| 41. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 42. |
- Fernando, Germain J. P., et al.
(författare)
-
Safety, tolerability, acceptability and immunogenicity of an influenza vaccine delivered to human skin by a novel high-density microprojection array patch (Nanopatch (TM))
- 2018
-
Ingår i: Vaccine. - : ELSEVIER SCI LTD. - 0264-410X .- 1873-2518. ; 36:26, s. 3779-3788
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Injection using needle and syringe (Namp;S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine. Methods: Healthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 mu g haemagglutinin (HA) per dose), applied to the volar forearm (NP-HAIFA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 11-11N1 I, 15 mu g HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvaxe (R) 2016 containing 15 mu g of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays. Findings: NP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with Namp;S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p amp;lt; 0.0001), with no statistical differences between the treatment groups (p amp;gt; 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189-593 95% CI), 160 (74-345 95% CI), and 221 (129-380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection. Interpretation: Influenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection. (C) 2018 The Author(s). Published by Elsevier Ltd.
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| 43. |
- Ferrando, Carlos, et al.
(författare)
-
Adjusting tidal volume to stress index in an open lung condition optimizes ventilation and prevents overdistension in an experimental model of lung injury and reduced chest wall compliance
- 2015
-
Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The stress index ( SI), a parameter derived from the shape of the pressure-time curve, can identify injurious mechanical ventilation. We tested the hypothesis that adjusting tidal volume (VT) to a non-injurious SI in an open lung condition avoids hypoventilation while preventing overdistension in an experimental model of combined lung injury and low chest-wall compliance (Ccw). Methods: Lung injury was induced by repeated lung lavages using warm saline solution, and Ccw was reduced by controlled intra-abdominal air-insufflation in 22 anesthetized, paralyzed and mechanically ventilated pigs. After injury animals were recruited and submitted to a positive end-expiratory pressure (PEEP) titration trial to find the PEEP level resulting in maximum compliance. During a subsequent four hours of mechanical ventilation, VT was adjusted to keep a plateau pressure (Pplat) of 30 cmH2O (Pplat-group, n = 11) or to a SI between 0.95 and 1.05 (SI-group, n = 11). Respiratory rate was adjusted to maintain a 'normal' PaCO2 (35 to 65 mmHg). SI, lung mechanics, arterial-blood gases haemodynamics pro-inflammatory cytokines and histopathology were analyzed. In addition Computed Tomography (CT) data were acquired at end expiration and end inspiration in six animals. Results: PaCO2 was significantly higher in the Pplat-group (82 versus 53 mmHg, P = 0.01), with a resulting lower pH (7.19 versus 7.34, P = 0.01). We observed significant differences in VT (7.3 versus 5.4 mlKg-1, P = 0.002) and Pplat values (30 versus 35 cmH2O, P = 0.001) between the Pplat-group and SI-group respectively. SI (1.03 versus 0.99, P = 0.42) and end-inspiratory transpulmonary pressure (PTP) (17 versus 18 cmH2O, P = 0.42) were similar in the Pplat-and SI-groups respectively, without differences in overinflated lung areas at end-inspiration in both groups. Cytokines and histopathology showed no differences. Conclusions: Setting tidal volume to a non-injurious stress index in an open lung condition improves alveolar ventilation and prevents overdistension without increasing lung injury. This is in comparison with limited Pplat protective ventilation in a model of lung injury with low chest-wall compliance.
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| 44. |
- Flores, Fernando
(författare)
-
After Capitalism: Cyborgism
- 2015
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- This second digital edition includes my research from 2013 until November 2015. There are many important changes from de first version. This version introduces the Technocratic Mode of Production based on the exploitation of the consumers. It includes a complete description of the cyborg society as it is today, the new castes that constitute it and the economic acts that regulate the new Mode of Production. Many of the new conclusions are derived from my current research which in a more didactical approach considers “order” at the center of the historical analysis instead of the vaguer concept of “information”. Our standpoint become clearer explaining better the primacy of knowledge and experience over ideology. Knowledge and experience for us are constituting aspects of the Civil Society -and therefore “irreversible” aspects of history- while ideology belongs to the political sphere, submitted to the changes of temporal and reversible acts. The immediate consequence of our standpoint is that the limits of history are Natural history; a Natural history which is driven by knowledge and experience and not by “ideological struggles” related to “class struggle”. In other words, the struggle for the constitution of a cyborg is prior and stronger than any other social struggle. Lund, November 2015. _________________ This book is a personal answer to the crisis of the left. The author of this texts belongs to a generation habituated to live with global explanations. During our youth, the future of the world was the future of democracy and socialism. We belong to a generation of “leftist” that found in Marx and Freud, phenomenology and structuralism the most important answers that made sense of the everyday world. However, the developments of events during the last sixty years, showed that our confidence was ungrounded. The depreciation of the theoretical thought accelerated in direct proportion to the development of technologies, and among them the impact of the digital developments was devastating. One of the most notable consequences of the digitalization of culture, was the depreciation of the Marxian thought, but also the less recognized depreciation of all kinds of political-economic thought. The collapse of the world created before the Second World War open for the end of the “grand narratives” and the enthronization of Postmodernism. The production of fragmentary explanations took over the historical perspective with an important influence on social and economic thought. After 60 years of postmodern thinking, we believe that the time of Postmodernism is over. Politicians and economists over the world cannot continue to produce results in small packages. The whole picture must be restituted. Of course it must be done incorporating the lessons of the past to avoid to make the same mistakes. Postmodernism has left behind lots of scattered modernist philosophical remnants. It left a chessboard with only few pieces to work with, and in this allegory, only as references. The philosophical schools remains, but the study of them is strictly for an education in the history of ideas. The situation is aggravating since the most important works from the 1960’s and forth, (post-structuralists) deliberately have avoided obvious identity patterns. A word in Rio de la Plata’s jargon language describes this situation, cambalache, a sort of “flea market” where everything lies higgledy-piggledy. Deconstruction and the focus on differences are vital to Postmodernism. Remaining is therefore the intersections, the contrasts, shadows, and sketches. When trying to orient in such an intellectual environment, the task reminds of patching scatterings, and building with tools of eclecticism. However, we believe that is time to reconstruct instead of deconstruct, moving back to Modernism that we will describe as Cyborgism. December 2013
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| 45. |
- Flores, Fernando
(författare)
-
Agnumetry; Quantifying Modernization
- 2013
-
Ingår i: [Host publication title missing]. ; , s. 1-8
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Is possible to quantify modernization? I will refer as "agnumetry" the measure of the brokenness of an environment; from "agnumy" the Greek word for "break". The presence of broken technologies makes an environment more or less broken; the measurement of this grade of brokenness could be an interesting manner to compare these environments with each other. In this paper, I introduce some criteria to make such a measurement useful.
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| 46. |
- Flores, Fernando
(författare)
-
Broken technologies : the humanist as engineer : an Introduction
- 2009
-
Ingår i: Broken technologies : the humanist as engineer. - 9789163336836 ; , s. 1-7
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- There are many possible definitions of “technology” and I will discuss some of these in this book. However, in this introduction let me use a definition of Svante Lindqvist who defines technology very intuitively as “those activities, directed towards the satisfaction of human wants, which produce change in the material world.” He says also “the distinction between human “wants” and more limited human “needs” is crucial, for we do not use technology only to satisfy our essential material requirements.” Consequently, from this perspective, a technology that is “broken” could be defined as those activities, directed towards the satisfaction of human wants that are intended to produce changes in the material world that either do not manage to satisfy these wants or do not produce changes in the material world, or both.
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| 47. |
- Flores, Fernando
(författare)
-
Broken technologies : the humanist as engineer. Updated November 2015
- 2009
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- There are many possible definitions of “technology” and I will discuss some of these in this book. However, in this introduction let me use a definition of Svante Lindqvist who defines technology very intuitively as “those activities, directed towards the satisfaction of human wants, which produce change in the material world.” He says also “the distinction between human “wants” and more limited human “needs” is crucial, for we do not use technology only to satisfy our essential material requirements.” Consequently, from this perspective, a technology that is “broken” could be defined as those activities, directed towards the satisfaction of human wants that are intended to produce changes in the material world that either do not manage to satisfy these wants or do not produce changes in the material world, or both. This is the third edition, updated October 2015.
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| 48. |
- Flores, Fernando
(författare)
-
Den nya människan. En handbok om 1900-talets idéhistoria
- 2005
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- We depart from the intuitive idea of action –which for us is the same as an “act” both mental and physical– and its opposite the idea of no–action or passivity (stillness, apathy, immobility) to which we have a special term acedia (from late Latin and from the Greek akedeia, meaning “indifference”). András Pöstényi studied Freud’s idea of intentionality and concludes that Freud was strongly influenced by Brentano’s identification of the “psychic” with the “meaningful” which conduce to a breakdown of the psychology that identified the “psychic” with “consciously”. So, after Brentano, Freud could conceive unconscious meaningful psychical acts. Freud concluded that if the representations in a dream were produced randomly they would be caused by a somatic cause and could not be psychic phenomena. According to Freud only psychical phenomena can be interpreted and everything that can be interpreted has to be psychic. The intentional act then, understands by Freud as an “action”. Because the dream is an intentional act, it is something we do and not something that happens to us. Freud give this a name, he called it “eine psychische Aktion”.
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| 49. |
- Flores, Fernando
(författare)
-
Después Del Capitalismo: El Modernismo (Ciborgismo).
- 2013
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Abstract in SpanishEste texto responde a una necesidad izquierdista, pero de una izquierda que por razones obvias ya no se encuentra. Trata de buscar todas las respuestas; de no renunciar a una visión compleja pero global, capaz de transformase en una “guía para la acción”. Se trata de un texto con respuestas, planes, ideas claras, objetivos, convicciones. Hasta hace no muchos años, el mundo era re-conocible, lo habían explicado los grandes pensadores del siglo XIX y del XX, el marxismo y el psicoanálisis, la fenomenología, el estructuralismo, etc. Ahora bien, el estancamiento de aquel ideario empezó ya en aquellos años, pero nosotros no lo sabíamos. Luego llegaron las derrotas, las debacles, la confusión y si hoy si se puede hablar de una izquierda, es de una izquierda puntual, postmodernista, impulsora de objetivos éticos puntuales, desconectados de un modelo impugnador global y excesivamente pragmática. La izquierda de hoy busca a tientas, es más empírica que nunca, tantea en las voluntades de las gentes para definir un programa político circunstancial. La izquierda de hoy es ecléctica, un poco de esto y un poco de lo otro, socialistas, capitalistas, nacionalistas, postmodernistas, etc.Nuestro aporte es este texto es el retomar precavidamente, tanteando también nosotros, el camino del materialismo histórico que al mismo tiempo criticaremos. Nos interesa la visión marxista como “gran narrativa”, teoría con todas o casi todas las explicaciones. Nos interesa descubrir los nexos entre política y economía y entre estos y la historia. Lo hacemos a sabiendas de los fracasos anteriores, a sabiendas de que hay un discurso marxista definitivamente obsoleto; como metodología económico-política, el marxismo hace tiempo que es una tecnología rota. Sin embargo, leer a Marx es saber que tiene razón, aunque no sepamos exactamente en qué ni cómo explicarlo. ¿Cómo empezar? Empezaremos con el único tema inevitable, la teoría de las clases sociales y del desarrollo de la historia de Marx como lucha de clases, y desde esta, paso a paso, trataremos de encontrar la lógica de un discurso histórico-político enraizado en la teoría del valor del trabajo. Trataremos de producir una teoría que se construya a sí misma, con ejemplos, evidencias y porque no interrogantes también. Hace ya muchos años estudiamos el impacto del descubrimiento de América en el pensamiento y cultura europeos del siglo XVI. Entonces anticipamos nuestras dudas acerca de la importancia heurística del concepto de “clase social”, y del peso real de la llamada “lucha de clases” en los acontecimientos históricos. Pasados los años, nos afirmamos en esa convicción, creemos en cambio que son otros fenómenos los verdaderos motores de la historia. Preocupado por reafirmar la predominancia de la materia sobre la idea, Marx desestimó la importancia del conocimiento y la experiencia en el desarrollo de la historia. Trataremos de corregir esta carencia, en tanto para nuestro tiempo “digitalizado”, esta oposición ya no es problemática. En ese sentido, una de las claves de nuestra investigación será el estudio del impacto decisivo de las tecnologías informacionales, impulsadoras de una emergente ciber-sociedad.The author of this texts belongs to a generation habituated to live with global explanations. During our youth, the future of the world was the future of democracy and socialism. We belong to a generation of “leftist” that found in Marx and Freud, phenomenology and structuralism the most important answers that made sense of the everyday world. However, the developments of events during the last sixty years, showed that our confidence was ungrounded. The depreciation of the theoretical thought accelerated in direct proportion to the development of technologies, and among them the impact of the digital developments was devastating. One of the most notable consequences of the digitalization of culture, was the depreciation of the Marxian thought, but also the less recognized depreciation of all kinds of political-economic thought. The collapse of the world created before the Second World War open for the end of the “grand narratives” and the enthronization of Postmodernism. The production of fragmentary explanations took over the historical perspective with an important influence on social and economic thought. After 60 years of postmodern thinking, we believe that the time of Postmodernism is over. Politicians and economists over the world cannot continue to produce results in small packages. The whole picture must be restituted. Of course it must be done incorporating the lessons of the past to avoid to make the same mistakes.Postmodernism has left behind lots of scattered modernist philosophical remnants. It left a chessboard with only few pieces to work with, and in this allegory, only as references. The philosophical schools remains, but the study of them is strictly for an education in the history of ideas. The situation is aggravating since the most important works from the 1960’s and forth, (post-structuralists) deliberately have avoided obvious identity patterns. A word in Rio de la Plata’s jargon language describes this situation, cambalache, a sort of “flea market” where everything lies higgledy-piggledy. Deconstruction and the focus on differences are vital to Postmodernism. Remaining is therefore the intersections, the contrasts, shadows, and sketches. When trying to orient in such an intellectual environment, the task reminds of patching scatterings, and building with tools of eclecticism. However, we believe that is time to reconstruct instead of deconstruct, moving back to Modernism that we will describe as Cyborgism.
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| 50. |
- Flores, Fernando
(författare)
-
El Algoritmo de la Vida.
- 1994
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Abstract in Spanish Estudio metafísico sobre los modelos epistemológicos de la filosofía de la Vida.
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