75 research outputs found

    Origins of the Ambient Solar Wind: Implications for Space Weather

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    The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

    Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas

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    O plasma rico em plaquetas (PRP) Ă© um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, hĂĄ controvĂ©rsia sobre a eficĂĄcia da terapia na cicatrização cutĂąnea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-ÎČ1 e PDGF-BB no PRP, plasma sanguĂ­neo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou nĂŁo com PRP. Foram utilizados sete equinos machos castrados, mestiços, hĂ­gidos, com idade entre 16 e 17 (16,14±0,63) anos. TrĂȘs lesĂ”es em formato quadrangular (6,25cmÂČ) foram produzidas cirurgicamente nas regiĂ”es glĂșteas direita e esquerda de todos os animais. Doze horas apĂłs indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiĂ”es glĂșteas (Grupo tratado = GT), escolhida aleatoriamente. A regiĂŁo contralateral foi utilizada como controle (GC). As feridas foram submetidas Ă  limpeza diĂĄria com ĂĄgua Milli Q, e amostras foram obtidas mediante biĂłpsias realizadas com Punch de 6mm. Foram obtidas seis biĂłpsias de pele, sendo a primeira realizada logo apĂłs a produção da ferida (T0), e as demais com 1 (T1) 2 (T2) 7 (T3) e 14 (T4) dias apĂłs a indução da lesĂŁo. A sexta biĂłpsia (T5) foi obtida apĂłs completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT). TambĂ©m foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-ÎČ1 e PDGF-BB na pele, PRP e plasma sanguĂ­neo foi realizada pela tĂ©cnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressĂŁo, utilizando nĂ­vel de significĂąncia de 5%. NĂŁo houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. TambĂ©m nĂŁo houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-ÎČ1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentraçÔes dos fatores de crescimento no T0, os maiores valores cutĂąneos (p<0,05) do TGF-ÎČ1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma nĂŁo houve alteração nas concentraçÔes desses fatores em relação ao T0, o que sugere que o PRP nĂŁo acarreta efeito sistĂȘmico, quando os procedimentos adotados na presente pesquisa sĂŁo utilizados. A administração local de PRP no volume estudado, 12 h apĂłs indução cirĂșrgica de ferida cutĂąnea na regiĂŁo glĂștea de equinos nĂŁo ocasiona maiores concentraçÔes dos fatores de crescimento TGF-ÎČ1 e PDGF-BB no plasma sanguĂ­neo e pele, durante o processo de cicatrização

    Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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    Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≄75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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