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7. EXPERIMENTAL RESEARCH ON ACCURACY OF AEROTRIANGULATION FOR UAV IMAGERY

Author

L. Ling, L. Ying-Cheng, and D. Xiao-Bo

Subjects
Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract

In this paper, the experimental research utilized UAV imageries of two areas, assessed the accuracy of aerial triangulation on the basis of different photo-control points distributions using two kinds of software (Geolord-AT and PixelGrid). The experimental results show that the accuracy of aerotriangulation of UAV imagery can be satifactory to the accuracy of 1:500 scale topographic maps in the intensive control conditions. The experimental processing steps and results provide experience and reference for production.

Published
2013
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8. Effect of Cement Stabilization on Shear Strength Parameters of Soft Soils on Agricultural Road

Author

Aldington Jian Cheng Liu, Aldington Jian Cheng Liu, Abu Talib, Zaihasra, Jia Yian Bong, Jia Yian Bong, Felix N. L. Ling, Felix N. L. Ling, Gambo Haruna Yunusa, Gambo Haruna Yunusa, Aldington Jian Cheng Liu, Aldington Jian Cheng Liu, Abu Talib, Zaihasra, Jia Yian Bong, Jia Yian Bong, Felix N. L. Ling, Felix N. L. Ling, and Gambo Haruna Yunusa, Gambo Haruna Yunusa

Abstract

Agricultural roads play a crucial role in facilitating transportation in agricultural regions, including horticulture, smallholder farms and plantations. However, the agricultural roads in Sungai Balang, Muar face challenges due to the poor condition of the soft soil. Soft soil is characterized by low shear strength, high compressibility and large settlements, making it unsuitable for efficient road infrastructure. To address these issues, cement stabilization has been proposed in this study as a potential solution to improve the soft soil on agricultural roads in the paddy field area of Sungai Balang. The objectives of this study are to identify the classification of the soft soil on agricultural roads in Sungai Balang through grain size analysis, moisture content test, specific gravity test, Atterberg limit test and standard proctor compaction test and to determine the effectiveness of cement stabilization through direct shear test. The direct shear test was carried out to evaluate the shear strength parameters of the soil on the agricultural roads before and after the addition of different percentages of cement (5%, 10% and 15% by dry weight of the soft soil). The results of soil classification showed that the soft soil on agricultural roads in Sungai Balang was classified as MH, which was silty soil with high plasticity. Besides, the results of direct shear test indicated that the 15% cement specimen achieved the optimum percentages compared to the others. The friction angle of the 15% cement specimen had increased from 28o to 43o and the cohesion had increased from 28.33 kPa to 85.00 kPa compared to the untreated soil samples. By studying the effects of different percentages of cement on soil settlements, the research provides insights into the performance and suitability of cement stabilization in enhancing the stability and strength of soft soils on agricultural roads.

Published
2024

9. Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors

Author

Joseph Toker, J. Bryan Iorgulescu, Alexander L. Ling, Genaro R. Villa, Josephina A.M.A. Gadet, Laxmi Parida, Gad Getz, Catherine J. Wu, David A. Reardon, E. Antonio Chiocca, and Marco Mineo

Subjects
Cancer Research, Oncology
Abstract

Purpose: mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy. Experimental Design: lncRNA expression profile was analyzed in one cohort of patients with melanoma and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells. Results: We identified the lncRNA NEAT1 as commonly upregulated between patients with melanoma with complete therapeutic response and patients with GBM with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the IFNγ pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNFα/NFκB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNFα and other inflammatory cytokines. Conclusions: These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.

Published
2023
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10. “Not in Your Backyard!”: A Community Struggle for the Rights of Immigrant Adult Education in San Francisco’s Chinatown

Author

Wang, L. Ling-chi

Abstract

This article is a case study of a protracted struggle to establish a branch campus of the San Francisco Community College in Chinatown for thousands of immigrants and working-class adults, focusing mostly on the period since 1997 when the community was slowly politicized and mobilized to fight for their educational rights. Although educational researchers continue to pay close attention to Asian American fights against discriminatory admission policies among the nation’s top colleges and universities, an urgent need to pay more scholarly and political attention to the neediest, poorest, and powerless among Asian Americans clearly exists. To this segment of the Asian American population, access to community college education is a matter of acquiring tools of survival in America. The study illustrates the equal significance of race and class in understanding the development of Asian American communities, how each can be used to obfuscate or disguise the other, and how both can be easily obscured by other issues, especially “progressive” issues or organizations. Asian American community activists and scholars need to pay more attention to class and class conflict with the communities and between the communities and the mainstream society.

Published
2009

12. Supplementary Fig. 4 from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors

Author

Marco Mineo, E. Antonio Chiocca, David A. Reardon, Catherine J. Wu, Gad Getz, Laxmi Parida, Josephina A.M.A. Gadet, Genaro R. Villa, Alexander L. Ling, J. Bryan Iorgulescu, and Joseph Toker

Abstract

Supplementary Fig. 4 NEAT1 counts are reduced in formalin-fixed paraffin-embedded (FFPE) tissues compared to freshfrozen tissues.

Published
2023
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14. Data from Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors

Author

Marco Mineo, E. Antonio Chiocca, David A. Reardon, Catherine J. Wu, Gad Getz, Laxmi Parida, Josephina A.M.A. Gadet, Genaro R. Villa, Alexander L. Ling, J. Bryan Iorgulescu, and Joseph Toker

Abstract

Purpose:mAbs targeting the PD-1/PD-L1 immune checkpoint are powerful tools to improve the survival of patients with cancer. Understanding the molecular basis of clinical response to these treatments is critical to identify patients who can benefit from this immunotherapy. In this study, we investigated long noncoding RNA (lncRNA) expression in patients with cancer treated with anti-PD-1/PD-L1 immunotherapy.Experimental Design:lncRNA expression profile was analyzed in one cohort of patients with melanoma and two independent cohorts of patients with glioblastoma (GBM) undergoing anti-PD-1/PD-L1 immunotherapy. Single-cell RNA-sequencing analyses were performed to evaluate lncRNA expression in tumor cells and tumor-infiltrating immune cells.Results:We identified the lncRNA NEAT1 as commonly upregulated between patients with melanoma with complete therapeutic response and patients with GBM with longer survival following anti-PD-1/PD-L1 treatment. Gene set enrichment analyses revealed that NEAT1 expression was strongly associated with the IFNγ pathways, along with downregulation of cell-cycle-related genes. Single-cell RNA-sequencing analyses revealed NEAT1 expression across multiple cell types within the GBM microenvironment, including tumor cells, macrophages, and T cells. High NEAT1 expression levels in tumor cells correlated with increased infiltrating macrophages and microglia. In these tumor-infiltrating myeloid cells, we found that NEAT1 expression was linked to enrichment in TNFα/NFκB signaling pathway genes. Silencing NEAT1 suppressed M1 macrophage polarization and reduced the expression of TNFα and other inflammatory cytokines.Conclusions:These findings suggest an association between NEAT1 expression and patient response to anti-PD-1/PD-L1 therapy in melanoma and GBM and have important implications for the role of lncRNAs in the tumor microenvironment.

Published
2023
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19. Role of MXRA8 in Ross River Virus Disease Pathogenesis

Author

Wern Hann Ng, Zheng L. Ling, Andrew J. Kueh, Marco J. Herold, Nicholas P. West, Nicholas J. C. King, Suresh Mahalingam, and Xiang Liu

Subjects
Virology, Microbiology
Abstract

Previous studies have shown the importance of the cell surface protein MXRA8 as an entry receptor for several different prominent alphaviruses such as CHIKV, RRV, MAYV, and ONNV. In particular, the role of MXRA8 in the tissue tropism, viral pathogenesis, and immune response of a CHIKV mouse model have already been briefly characterized.

Published
2023
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20. Computational drug discovery for castration-resistant prostate cancers through in vitro drug response modeling

Author

Weijie Zhang, Adam M. Lee, Sampreeti Jena, Yingbo Huang, Yeung Ho, Kiel T. Tietz, Conor R. Miller, Mei-Chi Su, Joshua Mentzer, Alexander L. Ling, Yingming Li, Scott M. Dehm, and R. Stephanie Huang

Subjects
Multidisciplinary
Abstract

Prostate cancer (PC) is the most frequently diagnosed malignancy and a leading cause of cancer deaths in US men. Many PC cases metastasize and develop resistance to systemic hormonal therapy, a stage known as castration-resistant prostate cancer (CRPC). Therefore, there is an urgent need to develop effective therapeutic strategies for CRPC. Traditional drug discovery pipelines require significant time and capital input, which highlights a need for novel methods to evaluate the repositioning potential of existing drugs. Here, we present a computational framework to predict drug sensitivities of clinical CRPC tumors to various existing compounds and identify treatment options with high potential for clinical impact. We applied this method to a CRPC patient cohort and nominated drugs to combat resistance to hormonal therapies including abiraterone and enzalutamide. The utility of this method was demonstrated by nomination of multiple drugs that are currently undergoing clinical trials for CRPC. Additionally, this method identified the tetracycline derivative COL-3, for which we validated higher efficacy in an isogenic cell line model of enzalutamide-resistant vs. enzalutamide-sensitive CRPC. In enzalutamide-resistant CRPC cells, COL-3 displayed higher activity for inhibiting cell growth and migration, and for inducing G1-phase cell cycle arrest and apoptosis. Collectively, these findings demonstrate the utility of a computational framework for independent validation of drugs being tested in CRPC clinical trials, and for nominating drugs with enhanced biological activity in models of enzalutamide-resistant CRPC. The efficiency of this method relative to traditional drug development approaches indicates a high potential for accelerating drug development for CRPC.

Published
2023
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22. Deciphering strontium sulfate precipitation via Ostwald’s rule of stages: From prenucleation clusters to solution-mediated phase tranformation

Author

A. R. Lauer, R. Hellmann, G. Montes-Hernandez, N. Findling, W. L. Ling, T. Epicier, A. Fernandez-Martinez, A. E. S. Van Driessche, Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], General Physics and Astronomy, Physical and Theoretical Chemistry
Abstract

Multiple-step nucleation pathways have been observed during mineral formation in both inorganic and biomineral systems. These pathways can involve precursor aqueous species, amorphous intermediates, or metastable phases. Despite the widespread occurrence of these processes, elucidating the precise nucleation steps and the transformation mechanisms between each step remains a challenging task. Using a suite of potentiometric, microscopic, and spectroscopic tools, we studied the nucleation pathway of SrSO4 as a function of the physico-chemical solution parameters. Our observations reveal that below a threshold supersaturation, nucleation is driven by bound species, akin to the prenucleation cluster model, which directly leads to the formation of the stable phase celestine, SrSO4. At higher supersaturations, this situation is altered, with nucleation dominated by the consumption of free ions. Importantly, this change in nucleation mechanism is coupled to the formation of a hemihydrate metastable phase, SrSO4 · 1/2H2O, which eventually transforms into celestine, adhering to Ostwald’s rule of stages. This transformation is a solution-mediated process, also occurring in the presence of a fluid film and is controlled by the physico-chemical parameters of the surrounding environment. It proceeds through the dissolution of the metastable phase and the de novo crystallization of the final phase. Overall, our results reveal that ion association taking place during the prenucleation stage dictates whether the nucleation pathway goes through an intermediate phase or not. This also underlines that although Ostwald’s rule of stages is a common process, it is not a prerequisite for mineral formation—even in systems where it can occur.

Published
2023
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29. Development and validation of the HARMS2-AF lifestyle risk score to predict incident AF

Author

L. Segan, R. Canovas, S. Nanayakkara, D. Chieng, S. Prabhu, H. Sugumar, A. Voskoboinik, L. Ling, J. Morton, G. Lee, J. Kalman, and P. Kistler

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine
Abstract

Background Lifestyle risk factors (RFs) are a modifiable target in atrial fibrillation (AF) management. However, the relative contribution of individual lifestyle RFs to AF incidence has not been described. Purpose Development and validation of a novel AF-lifestyle risk score to determine AF risk in the general population. Methods The UK Biobank (UKB) is a large prospective cohort with outcomes measured >10 years. In the UKB, we performed regression analysis of AF lifestyle RFs which were then evaluated in a multivariable model and a weighted score was developed. Next, the risk score was externally validated in the Framingham Heart Study (FHS) population. Kaplan-Meier estimates ascertained the 10-year risk of AF development. Results In the UKB, AF incidence was 5.3% among 302,926 participants, with a median time to AF 7.3 years (IQR 4.3–9.8). Hypertension, sleep apnoea, male sex, age, obesity (BMI>30 kg/m2), alcohol and smoking were predictive variables (all p5 points) was associated with a heightened 10-year AF risk (score 5–9: OR 9.35, score 10–14: OR 33.34). Conclusions The HARMS2-AF score is a novel lifestyle risk score which may help identify individuals at risk of AF and assists in general population screening. Funding Acknowledgement Type of funding sources: None.

Published
2022
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30. Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in South-East Asia

Author

Marina Gysin, Pei Yun Hon, Pisey Tan, Amphonesavanh Sengduangphachanh, Manivone Simmalavong, Pattaraporn Hinfonthong, Napaporn Kaewphanderm, Thai Duy Pham, Thanh Ha Nguyen, Klara Haldimann, Katja Becker, H. Rogier van Doorn, Jill Hopkins, Andrew J.H. Simpson, Elizabeth A. Ashley, Thomas Kesteman, Hoang Huy Tran, Shawn Vasoo, Clare L. Ling, Tamalee Roberts, Paul Turner, Sven N. Hobbie, and University of Zurich

Subjects
Microbiology (medical), Colistin, 10179 Institute of Medical Microbiology, 610 Medicine & health, General Medicine, Microbial Sensitivity Tests, Anti-Bacterial Agents, Cephalosporins, Infectious Diseases, Aminoglycosides, Carbapenems, Blood Culture, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria, Pseudomonas aeruginosa, Tobramycin, Nebramycin, 570 Life sciences, biology, Pharmacology (medical), Gentamicins, Amikacin, Asia, Southeastern
Abstract

Bloodstream infections (BSIs) are a leading cause of sepsis, which is a life-threatening condition that significantly contributes to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly being compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside-resistant and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections.This study collected a panel of 470 MDR GNB isolates from healthcare facilities in Cambodia, Laos, Singapore, Thailand and Vietnam for a multicentre assessment of their antimicrobial susceptibility to apramycin in comparison with other aminoglycosides and colistin by broth microdilution assays.Apramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem and third-generation cephalosporin-resistant Enterobacterales, all Acinetobacter baumannii and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, four (6.2%) had an apramycin MIC16 µg/mL.Apramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, third-generation cephalosporins and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of MDR BSIs.

Published
2022

32. Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Author

Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, ShouH Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, ChristianM Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, BorisG Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, FrancescoL Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, DanieleM Combaux, Fabien Grelon, Charlene Le Moal, EliseP Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, RachanaV Rhayakar, Nagarajan Ramakrishnan, VallishK Bhardwaj, HeeraL Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, EimhinS Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, ColinS Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, RobertoR Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, EttoreR Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, YvesD Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, AsiscloJ Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M Van Wezel, SergeJ Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, DanielleJ Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, BritÅ Sjøbø, AnneB Guttormsen, Hector H LeonYoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, AnaM Araujo, NunoT Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, IsabelM Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, AhmedS AlJabbary, Edgardo Tabhan, YaseenM Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, JuanC Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, GuillermoM Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, AntonioL RuizAguilar, LuisM Claraco-Vega, Juan Alfonso Soler, Maria Del CarmenLorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, JuanB López-Messa, ManuelP Perez, CesarP Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, M Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, AntonioG Jimenez, FranciscoP Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, CorcolesG Virgilio, NoeliaN Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, KarinE Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, SilviaL Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, HervéO Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, OnatO Akyol, SuleymanS Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, ChristopherJ Scott, HelenE Ellis, Stuart Mckechnie, PaulaJ Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, MichaelN Dean, JuliusH Cranshaw, EmmaL Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, PieterD Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, SimonK Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, KatieH McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, DonaldA Irvine, Charing Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, SamanthaJ Hagan, JadeM Cole, Caroline C MacFie, AnnaT Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M BannerGoodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz Mesar, DaleJ Yeatts, Jessica Warren, MichaelJ Lanspa, Russel R Miller, ColinK Grissom, SamuelM Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, RobertL Owens, Ashley Schomer, Amado-Rodríguez, Laura, Rodríguez-Garcia, Raquel, Bellani, Giacomo, Pham, Tài, Fan, Eddy, Madotto, Fabiana, Laffey, John G, Albaiceta, Guillermo M, Antonio Pesenti, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, DanielF McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Fernando Rios, Frank Van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, DanielF McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Sanatorio Las Lomas, San Isidro, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, JonasI Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, MarlusM Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid BinHJAbul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, ShouH Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, ChristianM Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, BorisG Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, FrancescoL Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, DanieleM Combaux, Fabien Grelon, Charlene Le Moal, EliseP Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, RachanaV Rhayakar, Nagarajan Ramakrishnan, VallishK Bhardwaj, HeeraL Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, EimhinS Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, ColinS Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Sara Sher, Anna Rossi, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, RobertoR Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, EttoreR Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, YvesD Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, AsiscloJ Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M Van Wezel, SergeJ Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, DanielleJ Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, BritÅ Sjøbø, AnneB Guttormsen, Hector H LeonYoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, AnaM Araujo, NunoT Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, IsabelM Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, AhmedS AlJabbary, Edgardo Tabhan, YaseenM Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, JuanC Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, GuillermoM Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, AntonioL RuizAguilar, LuisM Claraco-Vega, Juan Alfonso Soler, Maria Del CarmenLorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, JuanB López-Messa, ManuelP Perez, CesarP Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana Temprano, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, M Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, AntonioG Jimenez, FranciscoP Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, CorcolesG Virgilio, NoeliaN Recio, Richard O Adamsson, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik 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Subjects
Ventilator-induced lung injury, Cardiogenic pulmonary edema, Driving pressure, Mechanical ventilation, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Settore MED/41 - ANESTESIOLOGIA, Critical Care and Intensive Care Medicine
Abstract

Supported by Centro de Investigación Biomédica en Red (CIBER)‑Enfermedades respiratorias, Madrid, Spain (CB17/06/00021) and Fundación para el Fomento en Asturias de la Investigación Científica aplicada y la tecnología (FICYT, AYUD2021/52014). RRG is the recipient of a grant from Instituto de Salud Carlos III, Madrid, Spain (CM20/00083)., Amado-Rodríguez L., Rodríguez-Garcia R., Bellani G., Pham T., Fan E., Madotto F., Laffey J.G., Albaiceta G.M., Pesenti A., Brochard L., Esteban A., Gattinoni L., van Haren F., Larsson A., McAuley D.F., Ranieri M., Rubenfeld G., Taylor Thompson B., Wrigge H., Slutsky A.S., Rios F., Van Haren F., Sottiaux T., Depuydt P., Lora F.S., Azevedo L.C., Bugedo G., Qiu H., Gonzalez M., Silesky J., Cerny V., Nielsen J., Jibaja M., Wrigge H., Matamis D., Ranero J.L., Amin P., Hashemian S.M., Clarkson K., Kurahashi K., Villagomez A., Zeggwagh A.A., Heunks L.M., Laake J.H., Palo J.E., do Vale Fernandes A., Sandesc D., Arabi Y.M., Bumbasierevic V., Nin N., Lorente J.A., Larsson A., Piquilloud L., Abroug F., McAuley D.F., McNamee L., Hurtado J., Bajwa E., Démpaire G., Sula H., Nunci L., Cani A., Zazu A., Dellera C., Insaurralde C.S., Las Lomas S., Isidro S., Alejandro R.V., Daldin J., Vinzio M., Fernandez R.O., Cardonnet L.P., Bettini L.R., Bisso M.C., Osman E.M., Setten M.G., Lovazzano P., Alvarez J., Villar V., Pozo N.C., Grubissich N., Plotnikow G.A., Vasquez D.N., Ilutovich S., Tiribelli N., Chena A., Pellegrini C.A., Saenz M.G., Estenssoro E., Brizuela M., Gianinetto H., Gomez P.E., Cerrato V.I., Bezzi M.G., Borello S.A., Loiacono F.A., Fernandez A.M., Knowles S., Reynolds C., Inskip D.M., Miller J.J., Kong J., Whitehead C., Bihari S., Seven A., Krstevski A., Rodgers H.J., Millar R.T., McKenna T.E., Bailey I.M., Hanlon G.C., Aneman A., Lynch J.M., Azad R., Neal J., Woods P.W., Roberts B.L., Kol M.R., Wong H.S., Riss K.C., Staudinger T., Wittebole X., Berghe C., Bulpa P.A., Dive A.M., Verstraete R., Lebbinck H., Depuydt P., Vermassen J., Meersseman P., Ceunen H., Rosa J.I., Beraldo D.O., Piras C., Rampinelli A.M., Nassar Jr A.P., Mataloun S., Moock M., Thompson M.M., Gonçalves C.H., Antônio A.C.P., Ascoli A., Biondi R.S., Fontenele D.C., Nobrega D., Sales V.M., BinHJAbul Wahab A.Y., Ismail M., Shindhe S., Laffey J., Beloncle F., Davies K.G., Cirone R., Manoharan V., Ismail M., Goligher E.C., Jassal M., Nishikawa E., Javeed A., Curley G., Rittayamai N., Parotto M., Ferguson N.D., Mehta S., Knoll J., Pronovost A., Canestrini S., Bruhn A.R., Garcia P.H., Aliaga F.A., Farías P.A., Yumha J.S., Ortiz C.A., Salas J.E., Saez A.A., Vega L.D., Labarca E.F., Martinez F.T., Carreño N.G., Lora P., Liu H., Qiu H., Liu L., Tang R., Luo X., An Y., Zhao H., Gao Y., Zhai Z., Ye Z.L., Wang W., Li W., Li Q., Zheng R., Yu W., Shen J., Li X., Yu T., Lu W., Wu Y.Q., Huang X.B., He Z., Lu Y., Han H., Zhang F., Sun R., Wang H.X., Qin S.H., Zhu B.H., Zhao J., Liu J., Li B., Liu J.L., Zhou F.C., Li Q.J., Zhang X.Y., Li-Xin Z., Xin-Hua Q., Jiang L., Gao Y.N., Zhao X.Y., Li Y.Y., Li X.L., Wang C., Yao Q., Yu R., Chen K., Shao H., Qin B., Huang Q.Q., Zhu W.H., Hang A.Y., Hua M.X., Li Y., Xu Y., Di Y.D., Ling L.L., Qin T.H., Wang S.H., Qin J., Han Y., Zhou S., Vargas M.P., Jimenez J.I.S., Rojas M.A.G., SolisQuesada J.E., Ramirez-Alfaro C.M., Máca J., Sklienka P., Gjedsted J., Christiansen A., Nielsen J., Villamagua B.G., Llano I., Burtin P., Buzancais G., Beuret P., Pelletier N., Mortaza S., Mercat A., Chelly J., Jochmans S., Terzi N., Daubin C., Carteaux G., de Prost N., Chiche J.-D., Daviaud F., Fartoukh M., Barberet G., Biehler J., Dellamonica J., Doyen D., Arnal J.-M., Briquet A., Hraiech S., Papazian L., Follin A., Roux D., Messika J., Kalaitzis E., Dangers L., Combes A., Béduneau G., Carpentier D., Zogheib E.H., Dupont H., Ricome S., Santoli F.L., Besset S.L., Michel P., Gelée B., Danin P.-E., Goubaux B., Crova P.J., Phan N.T., Berkelmans F., Badie J.C., Tapponnier R., Gally J., Khebbeb S., Herbrecht J.-E., Schneider F., Declercq P.L.M., Rigaud J.-P., Duranteau J., Harrois A., Chabanne R., Marin J., Bigot C., Thibault S., Ghazi M., Boukhazna M., Zein S.O., Richecoeur J.R., Combaux D.M., Grelon F., Le Moal C., Sauvadet E.P., Robine A., Lemiale V., Reuter D., Dres M., Demoule A., Goldgran-Toledano D., Baboi L., Guérin C., Lohner R., Kraßler J., Schäfer S., Zacharowski K.D., Meybohm P., Reske A.W., Simon P., Hopf H.B.F., Schuetz M., Baltus T., Papanikolaou M.N., Papavasilopoulou T.G., Zacharas G.A., Ourailogloy V., Mouloudi E.K., Massa E.V., Nagy E.O., Stamou E.E., Kiourtzieva E.V., Oikonomou M.A., Avila L.E., Cortez C.A., Citalán J.E., Jog S.A., Sable S.D., Shah B., Gurjar M., Baronia A.K., Memon M., Muthuchellappan R., Ramesh V.J., Shenoy A., Unnikrishnan R., Dixit S.B., Rhayakar R.V., Ramakrishnan N., Bhardwaj V.K., Mahto H.L., Sagar S.V., Palaniswamy V., Ganesan D., Jamaati H., Heidari F., Meaney E.A., Nichol A., Knapman K.M., O’Croinin D., Dunne E.S., Breen D.M., Jaafar R.F., Dwyer R., Amir F., Ajetunmobi O.O., O’Muircheartaigh A.C., Black C.S., Treanor N., Collins D.V., Altaf W., Zani G., Fusari M., Spadaro S., Volta C.A., Graziani R., Brunettini B., Palmese S., Formenti P., Umbrello M., Lombardo A., Pecci E., Botteri M., Savioli M., Protti A., Mattei A., Schiavoni L., Tinnirello A., Todeschini M., Giarratano A., Cortegiani A., Sher S., Rossi A., Antonelli M.M., Montini L.M., Casalena P., Scafetti S., Panarello G., Occhipinti G., Patroniti N., Pozzi M., Biscione R.R., Poli M.M., Raimondi F., Albiero D., Crapelli G., Beck E., Pota V., Schiavone V., Molin A., Tarantino F., Monti G., Frati E., Mirabella L., Cinnella G., Fossali T., Colombo R., Terragni P., Pattarino I., Mojoli F., Braschi A., Borotto E.E., Cracchiolo A.N., Palma D.M., Raponi F., Foti G., Vascotto E.R., Coppadoro A., Brazzi L., Floris L., Iotti G.A., Venti A., Yamaguchi O., Takagi S., Maeyama H.N., Watanabe E., Yamaji Y., Shimizu K., Shiozaki K., Futami S., Ryosuke S., Saito K., Kameyama Y., Ueno K., Izawa M., Okuda N., Suzuki H., Harasawa T., Nasu M., Takada T., Ito F., Nunomiya S., Koyama K., Abe T., Andoh K., Kusumoto K., Hirata A., Takaba A., Kimura H., Matsumoto S., Higashijima U., Honda H., Aoki N., Imai H., Ogino Y., Mizuguchi I., Ichikado K., Nitta K., Mochizuki K., Hashida T., Tanaka H., Nakamura T., Niimi D., Ueda T., Kashiwa Y., Uchiyama A., Sabelnikovs O., Oss P., Haddad Y., Liew K.Y., Ñamendys-Silva S.A., Jarquin-Badiola Y.D., Sanchez-Hurtado L.A., Gomez-Flores S.S., Marin M.C., Lemus J.S., Fierro J.M., Cervantes M.R., Mejia F.J.F., Dector D., Rojas A., Gonzalez D.R., Estrella C.R., Sanchez-Medina J.R., Ramirez-Gutierrez A., George F.G., Aguirre J.S., Buensuseso J.A., Poblano M., Dendane T., Zeggwagh A.A., Balkhi H., Elkhayari M., Samkaoui N., Ezzouine H., Benslama A., Amor M., Maazouzi W., Cimic N., Beck O., Bruns M.M., Schouten J.A., Rinia M., Raaijmakers M., Heunks L.M., Van Wezel H.M., Heines S.J., Strauch U., Buise M.P., Simonis F.D., Schultz M.J., Goodson J.C., Browne T.S., Navarra L., Hunt A., Hutchison R.A., Bailey M.B., Newby L., McArthur C., Kalkoff M., Mcleod A., Casement J., Hacking D.J., Andersen F.H., Dolva M.S., Laake J.H., Barratt-Due A., Noremark K.A.L., Søreide E., Sjøbø B.Å., Guttormsen A.B., LeonYoshido H.H., Aguilar R.Z., Oscanoa F.A.M., Alisasis A.U., Robles J.B., Pasanting-Lim R.A.B., Tan B.C., Andruszkiewicz P., Jakubowska K., Coxo C.M., Alvarez A.M., Oliveira B.S., Montanha G.M., Barros N.C., Pereira C.S., Messias A.M., Monteiro J.M., Araujo A.M., Catorze N.T., Marum S.M., Bouw M.J., Gomes R.M., Brito V.A., Castro S., Estilita J.M., Barros F.M., Serra I.M., Martinho A.M., Tomescu D.R., Marcu A., Bedreag O.H., Papurica M., Corneci D.E., Negoita S.I., Grigoriev E., Gritsan A.I., Gazenkampf A.A., Almekhlafi G., Albarrak M.M., Mustafa G.M., Maghrabi K.A., Salahuddin N., Aisa T.M., AlJabbary A.S., Tabhan E., Trinidad O.A., Al Dorzi H.M., Bumbasirevic V., Jovanovic B., Bolon S., Smith O., Mancebo J., Aguirre-Bermeo H., Lopez-Delgado J.C., Esteve F., Rialp G., Forteza C., De Haro C., Artigas A., Albaiceta G.M., De Cima-Iglesias S., Seoane-Quiroga L., Ceniceros-Barros A., RuizAguilar A.L., Claraco-Vega L.M., Soler J.A., del CarmenLorente M., Hermosa C., Gordo F., PrietoGonzález M., López-Messa J.B., Perez M.P., Perez C.P., Allue R.M., RocheCampo F., Ibañez-Santacruz M., Temprano S., Pintado M.C., De Pablo R., Gómez P.R.A., Ruiz S.R., Moles S.I., Jurado M.T., Arizmendi A., Piacentini E.A., Franco N., Honrubia T., Cheng M.P., Losada E.P., Blanco J., Yuste L.J., Carbayo-Gorriz C., Cazorla-Barranquero F.G., Alonso J.G., Alda R.S., Algaba Á., Navarro G., Cereijo E., Diaz-Rodriguez E., Marcos D.P., Montero L.A., Para L.H., Sanchez R.J., Navalpotro M.A.B., Abad R.D., González R.M., Toribio D.P., Castro A.G., Artiga M.J.D., Penuelas O., Roser T.P., Olga M.F., Curto E.G., Sánchez R.M., Imma V.P., Elisabet G.M., Claverias L., Magret M., Pellicer A.M., Rodriguez L.L., Sánchez-Ballesteros J., González-Salamanca Á., Jimenez A.G., Huerta F.P., Diaz J.C.J.S., Lopez E.B., Moya D.D.L., Alfonso A.A.T., Luis P.S.E., Cesar P.S., Rafael S.I., Virgilio C.G., Recio N.N., Adamsson R.O., Rylander C.C., Holzgraefe B., Broman L.M., Wessbergh J., Persson L., Schiöler F., Kedelv H., Tibblin A.O., 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Boyd O., de Gordoa L.O.-R., Bramall J., Symmonds S., Chau S.K., Wenham T., Szakmany T., Toth-Tarsoly P., McCalman K.H., Alexander P., Stephenson L., Collyer T., Chapman R., Cooper R., Allan R.M., Sim M., Wrathall D.W., Irvine D.A., Zantua C.K.S., Adams J.C., Burtenshaw A.J., Sellors G.P., Welters I.D., Williams K.E., Hessell R.J., Oldroyd M.G., Battle C.E., Pillai S., Kajtor I., Sivashanmugavel M., Okane S.C., Donnelly A., Frigyik A.D., Careless J.P., May M.M., Stewart R., Trinder T.J., Hagan S.J., Cole J.M., MacFie C.C., Dowling A.T., Hurtado J., Nin N., Hurtado J., Nuñez E., Pittini G., Rodriguez R., Imperio M.C., Santos C., França A.G., Ebeid A., Deicas A., Serra C., Uppalapati A., Kamel G., BannerGoodspeed V.M., Beitler J.R., Mukkera S.R., Kulkarni S., Shinn III J.O., Gomaa D., Tainter C., Lee J., Mesar T., Yeatts D.J., Warren J., Lanspa M.J., Miller R.R., Grissom C.K., Brown S.M., Bauer P.R., Gosselin R.J., Kitch B.T., Cohen J.E., Beegle S.H., Choudry S., Gueret R.M., Tulaimat A., Stigler W., Batra H., Huff N.G., Lamb K.D., Oetting T.W., Mohr N.M., Judy C., Saito S., Kheir F.M., Kheir F., Schlichting A.B., Delsing A., Crouch D.R., Elmasri M., Crouch D.R., Ismail D., Dreyer K.R., Blakeman T.C., Baro R.M., Hou P.C., Seethala R., Aisiku I., Henderson G., Frendl G., Hou S.-K., Owens R.L., Schomer A.

Published
2022

33. Biosynthesis and Mechanism of Action of the Cell Wall Targeting Antibiotic Hypeptin

Author

Max Crüsemann, Daniel A. Wirtz, Aaron J. Peoples, Anthony Nitti, Gabriele M. König, Michaele Josten, Beate Henrichfreise, Kevin C Ludwig, Stefan Kehraus, Carina E Marx, Sebastian Krannich, Melina Arts, Kim Lewis, Paul Barac, Amy Spoering, Tanja Schneider, Losee L Ling, and Anna Müller

Subjects
hydroxylase, Teixobactin, cyclodepsipeptide, Microbial Sensitivity Tests, Gram-Positive Bacteria, 010402 general chemistry, Biochemistry, 01 natural sciences, Catalysis, Bacterial cell structure, Mixed Function Oxygenases, Hydroxylation, Cell wall, chemistry.chemical_compound, Biosynthesis, Cell Wall, antibiotic, Gram-Negative Bacteria, Gene cluster, Peptide Synthases, Lipid II, 010405 organic chemistry, Chemistry, Communication, lipid II, General Medicine, General Chemistry, Communications, In vitro, Anti-Bacterial Agents, 0104 chemical sciences, Lysobacter, Multigene Family, Antimicrobial Cationic Peptides
Abstract

Hypeptin is a cyclodepsipeptide antibiotic produced by Lysobacter sp. K5869, isolated from an environmental sample by the iChip technology, dedicated to the cultivation of previously uncultured microorganisms. Hypeptin shares structural features with teixobactin and exhibits potent activity against a broad spectrum of gram‐positive pathogens. Using comprehensive in vivo and in vitro analyses, we show that hypeptin blocks bacterial cell wall biosynthesis by binding to multiple undecaprenyl pyrophosphate‐containing biosynthesis intermediates, forming a stoichiometric 2:1 complex. Resistance to hypeptin did not readily develop in vitro. Analysis of the hypeptin biosynthetic gene cluster (BGC) supported a model for the synthesis of the octapeptide. Within the BGC, two hydroxylases were identified and characterized, responsible for the stereoselective β‐hydroxylation of four building blocks when bound to peptidyl carrier proteins. In vitro hydroxylation assays corroborate the biosynthetic hypothesis and lead to the proposal of a refined structure for hypeptin., The nonribosomal peptide hypeptin blocks cell wall biosynthesis of gram‐positive bacteria by binding to lipid II. It kills pathogens even in late exponential growth phase without detectable development of resistance. Investigation of the biosynthesis in vitro, combined with bioinformatic and NMR analyses led to the proposal of a refined structure.

Published
2021
Full Text
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34. PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models

Author

Mykola Zdioruk, Jorge-Luis Jimenez-Macias, Michal Oskar Nowicki, Katherine E. Manz, Kurt D. Pennell, Marilin S. Koch, Tomer Finkelberg, Bin Wu, Paul Boucher, Yuji Takeda, Weiyi Li, Raziye Piranlioglu, Alexander L. Ling, E. Antonio Chiocca, and Sean E. Lawler

Subjects
General Biochemistry, Genetics and Molecular Biology
Published
2023
Full Text
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36. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author

Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A 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C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, 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RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs

Subjects
Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract

BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

Published
2021
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39. Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

Author

Mia J. Coleman, Luis M. Espino, Hernan Lebensohn, Marija V. Zimkute, Negar Yaghooti, Christina L. Ling, Jessica M. Gross, Natalia Listwan, Sandra Cano, Vanessa Garcia, Debbie M. Lovato, Susan L. Tigert, Drew R. Jones, Rama R. Gullapalli, Neal E. Rakov, Euriko G. Torrazza Perez, and Eliseo F. Castillo

Subjects
Endocrinology, Diabetes and Metabolism, metabolic syndrome, metabolomics, lipidomics, dyslipidemia, Molecular Biology, Biochemistry
Abstract

Background: Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, elevated blood pressure, or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS. Methods: We examined MetS risk factors in individuals through body measurements and clinical and biochemical blood analysis. To evaluate intestinal health, gut inflammation was measured by fecal calprotectin, intestinal permeability through the lactulose-mannitol test, and utilized fecal metabolomics to examine alterations in the host–microbiota gut metabolism. Results: No signs of intestinal inflammation or increased intestinal permeability were observed in the MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. Although our MetS cohort showed no signs of intestinal inflammation, they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels and decreasing HDL cholesterol levels. Conclusion: Taken together, our main results show that MetS subjects showed major alterations in fecal lipid profiles suggesting alterations in the intestinal host–microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit that fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.

Published
2022

41. Resveratrol modulates the gut microbiota of cholestasis in pregnant rats

Author

Z, Li, L, Lei, L, Ling, Y, Liu, Z, Xiong, and Y, Shao

Subjects
Aspartic Acid, Alanine, Cholestasis, Ursodeoxycholic Acid, Alanine Transaminase, Cholestasis, Intrahepatic, Ethinyl Estradiol, Gastrointestinal Microbiome, Rats, Bile Acids and Salts, Pregnancy Complications, Glutamates, Pregnancy, Resveratrol, RNA, Ribosomal, 16S, Animals, Dysbiosis, Female
Abstract

This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing to the potential therapeutic strategies for ICP. ICP rat models were established by injecting 17α-ethinylestradiol (EE) subcutaneously from the thirteenth day of gestation for four days and then treated with EE (D group, n=5), resveratrol (R group, n=5), or ursodeoxycholic acid (UDCA; U group, n=5) from the seventeenth to the twentieth day of gestation. Fecal samples were analyzed with 16S ribosomal RNA (rRNA) sequencing. In results: the gut microbiota of pregnant rats was characterized with reduced alpha diversity (Chao1 index), and significant variation in the microbiota structure (ANOSIM) was also observed after being treated with EE. The richness of four phyla and ten genera was upregulated, and five phyla and ten genera were downregulated by EE treatment. The dysbiosis of Bilophila, Ruminococcus, and Actinobacteria caused by EE treatment was reversed by resveratrol administration. There was a correlation between total bile acid and alanine aminotransferase in ICP rats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results suggested that the secondary bile acid biosynthesis was decreased, and the alanine, aspartate, and glutamate metabolism was increased after being treated with EE in pregnant rats. In conclusion, EE treatment could lead to gut microbiome dysbiosis and bile acid metabolism dysregulation in pregnant rats. Resveratrol could partially rescue gut microbiota dysbiosis and improve the biochemical characteristics caused by EE treatment.

Published
2022

42. Individuals with Metabolic Syndrome show altered fecal lipidomic profiles with no signs of intestinal inflammation or increased intestinal permeability: a pilot study

Author

Mia J. Coleman, Luis M. Espino, Hernan Lebensohn, Marija V. Zimkute, Negar Yaghooti, Christina L. Ling, Jessica M. Gross, Natalia Listwan, Sandra Cano, Vanessa Garcia, Debbie M. Lovato, Susan L. Tigert, Drew Jones, Rama R. Gullapalli, Neal E. Rakov, Euriko G. Torrazza Perez, and Eliseo F. Castillo

Abstract

Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low HDL cholesterol, hyperglycemia, hypertension or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS with the goal to evaluate for any signs of underlying gut inflammation, increased intestinal permeability, and alterations in host-microbiota metabolism as assessed by fecal metabolites. No signs of intestinal inflammation or increased intestinal permeability were observed in MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. An although our MetS cohort showed no signs of intestinal inflammation they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels, and decreasing HDL cholesterol levels. Taken together, our main results show MetS subjects show major alterations in fecal lipid profiles suggesting alterations in intestinal host-microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.

Published
2022
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43. Target-enrichment sequencing yields valuable genomic data for difficult-to-culture bacteria of public health importance

Author

Tristan P. W. Dennis, Barbara K. Mable, Brian Brunelle, Alison Devault, Ryan Carter, Clare L. Ling, Blandina T. Mmbaga, Jo E. B. Halliday, Katarina Oravcova, and Taya L. Forde

Abstract

Genomic data contribute invaluable information to the epidemiological investigation of pathogens of public health importance. However, whole genome sequencing (WGS) of bacteria typically relies on culture, which represents a major hurdle for generating such data for a wide range of species for which culture is challenging. In this study, we assessed the use of culture-free target-enrichment sequencing as a method for generating genomic data for two bacterial species: 1) Bacillus anthracis, which causes anthrax in both people and animals and whose culture requires high level containment facilities; and 2) Mycoplasma amphoriforme, a fastidious emerging human respiratory pathogen. We obtained high quality genomic data for both species directly from clinical samples, with sufficient coverage (>15X) for confident variant calling over at least 80% of the baited genomes for over two thirds of the samples tested. Higher qPCR cycle threshold (Ct) values (indicative of lower pathogen concentrations in the samples), pooling libraries prior to capture, and lower captured library concentration were all statistically associated with lower capture efficiency. The Ct value had the highest predictive value, explaining 52% of the variation in capture efficiency. Samples with Ct values ≤ 30 were over 6 times more likely to achieve the threshold coverage than those with a Ct > 30. We conclude that target-enrichment sequencing provides a valuable alternative to standard WGS following bacterial culture and creates opportunities for an improved understanding of the epidemiology and evolution of many clinically important pathogens for which culture is challenging.Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. Scripts used in this study can be accessed on GitHub at https://github.com/tristanpwdennis/bactocap. All sequence data generated during this study have been deposited in the European Nucleotide Archive (ENA) Sequence Read Archive (SRA) under project accession numbers PRJEB46822 (B. anthracis) and PRJEB50216 (M. amphoriforme). Accession numbers for individual samples, along with metadata, laboratory parameters and sequence quality metrics, are available at the University of Glasgow’s data repository, Enlighten, at http://dx.doi.org/10.5525/gla.researchdata.1249.

Published
2022
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44. Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Author

L., Amado-Rodriguez, R., Rodriguez-Garcia, G., Bellani, T., Pham, E., Fan, F., Madotto, J. G., Laffey, G. M., Albaiceta, Pesenti, Antonio, Brochard, Laurent, Esteban, Andre, Gattinoni, Luciano, van Haren, Frank, Larsson, Ander, Mcauley, Danielf, Ranieri, Marco, Rubenfeld, Gordon, Taylor Thompson, B, Wrigge, Hermann, S Slutsky, Arthur, Rios, Fernando, Van Haren, Frank, Sottiaux, Thierry, Depuydt, Pieter, S Lora, Fredy, Cesar Azevedo, Luciano, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marco, Silesky, Juan, Cerny, Vladimir, Nielsen, Jona, Jibaja, Manuel, Matamis, Dimitrio, Luis Ranero, Jorge, Amin, Pravin, M Hashemian, S, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Ali Zeggwagh, Amine, M Heunks, Leo, Henrik Laake, Jon, Emmanuel Palo, Jose, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Nin, Nicola, A Lorente, Jose, Piquilloud, Lise, Abroug, Fekri, Mcnamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, S Insaurralde, Carolina, Las Lomas, Sanatorio, Isidro, San, V Alejandro, Risso, Daldin, Julio, Vinzio, Mauricio, O Fernandez, Ruben, P Cardonnet, Lui, R Bettini, Lisandro, Carboni Bisso, Mariano, M Osman, Emilio, G Setten, Mariano, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, C Pozo, Norberto, Grubissich, Nicola, A Plotnikow, Gustavo, N Vasquez, Daniela, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, A Pellegrini, Carlo, G Saenz, María, Estenssoro, Elisa, Brizuela, Matia, Gianinetto, Hernan, E Gomez, Pablo, I Cerrato, Valeria, G Bezzi, Marco, A Borello, Silvina, A Loiacono, Flavia, M Fernandez, Adriana, Knowles, Serena, Reynolds, Claire, M Inskip, Deborah, J Miller, Jennene, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, J Rodgers, Helen, T Millar, Rebecca, E McKenna, Toni, M Bailey, Irene, C Hanlon, Gabrielle, Aneman, Ander, M Lynch, Joan, Azad, Raman, Neal, John, W Woods, Paul, L Roberts, Brigit, R Kol, Mark, S Wong, Helen, C Riss, Katharina, Staudinger, Thoma, Wittebole, Xavier, Berghe, Caroline, A Bulpa, Pierre, M Dive, Alain, Verstraete, Rik, Lebbinck, Herve, Vermassen, Jori, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonasi, O Beraldo, Daniel, Piras, Claudio, M Rampinelli, Adenilton, P Nassar Jr, Antonio, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlusm, H Gonçalves, Claudio, P Antônio, Ana Carolina, Ascoli, Aline, S Biondi, Rodrigo, C Fontenele, Danielle, Nobrega, Danielle, M Sales, Vanessa, Yazid BinHJAbul Wahab, Ahmad, Ismail, Maizatul, Shindhe, Suresh, Laffey, John, Beloncle, Francoi, G Davies, Kyle, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, C Goligher, Ewan, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, D Ferguson, Niall, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, R Bruhn, Alejandro, H Garcia, Patricio, A Aliaga, Felipe, A Farías, Pamela, S Yumha, Jacob, A Ortiz, Claudia, E Salas, Javier, A Saez, Alejandro, D Vega, Lui, F Labarca, Eduardo, T Martinez, Felipe, G Carreño, Nicolá, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, L Ye, Zheng, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Q Wu, Ya, B Huang, Xiao, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, X Wang, Hua, H Qin, Shu, H Zhu, Bao, Zhao, Jun, Liu, Jian, Li, Bin, L Liu, Jing, C Zhou, Fa, J Li, Qiong, Y Zhang, Xing, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, N Gao, Yuan, Y Zhao, Xian, Y Li, Yuan, L Li, Xiao, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Q Huang, Qing, H Zhu, Wei, Y Hang, Ai, X Hua, Ma, Li, Yimin, Xu, Yonghao, D Di, Yu, L Ling, Long, H Qin, Tie, Wang, Shouh, Qin, Junping, Han, Yi, Zhou, Suming, P Vargas, Monica, I Silesky Jimenez, Juan, A González Rojas, Manuel, E SolisQuesada, Jaime, Ramirez-Alfaro, Christianm, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Borisg, Llano, Iguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicola, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicola, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicola, Chiche, Jean-Daniel, Daviaud, Fabrice, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Deni, Arnal, Jean-Michel, Briquet, Anai, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelo, Dangers, Laurence, Combes, Alain, Béduneau, Gaetan, Carpentier, Dorothée, H Zogheib, Elie, Dupont, Herve, Ricome, Sylvie, Santoli, Francescol, L Besset, Sebastien, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, J Crova, Philippe, T Phan, Nga, Berkelmans, Frantz, C Badie, Julio, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Franci, M Declercq, Pierreloui, Rigaud, Jean-Philippe, Duranteau, Jacque, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, R Richecoeur, Jack, Combaux, Danielem, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elisep, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jen, Schäfer, Susanne, D Zacharowski, Kai, Meybohm, Patrick, W Reske, Andrea, Simon, Philipp, F Hopf, Hansbernd, Schuetz, Michael, Baltus, Thoma, N Papanikolaou, Metaxia, G Papavasilopoulou, Theonymfi, A Zacharas, Gianni, Ourailogloy, Vasili, K Mouloudi, Eleni, V Massa, Eleni, O Nagy, Eva, E Stamou, Electra, V Kiourtzieva, Ellada, A Oikonomou, Marina, E Avila, Lui, A Cortez, Cesar, E Citalán, Johanna, A Jog, Sameer, D Sable, Safal, Shah, Bhagyesh, Gurjar, Mohan, K Baronia, Arvind, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, J Ramesh, Venkatapura, Shenoy, Anitha, Unnikrishnan, Ramesh, B Dixit, Subhal, Rhayakar, Rachanav, Ramakrishnan, Nagarajan, Bhardwaj, Vallishk, Mahto, Heeral, V Sagar, Sudha, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, A Meaney, Edel, Nichol, Alistair, M Knapman, Karl, O'Croinin, Donall, Dunne, Eimhin, M Breen, Dorothy, P Clarkson, Kevin, F Jaafar, Rola, Dwyer, Rory, Amir, Fahd, O Ajetunmobi, Olaitan, C O'Muircheartaigh, Aogan, Black, Colin, Treanor, Nuala, V Collins, Daniel, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, A Volta, Carlo, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, M Antonelli, Massimo, Montini, Luca, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Robertor, M Poli, Michela, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, E Borotto, Erika, N Cracchiolo, Andrea, M Palma, Daniela, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettorer, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, A Iotti, Giorgio, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, N Maeyama, Hiroki, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Oleg, Oss, Peteri, Haddad, Youssef, Y Liew, Kong, A Ñamendys-Silva, Silvio, Jarquin-Badiola, Yvesd, A Sanchez-Hurtado, Lui, S Gomez-Flores, Saira, C Marin, Maria, Villagomez, Asiscloj, S Lemus, Jordana, M Fierro, Jonathan, Ramirez Cervantes, Mavy, Javier Flores Mejia, Francisco, Dector, Dulce, Rojas, Alejandro, R Gonzalez, Daniel, R Estrella, Claudia, R Sanchez-Medina, Jorge, Ramirez-Gutierrez, Alvaro, G George, Fernando, S Aguirre, Janet, A Buensuseso, Juan, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, M Bruns, Monique, A Schouten, Jeroen, Rinia, Myra, Raaijmakers, Monique, M Van Wezel, Hellen, J Heines, Serge, Strauch, Ulrich, P Buise, Marc, D Simonis, Fabienne, J Schultz, Marcu, C Goodson, Jennifer, S Browne, Troy, Navarra, Leanlove, Hunt, Anna, A Hutchison, Robyn, B Bailey, Mathew, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Daniellej, H Andersen, Finn, S Dolva, Merete, H Laake, Jon, Barratt-Due, Andrea, L Noremark, Kim Andre, Søreide, Eldar, Sjøbø, Britå, Guttormsen, Anneb, H LeonYoshido, Hector, Zumaran Aguilar, Ronald, A Montes Oscanoa, Fredy, U Alisasis, Alain, B Robles, Joanne, B Pasanting-Lim, Rossini Abbie, C Tan, Beatriz, Andruszkiewicz, Pawel, Jakubowska, Karina, M Coxo, Cristina, M Alvarez, António, S Oliveira, Bruno, M Montanha, Gustavo, C Barros, Nelson, S Pereira, Carlo, M Messias, António, M Monteiro, Jorge, Araujo, Anam, Catorze, Nunot, M Marum, Susan, J Bouw, Maria, M Gomes, Rui, A Brito, Vania, Castro, Silvia, M Estilita, Joana, M Barros, Filipa, Serra, Isabelm, M Martinho, Aurelia, R Tomescu, Dana, Marcu, Alexandra, H Bedreag, Ovidiu, Papurica, Mariu, E Corneci, Dan, Ioan Negoita, Silviu, Grigoriev, Evgeny, I Gritsan, Alexey, A Gazenkampf, Andrey, Almekhlafi, Ghaleb, M Albarrak, Mohamad, M Mustafa, Ghanem, A Maghrabi, Khalid, Salahuddin, Nawal, M Aisa, Tharwat, Aljabbary, Ahmed, Tabhan, Edgardo, Arabi, Yaseenm, M Arabi, Yaseen, A Trinidad, Olivia, M Al Dorzi, Hasan, E Tabhan, Edgardo, Bumbasirevic, Vesna, Jovanovic, Bojan, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juanc, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermom, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruizaguilar, Antoniol, Claraco-Vega, Luism, Alfonso Soler, Juan, Del CarmenLorente, Maria, Hermosa, Cecilia, Gordo, Federico, Prietogonzález, Miryam, López-Messa, Juanb, Perez, Manuelp, Perez, Cesarp, Montoiro Allue, Raquel, Rochecampo, Ferran, Ibañez-Santacruz, Marco, Temprano, Susana, C Pintado, Maria, De Pablo, Raul, Ricart Aroa Gómez, Pilar, Rodriguez Ruiz, Silvia, Iglesias Moles, Silvia, Teresa Jurado, M, Arizmendi, Alfon, A Piacentini, Enrique, Franco, Nieve, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, J Yuste, Lui, Carbayo-Gorriz, Cecilia, G Cazorla-Barranquero, Francisca, G Alonso, Javier, S Alda, Rosa, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Pastor Marcos, Diego, Alvarez Montero, Laura, Herrera Para, Lui, Jimenez Sanchez, Roberto, Angel Blasco Navalpotro, Miguel, Diaz Abad, Ricardo, Montiel González, Raquel, Parrilla Toribio, Dácil, G Castro, Alejandro, D Artiga, Maria Jose, Penuelas, Oscar, P Roser, Toma, F Olga, Moreno, Gallego Curto, Elena, Manzano Sánchez, Rocío, P Imma, Vallverdu, M Elisabet, Garcia, Claverias, Laura, Magret, Monica, M Pellicer, Ana, L Rodriguez, Lucia, Sánchez-Ballesteros, 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Srinivasa, Latha, Mcauley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, K Humphreys, Sally, Ferguson, Andrew, Mckee, Raymond, S Raj, Ashok, A Fawkes, Danielle, Watt, Philip, Twohey, Linda, R Jha, Rajeev, Thomas, Matthew, Morton, Alex, Kadaba, Varsha, J Smith, Mark, P Hormis, Anil, G Kannan, Santhana, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolc, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopherj, Ellis, Helene, Mckechnie, Stuart, Hutton, Paulaj, N Di Tomasso, Nora, N Vitale, Michela, O Griffin, Ruth, Dean, Michaeln, Cranshaw, Juliush, Willett, Emmal, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieterd, J Williams, Alexandra, Boyd, Owen, Ortiz-Ruiz de Gordoa, Laura, Bramall, Jon, Symmonds, Sophie, Chau, Simonk, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katieh, Alexander, Peter, Stephenson, 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G., Laffey, G. 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Carreño, Nicolá, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, L Ye, Zheng, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Q Wu, Ya, B Huang, Xiao, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, X Wang, Hua, H Qin, Shu, H Zhu, Bao, Zhao, Jun, Liu, Jian, Li, Bin, L Liu, Jing, C Zhou, Fa, J Li, Qiong, Y Zhang, Xing, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, N Gao, Yuan, Y Zhao, Xian, Y Li, Yuan, L Li, Xiao, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Q Huang, Qing, H Zhu, Wei, Y Hang, Ai, X Hua, Ma, Li, Yimin, Xu, Yonghao, D Di, Yu, L Ling, Long, H Qin, Tie, Wang, Shouh, Qin, Junping, Han, Yi, Zhou, Suming, P Vargas, Monica, I Silesky Jimenez, Juan, A González Rojas, Manuel, E SolisQuesada, Jaime, Ramirez-Alfaro, Christianm, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, 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Subhal, Rhayakar, Rachanav, Ramakrishnan, Nagarajan, Bhardwaj, Vallishk, Mahto, Heeral, V Sagar, Sudha, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, A Meaney, Edel, Nichol, Alistair, M Knapman, Karl, O'Croinin, Donall, Dunne, Eimhin, M Breen, Dorothy, P Clarkson, Kevin, F Jaafar, Rola, Dwyer, Rory, Amir, Fahd, O Ajetunmobi, Olaitan, C O'Muircheartaigh, Aogan, Black, Colin, Treanor, Nuala, V Collins, Daniel, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, A Volta, Carlo, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, M Antonelli, Massimo, Montini, Luca, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, 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Bruns, Monique, A Schouten, Jeroen, Rinia, Myra, Raaijmakers, Monique, M Van Wezel, Hellen, J Heines, Serge, Strauch, Ulrich, P Buise, Marc, D Simonis, Fabienne, J Schultz, Marcu, C Goodson, Jennifer, S Browne, Troy, Navarra, Leanlove, Hunt, Anna, A Hutchison, Robyn, B Bailey, Mathew, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, Casement, Jonathan, Hacking, Daniellej, H Andersen, Finn, S Dolva, Merete, H Laake, Jon, Barratt-Due, Andrea, L Noremark, Kim Andre, Søreide, Eldar, Sjøbø, Britå, Guttormsen, Anneb, H LeonYoshido, Hector, Zumaran Aguilar, Ronald, A Montes Oscanoa, Fredy, U Alisasis, Alain, B Robles, Joanne, B Pasanting-Lim, Rossini Abbie, C Tan, Beatriz, Andruszkiewicz, Pawel, Jakubowska, Karina, M Coxo, Cristina, M Alvarez, António, S Oliveira, Bruno, M Montanha, Gustavo, C Barros, Nelson, S Pereira, Carlo, M Messias, António, M Monteiro, Jorge, Araujo, Anam, Catorze, Nunot, M Marum, Susan, J Bouw, Maria, M Gomes, Rui, A Brito, Vania, Castro, Silvia, M Estilita, Joana, M Barros, Filipa, Serra, Isabelm, M Martinho, Aurelia, R Tomescu, Dana, Marcu, Alexandra, H Bedreag, Ovidiu, Papurica, Mariu, E Corneci, Dan, Ioan Negoita, Silviu, Grigoriev, Evgeny, I Gritsan, Alexey, A Gazenkampf, Andrey, Almekhlafi, Ghaleb, M Albarrak, Mohamad, M Mustafa, Ghanem, A Maghrabi, Khalid, Salahuddin, Nawal, M Aisa, Tharwat, Aljabbary, Ahmed, Tabhan, Edgardo, Arabi, Yaseenm, M Arabi, Yaseen, A Trinidad, Olivia, M Al Dorzi, Hasan, E Tabhan, Edgardo, Bumbasirevic, Vesna, Jovanovic, Bojan, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juanc, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermom, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruizaguilar, Antoniol, Claraco-Vega, Luism, Alfonso Soler, Juan, Del CarmenLorente, Maria, Hermosa, Cecilia, Gordo, Federico, Prietogonzález, Miryam, López-Messa, Juanb, Perez, Manuelp, Perez, Cesarp, Montoiro Allue, Raquel, Rochecampo, Ferran, Ibañez-Santacruz, Marco, Temprano, Susana, C Pintado, Maria, De Pablo, Raul, Ricart Aroa Gómez, Pilar, Rodriguez Ruiz, Silvia, Iglesias Moles, Silvia, Teresa Jurado, M, Arizmendi, Alfon, A Piacentini, Enrique, Franco, Nieve, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, J Yuste, Lui, Carbayo-Gorriz, Cecilia, G Cazorla-Barranquero, Francisca, G Alonso, Javier, S Alda, Rosa, Algaba, Ángela, Navarro, Gonzalo, Cereijo, Enrique, Diaz-Rodriguez, Esther, Pastor Marcos, Diego, Alvarez Montero, Laura, Herrera Para, Lui, Jimenez Sanchez, Roberto, Angel Blasco Navalpotro, Miguel, Diaz Abad, Ricardo, Montiel González, Raquel, Parrilla Toribio, Dácil, G Castro, Alejandro, D Artiga, Maria Jose, Penuelas, Oscar, P Roser, Toma, F Olga, Moreno, Gallego Curto, Elena, Manzano Sánchez, Rocío, P Imma, Vallverdu, M Elisabet, Garcia, Claverias, Laura, Magret, Monica, M Pellicer, Ana, L Rodriguez, Lucia, Sánchez-Ballesteros, Jesú, González-Salamanca, Ángela, Jimenez, Antoniog, Huerta, Franciscop, J Sotillo Diaz, Juan Carlo, Bermejo Lopez, Esther, D Llinares Moya, David, A Tallet Alfonso, Alec, Sanchez Eugenio Luis, Palazon, Sanchez Cesar, Palazon, I Rafael, Sánchez, Virgilio, Corcolesg, Recio, Noelian, O Adamsson, Richard, C Rylander, Christian, Holzgraefe, Bernhard, M Broman, Lar, Wessbergh, Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Han, Oscarsson Tibblin, Anna, Appelberg, Henrik, Hedlund, Lar, Helleberg, Johan, Eriksson, Karine, Glietsch, Rita, Larsson, Nikla, Nygren, Ingela, Nunes, Silvial, Morin, Anna-Karin, Kander, Thoma, Adolfsson, Anne, Zender, Hervéo, Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Kelebek Girgin, Nermin, Ozcelik, Menekse, Ünal, Necmettin, Ceyda Meco, Basak, Akyol, Onato, Derman, Suleyman, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, Mcauley, Danny, Hopkins, Phil, Mellis, Clare, Kakar, Vivek, Hadfield, Dan, Vercueil, Andre, Bhowmick, Kaushik, K Humphreys, Sally, Ferguson, Andrew, Mckee, Raymond, S Raj, Ashok, A Fawkes, Danielle, Watt, Philip, Twohey, Linda, R Jha, Rajeev, Thomas, Matthew, Morton, Alex, Kadaba, Varsha, J Smith, Mark, P Hormis, Anil, G Kannan, Santhana, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolc, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopherj, Ellis, Helene, Mckechnie, Stuart, Hutton, Paulaj, N Di Tomasso, Nora, N Vitale, Michela, O Griffin, Ruth, Dean, Michaeln, Cranshaw, Juliush, Willett, Emmal, Ioannou, Nichola, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieterd, J Williams, Alexandra, Boyd, Owen, Ortiz-Ruiz de Gordoa, Laura, Bramall, Jon, Symmonds, Sophie, Chau, Simonk, Wenham, Tim, Szakmany, Tama, Toth-Tarsoly, Piroska, Mccalman, Katieh, Alexander, Peter, Stephenson, Lorraine, Collyer, Thoma, Chapman, Rhiannon, Cooper, Raphael, M Allan, Russell, Sim, Malcolm, W Wrathall, David, Irvine, Donalda, S Zantua, Charing Kim, C Adams, John, J Burtenshaw, Andrew, P Sellors, Gareth, D Welters, Ingeborg, E Williams, Karen, J Hessell, Robert, G Oldroyd, Matthew, E Battle, Ceri, Pillai, Suresh, Kajtor, Istvan, Sivashanmugavel, Mageswaran, C Okane, Sinead, Donnelly, Adrian, D Frigyik, Aniko, P Careless, Jon, M May, Martin, Stewart, Richard, John Trinder, T, Hagan, Samanthaj, Cole, Jadem, C MacFie, Caroline, Dowling, Annat, Nin, Nicolá, Nuñez, Edgardo, Pittini, Gustavo, Rodriguez, Ruben, C Imperio, María, Santos, Cristina, G França, Ana, Ebeid, Alejandro, Deicas, Alberto, Serra, Carolina, Uppalapati, Aditya, Kamel, Ghassan, M BannerGoodspeed, Valerie, R Beitler, Jeremy, Reddy Mukkera, Satyanarayana, Kulkarni, Shreedhar, O Shinn Iii, John, Gomaa, Dina, Tainter, Christopher, Lee, Jarone, Mesar, Tomaz, Yeatts, Dalej, Warren, Jessica, Lanspa, Michaelj, R Miller, Russel, Grissom, Colink, Brown, Samuelm, R Bauer, Philippe, J Gosselin, Ryan, T Kitch, Barrett, E Cohen, Jason, H Beegle, Scott, Choudry, Shazia, M Gueret, Renaud, Tulaimat, Aiman, Stigler, William, Batra, Hitesh, G Huff, Nidhi, D Lamb, Keith, W Oetting, Trevor, M Mohr, Nichola, Judy, Claine, Saito, Shigeki, M Kheir, Fayez, Kheir, Fayez, B Schlichting, Adam, Delsing, Angela, R Crouch, Daniel, Elmasri, Mary, Ismail, Dina, R Dreyer, Kyle, C Blakeman, Thoma, M Baro, Rebecca, C Hou, Peter, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robertl, Schomer, Ashley, Rossi, Anna, and Luca Montini (ORCID:0000-0003-4602-5134)

Abstract

Background: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results: From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p < 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH2O, p < 0.001), plateau (20 [15–23] vs 22 [19–26] cmH2O, p < 0.001) and peak (21 [17–27] vs 26 [20–32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival. Conclusions: Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073.

Published
2022

46. [Clinical features of young inpatients with angle-closure glaucoma]

Author

S F, Lin, H, Xiao, L M, Chen, Y L, Ling, W, Wei, L, Fang, Y H, Su, J Y, Luo, and X, Liu

Subjects
Adult, Male, Angiotensin Receptor Antagonists, Inpatients, Young Adult, Humans, Angiotensin-Converting Enzyme Inhibitors, Female, Glaucoma, Angle-Closure, Intraocular Pressure, Retrospective Studies
Published
2022

47. A stochastic extended Rippa's algorithm for LpOCV

Author

L. Ling and F. Marchetti

Subjects
Stochastic low-rank approximation, RBF interpolation, Applied Mathematics, Cross validation, Extended Rippa's Algorithm, FOS: Mathematics, Numerical Analysis (math.NA), Mathematics - Numerical Analysis
Abstract

In kernel-based approximation, the tuning of the so-called shape parameter is a fundamental step for achieving an accurate reconstruction. Recently, the popular Rippa's algorithm [14] has been extended to a more general cross validation setting. In this work, we propose a modification of such extension with the aim of further reducing the computational costs. The resulting Stochastic Extended Rippa's Algorithm (SERA) is first detailed and then tested by means of various numerical experiments, which show its efficacy and effectiveness in different approximation settings.

Published
2022

49. Lau v. Nichols: History of a Struggle for Equal and Quality Education (An Excerpt).

Author

Berkeley Unified School District, CA. Asian American Bilingual Center. and Wang, L. Ling-Chi

Abstract

The history and issues leading to the Supreme Court decision which recognized the special educational needs and rights of limited English speaking students is traced in this article. Also discussed are the ensuing community struggles for the right to fashion the appropriate relief mandated by the Supreme Court and for the right to have quality bilingual bicultural education for students of all language and cultural backgrounds. The suit of Lau v. Nichols relating to San Francisco Unified School District was the last resort after all known channels for seeking equal educational opportunity had been exhausted. Paralleling the deteriorating situation in the school district were the accelerating juvenile delinquency rates in the 1960's in the Chinese community. The significance of the Lau v. Nichols decision nation-wide was immediately felt. There are, according to the U.S. Office of Education, approximately five million school children in the U.S. covered by the decision. Beyond its impact on public education, this decision has long-range legal implications on both the effectiveness and quality of government sponsored social and legal services now provided to non-English speakers across the nation. (Author/AM)

Published
1975

50. Impact of delayed processing of positive blood cultures on organism detection: a prospective multi-centre study

Author

Tamalee Roberts, Arjun Chandna, Wanitda Watthanaworawit, Areerat Thaiprakong, Sona Soeng, Manivone Simmalavong, Phonelavanh Phoumin, Weerawut Saengchun, Nongyao Khatta, Pattaraporn Hinfonthong, Napaporn Kaewpundoem, Sue J. Lee, Carlo Perrone, Ben Amos, Paul Turner, Elizabeth A. Ashley, and Clare L. Ling

Subjects
Bacteriological Techniques, Infectious Diseases, Bacteria, Blood Culture, Escherichia coli, Humans, Bacteremia, Prospective Studies, Culture Media
Abstract

Background Blood cultures remain the gold standard investigation for the diagnosis of bloodstream infections. In many locations, quality-assured processing of positive blood cultures is not possible. One solution is to incubate blood cultures locally, and then transport bottles that flag positive to a central reference laboratory for organism identification and antimicrobial susceptibility testing. However, the impact of delay between the bottle flagging positive and subsequent sub-culture on the viability of the isolate has received little attention. Methods This study evaluated the impact of delays to sub-culture (22 h to seven days) in three different temperature conditions (2–8 °C, 22–27 °C and 35 ± 2 °C) for bottles that had flagged positive in automated detection systems using a mixture of spiked and routine clinical specimens. Ninety spiked samples for five common bacterial causes of sepsis (Escherichia coli, Haemophilus influenzae, Staphylococcus aureus, Streptococcus agalactiae and Streptococcus pneumoniae) and 125 consecutive positive clinical blood cultures were evaluated at four laboratories located in Cambodia, Lao PDR and Thailand. In addition, the utility of transport swabs for preserving organism viability was investigated. Results All organisms were recoverable from all sub-cultures in all temperature conditions with the exception of S. pneumoniae, which was less likely to be recoverable after longer delays (> 46–50 h), when stored in hotter temperatures (35 °C), and from BacT/ALERT when compared with BACTEC blood culture bottles. Storage of positive blood culture bottles in cooler temperatures (22–27 °C or below) and the use of Amies bacterial transport swabs helped preserve viability of S. pneumoniae. Conclusions These results have practical implications for the optimal workflow for blood culture bottles that have flagged positive in automated detection systems located remotely from a central processing laboratory, particularly in tropical resource-constrained contexts.

Published
2021

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