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- Heavy Ion Experiments (20)
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Institute
Trebicka, Jonel ; Amoros, Alex ; Pitarch, Carla ; Titos, Esther ; Alcaraz Quiles, Francisco José ; Schierwagen, Robert ; Deulofeu, Carmen ; Fernandez-Gomez, Javier ; Piano, Salvatore ; Caraceni, Paolo ; Öttl, Karl ; Solà, Elsa ; Laleman, Wim ; McNaughtan, Jane ; Mookerjee, Rajeshwar Prosad ; Coenraad, Minneke J. ; Welzel, Tania Mara ; Steib, Christian Johannes ; Garcia, Rita ; Gustot, Thierry ; Rodriguez Gandia, Miguel A. ; Bañares, Rafael ; Albillos, Agustin ; Zeuzem, Stefan ; Vargas Blasco, Victor Manuel ; Saliba, Faouzi ; Nevens, Frederic ; Alessandria, Carlo ; De Gottardi, Andrea ; Zoller, Heinz ; Ginès, Pere ; Sauerbruch, Tilman ; Gerbes, Alexander L. ; Stauber, Rudolf E. ; Bernardi, Mauro ; Angeli, Paolo ; Pavesi, Marco ; Moreau, Richard ; Clària, Joan ; Jalan, Rajiv ; Arroyo, Vicente
Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.
Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5–2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF).
Results: Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating “full-blown” systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF (p < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes.
Conclusions: Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.
Ordoñez-Jiménez, Fernanda ; Blanco Rodríguez, Rodolfo Guadalupe ; Almocera, Alexis Erich S. ; Chinney-Herrera, Gustavo ; Hernández-Vargas, Esteban A.
COVID-19 pandemic is a major public health threat with unanswered questions regarding the role of the immune system in the severity level of the disease. In this paper, based on antibody kinetic data of patients with different disease severity, topological data analysis highlights clear differences in the shape of antibody dynamics between three groups of patients, which were non-severe, severe, and one intermediate case of severity. Subsequently, different mathematical models were developed to quantify the dynamics between the different severity groups. The best model was the one with the lowest media value of Akaike Information Criterion for all groups of patients. Although it has been reported high IgG level in severe patients, our findings suggest that IgG antibodies in severe patients may be less effective than non-severe patients due to early B cell production and early activation of the seroconversion process from IgM to IgG antibody.
Al-Shahi Salman, Rustam ; Frantzias, Joseph ; Lee, Robert J. ; Lyden, Patrick D. ; Battey, Thomas W. K. ; Ayres, Alison M. ; Goldstein, Joshua Norkin ; Mayer, Stephan A. ; Steiner, Thorsten ; Wang, Xia ; Arima, Hisatomi ; Hasegawa, Hitoshi ; Oishi, Makoto ; Godoy, Daniel Agustín ; Masotti, Luca ; Dowlatshahi, Dar ; Rodríguez-Luna, David ; Molina, Carlos ; Jang, Dong-Kyu ; Davalos, Antonio ; Castillo, José ; Yao, Xiaoying ; Claassen, Jan ; Volbers, Bastian ; Kazui, Seiji ; Okada, Yasushi ; Fujimoto, Shigeru ; Toyoda, Kazunori ; Li, Qi ; Khoury, Jane ; Delgado, Pilar ; Álvarez-Sabín, José ; Hernández-Guillamon, Mar ; Prats-Sánchez, Luis ; Cai, Chunyan ; Kate, Mahesh ; McCourt, Rebecca ; Venkatasubramanian, Chitra ; Diringer, Michael N. ; Ikeda, Yukio ; Worthmann, Hans ; Ziai, Wendy C. ; D’Esterre, Christopher D. ; Aviv, Richard I. ; Raab, Peter ; Murai, Yasuo ; Zazulia, Allyson R. ; Butcher, Kenneth ; Seyedsaadat, Seyed Mohammad ; Grotta, James C. ; Martí-Fàbregas, Joan ; Montaner, Joan ; Broderick, Joseph ; Yamamoto, Haruko ; Staykov, Dimitre ; Connolly, Edward Sander ; Selim, Magdy ; Leira, Rogelio ; Moon, Byung Hoo ; Demchuk, Andrew M. ; Di Napoli, Mario ; Fujii, Yukihiko ; Anderson, Craig S. ; Rosand, Jonathan
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
Santillán, Vinicio ; Quitián Rodríguez, Marta ; Tinoco, Boris A. ; Zárate, Edwin ; Schleuning, Matthias ; Böhning-Gaese, Katrin ; Neuschulz, Eike Lena
Understanding the spatial and temporal dynamics of species assemblages is a main challenge in ecology. The mechanisms that shape species assemblages and their temporal fluctuations along tropical elevational gradients are particularly poorly understood. Here, we examined the spatio-temporal dynamics of bird assemblages along an elevational gradient in Ecuador. We conducted bird point counts at three elevations (1000, 2000 and 3000 m) on 18 1-ha plots and repeated the sampling eight times over two years (216 hours in total). For each plot, we obtained data of monthly temperatures and precipitation and recorded the overall resource availability (i.e., the sum of flower, fruit, and invertebrate resources). As expected, bird richness decreased from low to high elevations. Moreover, we found a significant decrease in bird abundance and richness and an increase in evenness between the most and least humid season at each of the three elevations. Climatic factors were more closely related to these temporal fluctuations than local resource availability. While temperature had significant positive effects on the abundance of birds at mid and high elevations, precipitation negatively affected bird abundance at low and mid elevations. Our study highlights that bird assemblages along tropical elevational gradients can show pronounced seasonal fluctuations. In particular, low temperatures and high precipitation seem to impose important constraints on birds. We conclude that potential changes in climate, due to global warming, are likely to affect the spatio-temporal dynamics of bird assemblages along tropical elevational gradients.
Untangling the cell immune response dynamic for severe and critical cases of SARS-CoV-2 infection
(2021)
COVID-19 is a global pandemic leading high death tolls worldwide day by day. Clinical evidence suggests that COVID-19 patients can be classified as non-severe, severe and critical cases. In particular, studies have highlighted the relationship between the lymphopenia and the severity of the illness, where CD8+ T cells have the lowest levels in critical cases. In this work, we aim to elucidate the key parameters that define the course of the disease deviating from severe to critical case. To this end, several mathematical models are proposed to represent the dynamic of the immune response in patients with SARS-CoV-2 infection. The best model had a good fit to reported experimental data, and in accordance with values found in the literature. Our results suggest that a rapid proliferation of CD8+ T cells is decisive in the severity of the disease.
Kocsis, Vilmos ; Kaib, David A. S. ; Riedl, Kira Marina ; Gass, Sebastian ; Lampen-Kelley, Paula ; Mandrus, David G. ; Nagler, Stephen E. ; Pérez Rodriguez, Nicolás ; Nielsch, Kornelius ; Büchner, Bernd ; Wolter, Anja U. B. ; Valentí, Roser
The Kitaev material α-RuCl3 is among the most prominent candidates to host a quantum spin-liquid state endowed with fractionalized excitations. Recent experimental and theoretical investigations have separately revealed the importance of both the magnetoelastic coupling and the magnetic anisotropy, in dependence of the applied magnetic field direction. In this combined theoretical and experimental research, we investigate the anisotropic magnetic and magnetoelastic properties for magnetic fields applied along the main crystallographic axes as well as for fields canted out of the honeycomb plane. We found that the magnetostriction anisotropy is unusually large compared to the anisotropy of the magnetization, which is related to the strong magnetoelastic Γ′˜-type coupling in our \textit{ab-initio} derived model. We observed large, non-symmetric magnetic anisotropy for magnetic fields canted out of the honeycomb ab-plane in opposite directions, namely towards the +c∗ or −c∗ axes, respectively. The observed directional anisotropy is explained by considering the relative orientation of the magnetic field with respect to the co-aligned RuCl6 octahedra. Magnetostriction measurements in canted fields support this non-symmetric magnetic anisotropy, however these experiments are affected by magnetic torque effects. Comparison of theoretical predictions with experimental findings allow us to recognize the significant contribution of torque effects in experimental setups where α-RuCl3 is placed in canted magnetic fields.