dynamic seperator in ball mill ball mill dynamic load calculationmill for sale ball mill dynamic load calculation Finer is the cement and higher is the circulating load Ball Mill Get Info how to calculate dyna mic load of ball mill Nov 10 2017 Details ball.
Jun 19, 2015 The basic parameters used in ball mill design (power calculations), rod mill or any tumbling mill sizing are material to be ground, characteristics, Bond Work Index, bulk density, specific density, desired mill tonnage capacity DTPH, operating solids or pulp density, feed size as F80 and maximum ‘chunk size’, product size as P80 and maximum and finally the type of circuit open closed.
Static Dynamic Analysis The Ball-Mill was analyzed using Finite Element Method to determine the induced stresses due to various loading conditions. In order to assess strength of complete ball-mill, guidelines from ASME Section VIII Div. 2 Ed. 2013 was utilized. Stress Linearization has been carried out at various locations.
DESIGN AND ANALYSIS OF BALL MILL INLET CHUTE FOR ROLLER PRESS CIRCUIT IN CEMENT INDUSTRY D. Sankar prasath1, N.Venkatesh2 1PG Scholar, Department of Mechanical Engineering, Knowledge Institute of Technology, Tamil Nadu, India 2Assistant. Professor, Department of Mechanical Engineering, Knowledge Institute Of Technology, Tamil Nadu, India.
The ball mill is the important equipment in the mining industry, with the development of the macro-scale ball mill, and is difficult of liner’s wearing,installation and taking apart. The service life which raises a liner will prolong the production period that the ball mill, influencing an economic benefit of the concentrating mill.
The service life which raises a liner will prolong the production period that the ball mill, influencing an economic benefit of the concentrating mill. Therefore, it is of great significance for dynamics simulating on the grinding ball, studying of grinding ball on dynamics characteristic and improving the liner shape,reducing relative slide, and extending the liner’s age.
Apr 01, 1999 The first systematic formulation of power draft by analyzing ball trajectories goes back to 1919 and since then a considerable amount of effort has been put to correlate power draft and operating and design parameters of the ball mill. However, most of the theoretical formulae available to quantify power draft until now, do not take into.
Mill Foundation comprises of i) Base Block ii) Pedestals for Mill, Pinion, Motor, Gear Box and Inching Motor. Bottom of the Base Block is supported on the soil @ – 3.8 m level below FGL whereas its top is at + 0.2 m level. Foundation spans about 24 m x 7 m in plan.
This work, the high-energy planetary ball mill process is modeled using the software Automated Dynamic Analysis of Mechanical System MSC Adams [ 22 ]. Figure 2 illustrates a schematic of a high-energy planetary ball mill equipped with two cylindrical vials. The mill was powered by a 0.37 kW electric motor.
Design Safer Chemicals Real-time Analysis for Planetary ball mills 9 . Vibration Mills 10 . Mixer Mill MM 400 11 Feed material hard, medium-hard, soft, brittle, elastic, fibrous Material feed size ≤ 8 mm Final fineness ~ 5 m.
Mar 01, 2017 Kibble model and stress analysis. Kibble model and stress analysis. The photos below show the fabricated kibble being used on site. First an operator charges the kibble with mill balls. Because of its size and design, filling the kibble is an easy task.
Feb 17, 2018 Modelling and Control of Ball Mill Grinding. Dynamic experiments were performed in a continuous open-circuit 40 40 cm ball mill using a pseudo-random binary sequence of the feed rate and measuring the variations of the discharge particle-size distribution. The impulse response is calculated by a cross- correlation technique.
Design parameters need to be understood. Figure 3 exploded ball mill assembly, computational model Pinion The original design calculations were not available so Principia had to reverse-engineer most of the design (see Figures 3, 5 and 6). This is a common issue when analysing legacy or obsolete equipment. To get the geometry of the mill, a solid.
Design Method of Ball Mill by Discrete Element Method collected. The diameter of the gibbsite powder was measured using a Master Sizer 2000 (Sysmex Corpora-tion). Details of the experimental conditions are given in Table 2. Results and Discussion 1. Effects of Fins on Ball Motion in the Mill To predict ball mill grinding behavior using the dis-.
Optimization of mill performance by using online ball and pulp measurements by B. Clermont and B. de Haas Synopsis Ball mills are usually the largest consumers of energy within a mineral concentrator. Comminution is responsible for 50 of the total mineral processing cost. In today’s global markets, expanding mining groups are trying.
Ball mill using a conveyor belt. The ball mill grinding circuit is illustrated in Figure 2. Solids 78.9 Circulating Load 474 Advance Control Optimizer Manual Mode Preset Output Alarm Summary 6 Mills Display Group Display sump level 86.4 13.1 AMPS Primary Ball Mill No. 5 Solids, Flow GPM 66.7 1.72 9.1 SGU PSI 35.5 PSM 28.6 +65 32.6.
When the ball mill rotates, the abrasive body is brought up in the direction of mechanical design, mechanical manufacturing and engineering analysis. It has a unified user 3D softwares. Engineering analysis in CATIA refers to finite . 2018) 40. element analysis, including static analysis and dynamic analysis. Dynamic analysis is divided.
Feb 14, 2021 By analyzing the influence factors of the output of double inlet and double outlet ball mill, and combining with system dynamics, the dynamic model of double inlet and double outlet ball mill output system is established, and SPSS is used to fit the model data with the real data. The fitting degree is above 0.8, and the authenticity is high.
A.2 Results of size analysis for + 9500 – 6700 microns coal using 30.6 mm balls 82 A.3 Results of size analysis for + 2360 – 1700 microns coal using 30.6 mm balls 83 A.4 Results of size analysis for + 26500 – 22400 microns coal using 38.8 mm balls 83 A.5 Results of size analysis for + 16000 – 13200 microns coal using 38.8 mm balls 84.
Jun 03, 2020 The design of such grinding mills is extremely critical, requiring sophisticated software tools, proprietary calculation worksheets, and experienced technical engineers and drafters. This blog will review how the mill design process has changed over the last 30 years. While most of the changes have been positive, new issues and problems have risen in the process.


text:
This is very much a personal anthology, a reflection of the books on my shelves, my work and the recommendations of friends and colleagues, not necessarily of Spanish classics. There are no stories, for example, by Leopoldo Alas (Clarín), Carmen Laforet, Enrique Vila-Matas or Manuel Rivas, because, much though I love their novels, I have not read any of their short fiction. Revisiting these stories has been hugely enjoyable – like retracing the Spanish strand of my career, from school to the present day.
‘The Glass Lawyer’, by Miguel de Cervantes, translated by Edith Grossman
My book Don Quixote’s Delusions: Travels in Castilian Spain (Phoenix), was partly dedicated to exploring the revolutionary effect of Don Quixote (1605), especially on writers and thinkers, including Nabokov, Woolf and Freud. Often described as the world’s first modern novel, Don Quixote is the first to feature a fully rounded psychological character who can doubt his own motives. If you haven’t got the time or the inclination to peruse its one thousand pages, though, you can find quicker evidence of the author’s genius in the Exemplary Novels, a collection of twelve short stories that appeared in 1613, midway between the publications of Volumes One and Two of Don Quixote.
In ‘The Glass Lawyer’ a prodigiously clever graduate of Salamanca University is given a love potion by his spurned admirer and becomes convinced that he is made of glass. So terrified is Tomás of his own fragility that he begs curious onlookers not to approach him and insists on being transported in a box lined with straw. While in the grip of this delusion, he starts spouting aphorisms about society, Forrest Gump-style, and becomes a cause célèbre. As soon as he recovers his sanity – and now mortified by his previous indiscretion – he is no longer of interest to anyone. Here, in microcosm, Cervantes explores some of the ideas about mental instability, character and truth-telling that shaped el Quijote. The story has spawned numerous literary and psychological studies and inspired Deborah Levy to write her own take on it, ‘The Glass Woman’, published in Lunatics, Lovers and Poets: Twelve Stories after Cervantes and Shakespeare (And Other Stories, 2016)
First published as ‘El licenciado Vidriera’ in Novelas Ejemplares, Juan de la Cuesta 1613, translation in The Exemplary Novels, Yale University Press 2016
‘The Foolish Children’ by Ana María Matute, translated by María del Carmen Luengo Santaló and Aileen Dever
Matute’s Primera Memoria was the first novel I ever read in Spanish, aged sixteen, and I was affected by it in the way perhaps only a teenager can be. The thrill of gaining access to another world, one not available to your monolingual friends, not even to your parents, rewarded the effort of learning to read in a foreign language. It’s hugely regrettable that books have largely been stripped out of the A-Level foreign languages syllabuses now.
Matute is a quintessentially Spanish writer, one was strongly affected by the war-torn rural landscape in which she had had grown up. ‘The Foolish Children’, first published in 1956, is a sequence of very short stories – micro-fictions before the invention of that term – encapsulating a disturbing vision of childhood, and one that reminds me of the paintings made by Paula Rego, inspired by nursery rhymes. The children in the stories are often troubled, or mistreated, grotesque and reviled. Insects and animals, trees and plant life are sometimes comforting but at other times a menacing presence. Matute claimed to relate better to eleven-year-olds than anyone else and was, herself, one of a group of writers dubbed “the frightened children”, because of the effect of Spain’s civil war on their childhood and fiction.
First published as ‘Los niños tontos’ by Ediciones Arión, 1956, translation in Small Stations Press, bilingual edition, 2016
‘Saint Manuel Bueno, Martyr’ by Miguel de Unamuno, translated by Paul Burns and Salvador Ortiz-Carboneres
In 1898, Spain lost its last colonies in the Spanish-American war and suffered a national identity crisis that might not seem entirely unfamiliar to people in Britain today. The generation of 1898 writers, of whom Unamuno is the towering figure, probed the reasons for that catastrophic loss, proposing a radical reinterpretation of Spanish values. A longtime rector of Salamanca University (although forced into exile during the dictatorship of Primo de Rivera), Unamuno is Spain’s most famous philosopher. On his return to teaching, after six years in exile, he famously began his lecture, “As we were saying yesterday.”
‘Saint Manuel Bueno, Martyr’, is a short novella, the story of an exemplary priest, a man of Christlike kindness, revered by his parishioners as a living saint. But when a nonbeliever tries to find God by emulating Manuel, he discovers that the priest’s faith is a travesty, because he does not believe in the resurrection. Manuel simply sees religion as the best route to a good and contented life and so strives to make it available to others. Should he be deplored for acting in bad faith, then, or admired, for helping others to believe? The idea that someone might espouse religion while not believing in God is not altogether original, but it appealed to me in my heated early twenties, perhaps because my own father was a philosopher-priest who was often preoccupied by doubt. I lived in Salamanca for six months before going to university, and used to sit in the room where Unamuno once delivered his lectures.
First published as ‘San Manuel Bueno, mártir’, 1931, translation published by Aris and Phillips Hispanic Classics 2009
‘A Clear Conscience’ by Carmen Martín Gaite, translated by Margaret Jull Costa
In 1986 I was a student in Madrid, thrust into the tumult of the post-dictatorship social revolution known as La Movida. On my first morning at the Universidad Complutense, I fell down some stairs, had a nose bleed and got taken off to the women’s lavatories by some kind fellow students. On emerging I discovered that the novelist Carmen Martín Gaite was giving a talk in the lecture theatre. I still remember her distinctive look, bohemian in a felt hat and scarf – and her observation that when you have been restricted to the home, as Spanish women so often had been in the twentieth century, you learn observational skills that come in very useful for novelists. Writing about the home has so often been disparaged as a lesser art, but it is in homes and families that our most intense experiences take place.
The short story, Martín Gaite once observed, could sometimes slip past censors who paid closer attention to novels. In this 1956 story – deeply subversive in its way – a poor young woman from a shanty town on the edge of Madrid persuades a doctor to come and visit her sick child. He agrees to drive them both to hospital, but the child dies on the journey. The woman’s hopeless situation – she will probably resort to prostitution to raise money for medical bills – and the contrast between her desperation and the doctor’s sangfroid is beautifully evoked, and painful to observe.
First published as La conciencia tranquila, 1956. Translation in Madrid Tales, edited by Helen Constantine, Oxford University Press, 2012
‘While the Women are Sleeping’ by Javier Marías, translated by Margaret Jull Costa
In some parallel universe, Marías is the love child of Alfred Hitchcock and Jorge Luis Borges. Spain’s most successful contemporary writer, and a likely contender for the Nobel Prize, he is both highly intellectual and highly attuned to the tricks and thrills of popular fiction. His cerebral games recall Borges; his slow-building suspense is worthy of Hitchcock. In Spain Marías is almost as famous for his eccentricity as his writing. He owns two near identical flats in Madrid’s Plaza Mayor, one in which all the furniture is dark and another in which everything is white. He is also the appointed king of a tiny island, Redonda, of which AS Byatt, Alice Munro and Umberto Eco have dukedoms. Not surprisingly, perhaps, Marías’s cleverness has prompted something of an Amis-style backlash in Spain; all the same, he is a dazzling writer.
‘While the Women Are Sleeping’, first published in 1990, contains, in miniature, Marias’s favourite themes: human obsession, voyeurism and abusive relationships. A couple on the beach notice that a man close by is compulsively filming his much younger girlfriend, amassing hours of microscopic footage of her, while she lies almost motionless. When the narrator meets him at their hotel one night, he quizzes the man about his obsession and discovers the chilling reason for it.
First published as ‘Mientras ellas duermen’ in Mientras ellas duermen, Anagrama 1990, translation in While the Women are Sleeping, Chatto and Windus, 2010
‘La asesina de insectos’ (The insect killer) by Rosa Montero
Rosa Montero is one of Spain’s best-known columnists. She started working at El País in 1976, the year after General Franco’s death, and her career has run in parallel with the development of Spain’s democracy. Montero’s writing often reflects the mores of post-Franco Spain, although she has turned her sights on Britain, too. Recently she wrote that “I have always been a great anglophile, but now I see the British turning against history and submerging themselves in a reactionary chaos.”
This story was commissioned for a Spanish anthology marking the turn of the millennium, and describes inter-generational friction, but not of the usual kind. Marina and Juan are children of the dictatorship and spent their youths on demonstrations or running away from police, young hippies in full rebellion against their parents and the establishment. Now neither of them can get work, while their son Carlos has become the reincarnation of his bourgeois grandfather, a “grey suit man with tame ideas”. He’s considerate, responsible and fluent in English to the standard obligatory now for anyone wanting a well-paid job in Spain. He supports both his parents, who find the role-reversal hard to take. They grew up fighting the system; their son has become a slave to it.
First published in Relatos para un fin de milenio, Plaza Janés, 1998
‘A Literary Adventure’ by Roberto Bolaño, translated by Chris Andrews
Bolaño, a Chilean, has been described by The New Yorker as the greatest Latin American writer of his generation, but he spent more than half of his life in Barcelona, having endured torture and imprisonment under the Pinochet regime. It was in Barcelona that he wrote his monumental novel 2666, while awaiting a liver transplant. Unfortunately he died before its publication – in 2003, at the age of fifty – and before an avalanche of acclaim and accolades came his way.
Bolaño, who once said, “I could live under a table reading Borges”, has elements in common with other Borges-inspired novelists such as Enrique Vila-Matas and Javier Marías, except that there is also a sad awareness of the reality of life in Chile, of exile and violence, in his writing. In ‘A Literary Adventure’, a writer, B, is envious of A, his more successful contemporary: “he longs to plant his fist in A’s increasingly prudish face, oozing self-assurance and righteous anger, as if he thought he were the reincarnation of Unamuno or something.” Instead of violence, B takes a more cowardly, writerlyrevenge: he includes an unflattering portrait of A in his novel. To his consternation, though, A writes a flattering review of the novel. More and more fulsome praise from A follows, including of a book that is not yet officially available to reviewers. How did he get it, and what’s he playing at? B becomes obsessed with A, cancels all other plans in order to spend his days stalking A and ends up fearing for his sanity and even his life. A delicious tale of literary paranoia.
First published in Llamadas telefónicas, Anagrama, 1997, translation in Last Evenings on Earth, Harvill Secker, 2007
‘Strategies Against Sleeping’ by Liliana Heker, translated by Alberto Manguel and Miranda France
Another Latin American – from Argentina this time – and not even one who has lived in Spain, but Heker’s short story ‘Strategies Against Sleeping’ was inspired by a long car journey the author took from Segovia to Madrid, and since it was the first short story of hers I ever translated, it has a special place in my heart. The story starts with the narrator setting off on her journey and looking forward to nodding off on the back seat, but the driver – who is himself fighting an urge to sleep – keeps asking her to talk to him (“Please, Talk to Me” provides the title for this collection). The woman makes some half-hearted attempts at conversation but, as is often the case with Heker’s work, what seems like a fairly straightforward situation gradually reveals itself to be charged with unexpected menace, taking an extraordinary turn at the end. The Argentine writer and intellectual Alberto Manguel asked me to translate Heker’s stories with him for this collection and I was grateful to be introduced to a woman is unusual and engaging, both on the page and in person. Her writing, recalling both Saki and Roald Dahl, can be devilishly difficult to translate, though. Once when I asked her what she had meant by a particular phrase she said “I don’t really know, put whatever you think.
First published as ‘Maniobras contra el sueño’, in La crueldad de la vida, Alfaguara, 2001, translation in Please Talk to Me, Yale University Press, 2015
‘Feminist’ by Emilia Pardo Bazán, translated by Maria Cristina Urruela
Emilia Pardo Bazán (1851-1921) is an extraordinary figure in Spanish literature. Encouraged by her enlightened father to pursue her education and read whatever she wanted, she was an admirer of Zola and both praised and reviled for introducing Naturalism to Spain. Her ideas on feminism were extremely radical for the time (she judged Spain to be about two hundred years behind the rest of European in terms of sexual equality) and she spoke often about the need for women to receive the same access to education as men.
Pardo Bazán’s outspoken views on female emancipation were considered so scandalous that her husband finally demanded she end her career. She ended her marriage instead, and went on to become Spain’s first female university professor. Best known for her novels, Pardo Bazán also produced nearly six hundred short stories, many of which are very brief, little more than telling vignettes. In ‘Feminist’ – the title itself is a bold statement – we learn how a man has kept his doting wife in her place: on their wedding night he commanded her to put on his trousers, then told her that she would never “wear the trousers” in their relationship again. The tables are turned, though, when the man becomes an invalid, dependent on his wife’s care. Then she gets her own back by making him wear her petticoat every morning and leaving him in it while she goes about other duties, “Just so you know that now you must wear it for the rest of your life.”
First published as ‘Feminista’, translation in Torn Lace and Other Stories, The Modern Language Association of America, 1996
‘Post tenebras spero lucem’ by Bernardo Atxaga, translated by Margaret Jull Costa
My Basque friend Jokim once made me wait at Bilbao bus station for a coach to the airport while he ran to the nearest bookshop to get me a copy of Obabakoak. The publication of this book in 1989 was hugely significant in the Basque Country and across Spain. There is very little literature published in Euskera (Basque), because the language is so hard to learn: a pre-Indo-European language, its origins are mysterious. Euskera was suppressed during the dictatorship (signs in telephone boxes would warn the public to “speak Christian”) and Jokim was among a generation who learned the language of their forebears in clandestine schools.
Obabakoak was not only a vibrant addition to the Basque canon, but the first Euskera novel to win Spain’s National Prize for literature, in a Spanish translation Atxaga produced himself. The title means “the people and events of Obaba”(a fictional village)and the book comprises a series of tales about different characters in a fictional Basque village, a place Atxaga has described an “an interior landscape.”
In this story, a young schoolmistress, far from home and feeling starved of affection, begins to lose her mind in the cold and forbidding landscape of her new posting. A serious soul whose penchant for maths means that she is always counting steps, or mountains or swallows (“one hundred and twenty swallows on one wire and one hundred and forty on the other, two hundred and sixty swallows in all”), she is finally driven by loneliness to seduce one of her young pupils, with disastrous results. Once more, this translation is by the peerless Margaret Jull Costa, who has played such an important part in making Spanish fiction available to a wider audience.
First published in Obabakoak, Erein, 1988 and in translation from Hutchinson, 1992
‘Con Agata en Estamboul’ (With Agatha, in Istanbul) by Cristina Fernández Cubas
Although I have been aware of her for a few years, I hadn’t read any Fernández Cubas until staff in the cultural office of the Spanish Embassy in London recommended her to me. She is known as a writer of fantasy in Spain, but her stories might better be described as unsettling, taking place in realities that are other-worldly and may be permeated by unexplained influences. Her taste for mystery began in childhood, whenFernández Cubas’s brother would tell her stories from Edgar Allan Poe and Agatha Christie.
In this story the narrator travels with her husband to Istanbul for a two-week stay at the Pera Palace, where Christie famously was a regular guest (always staying in room 411). That room is thought to hold answers to the author’s mysterious disappearance in 1926, after a clairvoyant guided investigators to the discovery of a key, under its floorboards, in 1979.
From the start, this story’s characters seem to have entered a parallel world. Istanbul itself, which is permanently shrouded in fog, seems barely to exist; they can’t pick out any of its famous sights. Moreover, the story’s narrator has just turned forty and is troubled by her own identity, just as Christie was at the time of her disappearance. When her husband keeps bumping into a beautiful acquaintance, she becomes increasingly uneasy, especially when a sprained ankle hobbles her and keeps her from joining them. This is not only a strange, compulsive read, but a strong argument for having more of Fernández Cubas available in English. At present one selection of her stories, Nona’s Room, is available, published by Peter Owen.
Published in Todos los Cuentos, Tusquets, 2009
‘The Novel on a Tram’ by Benito Pérez Galdós, translated by Margaret Jull Costa
Gladós is the Spanish Dickens, a nineteenth-century writer of substantial, satisfying realist novels,the most famous being Fortunata y Jacinta. As a student in Madrid, I devoured this novel, especially a passage which showed Fortunata, a poor woman who suffers at the hands of a series of exploitative men, walking back to her lodgings in Chueca, a rundown area of Madrid. The narrative followed her all the way to my barrio – we were living in the same street! More than a century later, Chueca was still a dodgy part of town and the centre of Madrid’s sex trade. These days it’s very fashionable. Although he was a nineteenth-century novelist, Galdós had distinctly modern traits, and three of his books were brought to the screen by the surrealist filmmaker Luis Buñuel. ‘The Novel on the Tram’ (1871) is, in its turn, inspired by Don Quixote. Its protagonist is travelling across Madrid by tram, carrying a parcel of books. He encounters a friend who passes on some gossip about a Countess whose unkind and jealous husband suspects her of having an affair, and whose butler is blackmailing her. After his friend has got off the tram, the narrator falls into a kind of delirium in which he imagines that different people getting on and off the tram are characters from involved in this scandal. Apart from being an entertaining story, ‘The Novel on the Tram’ is a kind of paean to public transport:
…a tram contains a miniature world of passions. We judge many of those we see there to be excellent people, we like their looks and are even saddened when they leave. Then there are those who, on the contrary, we loathe on sight: we hate them for ten minutes, rather rancorously examine their phrenological character, and feel real pleasure when they leave. And meanwhile, the tram, that imitation of human life, keeps moving, constantly receiving and letting go, uniform, tireless, majestic, indifferent to what is going on inside, entirely unstirred by the barely repressed emotions of that dumbshow, always travelling along those two endless parallel steel lines, as long and slippery as the centuries.
First published as La novela en el tranvía, translation in Madrid Tales, edited by Helen Constantine, Oxford University Press, 2012. Also available online, including in a translation by Michael Wooff at the Gutenberg Project)

domain: artistic


text:
Sicily used to have a different name before
the current one (we would call it Sicania): it
originated from the �Sicani� people: anthropologists
tell us that the �Sicani� had nothing in common with
the �Siculi�, who came later. The former originated
from Libya, and geologists admit they could have come to the western part of
the island when a strip of land emerged during glacial eras used to connect
Africa to Sicily, therefore these people were of Camitic origin. About 1,000 BC these people were
exterminated by the Carthaginese.
The History of Sicily
of Sicily begins with the history of Europe, during the upper Paleolithic
(20,000 � 10,000 BC): it was populated by peoples of the modern human type.
Settlements and new civilizations followed in waves, then followed by new ones
over and over: the Phoenician, the Greeks, the Arabs (the Moors)�..
The most ancient Sicilian culture we know is
dated around 10,000 BC (as established from rock carvings at Mount Pellegrino),
followed by others until in the Eneolithic (Copper age,
3,500-3,000 BC) the island began to be subjected to ever increasing influences
by oriental and Mediterranean civilizations.
During the same period, either before or
after the disappearance of the �Sicani�, on the
eastern part of the island began to land the �Siculi�,
a Pelasgic tribe, of hindo-european
origin, therefore Semitic. Before the arrival of further migrational
waves of Phoenicians first, then Greeks, local populations had already melted
and the only name left was �Siculi� (hence �Sicily�).
Between the end of the 9th century BC and the
beginning of the 8th century BC, when major political readjustments in both the
Middle East and the rising Hellades (Greece)
occurred, the exploration of the Sicilian island resumed: first with just some
scouting, then (tradition places it around 734 BC) the Corinthians founded the
city of Siracusa and right after that (in 728 BC) the
Megarese founded the city of Megara Iblea. In 688 the Rhodese (from
the island of Rhodes) and Cretese (from the island of
Crete) founded Gela (today a major oil refinery center, editor�s note), while
the Calcidaeses founded Messina, Reggio, Nasso, Taormina (on the island), Lentini,
Catania. In 580 BC the people of Gela founded Agrigento and Selinunte.
Over a century span, the Greeks completely changed Sicily�s face: politically,
socially and culturally.
Phoenicians landed there too, but only to
establish trading bases.
The relationship between the occupiers and
the local populations were fairly good, which favored the process of �hellenization� (i.e. absorption of the Greek culture) of
the territory, also because the new culture and the associated political system
were very much appreciated, since 1) they provided benefits for everybody and
2) they came from millenarian oriental civilizations, and brought new
technologies which began to change the island outlook.
Only the Siculi of Siracusa rebelled against the Greek hegemony, and it was
this city, ever more powerful, which extended its supremacy over the island,
and, keeping Carthago at bay, favored the economic,
cultural and political evolution of the island, which lasted over 4 centuries.
This period�s wonders, can be admired at the Archaelogical Museum of Siracusa,
amongst the richest in the world.
However the Siracusans
could not dodge the Roman hegemony, which began in 241 BC. Their domination
terminated in 476 AD, when the Romans where not only unable to conquer anything
else, but not even to defend themselves.
After the fall of the Roman empire, there was an invasion by Theodoric�s Ostrogots in 493 AD, a very bad period of byzantine
domination (535 AD, 827 AD). Then the Arab invasion (probably requested by some
locals, to stop the byzantine�s oppression). The
Moors landed at Mars-Allah (Allah�s port), today�s Marsala,
and beat the Byzantines. In 831 AD they entered Palermo, in 859 AD Enna, in 902
AD Taormina. So inserted in the Islamic area of influence, Sicily experienced a
long period of growth, both economically and culturally. This is when things
such as the citrus cultivation (still a major economical resource today), water
seeking technologies (new for the times) and new agricultural tools were


Monica Yates a trauma healer, feminine/masculine embodiment coach, period whisperer and podcast host of Feminine As F*ck joins Enterprise Radio to discuss feminine leadership.
This episode of Enterprise Radio is on association with the Author Channels.
Listento hostEric Dye & guest Monica Yates discuss the following:
- How have women been taught to show up in the workplace, and are there things we need to unlearn?
- Tell us how women can embody boundaries at work?
- How can women that are running businesses balance the grind with the feminine flow and why is this important?
- Is there a time when women are better off being masculine?
- What are the main reasons why so many women struggle to let go and trust men?
Monica Yates is a trauma healer, feminine/masculine embodiment coach, and period whisperer. She’s also the podcast host of Feminine As F*ckand runs a business helping people from all walks of life get into their magnetic feminine energy, feel safe letting men lead, heal their cycle, and free themselves from the trauma and energetic blocks that hold them back from living their dream life. She has been featured in Vogue, Glamour, Men’s Health and more.
People also listened to this: How Play and Humor Fuel Innovation and Design


Wool and mohair trousers
Wide trousers in wool and mohair canvas with double pleats on the front, small pockets on the back and slash pockets at the sides. Concealed zip fastening with small hook.
Fabric 65% virgin wool, 35% mohair; lining 95% acetate, 5% elastane.
Do not wash; do not bleach; do not tumble dry; cool iron; professionally dry clean perchloroethylene - mild process; do not wet clean. do not wash do not bleach do not tumble dry cool iron professionally dry clean perchloroethylene - mild process do not wet clean.; protect buttons before washing.
Distributed by Max Mara S.r.l., registered office in Reggio Emilia (Italy), Via Giulia Maramotti 4, 42124 (IT)
Delivery usually takes place within 7 working days.
Collection Max Mara
Product code: 1131010106001 - VILLAR


text:
Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COVID-19 disease severity and indicator of the need for mechanical ventilation, ARDS and mortality
Annals of Intensive Care volume 11, Article number: 50 (2021)
COVID-19 pneumonia and subsequent respiratory failure is causing an immense strain on intensive care units globally. Early prediction of severe disease enables clinicians to avoid acute respiratory distress syndrome (ARDS) development and improve management of critically ill patients. The soluble receptor of advanced glycation endproducts (sRAGE) is a biomarker shown to predict ARDS. Although sRAGE level varies depending on the type of disease, there is limited information available on changes in sRAGE levels in COVID-19. Therefore, sRAGE was measured in COVID-19 patients to determine sRAGE level variation in COVID-19 severity and to examine its ability to predict the need for mechanical ventilation (MV) and mortality in COVID-19.
In this single-centre observational cohort study in Germany, serum sRAGE during acute COVID-19, 20 weeks after the start of COVID-19 symptoms, as well as in control groups of non-COVID-19 pneumonia patients and healthy controls were measured using ELISA. The primary endpoint was severe disease (high-flow nasal oxygen therapy (HFNO)/MV and need of organ support). The secondary endpoints were respiratory failure with need of MV and 30-day mortality. The area under the curve (AUC), cut-off based on Youden’s index and odds ratio with 95% CI for sRAGE were calculated with regard to prediction of MV need and mortality.
Serum sRAGE in 164 COVID-19 patients, 101 matched COVID-19 convalescent patients, 23 non-COVID-19 pneumonia patients and 15 healthy volunteers were measured. sRAGE level increased with COVID-19 severity, need for oxygen therapy, HFNO/MV, ARDS severity, need of dialysis and catecholamine support, 30-day mortality, sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) score. sRAGE was found to be a good predictor of MV need in COVID-19 inpatients and mortality with an AUC of 0.871 (0.770–0.973) and 0.903 (0.817–0.990), respectively. When adjusted for male gender, age, comorbidity and SOFA score ≥ 3, sRAGE was independently associated with risk of need for HFNO/MV. When adjusted for SOFA score ≥ 3, sRAGE was independently associated with risk of need for MV.
Serum sRAGE concentrations are elevated in COVID-19 patients as disease severity increases. sRAGE should be considered as a biomarker for predicting the need for MV and mortality in COVID-19.
The current COVID-19 global pandemic is caused by the virus SARS-CoV-2 and has a case-fatality ratio ranging from 1.3 to 9.8% as of 14th Nov 2020 . In COVID-19 patients with severe disease progression, a hyperinflammatory status, severe endothelial damage, thromboembolic diseases, micro- and macroangiopathy, capillary leakage resulting in acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, and multiorgan failure can be observed . Among the many organ systems affected, COVID-19 pneumonia is the most common and causes the greatest need for intensive care support .
There are a number of biomarkers that indicate severe disease progression in COVID-19. The aim of this study was, therefore, to identify a reliable biomarker that can accurately reflect COVID-19 disease severity to enable early detection of patients needing MV and allow close monitoring, early prevention and early treatment to be carried out.
Knowledge regarding the pathophysiology of SARS-CoV-2, which allows such therapeutic intervention, is limited. The receptor for advanced glycation end products (RAGE) facilitates inflammation, the immune response to infection and subsequent endothelial damage [4, 5] and is expressed most prominently on alveolar epithelial cells in the lungs [6,7,8]. The soluble RAGE (sRAGE) in serum has the extracellular domain of RAGE but lacks the transmembrane and intracytoplasmic domains . sRAGE binds to RAGE ligands without activating the RAGE-mediated signaling pathway, thereby acting as a competitive inhibitor of RAGE. There are many isoforms of sRAGE [9, 10] and their measurement is receiving increasing attention as reporters of immune system function.
sRAGE level in blood correlates with high levels of ongoing bacterial infection, inflammatory diseases , indicates lung epithelial injury , and is known as a predictor of the development of ARDS in non-COVID-19 patients . Furthermore, it has been hypothesized that the RAGE pathway plays a central role in the pathogenesis of COVID-19 [14, 15]. For these reasons, we hypothesised that serum sRAGE may indicate COVID-19 disease severity, defined as the highest level reached on the WHO clinical progression scale  in each individual patient.
sRAGE levels in COVID-19 patients were, therefore, measured to verify the reliability of sRAGE in predicting the need of mechanical ventilation (MV) and mortality in COVID-19 patients.
Study design and patient selection
Consecutive symptomatic SARS-CoV-2-positive patients treated at the University Hospital of Heidelberg were screened for this prospective non-interventional register with biobanking study, that was approved by the Ethics Committee of the Medical Faculty of Heidelberg University Hospital (number S-148/2020) and in accordance to the Declaration of Helsinki . All patients with laboratory-confirmed SARS-CoV-2 infection as well as patients suspected of SARS-CoV-2 infection aged 18 years or older treated as out- or inpatients between 18.03.2020 and 02.10.2020 were considered for inclusion in this study. Written informed consent was obtained for all patients included in the study. Patient data and serum samples were collected prospectively. Additionally, patients who were seen as post-COVID-19 patients in follow-up and who gave their informed consent were included in a follow-up study, that was approved by the Ethics Committee of the Medical Faculty of Heidelberg University Hospital (number S-546/2020) and in accordance with the Declaration of Helsinki . In this follow-up study, patient data and serum samples were collected prospectively. Previously not collected additionally needed patient data were assessed in retrospect by review of the records.
The diagnosis of COVID-19 was based on a positive detection of viral genome in nasopharyngeal swabs or airway surface liquid using reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) . CT imaging of the lungs was used as a supportive diagnostic criterion for ARDS according to the discretion of the attending physician. In general, HFNO was initiated when 4 L/min of oxygen was insufficient to reach a peripheral oxygen saturation of 93%, whereas MV was initiated when the Horowitz index was < 100. However, patients were managed also according to the discretion of the attending physician, taking into account factors not reflected in our data, such as subjective dyspnoea and breathing mechanics.
The COVID-19 patients were divided into four cohorts: mild disease (cohort A), moderate disease (cohort B), severe disease (cohort C) and convalescent (cohort D). Cohorts A, B and C were divided according to the WHO clinical progression scale of COVID-19  according to the stage of their most severe disease progression. The cohort with mild disease (cohort A) consisted of outpatients who were visited by medically trained staff at their homes after reporting symptoms such as light dyspnoea or continuously high fever (≥ 38.3 °C). The cohort with moderate disease (cohort B) consisted of inpatients with neurological symptoms or dyspnoea requiring no or low flow oxygen therapy using nasal prongs treated at the non-intensive care ward. The cohort with severe disease (cohort C) consisted of inpatients treated at the intermediate care and intensive care unit requiring high-flow nasal oxygen therapy or endotracheal intubation and mechanical ventilation. Non-invasive ventilation was not used at our center for COVID-19 patients. In addition to acutely ill patients, a cohort of convalescent patients 20 weeks after initial onset of symptoms was analysed (cohort D). Of all patients contacted for follow-up, only those who were in cohort A, B or C were included in cohort D. The non-COVID-19 pneumonia control group consisted of patients admitted under the suspicion of having COVID-19 but who tested negatively by PCR for SARS-CoV-2 in nasopharyngeal swabs. The healthy controls were volunteers with no previous medical history.
sRAGE was measured in the earliest blood sample available. Other exclusion criteria for this study were patients younger than 18 years old, patients who did not consent to this study and patients from whom blood samples were not available within 7 days after admission or after the first house call.
The demographic characteristics, medical history, clinical and laboratory data were collected during COVID-19 infection and during follow-up. The primary outcome was severe disease (defined as the need of HFNO/MV, need for catecholamine therapy or need for dialysis). The secondary outcomes were respiratory failure with need of MV and 30-day mortality. Clinical variables measured were SOFA score, qSOFA score  and the Horowitz Index (PaO2:FiO2) .
sRAGE levels in serum were measured using an enzyme-linked immunosorbent assay (ELISA) kit from R&D Systems (Minneapolis, MN, USA). Patient sera were obtained by centrifuging whole blood for 15 min at 1800 × g. The pipetted sera were stored at − 80 °C until shortly before ELISA was carried out. The accuracy of the ELISAs carried out were controlled using Quantikine® ELISA Kit Controls, Control Set 832 from R&D Systems (Minneapolis, MN, USA). For sera with RAGE concentrations that were too high to be measured, an initial dilution of 1:3 was carried out, with one part serum and two parts Calibrator Diluent RD6-10. Subsequently, when the RAGE concentrations were still too high under the 1:3 dilution, a dilution of 1:5 was carried out, with one part serum and four parts Calibrator Diluent RD6-10. For sera with RAGE concentrations that were still too high under the 1:5 dilution, a maximum sRAGE concentration of 25,000 pg/mL (5000 pg/mL × 5) was assumed. There were no sera with RAGE concentrations below the lower ELISA detection limit. The means of sRAGE duplicates were reported.
The sample size was not predefined, as all patients with written consent and met the inclusion criteria were included. To choose the appropriate statistical tests, descriptive statistics was used initially to determine the normality of data distribution across each level of comparison and homogeneity of variance of data. sRAGE levels showed a left skewed distribution and were therefore subject to natural log (Ln) transformation for analysis. Continuous variables are reported as median with interquartile range. Categorical variables are expressed as numbers with percentage. Parametric tests were preferred if the assumptions were fulfilled to increase the power, otherwise non-parametric tests were applied for analysis. Welch’s t test and Mann–Whitney U test were used as appropriate to determine the relationship between a continuous and categorical variable with two levels. Spearman’s correlation was used as appropriate to determine the correlation between two continuous variables. Brown–Forsythe ANOVA and Kruskal–Wallis tests were used as appropriate to compare means or rank of continuous variable across an independent variable with more than two levels. Where homogeneity of variance was not assumed, Dunnett’s T3 post hoc test was used. For the Brown–Forsythe ANOVA comparing sRAGE levels and ARDS severity, there was only one patient with mild ARDS and this was, therefore, disregarded, as it was not possible to perform this test for this group of mild ARDS. When Kruskal–Wallis test was used, significance values have been adjusted by the Bonferroni correction for multiple tests to avoid Type-I error. Wilcoxon matched-pairs signed rank test was used to compare sRAGE during acute disease and during convalescence. The effect sizes were reported as Cohen’s d or η2 as appropriate. Missing data and loss to follow-up were excluded pairwise in all analyses. Area under the curve (AUC) derived from the receiver operating characteristic (ROC) curved was used to determine the ability of different variables to predict analysed outcomes . AUC was reported as AUC (95%CI). The thresholds were derived based on clinical relevance and Youden’s index . Univariate binary logistic regression was used to determine the odds ratio (OR) with 95% confidence intervals (CI) for predicting the need for HFNO therapy or mechanical ventilation. Multivariate binary logistic regression was used to analyse the need for HFNO/MV and MV. The Hosmer–Lemeshow goodness-of-fit test was used to evaluate the adequacy of the regression model to describe the data . The known risk factors for severe disease progression (male gender, age, comorbidity and SOFA score ≥ 3 [24,25,26]) were fitted into the model for analysing the need for HFNO/MV. Due to limited number of events (N = 19), only one of the known risk factors for severe disease progression with the largest effect size in the univariate binary logistic regression was fitted into the model for predicting the need for MV. Kaplan–Meier estimation  was used to estimate survival, using the threshold derived from Youden’s index. The endpoint here was death of any cause. Survival was calculated from date of first sRAGE measurement up to 30 days or death of any cause. Patients who were alive were censored at 30 days. Univariate COX regression was used to determine the hazard ratio of sRAGE predicting 30-day mortality. 2-way ANOVA was used to determine the effect of two categorical variables on a continuous variable. All tests were two-sided and p ≤ 0.05 was considered significant. All data were analysed using IBM SPSS Statistics Version 27, Graphpad Prism 9 and Microsoft Excel.
187 patients with COVID-19 or suspicion of COVID-19 treated at the University hospital of Heidelberg were included in this study. Nine patients who were initially treated in other hospitals or departments were excluded from the study, as there were no blood samples available during the first 7 days of admission. There was a total of 164 COVID-19 patients, 23 patients with non-COVID pneumonia as well as 15 healthy volunteers included in this study. Out of the 164 COVID-19 patients, 101 patients came for follow-up during convalescence. The patients were further categorized as shown in Fig. 1. Table 1 shows the baseline characteristics of these cohorts. The baseline characteristics of patients with severe COVID-19 with the need of HFNO and MV were further distinguished (Additional file 1).
sRAGE increased in severe disease and correlated with disease severity
The median number of days between sRAGE measurement and the need for HFNO/MV was 0 (0–1) days. sRAGE levels correlated to disease severity, p < 0.001, η2 = 0.377 (Fig. 2a). sRAGE level was not only significantly higher in patients needing HFNO/MV, p < 0.001, d = 0.648 (Fig. 2b), but also increased in patients with need of hemodialysis, p < 0.001, η2 = 0.106 (Fig. 2c) and need of catecholamine therapy, p < 0.001, η2 = 0.158 (Fig. 2d). Investigating other aspects of disease severity as measured by the SOFA score, there was a significant strong positive correlation between sRAGE level and SOFA score, rs (162) = 0.525, p < 0.001 (Fig. 2e). sRAGE level increases significantly as qSOFA score increases, p < 0.001 (Additional file 2a). sRAGE was also found to be moderately positively correlated to duration of hospitalization, rs (89) = 0.375, p < 0.001 (Additional file 2b). sRAGE was significantly higher in patients with elevated D-Dimer, p < 0.001, η2 = 0.210 (Additional file 2c). sRAGE levels were 38% lower in the same patients during convalescence compared to during acute disease (Additional file 2d).
sRAGE distinguished HFNO/MV need in COVID-19 with an AUC of 0.853 (0.765–0.940) with 78.1% sensitivity and 81.1% specificity when set at a threshold of 2348 pg/mL. Table 2 shows odds ratios of the need for HFNO/MV based on univariate binary logistic analyses. The variable with the largest effect size was the SOFA score. Adjusting for male gender, age, comorbidity and SOFA Score ≥ 3, sRAGE Ln was associated with need for HFNO/MV (Table 3). The model was able to distinguish the need of HFNO/MV with 97% sensitivity and 90.3% specificity. Adding sRAGE to the model improved the accuracy of distinguishing the need of HFNO/MV from 95.1 to 95.7%.
sRAGE and the need for MV
The median number of days between sRAGE measurement and the need for MV was 1 (0–4) day. sRAGE level increased not only with the maximum oxygen and ventilation therapy needed, p < 0.001, η2 = 0.432 (Fig. 2f) but also with ARDS severity, p < 0.001, η2 = 0.391 (Fig. 2g). There was a significant, moderately strong negative correlation between sRAGE and the Horowitz Index, rs (85) = − 0.474, p < 0.001 (Fig. 2h).
When investigating the predictive value of sRAGE as a predictor of the need of MV for inpatients, the AUC in the ROC curve showed good discrimination with an AUC of 0.871 (0.770–0.973) and predicts with 84.2% sensitivity and 88.3% specificity when set at a threshold of 3108 pg/mL. Out of the seven patients that were intubated at least 2 days after the time of sampling, six out of seven (85.7%) of the patients had sRAGE levels above the threshold of 3108 pg/mL. Notably, when predicting MV only for inpatients (N = 84), sRAGE was the best predictor among other laboratory data when compared with CRP, IL-6 and D-Dimer (Fig. 3a). A comparison of different combinations using cut-offs of sRAGE, CRP, IL-6 and D-Dimer to predict MV in inpatients showed that the combination of high sRAGE and IL-6 had the highest AUC of 0.867 (0.762–0.972) (Additional file 3). Adjusting for SOFA Score ≥ 3, sRAGE remained associated with need for MV (Table 3). The model was able to predict MV with 95.9% sensitivity and 81.3% specificity. Adding sRAGE to the model improved the accuracy of MV prediction from 92.1 to 94.5%.
sRAGE may help predict mortality
The median number of days between sRAGE measurement and mortality were 3 (2–10) days. When investigating sRAGE levels according to 30-day mortality, sRAGE levels were found to be much higher in patients who died [8.96 (8.68–9.49) vs 7.360 (7.015–7.825), p < 0.001, η2 = 0.121] (Fig. 2i). When only taking into account the cohort with the need for HFNO/MV, sRAGE levels were higher in patients who died but the difference was not statistically significant, p = 0.092 (Additional file 2e). The AUC in the ROC analysis of sRAGE predicting 30-day mortality was excellent, 0.903 (0.817–0.990). Setting the sRAGE threshold at 5833.13 pg/mL, 30-day mortality was correctly predicted with 81.8% sensitivity and 92.8% specificity. When predicting mortality for inpatients (N = 84), sRAGE was the best predictor of mortality when compared with CRP, IL-6 and D-Dimer (Fig. 3b). The corresponding Kaplan–Meier survival plots for patients with high (≥ 5833 pg/mL) versus low (< 5833 pg/mL) sRAGE levels is given in Fig. 4. In univariate Cox regression, high sRAGE (≥ 5833 pg/mL) was associated with higher risk of 30-day mortality (HR 38.68, 95% CI 8.33–179.7, p < 0.001).
sRAGE increase might not be COVID-19 specific
Interestingly, there was no difference in sRAGE levels in COVID-19 compared to non-COVID pneumonia. Taking this comparison a step further by stratifying according to disease severity, only the effect of disease severity, p < 0.0001 but not the type of pneumonia, p > 0.05, or the interaction effect was significant, p > 0.05 (Fig. 2j). In addition, there was no difference in sRAGE levels of patients with mild COVID-19 and the healthy controls.
The key results of this study are as follows: sRAGE levels increased with COVID-19 severity and were found to be helpful in predicting respiratory failure with the need for MV as well as mortality from COVID-19. Interestingly, sRAGE levels in patients with COVID-19 pneumonia and non-COVID-19 pneumonia did not differ at a significant level.
Although sRAGE level increase in influenza A pneumonia (in the bronchoalveolar lavage fluid of mice) , community acquired pneumonia , sepsis  and lung injury are well documented [12, 31,32,33,34], there is currently limited information about how sRAGE levels vary in COVID-19. Spadaro et. al. described plasma RAGE levels in COVID-19 patients after MV . To the best of our knowledge, the present study is the first to show that serum sRAGE levels increase with COVID-19 severity, measured in terms of need for hospitalisation, need for HFNO/MV, need for organ support, SOFA scores, maximum ARDS severity, and 30-day mortality. The positive correlation of sRAGE levels and duration of hospitalisation appears in line with results shown by Calfee and colleagues for lung transplantation studies . In our results, sRAGE levels were 38% lower in the same patients during convalescence compared to during acute disease. This further shows that sRAGE is increased in acute COVID-19, which agrees with the findings of Dozio et al.  but contradicts the finding that sRAGE levels were lower in elderly patients with COVID-19 with lung involvement than in healthy controls . As sRAGE levels are found to vary differently in different diseases, this finding helps to clarify serum sRAGE levels in the context of COVID-19 and adds to the existing knowledge of sRAGE.
It is known that RAGE expression is enhanced in the lung , specifically on epithelial alveolar type I  and type II lung epithelial cells . Our data echo this by showing that sRAGE was negatively correlated to Horowitz Index. Beyond that, sRAGE increased as the oxygen therapy demand and ARDS severity increased. Based on these, it could be inferred that sRAGE may provide insights into the extent of lung tissue damage and could, therefore, be a valuable biomarker in COVID-19. Monitoring sRAGE levels could be useful in both outpatient and inpatient settings to support clinical decision-making, including need of hospitalisation as well as admission into the ICU.
Early detection of the potential need of MV and mortality is essential in optimising strategies used for patient monitoring and patient management. Despite efforts to optimise therapy for ARDS, mortality rates of ARDS remain high . This has spurred the switch of focus in management toward primary, secondary and tertiary ARDS prevention to positively influencing patient outcomes . Here, we show that a sRAGE level set at a threshold of 2348 pg/mL distinguishes COVID-19 patients with a need for HFNO/MV. This corresponds well to the median sRAGE levels reported for community acquired pneumonia without ARDS [1829.75 (1079–2629) pg/mL] and with ARDS [3296 (2168–3793) pg/mL]  but is higher than the sRAGE cut-off value of 1340 pg/mL for ARDS of all causes . Furthermore, our results show that sRAGE level set at a threshold of 3108 pg/mL is a good predictor of the need for MV in COVID-19 inpatients, with 84.2% sensitivity and 88.3% specificity. As COVID-19 is known to cause diffuse lung damage , this threshold corresponds well to sRAGE cut-off values described in some [33, 42] but not in other studies [43, 44], particularly when aiming to differentiate focal and nonfocal lung damage in ARDS. This shows that measuring sRAGE levels in serum early is valuable in predicting ARDS and the need for MV and, therefore, has the potential to improve daily clinical practice.
sRAGE levels were found to be significantly higher in patients with 30-day mortality when taking into account patients of all disease severity but not significantly higher when taking into account only patients with severe disease. Interestingly, Spadaro et al. also showed, when investigating COVID-19 ARDS patients, that RAGE levels one day after MV did not differ between survivors and non-survivors . Severe COVID-19 disease progression is characterised not only by lung injury but also by multiorgan failure. Therefore, monitoring sRAGE levels early may help predict mortality in the whole population by early identification of patients with severe disease, but appears to be less helpful, for patients already having severe disease. By setting the sRAGE threshold at 5833.13 pg/mL, 30-day mortality was predicted with 81.8% sensitivity and 92.8% specificity. The high sensitivity and specificity of sRAGE in predicting mortality may justify its utility in clinical practice to improve medical decisions and resource management. Jabaudon and colleagues showed that sRAGE was able to predict ARDS of different causes and ARDS mortality . Our results suggest that sRAGE monitoring may also be useful in the context of COVID-19.
Several studies indicate that combining different biomarkers can be useful to improve patient management [45, 46]. Our results resonate with these findings in that a combination of sRAGE and IL-6 measurement improved the prediction of the need for MV in inpatients as compared to sRAGE, IL-6, CRP or D-Dimer.
The role of clinical and severity scores for risk-stratification in COVID-19 have been studied. SOFA score was found to be superior to qSOFA score in predicting mortality in severe COVID-19 . A-DROP was found to be reliable in predicting in-hospital death in COVID-19 . However, subjective dyspnea scores were found to be inadequate in assessing hypoxemia in COVID-19 [48, 49]. Interestingly, high sRAGE discriminated the need for HFNO/MV and MV independently from a high SOFA score in our multivariate models. This shows that knowledge of serum sRAGE levels brings additional value in HFNO/MV prediction.
Our study contributes to the growing body of evidence that sRAGE monitoring is clinically useful for managing patients with potential need of intensive care and MV. Measurement of sRAGE levels may assist in the selection of COVID-19 patients to be admitted into the ICU as well as their timely intubation with lung-protective ventilation. However, the cost may be a factor limiting widespread use in daily clinical practice.
In experiments with mice, RAGE-deficient mice have been shown to increase mortality in Klebsiella pneumoniae pneumonia but better survival in influenza A pneumonia, pneumococcal pneumonia  and RSV pneumonia . In mice models, administration of sRAGE has also shown promising results in reducing acute lung injury . Further investigations regarding RAGE expression and the effects of RAGE deficiency in COVID-19 will be required to understand whether RAGE modulation is of therapeutic value in COVID-19 patients.
It has been postulated, that RAGE plays a role in the SARS-CoV-2-mediated inflammatory response in the lungs [14, 15]. Here, it has been hypothesised, that RAGE activation is triggered by activation of the ACE/Ang II/AT1R pathway after binding of SARS-CoV-2 to Angiotensin-converting enzyme 2 (ACE2) via its spike protein (S-protein) to invade host cells. Angiotensin II increase was also hypothesised as the cause of the complex clinical picture of COVID-19 . However, our data showed no difference in sRAGE levels when comparing COVID-19 and non-COVID-19 pneumonia. Furthermore, there was no difference in sRAGE levels between COVID-19 patients with mild disease and healthy controls. It could, therefore, be postulated that RAGE and Angiotensin II increase is not COVID-19 specific, but rather mirrors the severity of lung injury.
It is important to recognise the study limitations. First, the group of non-COVID-19 pneumonia cohort is small (n = 23) compared to the group of COVID-19 pneumonia cohort (n = 164) and the patients are not matched. Therefore, individual characteristics of studied patients affecting the results cannot be excluded. Further studies with more patients will contribute to the further validation of these results. Second, the bedside assessment and mechanics of breathing was not captured in this study. These factors also play a role in recognition of patients needing HFNO/MV. Third, the HFNO/MV and MV cohort as well as the number of patients with 30-day mortality was low, such that the different clinical and laboratory aspects could not be included in the regression models for more thorough interpretation of the role of sRAGE with respect to these outcomes. Therefore, continued monitoring and the inclusion of larger numbers of patients in future studies would be useful. Other limitations of this study are its retrospective analysis and single-center design as well as the lack of external validation. Furthermore, the lack of sRAGE kinetics needs to be acknowledged. It should also be noted that CT imaging of lungs was carried out only at the discretion of the attending physician and not in all patients. Therefore, future studies exploring the association of sRAGE levels with lung CT findings in COVID-19 may reveal further insights useful for improving patient care.
This is to our knowledge the first study to describe elevated serum sRAGE concentrations in hospitalised COVID-19 patients, linking high sRAGE with the need of HFNO/MV, MV and 30-day mortality. Our results indicate that close monitoring of serum sRAGE levels may help to improve management of patients in the ICU and warrant further studies on RAGE modulation as a potential therapy in COVID-19.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
- ACE/Ang II/AT1R pathway:
Angiotensin-converting enzyme/ angiotensin II/ angiotensin type 1 receptor pathway
Analysis of variance
Acute respiratory distress syndrome
Area under the curve
Coronavirus disease 2019
Enzyme-linked immunosorbent assay
- FiO2 :
Inspired fraction of oxygen
High-flow nasal oxygen therapy
- PaO2 :
Arterial partial pressure of oxygen
- qSOFA score:
Quick sequential organ failure assessment score
Receptor of advanced glycation endproducts
- ROC analysis:
Receiver operating characteristic analysis
Reverse-transcriptase quantitative polymerase chain reaction
Severe acute respiratory syndrome coronavirus 2
- SOFA score:
Sequential organ failure assessment score
- SpO2 :
Peripheral blood oxygen saturation
Soluble receptor of advanced glycation endproducts
- sRAGE Ln:
Natural log transformed sRAGE
Mortality Analyses. Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/data/mortality.
Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical–therapeutic staging proposal. J Heart Lung Transpl. 2020;39(5):405–7.
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.
Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992;267(21):14998–5004.
Hudson B, Lippman M. Targeting RAGE signaling in inflammatory disease. Annu Rev Med. 2018;18:69.
Schmidt AM, Yan SD, Yan SF, Stern DM. The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta. 2000;1498(2):99–111.
Shirasawa M, Fujiwara N, Hirabayashi S, Ohno H, Iida J, Makita K, et al. Receptor for advanced glycation end-products is a marker of type I lung alveolar cells. Genes Cells. 2004;9(2):165–74.
Katsuoka F, Kawakami Y, Arai T, Imuta H, Fujiwara M, Kanma H, et al. Type II alveolar epithelial cells in lung express receptor for advanced glycation end products (RAGE) gene. Biochem Biophys Res Commun. 1997;238(2):512–6.
Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003;370(Pt 3):1097–109.
Raucci A, Cugusi S, Antonelli A, Barabino SM, Monti L, Bierhaus A, et al. A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J. 2008;22(10):3716–27.
Ramasamy R, Yan SF, Schmidt AM. RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts. J Leukoc Biol. 2009;86(3):505–12.
Uchida T, Shirasawa M, Ware LB, Kojima K, Hata Y, Makita K, et al. Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med. 2006;173(9):1008–15.
Jabaudon M, Berthelin P, Pranal T, Roszyk L, Godet T, Faure J-S, et al. Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study. Sci Rep. 2018;8(1):2603.
Kerkeni M, Gharbi J. RAGE receptor: may be a potential inflammatory mediator for SARS-COV-2 infection? Med Hypotheses. 2020;144:109950.
Rojas A, Gonzalez I, Morales MA. SARS-CoV-2-mediated inflammatory response in lungs: should we look at RAGE? Inflamm Res. 2020;69(7):641–3.
Marshall JC, Murthy S, Diaz J, Adhikari NK, Angus DC, Arabi YM, et al. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020;20(8):e192–7.
WMA—The World Medical Association-WMA Declaration of Helsinki—ethical principles for medical research involving human subjects. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/.
Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance. 2020;25(3):2000045.
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–10.
ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.
Fawcett T. An introduction to ROC analysis. Pattern Recognit Lett. 2006;27(8):861–74.
Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3(1):32–5.
Lemeshow S, Hosmer DW. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol. 1982;115(1):92–106.
Shi Y, Yu X, Zhao H, Wang H, Zhao R, Sheng J. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Crit Care. 2020;24(1):108.
Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–5.
Liu S, Yao N, Qiu Y, He C. Predictive performance of SOFA and qSOFA for in-hospital mortality in severe novel coronavirus disease. Am J Emerg Med. 2020;38(10):2074–80.
Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc. 1958;53(282):457–81.
van Zoelen MAD, van der Sluijs KF, Achouiti A, Florquin S, Braun-Pater JM, Yang H, et al. Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia. Virology. 2009;391(2):265–73.
Narvaez-Rivera RM, Rendon A, Salinas-Carmona MC, Rosas-Taraco AG. Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis. BMC Infect Dis. 2012;12(1):15.
Bopp C, Hofer S, Weitz J, Bierhaus A, Nawroth PP, Martin E, et al. sRAGE is elevated in septic patients and associated with patients outcome. J Surg Res. 2008;147(1):79–83.
Calfee CS, Ware LB, Eisner MD, Parsons PE, Thompson BT, Wickersham N, et al. Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury. Thorax. 2008;63(12):1083–9.
Gu W, Xu Z, Qi F, Sang Z, Wang C, Li F. Plasma levels of soluble receptor for advanced glycation end products in patients with acute respiratory distress syndrome. Int J Clin Exp Med. 2014;7(12):5558–62.
Jabaudon M, Blondonnet R, Roszyk L, Bouvier D, Audard J, Clairefond G, et al. Soluble receptor for advanced glycation end-products predicts impaired alveolar fluid clearance in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2015;192(2):191–9.
Mukherjee TK, Mukhopadhyay S, Hoidal JR. Implication of receptor for advanced glycation end product (RAGE) in pulmonary health and pathophysiology. Respir Physiol Neurobiol. 2008;162(3):210–5.
Spadaro S, Fogagnolo A, Campo G, Zucchetti O, Verri M, Ottaviani I, et al. Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients. Crit Care Lond Engl. 2021;25(1):74.
Calfee CS, Budev MM, Matthay MA, Church G, Brady S, Uchida T, et al. Plasma receptor for advanced glycation endproducts predicts duration of ICU stay and mechanical ventilation in patients following lung transplantation. J Heart Lung Transpl. 2007;26(7):675–80.
Dozio E, Sitzia C, Pistelli L, Cardani R, Rigolini R, Ranucci M, et al. Soluble receptor for advanced glycation end products and its forms in COVID-19 patients with and without diabetes mellitus: a pilot study on their role as disease biomarkers. J Clin Med. 2020;9(11):3785.
Yalcin Kehribar D, Cihangiroglu M, Sehmen E, Avci B, Capraz A, Yildirim Bilgin A, et al. The receptor for advanced glycation end product (RAGE) pathway in COVID-19. Biomark Biochem Indic Expo Response Susceptibility Chem. 2021;13:1–5.
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315(8):788.
Yadav H, Thompson BT, Gajic O. Fifty years of research in ARDS. Is acute respiratory distress syndrome a preventable disease? Am J Respir Crit Care Med. 2016;195(6):725–36.
Guan W, Liu J, Yu C. CT findings of coronavirus disease (COVID-19) severe pneumonia. Am J Roentgenol. 2020;214(5):W85–6.
Jabaudon M, Blondonnet R, Roszyk L, Pereira B, Guérin R, Perbet S, et al. Soluble forms and ligands of the receptor for advanced glycation end-products in patients with acute respiratory distress syndrome: an observational prospective study. PLoS ONE. 2015;10(8):e0135857.
Jabaudon M, Futier E, Roszyk L, Chalus E, Guerin R, Petit A, et al. Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients. Crit Care Med. 2011;39(3):480–8.
Mrozek S, Jabaudon M, Jaber S, Paugam-Burtz C, Lefrant J-Y, Rouby J-J, et al. Elevated plasma levels of sRAGE are associated with non-focal CT-based lung imaging in patients with ARDS: a prospective multicenter study. Chest. 2016;150:998–1007.
Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020;92(7):791–6.
Wang C, Deng R, Gou L, Fu Z, Zhang X, Shao F, et al. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann Transl Med. 2020;8(9):593.
Fan G, Tu C, Zhou F, Liu Z, Wang Y, Song B, et al. Comparison of severity scores for COVID-19 patients with pneumonia: a retrospective study. Eur Respir J. 2020;56(3):2002113.
Berezin L, Zhabokritsky A, Andany N, Chan AK, Gershon A, Lam PW, et al. The diagnostic accuracy of subjective dyspnea in detecting hypoxemia among outpatients with COVID-19. medRxiv. 2020. https://doi.org/10.1101/2020.08.10.20172262.
Brouqui P, Amrane S, Million M, Cortaredona S, Parola P, Lagier J-C, et al. Asymptomatic hypoxia in COVID-19 is associated with poor outcome. Int J Infect Dis. 2021;1(102):233–8.
van Zoelen MAD, Achouiti A, van der Poll T. The role of receptor for advanced glycation endproducts (RAGE) in infection. In: Vincent J-L, editor. Annual update in intensive care and emergency medicine 2011. Berlin, Heidelberg: Springer; 2011. p. 3–15.
Miller AL, Sims GP, Brewah YA, Rebelatto MC, Kearley J, Benjamin E, et al. Opposing roles of membrane and soluble forms of the receptor for advanced glycation end products in primary respiratory syncytial virus infection. J Infect Dis. 2012;205(8):1311–20.
Blondonnet R, Audard J, Belville C, Clairefond G, Lutz J, Bouvier D, et al. RAGE inhibition reduces acute lung injury in mice. Sci Rep. 2017;7(1):7208.
Miesbach W. Pathological role of angiotensin II in severe COVID-19. TH Open. 2020;04(2):e138–44.
Petra Kloeters-Plachky was a major contributor in carrying out the ELISAs. Jessica Langel was a major contributor in organising and carrying out the follow-up of convalescent patients. Christopher Buesch contributed to statistical analysis of the study. Doctors at the Internal Medicine Department of University of Heidelberg collected the blood samples.
Open Access funding enabled and organized by Projekt DEAL.
Ethics approval and consent to participate
Data analysis was approved (Number S-148/2020, S-546/2020) by the Ethics Committee of the Medical Faculty of Heidelberg University Hospital and was conducted in accordance with the Declaration of Helsinki .
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Basic characteristics of patients with COVID-19 severe disease.
sRAGE levels vary with disease severity. sRAGE values were subject to natural log transformation (sRAGE Ln) due to highly skewed distribution. sRAGE increases as qSOFA score increases. The increase in sRAGE level is significant when qSOFA score increases from 0 to 1, p<0.001 and from 0 to 2, p<0.01 (a). There is a moderately strong significant correlation between sRAGE Ln and duration of hospitalisation, rs (89)=0.375, p<0.001 (b). sRAGE Ln was significantly higher in patients with elevated D-Dimer >0.5 mg/L [U(Nlow D-Dimer=35, Nhigh D-Dimer=77)=2120, z=4.85, p<0.001] (c). A Wilcoxon signed-ranks test indicated that sRAGE during convalescence was statistically significantly lower than sRAGE during acute disease, Z= -0.350, p<0.001 (d). Among patients with severe disease, sRAGE Ln was higher in non-survivors but the difference was not significant, [t(30)=-1.74, p=0.092] (e).
Comparison of ROC curves using cut-offs for predicting mechanical ventilation. Top: ROC curves for sRAGE, CRP, IL-6, D-Dimer and in their combination with sRAGE using cut-offs predicting MV for inpatients. Bottom: AUC with 95% CI and p value for all variables predicting MV for inpatients. A combination of sRAGE and IL-6 is the best parameter at predicting MV. AUC: Area under the curve. ROC: receiver operating curve. sRAGE: soluble receptor for advanced glycation end products. CRP: C-reactive protein. IL-6: Interleukin-6. CI: confidence interval. MV: mechanical ventilation.
About this article
Cite this article
Lim, A., Radujkovic, A., Weigand, M.A. et al. Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COVID-19 disease severity and indicator of the need for mechanical ventilation, ARDS and mortality. Ann. Intensive Care 11, 50 (2021). https://doi.org/10.1186/s13613-021-00836-2

domain: literature


text:
It had been nearly a year since my ecstatic daylight ride through the Wind River Canyon of Wyoming. I flewRead more
Abdul Rahimov has a Ph.D. in Russian history from Stanford. He studied earlier at Harvard and grew up in Illinois in a railroad-dominated town.Rahimov prefers to use a pen name to avoid attracting unnecessary attention from railroads. He lives on the East Coast when he’s not living in a train.
There are few experiences sadder than returning to a Western railroad yard 12 years later. In 1993, starting out ofRead more
My plan was to hit two separate lines, the Royal Gorge route and the Santa Fe’s Raton Pass route. TheRead more
It was time for a modest day trip to escape my burdens: I had two commitments in the East BayRead more
There are better places than Richmond to hang out in after midnight. I was reluctantly eyeballing the BNSF yard inRead more
On Friday night, August 2, 1991, I rode Tri-Met bus #17 to the Southern Pacific yard adjoining the Eastmoreland golfRead more
I’d been sitting beside the loading dock of some factory and geared upward to a sprint. Determined to catch outRead more


text:
Antofagasta sees solid 2021 after strong final quarter
Antofagasta said it expected a solid performance in 2021 as the miner reported a strong final quarter that supported annual production in line with guidance.
Annual copper production fell 4.7% to 733,900 tonnes in the six months to the end of December. Copper production rose 13.6% to 192,600 tonnes in the fourth quarter from the previous quarter as throughput increased at all operations.
Full-year gold production fell 28% to 204,100 ounces from a year earlier but was above guidance after production jumped 43% to 54,700 ounces from the previous quarter.
Net cash costs for the year fell 6.6% to $1.14 per, below guidance, as cash costs before byproduct credits dropped.
The FTSE 100 company forecast copper production of 730-760 tonnes for 2021 and 240-260,000 ounces of gold. Cash costs are expected to be $1.65 per lb before by-product credits and $1.25 per lb after the credits. Capital spending will be $1.6bn as spending on growth projects increases after $200m of 2020 spending was deferred.
Chief Executive Iván Arriagada said: "Despite a challenging year that was placed on the world by COVID-19, the resilience and flexibility of our operations has meant that we have finished the year strongly, achieving full year production guidance and lower cash costs than in 2019. We expect another solid performance in 2021."
Antofagasta shares were little changed at £15.10.50 at 09:02 GMT.

domain: finance


text:
Slots magic free spins
SecretSlots.com: Fresh New Look For 2017!Games and Software at Slots Magic. Slots Magic Casino offers a unique mix of online slots,. as well as a total of another 200 free spins on Netent Slots,.Totally free Magicious slot machine. Are you ready to take part in a vintage style magic show,. expanding wilds, free spins, and stacked symbols.Play Free Online Casino Slot Games no registration and no download. You will find bonus features in a plethora of Slots. You will have free spins,.A Joker Wild aligning with identical regular-paying images can complete the grouping into a winning payline arrangement.Turn up the heat in this free video slot game from Slotomania! Any spin can trigger free spins with Bouncin’ Beans. FREE SLOTS GAMES;. Magic Trixie Slot.
GameSense involves learning how the games work and the odds of winning and losing.Any line win or Expanded Pay will advance the Speed Spins Active Reels two reels to the right and may increase the Speed Spins Multiplier up to 5x.
Online Slots » Free Spins & Bonus Rounds » Betfair CasinoUsing your GameSense means balancing the fun part of gambling with the need to stay in control and within your boundaries.
#1 Online Slots Guide 2018 - FREE & Real Money SlotsSlots Magic casino was founded in. All Slots4Play members can take advantage of an exclusive Slots Magic Welcome Bonus package filled with free cash and bonus spins.
The Grand, Major, and Minor Jackpots are displayed above the Speed Spins reels.
Freespins Slots – Find the best freespins offer on onlineClaim 10 free spins at SlotsMagic Casino immediately upon. If you have received an exclusive free. meaning that you can place bets on Slots and.Hottest Casino in the United Kingdom Huge collection of online slots and table Games Extremely High Payout Percentage Monthly Promotions and Free Play.
In a Free-Spins Bonus Game, either one appears as main win-boosting element of every bonus spin.10 Free Spins at Slots Magic Casino. You are now subscribed to the No Deposit Bonus Newsletter, where you receive the latest and hottest No Deposit Bonuses.Wizard of Oz: Road to Emerald City Creatures Of Rock 9 Line Fruit Smoothie 9 Line Gods Of The Nile 9 Line Heaven And Hell 9 Line Monster Carlo 9 Line Rich Girl Texas Tea Triple Diamond.
Slots magic casino free spins. - YouTube
Here at FreeSpins,. You will find a range of different free spins slots to enjoy online, including games from top developers like NetEnt and Microgaming.Magic Castle online slot by IGT features a Wild Symbol capable of spawning a Win-Multiplier that can increase not only payouts, but also Free-Spins rewards.
Play Mirror Magic video slots online at Videoslots.com. Get £10 free spins and 100% up to £200 welcome bonus.The Tower Wild is a Wild that always emerges in its entirety as full-reel Wild.
Netent Free Spins & No Deposit Required | Best New List 2018The highest paying icon is the image of the symbolic bronze Lion of Venice.Beehive Bedlam Bingo Reactors Bon Bon Bonanza Bubble Craze Cash Drop Cash Machine Chain Reactors Chain Reactors 100 Chain Reactors Super Trails Cool Jewels Da Vinci Diamonds Da Vinci Diamonds Dual Play Feathered Frenzy Furballs Hockey Reactors Joker Jackpot Mr Multiplier Rocky Reactors SuperCubes.Looking for a new place to play slots? Check our Slots Promo Codes. Slots Magic where they’ll match your first deposit up to £/$/€50 plus 15 wager free spins.
Three, four, or five Lion images award a cash prize equivalent to 100x, 200x, or 2,500x the Line Bet when landing as eligible payline combination.Get any NetEnt Free Spins or no deposit bonuses from the best online casinos. Slots Magic: 50 Free Spins: Deposit Bonus:. 30 No Deposit Free Spins & more.
Play Mirror Magic Video Slot Free at Videoslots.comEveryone's favorite wizard is back in 50-lines of Yuletide fun in Merlins Magic Respins Christmas edition! Spin the reels to win your. Free Slots and Slots.
Loco Slots | Multiplayer games | PlayspaceSlots Magic are ready to dazzle new gamers with 50 Free Spins and double the money on deposit! Play 50 spins on Valley of the Gods slot on deposit!.
Online Casino Free Spins Codes! Free Spins Blog, Casino Free Spins,. Slots Ltd Casino; Slots Magic Casino + Slots Plus + Slots Village Casino + Slots of Vegas +.One is a Tower Wild that emerges only in its entirety as a full-reel Wild Symbol, usually in 1 or 2 reels.Register at Slots Magic Casino today and receive 100% up to $/€100 + 15 FREE Spins. View all Slots Magic bonus codes. Updated on 28/07/2017.Magic Mirror Slot is a well-known and a well-respected game, which has five reels, ten payline slots with a chance of winning 50 free spins if a player gets three.Download Slots Magic Casino & use our Bonus Code to get and EXCLUSIVE 50 FREE Spins to play slots games online. Get yourself a FREE account here.
Merlins Magic Respins online slot by NextGen Gaming has stunning 5 Reel Slots, Free Spins, Multiplier, Scatter Symbol, Wild Symbol features Play Merlins Magic Respins.If gambling no longer feels like a game, the Voluntary Self-Exclusion program can help.The other is a Joker Wild with a natural 2x Multiplier, which if featured as Free-Spins reel modifier, doubles the multiplier factor awarded by the corresponding Bonus Wheel.Slots Magic Casino has just revamped their entire welcome bonus structure for 2017 with some major improvements to things such as free spins which now come with.Slots Magic offer 15 Free Spins with No Wagering and a 100% Match Bonus worth up to £150 to new casino customers who sign up though us. You can enjoy classic NetEnt.Find out what Exclusive Casinos that offer WMS Slots and grab the Biggest Casino Bonuses to. Claim £100 + 25 Free Spins. Slots Magic is one of the few.

domain: entertainment


text:
About your Hoya Rope Plant - If you are a houseplant novice and looking for something that doesn't require too much maintenance, then a Hindu Rope plant could be a perfect choice. They just need a well-drained potting mix, a decent amount of warmth, and bright, indirect sunlight to thrive.
The curled leaves are tightly packed and resemble rope. The unique look gives this plant its common name of the “Rope Plant.” These plants are native to Australia and Eastern Asia and are part of the Apocynaceae family. Child and pet-friendly.
Size - Small-size, shelf or counter plant. 8-12" tall (including pot.
Light - Thrives in bright indirect light.
Water - Water every 3-4 weeks. Allow soil to dry out between watering. do not overwater.
Preferred Rooms - Suitable for all rooms including home office.
What comes with your plant - Includes it's own recycled container and care instructions.

domain: biology