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286 results on '"Juan Garcia"'

1. A decade of collaboration in medicines regulation: healthcare professionals engaging with the European Medicines Agency

Author

Ivana Silva, Giulia Gabrielli, Juan Garcia Burgos, Isabelle Moulon, Gonzalo Calvo Rojas, Ulrich Jaeger, and Rosa Giuliani

Subjects
European Medicines Agency, stakeholder engagement, healthcare professionals (HCPs), public Health, regulation of medicines, Medicine (General), R5-920
Abstract

The article shows that the input given by healthcare professionals (HCPs) adds value to the regulatory processes surrounding the development, authorisation, and monitoring of a medicine, but is also an instrument for accountability, trust, mutual exchange as well as an insight into the public health issues that matter most to one of the key stakeholder groups the Agency works with. We highlight the role of HCPs in the EU regulatory process and take stock of the first 10 years of the Framework for Interaction with HCPs to describe how practises have evolved over this time to meet the goals of informing, consulting and improving trust in the EU regulatory system. We will analyse what led European Medicines Agency (EMA) to develop this framework through to the next steps and where the interaction might lead in the future.

Published
2024
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2. Leveraging patient experience data to guide medicines development, regulation, access decisions and clinical care in the EU

Author

Diogo Almeida, Denise Umuhire, Rosa Gonzalez-Quevedo, Ana António, Juan Garcia Burgos, Patrice Verpillat, Nathalie Bere, Bruno Sepodes, and Carla Torre

Subjects
patient experience data, patient-reported outcomes, patient preferences, regulatory, decision-making, challenges, Medicine (General), R5-920
Abstract

Patient experience data (PED), provided by patients/their carers without interpretation by clinicians, directly capture what matters more to patients on their medical condition, treatment and impact of healthcare. PED can be collected through different methodologies and these need to be robust and validated for its intended use. Medicine regulators are increasingly encouraging stakeholders to generate, collect and submit PED to support both scientific advice in development programs and regulatory decisions on the approval and use of these medicines. This article reviews the existing definitions and types of PED and demonstrate the potential for use in different settings of medicines’ life cycle, focusing on Patient-Reported Outcomes (PRO) and Patient Preferences (PP). Furthermore, it addresses some challenges and opportunities, alluding to important regulatory guidance that has been published, methodological aspects and digitalization, highlighting the lack of guidance as a key hurdle to achieve more systematic inclusion of PED in regulatory submissions. In addition, the article discusses opportunities at European and global level that could be implemented to leverage PED use. New digital tools that allow patients to collect PED in real time could also contribute to these advances, but it is equally important not to overlook the challenges they entail. The numerous and relevant initiatives being developed by various stakeholders in this field, including regulators, show their confidence in PED’s value and create an ideal moment to address challenges and consolidate PED use across medicines’ life cycle.

Published
2024
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5. Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine

Author

Jean-Jacques Fournié, Cathy Quelen, Camille Laurent, Patricia Pérez-Galán, Juan Garcia Valero, Carla Faria, Fabien Gava, Pauline Gravelle, Celia Dobaño-López, Nathalie Van Acker, Gael Jalowicki, Renaud Morin, Cédric Rossi, Jean-Michel Lagarde, Loïc Ysebaert, and Christine Bezombes

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Follicular lymphoma (FL), the most common indolent non-Hodgkin’s Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses.Methods To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability.Results FL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+ T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+ cells positive for PD-1 and TIM-3.Conclusions In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.

Published
2023
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6. Hábitos de consumo de medicamentos de venta libre por estudiantes del área de la salud en Cartagena-Colombia

Author

Antistio Alviz-Amador, Hermides Bastos-Zayas, and Juan Garcia-Valdelamar

Subjects
otc, automedicación, acetaminofén, antiinflamatorios no esteroideos, Medicine (General), R5-920, Social history and conditions. Social problems. Social reform, HN1-995
Abstract

Introducción: Los medicamentos de venta libre (OTC por su sigla en inglés Over The Counter), son ampliamente usados por la mayoría de las personas a nivel mundial, sin embargo, solamente son usados de forma responsable en países donde existe una farmacia comunitaria profesional legalizada. Objetivo: Describir los hábitos de consumo de medicamentos de venta libre por estudiantes universitarios del área de la salud. Materiales y métodos: Estudio descriptivo transversal, desarrollado en tres universidades de Cartagena. Se aplicó un instrumento tipo encuesta a 140 estudiantes acerca de hábitos de consumo y conocimiento sobre OTC, creencias, actitudes y prácticas. Resultados: El cuestionario presentó una consistencia interna alta con Alfa de Cronbach’s de 0,77. El 59% fueron mujeres, las en edades entre 16-30 años, el 91% estuvo de acuerdo que la automedicación es perjudicial. Sin embargo, 61% asegura automedicarse porque los padecimientos son menores y frecuentes. Los medicamentos de mayor consumo, fueron el acetaminofén 52,9% y los medicamentos antiinflamatorios no esteroides (AINES) con 16,48%, incluyeron en sus respuestas medicamentos de no venta libre. Conclusión: Los estudiantes son conscientes del riesgo de la automedicación, sin embargo, la practican de forma frecuente. Muchos reportaron consumo de medicamentos como amitriptilina, antibióticos, opiáceos, furosemida y corticoides.

Published
2023
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7. Physical fitness and throwing speed in U13 versus U15 male handball players

Author

Jaime Fernandez-Fernandez, Urs Granacher, Isidoro Martinez-Martin, Vicente Garcia-Tormo, Alba Herrero-Molleda, David Barbado, and Juan Garcia-Lopez

Subjects
Overhead athletes, Shoulder, Injury risk, Sport-specific performance, Sports medicine, RC1200-1245
Abstract

Abstract Background The aim of this study was to analyze the shoulder functional profile (rotation range of motion [ROM] and strength), upper and lower body performance, and throwing speed of U13 versus U15 male handball players, and to establish the relationship between these measures of physical fitness and throwing speed. Methods One-hundred and nineteen young male handball players (under (U)-13 (U13) [n = 85]) and U15 [n = 34]) volunteered to participate in this study. The participating athletes had a mean background of sytematic handball training of 5.5 ± 2.8 years and they exercised on average 540 ± 10.1 min per week including sport-specific team handball training and strength and conditioning programs. Players were tested for passive shoulder range-of-motion (ROM) for both internal (IR) and external rotation (ER) and isometric strength (i.e., IR and ER) of the dominant/non-dominant shoulders, overhead medicine ball throw (OMB), hip isometric abductor (ABD) and adductor (ADD) strength, hip ROM, jumps (countermovement jump [CMJ] and triple leg-hop [3H] for distance), linear sprint test, modified 505 change-of-direction (COD) test and handball throwing speed (7 m [HT7] and 9 m [HT9]). Results U15 players outperformed U13 in upper (i.e., HT7 and HT9 speed, OMB, absolute IR and ER strength of the dominant and non-dominant sides; Cohen’s d: 0.76–2.13) and lower body (i.e., CMJ, 3H, 20-m sprint and COD, hip ABD and ADD; d: 0.70–2.33) performance measures. Regarding shoulder ROM outcomes, a lower IR ROM was found of the dominant side in the U15 group compared to the U13 and a higher ER ROM on both sides in U15 (d: 0.76–1.04). It seems that primarily anthropometric characteristics (i.e., body height, body mass) and upper body strength/power (OMB distance) are the most important factors that explain the throw speed variance in male handball players, particularly in U13. Conclusions Findings from this study imply that regular performance monitoring is important for performance development and for minimizing injury risk of the shoulder in both age categories of young male handball players. Besides measures of physical fitness, anthropometric data should be recorded because handball throwing performance is related to these measures.

Published
2022
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8. Stakeholders’ Understanding of European Medicine Agency’s COVID-19 Vaccine Information Materials in EU and Regional Contexts

Author

Indiana Castro, Marie Van Tricht, Nicole Bonaccorso, Martina Sciortino, Juan Garcia Burgos, Claudio Costantino, and Rosa Gonzalez-Quevedo

Subjects
vaccination, COVID-19, EMA, misinformation, hesitancy, Medicine
Abstract

The COVID-19 pandemic posed challenges to communicating accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reassure the public by communicating early on about the development and approval of COVID-19 vaccines. The EMA surveyed patients/consumers, healthcare professional organizations, and individual stakeholders, both at the EU level and in an Italian regional context. The objectives of the study were to see if the EMA’s core information materials were informative and well-understood and which communication channels were preferred by the public. The main findings showed that individual patients/consumers generally prefer to obtain information about COVID-19 vaccines from the internet or mass media, while organizations and individual healthcare professionals prefer to obtain information from national and international health authorities. Both at EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some improvements were recommended to the visual, text, and dissemination formats, including publishing more information on safety and using a more public-friendly language. Also, it was recommended to maintain the EMA’s approach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. In conclusion, user-testing of proactive communication materials aimed to prebunk misinformation during a public health crisis helps to ensure that users understand the development and safety of novel vaccine technologies. This information can then be used as a basis for further evidence-based communication activities by regulators and public health bodies in an emergency context.

Published
2023
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10. Venetoclax improves CD20 immunotherapy in a mouse model of MYC/BCL2 double-expressor diffuse large B-cell lymphoma

Author

Patricia Pérez-Galán, Javier Melchor, Marcos Garcia-Lacarte, Sara C. Grijalba, Adrián Arnaiz-Leché, Marién Pascual, Carlos Panizo, Oscar Blanco, Victor Segura, Francisco J. Novo, Juan Garcia Valero, Jose A. Martinez-Climent, and Sergio Roa

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Approximately one-third of diffuse large B cell lymphoma (DLBCL) patients exhibit co-expression of MYC and BCL2 (double-expressor lymphoma, DEL) and have a dismal prognosis. Targeted inhibition of the anti-apoptotic protein BCL2 with venetoclax (ABT-199) has been approved in multiple B-cell malignancies and is currently being investigated in clinical trials for DLBCL. Whether BCL2 anti-apoptotic function represents a multifaceted vulnerability for DEL-DLBCL, affecting both lymphoma B cells and T cells within the tumor microenvironment, remains to be elucidated.Methods Here, we present novel genetically engineered mice that preclinically recapitulate DEL-DLBCL lymphomagenesis, and evaluate their sensitivity ex vivo and in vivo to the promising combination of venetoclax with anti-CD20-based standard immunotherapy.Results Venetoclax treatment demonstrated specific killing of MYC+/BCL2+ lymphoma cells by licensing their intrinsically primed apoptosis, and showed previously unrecognized immunomodulatory activity by specifically enriching antigen-activated effector CD8 T cells infiltrating the tumors. Whereas DEL-DLBCL mice were refractory to venetoclax alone, inhibition of BCL2 significantly extended overall survival of mice that were simultaneously treated with a murine surrogate for anti-CD20 rituximab.Conclusions These results suggest that the combination of anti-CD20-based immunotherapy and BCL2 inhibition leads to cooperative immunomodulatory effects and improved preclinical responses, which may offer promising therapeutic opportunities for DEL-DLBCL patients.

Published
2023
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11. Brainstorm-DUNEuro: An integrated and user-friendly Finite Element Method for modeling electromagnetic brain activity

Author

Takfarinas Medani, Juan Garcia-Prieto, Francois Tadel, Marios Antonakakis, Tim Erdbrügger, Malte Höltershinken, Wayne Mead, Sophie Schrader, Anand Joshi, Christian Engwer, Carsten H. Wolters, John C. Mosher, and Richard M. Leahy

Subjects
Head modeling, Electrophysiology, EEG/MEG/SEEG, Finite element method, Forward model, Brainstorm, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Human brain activity generates scalp potentials (electroencephalography – EEG), intracranial potentials (iEEG), and external magnetic fields (magnetoencephalography – MEG). These electrophysiology (e-phys) signals can often be measured simultaneously for research and clinical applications. The forward problem involves modeling these signals at their sensors for a given equivalent current dipole configuration within the brain. While earlier researchers modeled the head as a simple set of isotropic spheres, today's magnetic resonance imaging (MRI) data allow for a detailed anatomic description of brain structures and anisotropic characterization of tissue conductivities. We present a complete pipeline, integrated into the Brainstorm software, that allows users to automatically generate an individual and accurate head model based on the subject's MRI and calculate the electromagnetic forward solution using the finite element method (FEM). The head model generation is performed by integrating the latest tools for MRI segmentation and FEM mesh generation. The final head model comprises the five main compartments: white-matter, gray-matter, CSF, skull, and scalp. The anisotropic brain conductivity model is based on the effective medium approach (EMA), which estimates anisotropic conductivity tensors from diffusion-weighted imaging (DWI) data. The FEM electromagnetic forward solution is obtained through the DUNEuro library, integrated into Brainstorm, and accessible with either a user-friendly graphical interface or scripting. With tutorials and example data sets available in an open-source format on the Brainstorm website, this integrated pipeline provides access to advanced FEM tools for electromagnetic modeling to a broader neuroscience community.

Published
2023
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12. Ipconazole Induces Oxidative Stress, Cell Death, and Proinflammation in SH-SY5Y Cells

Author

Carlos Villaorduña, Mariano Mendoza-Carlos, Manuel Chuyma, Jhon Avilés, Ayda Avalos-Diaz, Ronald Lozano-Reategui, Juan Garcia-Ruiz, Nadia Panduro-Tenazoa, Jessy Vargas, Ysabel Moran-Quintanilla, and José-Luis Rodríguez

Subjects
ipconazole, oxidative stress, cell death, neurotoxicity, Chemical technology, TP1-1185
Abstract

Ipconazole is an antifungal agrochemical widely used in agriculture against seed diseases of rice, vegetables, and other crops; due to its easy accumulation in the environment, it poses a hazard to human, animal, and environmental health. Therefore, we investigated the cytotoxic effect of ipconazole on SH-SY5Y neuroblastoma cells using cell viability tests (MTT), ROS production, caspase3/7 activity, and molecular assays of the biomarkers of cell death (Bax, Casp3, APAF1, BNIP3, and Bcl2); inflammasome (NLRP3, Casp1, and IL1β); inflammation (NFκB, TNFα, and IL6); and antioxidants (NRF2, SOD, and GPx). SH-SY5Y cells were exposed to ipconazole (1, 5, 10, 20, 50, and 100 µM) for 24 h. The ipconazole, in a dose-dependent manner, reduced cell viability and produced an IC50 of 32.3 µM; it also produced an increase in ROS production and caspase3/7 enzyme activity in SH-SY5Y cells. In addition, ipconazole at 50 µM induced an overexpression of Bax, Casp3, APAF1, and BNIP3 (cell death genes); NLRP3, Casp1, and IL1B (inflammasome complex genes); and NFκB, TNFα, and IL6 (inflammation genes); it also reduced the expression of NRF2, SOD, and GPx (antioxidant genes). Our results show that ipconazole produces cytotoxic effects by reducing cell viability, generating oxidative stress, and inducing cell death in SH-SY5Y cells, so ipconazole exposure should be considered as a factor in the presentation of neurotoxicity or neurodegeneration.

Published
2023
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13. Monodelphis domestica as a Fetal Intra-Cerebral Inoculation Model for Zika Virus Pathogenesis

Author

John Thomas, Juan Garcia, Matthew Terry, Susan Mahaney, Oscar Quintanilla, Dionn Carlo Silva, Marisol Morales, and John L VandeBerg

Subjects
Zika, fetal, Monodelphis, model, animal, intra-cerebral, Medicine
Abstract

Monodelphis domestica (the laboratory opossum) is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation, which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have made M. domestica a valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially neurotropic viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistology and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists, and that viral replication results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility of M. domestica as a new animal model for investigating ZIKV infection in vivo and facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that require a host with the ability to sustain sustained viremia, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.

Published
2023
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14. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

Author

Anna M. Cervantes-Arslanian, MD, Chakradhar Venkata, MD, Pria Anand, MD, Joseph D. Burns, MD, Charlene J. Ong, MD, Allison M. LeMahieu, MS, Phillip J. Schulte, PhD, Tarun D. Singh, MD, Alejandro A. Rabinstein, MD, Neha Deo, BS, Vikas Bansal, MBBS, MPH, Karen Boman, BS, Juan Pablo Domecq Garces, MD, Donna Lee Armaignac, PhD, APRN, Amy B. Christie, MD, Roman R. Melamed, MD, Yasir Tarabichi, MD, MSCR, Sreekanth R. Cheruku, MD, MPH, Ashish K. Khanna, MD, FCCP, FCCM, FASA, Joshua L. Denson, MD, MS, Valerie M. Banner-Goodspeed, MPH, Harry L. Anderson, III, MD, FACS, FICS, FCCM, FCCP, FAIM, Ognjen Gajic, MD, MS, Vishakha K. Kumar, MD, MBA, Allan Walkey, MD, Rahul Kashyap, MD, MBA, on behalf of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Danijel knežević, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Dimitrios Kantas, Vasileios Koulouras, Estela Pineda, Gabina María Reyes Guillen, Helin Archaga Soto, Ana Karen Vallecillo Lizardo, Csaba Kopitkó, Ágnes Bencze, István Méhész, Zsófia Gerendai,, Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Sridhar Papani, Mahesh Kamuram, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Phaneendra Doddaga, Neethi Chandra, Puneet Rijhwani, Ashish Jain, Aviral Gupta, Ram Mohan Jaiswal, Ambika Tyagi, Nimish Mathur, Madhav Prabhu, Vishal Jakati, Mukur Petrolwala, Bharat Ladva, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Wataru Matsuda, Reina Suzuki, Michihito Kyo, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Takuya Shiga, Yudai Iwasaki, Hidenobu Shigemitsu, Yuka Mishima, Nobuyuki Nosaka, Michio Nagashima, Abdulrahman Al-Fares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Mariana Janeth Hermosillo Ulloa, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh,, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Marwa Ridha Amer, Mohammed Abdullah, Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Yaseen M Arabi, Sheryl Ann Abdukahil, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Ana Andrijevic, Srdjan Gavrilovic, Vladimir Carapic, Bojan Kovacevic, Jovana Bojicic, Stevanovic Predrag, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Santiago Y. Teruel, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Suzanne Barry, Christopher Woll, Gregory Wu, Erin Carrole, Kathryn Burke, Mustafa Mohammed, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Jennifer M. Jarvis, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Gabriela “Hope” Gonzales, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Maj Andrew M. Hersh, CPT Stephanie L Wachs, Brittany S. Swigger, Stephanie L Wachs, Capt Lauren A. Sattler, Capt Michael N. Moulton, Kimberly Zammit, Patrick, J McGrath, William Loeffler, Maya, R. Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Pooja A. Nawathe, Isabel Pedraza, Jennifer Tsing, Karen Carr, Anila Chaudhary, Kathleen Guglielmino, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Dana D Byrne, Christa A Schorr, Katie Grant, Katherine L Doktor, Maura C Porto, Olga Kaplan, James E. Siegler, III, Brian Schonewald, Ashley Woodford, Alan Tsai, Savina Reid, Kuntal Bhowmick, Saba Daneshpooy, Cyrus Mowdawalla, Trishna Akshay Dave, Wilhemina Kennedy, Connor Crudeli, Christopher Ferry, Long Nguyen, Sneha Modi, Niharika Padala, Pavan Jitendra Patel, Belle Lin, Lena Chatterjee, Jamie Qiuyun, Fan Mandi Liu, Rasagna Kota, Annesha Banerjee, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Nicholas Perkins, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Héctor Collazo Santiago, Ricardo Alan Hernandez, Norma Smalls, Asher G Bercow, Mark Shlomovich, Christine Crandall, Sasko Stojanovski, Kristin Johnson, Kelly Michienzi, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, Namrata Nag, Jeff Brauer, Ashwin Dharmadhikari, Sahib Singh, Franco Laghi, Ghania Naeem, Andrew Wang, Kevin Bliden, Amit Rout, Jaime Barnes, Martin Gesheff, Asha Thomas, Melbin Thomas, Alicia R. Liendo, Jovan Milosavljevic, Kenan Abbasi, Nicholas B. Burley, Nicole Rapista, Samuel Amankwah, Sanjay K Poude, Saroj Timilsina, Sauradeep Sarkar, Oluwasayo Akinyosoye, Shashi K. Yalamanchili, Sheena Moorthy, Sonia Sugumar, Jonathan Ford, Martin C. Taylor, Charlotte Dunderdale, Alyssa Henshaw, Mary K. Brunk, Jessica Hagy, Shehryar Masood, Sushrutha Sridhar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Fahimeh Talaei, Rahul Kashyap, Juan Pablo Domecq, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Romil Singh, Diana J. Valencia Morales, Abigail T. La Nou, Marija Bogojevic, Simon Zec, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Mohammed Mustafa Hasan, Ashrita Donepudi, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Jessica Timmer, Kimberly Welker, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Nasar A Siddiqi, Lesly Jurado, Lindsey Tincher, Carolyn Brown, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Neha Gupta, Brent R Brown, Tracy L Jones, Kassidy Malone, Lauren A Sinko, Amy B Harrell, Shonda C Ayers, Lisa M Settle, Taylor J Sears, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Victoria Schauf, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Majdi Hamarshi, Jeannette Ploetz, Nick Bennett, Kyle Klindworth, Moustafa Younis, Adham Mohamed, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Diane Barkas, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, Krunal Kumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Jason Block, James Mitchel, Connor G O’Brien, Sylvan Cox, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mary Barletta, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn II, Robert MacLaren, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Ozan Akca, Rainer Lenhardt, Rodrigo S. Cavallazzi, Ann Jerde, Alexa Black, Allison Polidori, Haily Griffey, Justin Winkler, Thomas Brenzel, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Sreekanth R. Cheruku, Catherine Chen, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, Samuel Chakola, Kevin Sheth, Abdalla Ammar, Mahmoud Ammar, Victor Torres Lopez, Charles Dela Cruz,, Akhil Khosla, and Samir Gautam

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Published
2022
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15. Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

Author

Nabil Hajji, Juan Garcia-Revilla, Manuel Sarmiento Soto, Richard Perryman, Jake Symington, Chad C. Quarles, Deborah R. Healey, Yijie Guo, Manuel Luis Orta-Vázquez, Santiago Mateos-Cordero, Khalid Shah, John Bomalaski, Giulio Anichini, Andreas G. Tzakos, Timothy Crook, Kevin O’Neill, Adrienne C. Scheck, Jose Luis Venero, and Nelofer Syed

Subjects
Oncology, Therapeutics, Medicine
Abstract

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.

Published
2022
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16. Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19

Author

Shelsey W. Johnson, MD, Michael A. Garcia, MD, Emily K. Q. Sisson, MA, Christopher R. Sheldrick, PhD, Vishakha K. Kumar, MD, MBA, Karen Boman, BA, Scott Bolesta, PharmD, Vikas Bansal, MBBS, MPH, Amos Lal, MBBS, J. P. Domecq, MD, MS, Roman R. Melamed, MD, Amy B. Christie, MD, Abdurrahman Husain, MD, Santiago Yus, MBBS, Ognjen Gajic, MD, MSc, Rahul Kashyap, MBBS, MBA, Allan J. Walkey, MD, MSc, from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Oscar Y. Gavidia, Felipe Pachon, Yeimy A. Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Wataru Matsuda, Reina Suzuki, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Muhammad Sohaib, Asghar, Mashaal Syed, Syed Anosh, Ali Naqvi, Borisovich Zabolotskikh, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Mohammed A. Almazyad, Mohammed I. Alarifi, Jara M. Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N. Asfina, Kaltham M. Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Predrag D. Stevanovic, Dejan S. Stojakov, Duska K. Ignjatovic, Suzana C. Bojic, Marina M. Bobos, Irina B. Nenadic, Milica S. Zaric, Marko D. Djuric, Vladimir R. Djukic, Santiago Yus, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Abdulrahman Al-Fares, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Kimberly Zammit, Patrick J. McGrath, William Loeffler, Maya R. Chilbert, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Raquel R. Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Katharine Nault, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Mayo Clinic Arizona, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Juan Pablo Domecq, Romil Singh, Alex Niven, Mayo Clinic, Eau Claire, Abigail T. La Nou, Marija Bogojevic, Barbara Mullen, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M. Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Neha Gupta, Tracy L. Jones, Shonda C. Ayers, Amy B. Harrell, Dr. Brent R. Brown, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Dragana Markotić, Ivana Bošnjak, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, and Samuel Chakola

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN:. Retrospective, observational study. SETTING:. The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS:. Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS:. Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS:. Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3–1.9; p = 0.49). CONCLUSIONS:. During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Published
2022
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17. Risk factors for graft loss and death among kidney transplant recipients: A competing risk analysis.

Author

Jessica Pinto-Ramirez, Andrea Garcia-Lopez, Sergio Salcedo-Herrera, Nasly Patino-Jaramillo, Juan Garcia-Lopez, Jefferson Barbosa-Salinas, Sergio Riveros-Enriquez, Gilma Hernandez-Herrera, and Fernando Giron-Luque

Subjects
Medicine, Science
Abstract

IntroductionKidney transplantation is the best therapeutical option for CKD patients. Graft loss risk factors are usually estimated with the cox method. Competing risk analysis could be useful to determine the impact of different events affecting graft survival, the occurrence of an outcome of interest can be precluded by another. We aimed to determine the risk factors for graft loss in the presence of mortality as a competing event.MethodsA retrospective cohort of 1454 kidney transplant recipients who were transplanted between July 1, 2008, to May 31, 2019, in Colombiana de Trasplantes, were analyzed to determine risk factors of graft loss and mortality at 5 years post-transplantation. Kidney and patient survival probabilities were estimated by the competing risk analysis. The Fine and Gray method was used to fit a multivariable model for each outcome. Three variable selection methods were compared, and the bootstrapping technique was used for internal validation as split method for resample. The performance of the final model was assessed calculating the prediction error, brier score, c-index and calibration plot.ResultsGraft loss occurred in 169 patients (11.6%) and death in 137 (9.4%). Cumulative incidence for graft loss and death was 15.8% and 13.8% respectively. In a multivariable analysis, we found that BKV nephropathy, serum creatinine and increased number of renal biopsies were significant risk factors for graft loss. On the other hand, recipient age, acute cellular rejection, CMV disease were risk factors for death, and recipients with living donor had better survival compared to deceased-donor transplant and coronary stent. The c-index were 0.6 and 0.72 for graft loss and death model respectively.ConclusionWe developed two prediction models for graft loss and death 5 years post-transplantation by a unique transplant program in Colombia. Using a competing risk multivariable analysis, we were able to identify 3 significant risk factors for graft loss and 5 significant risk factors for death. This contributes to have a better understanding of risk factors for graft loss in a Latin-American population. The predictive performance of the models was mild.

Published
2022
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18. Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy

Author

Lara Heij, Jan Bednarsch, Xiuxiang Tan, Mika Rosin, Simone Appinger, Konrad Reichel, Dana Pecina, Michail Doukas, Ronald M. van Dam, Juan Garcia Vallejo, Florian Ulmer, Sven Lang, Tom Luedde, Flavio G. Rocha, Shivan Sivakumar, and Ulf Peter Neumann

Subjects
cholangiocarcinoma, tumor microenvironment, checkpoint molecules, multiplexed imaging, immunotherapy, Cytology, QH573-671
Abstract

Background: The tumor microenvironment (TME) in cholangiocarcinoma (CCA) influences the immune environment. Checkpoint blockade is promising, but reliable biomarkers to predict response to treatment are still lacking. Materials and Methods: The levels of checkpoint molecules (PD-1, PD-L1, PD-L2, LAG-3, ICOS, TIGIT, TIM-3, CTLA-4), macrophages (CD68), and T cells (CD4 and CD8 cells) were assessed by multiplexed immunofluorescence in 50 intrahepatic cases. Associations between marker expression, immune cells, and region of expression were studied in the annotated regions of tumor, interface, sclerotic tumor, and tumor-free tissue. Results: ICCA demonstrated CD4_TIM-3 high densities in the tumor region of interest (ROI) compared to the interface (p = 0.014). CD8_PD-L1 and CD8_ICOS densities were elevated in the sclerotic tumor compared to the interface (p = 0.011 and p = 0.031, respectively). In a multivariate model, high expression of CD8_PD-L2 (p = 0.048) and CD4_ICOS_TIGIT (p = 0.011) was associated with nodal metastases. Conclusions: High densities of PD-L1 were more abundant in the sclerotic tumor region; this is meaningful for the stratification of immunotherapy. Lymph node metastasis correlates with CD4_ICOS_TIGIT co-expression and CD8_PD-L2 expression, indicating the checkpoint expression profile of patients with a poor prognosis. Also, multiple co-expressions occur, and this potentially suggests a role for combination therapy with different immune checkpoint targets than just PD-1 blockade monotherapy.

Published
2023
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19. Detecting and Characterizing Mg ii Absorption in DESI Survey Validation Quasar Spectra

Author

Lucas Napolitano, Agnesh Pandey, Adam D. Myers, Ting-Wen Lan, Abhijeet Anand, Jessica Aguilar, Steven Ahlen, David M. Alexander, David Brooks, Rebecca Canning, Chiara Circosta, Axel De La Macorra, Peter Doel, Sarah Eftekharzadeh, Victoria A. Fawcett, Andreu Font-Ribera, Juan Garcia-Bellido, Satya Gontcho A Gontcho, L. Le Guillou, Julien Guy, Klaus Honscheid, Stephanie Juneau, T. Kisner, Martin Landriau, Aaron M. Meisner, Ramon Miquel, J. Moustakas, Will J. Percival, J. Xavier Prochaska, Michael Schubnell, Gregory Tarlé, B. A. Weaver, Benjamin Weiner, Zhimin Zhou, Hu Zou, and Siwei Zou

Subjects
Catalogs, Sky surveys, Cosmology, Large-scale structure of the universe, AGN host galaxies, Galaxies, Astronomy, QB1-991
Abstract

We present findings of the detection of Magnesium II (Mg ii , λ = 2796, 2803 Å) absorbers from the early data release of the Dark Energy Spectroscopic Instrument (DESI). DESI is projected to obtain spectroscopy of approximately 3 million quasars (QSOs), of which over 99% are anticipated to be at redshifts greater than z > 0.3, such that DESI would be able to observe an associated or intervening Mg ii absorber illuminated by the background QSO. We have developed an autonomous supplementary spectral pipeline that detects these systems through an initial line-fitting process and then confirms the line properties using a Markov Chain Monte Carlo sampler. Based upon a visual inspection of the resulting systems, we estimate that this sample has a purity greater than 99%. We have also investigated the completeness of our sample in regard to both the signal-to-noise properties of the input spectra and the rest-frame equivalent width ( W _0 ) of the absorber systems. From a parent catalog containing 83,207 quasars, we detect a total of 23,921 Mg ii absorption systems following a series of quality cuts. Extrapolating from this occurrence rate of 28.8% implies a catalog at the completion of the five-year DESI survey that will contain over eight hundred thousand Mg ii absorbers. The cataloging of these systems will enable significant further research because they carry information regarding circumgalactic medium environments, the distribution of intervening galaxies, and the growth of metallicity across the redshift range 0.3 ≤ z < 2.5.

Published
2023
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20. The Hitchhiker’s Guide to the Galaxy Catalog Approach for Dark Siren Gravitational-wave Cosmology

Author

Jonathan R. Gair, Archisman Ghosh, Rachel Gray, Daniel E. Holz, Simone Mastrogiovanni, Suvodip Mukherjee, Antonella Palmese, Nicola Tamanini, Tessa Baker, Freija Beirnaert, Maciej Bilicki, Hsin-Yu Chen, Gergely Dálya, Jose Maria Ezquiaga, Will M. Farr, Maya Fishbach, Juan Garcia-Bellido, Tathagata Ghosh, Hsiang-Yu Huang, Christos Karathanasis, Konstantin Leyde, Ignacio Magaña Hernandez, Johannes Noller, Gregoire Pierra, Peter Raffai, Antonio Enea Romano, Monica Seglar-Arroyo, Danièle A. Steer, Cezary Turski, Maria Paola Vaccaro, and Sergio Andrés Vallejo-Peña

Subjects
Gravitational wave astronomy, Hubble constant, Cosmology, Astronomy, QB1-991
Abstract

We outline the “dark siren” galaxy catalog method for cosmological inference using gravitational wave (GW) standard sirens, clarifying some common misconceptions in the implementation of this method. When a confident transient electromagnetic counterpart to a GW event is unavailable, the identification of a unique host galaxy is in general challenging. Instead, as originally proposed by Schutz, one can consult a galaxy catalog and implement a dark siren statistical approach incorporating all potential host galaxies within the localization volume. Trott & Huterer recently claimed that this approach results in a biased estimate of the Hubble constant, H _0 , when implemented on mock data, even if optimistic assumptions are made. We demonstrate explicitly that, as previously shown by multiple independent groups, the dark siren statistical method leads to an unbiased posterior when the method is applied to the data correctly. We highlight common sources of error possible to make in the generation of mock data and implementation of the statistical framework, including the mismodeling of selection effects and inconsistent implementations of the Bayesian framework, which can lead to a spurious bias.

Published
2023
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21. Primordial Black Hole clusters, phenomenology & implications

Author

Siles, Jose Francisco Nuño and Capdevila, Juan García-Bellido

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, Astrophysics - High Energy Astrophysical Phenomena, General Relativity and Quantum Cosmology
Abstract

We present direct N-body simulations of black-hole-only clusters with up to $2 \cdot 10^4$ compact objects, zero natal spin and no primordial binaries as predicted by various primordial black hole (PBH) Dark Matter models. The clusters' evolution is computed using ${\tt NBODY6\!+\!+GPU}$, including the effects of the tidal field of the galaxy, the kicks of black hole mergers and orbit-averaged energy loss by gravitational radiation of binaries. We investigate clusters with four initial mass distributions, three of which attempt to model a generic PBH scenario using a lognormal mass distribution and a fourth one that can be directly linked to a monochromatic PBH scenario when accretion is considered. More specifically, we dive into the clusters' internal dynamics, describing their expansion and evaporation, along with the resultant binary black hole mergers. We also compare several simulations with and without black hole merger kicks and find modelling implications for the probability of hierarchical mergers., Comment: 14 pages, 9 figures, 2 tables

Published
2024

22. First detection in space of the high-energy isomer of cyanomethanimine: H2CNCN

Author

Andrés, David San, Rivilla, Víctor M., Colzi, Laura, Jiménez-Serra, Izaskun, Martín-Pintado, Jesús, Megías, Andrés, López-Gallifa, Álvaro, Martínez-Henares, Antonio, Massalkhi, Sarah, Zeng, Shaoshan, Sanz-Novo, Miguel, Tercero, Belén, de Vicente, Pablo, Martín, Sergio, Requena-Torres, Miguel A., Molpeceres, Germán, and de la Concepción, Juan García

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We report the first detection in the interstellar medium of $N$-cyanomethanimine (H$_2$CNCN), the stable dimer of HCN of highest energy, and the most complex organic molecule identified in space containing the prebiotically relevant NCN backbone. We have identified a plethora of $a$-type rotational transitions with 3 $\leq J_\text{up} \leq$ 11 and $K_\text{a} \leq$ 2 that belong to this species towards the Galactic Center G+0.693-0.027 molecular cloud, the only interstellar source showing the three cyanomethanimine isomers (including the $Z$- and $E$- isomers of $C$-cyanomethanimine, HNCHCN). We have derived a total column density for H$_2$CNCN of (2.9$\, \pm \,$0.1)$\times$10$^{12}$ cm$^{-2}$, which translates into a total molecular abundance with respect to H$_2$ of (2.1$\, \pm \,$0.3)$\times$10$^{-11}$. We have also revisited the previous detection of $E$- and $Z$-HNCHCN, and found a total $C/N$-cyanomethanimine abundance ratio of 31.8$\, \pm \,$1.8 and a $Z/E$-HNCHCN ratio of 4.5$\, \pm \,$0.2. While the latter can be explained on the basis of thermodynamic equilibrium, chemical kinetics are more likely responsible for the observed $C/N$-cyanomethanimine abundance ratio, where the gas-phase reaction between methanimine (CH$_2$NH) and the cyanogen radical (CN) arises as the primary formation route., Comment: 22 pages, 8 figures, 3 tables, 2 appendix - Accepted for publication in The Astrophysical Journal

Published
2024
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23. The Robotic Multiobject Focal Plane System of the Dark Energy Spectroscopic Instrument (DESI)

Author

Joseph Harry Silber, Parker Fagrelius, Kevin Fanning, Michael Schubnell, Jessica Nicole Aguilar, Steven Ahlen, Jon Ameel, Otger Ballester, Charles Baltay, Chris Bebek, Dominic Benton Beard, Robert Besuner, Laia Cardiel-Sas, Ricard Casas, Francisco Javier Castander, Todd Claybaugh, Carl Dobson, Yutong Duan, Patrick Dunlop, Jerry Edelstein, William T. Emmet, Ann Elliott, Matthew Evatt, Irena Gershkovich, Julien Guy, Stu Harris, Henry Heetderks, Ian Heetderks, Klaus Honscheid, Jose Maria Illa, Patrick Jelinsky, Sharon R. Jelinsky, Jorge Jimenez, Armin Karcher, Stephen Kent, David Kirkby, Jean-Paul Kneib, Andrew Lambert, Mike Lampton, Daniela Leitner, Michael Levi, Jeremy McCauley, Aaron Meisner, Timothy N. Miller, Ramon Miquel, Juliá Mundet, Claire Poppett, David Rabinowitz, Kevin Reil, David Roman, David Schlegel, Santiago Serrano, William Van Shourt, David Sprayberry, Gregory Tarlé, Suk Sien Tie, Curtis Weaverdyck, Kai Zhang, Marco Azzaro, Stephen Bailey, Santiago Becerril, Tami Blackwell, Mohamed Bouri, David Brooks, Elizabeth Buckley-Geer, Jose Peñate Castro, Mark Derwent, Arjun Dey, Govinda Dhungana, Peter Doel, Daniel J. Eisenstein, Nasib Fahim, Juan Garcia-Bellido, Enrique Gaztañaga, Satya Gontcho A Gontcho, Gaston Gutierrez, Philipp Hörler, Robert Kehoe, Theodore Kisner, Anthony Kremin, Luzius Kronig, Martin Landriau, Laurent Le Guillou, Paul Martini, John Moustakas, Nathalie Palanque-Delabrouille, Xiyan Peng, Will Percival, Francisco Prada, Carlos Allende Prieto, Guillermo Gonzalez de Rivera, Eusebio Sanchez, Justo Sanchez, Ray Sharples, Marcelle Soares-Santos, Edward Schlafly, Benjamin Alan Weaver, Zhimin Zhou, Yaling Zhu, Hu Zou, and (DESI Collaboration)

Subjects
Dark energy, Astronomical instrumentation, Spectrometers, Galaxy spectroscopy, Astronomy, QB1-991
Abstract

A system of 5020 robotic fiber positioners was installed in 2019 on the Mayall Telescope, at Kitt Peak National Observatory. The robots automatically retarget their optical fibers every 10–20 minutes, each to a precision of several microns, with a reconfiguration time of fewer than 2 minutes. Over the next 5 yr, they will enable the newly constructed Dark Energy Spectroscopic Instrument (DESI) to measure the spectra of 35 million galaxies and quasars. DESI will produce the largest 3D map of the universe to date and measure the expansion history of the cosmos. In addition to the 5020 robotic positioners and optical fibers, DESI’s Focal Plane System includes six guide cameras, four wave front cameras, 123 fiducial point sources, and a metrology camera mounted at the primary mirror. The system also includes associated structural, thermal, and electrical systems. In all, it contains over 675,000 individual parts. We discuss the design, construction, quality control, and integration of all these components. We include a summary of the key requirements, the review and acceptance process, on-sky validations of requirements, and lessons learned for future multiobject, fiber-fed spectrographs.

Published
2022
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25. Constraining LLTB models with galaxy cluster counts from next generation surveys

Author

Sakr, Ziad, Carvalho, Ana, Da Silva, Antonio, Bellido, Juan Garcia, Mimoso, Jose P., Camarena, David, Nesseris, Savvas, Martins, Carlos J. A. P., Nunes, Nelson J., and Sapone, Domenico

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract

The Universe's assumed homogeneity and isotropy is known as the cosmological principle. It is one of the assumptions that lead to the Friedmann-Lema\^{\i}tre-Robertson-Walker (FLRW) metric and it is a cornerstone of modern cosmology, because the metric plays a crucial role into the determination of the cosmological observables. Thus, it is of paramount importance to question this principle and perform observational tests that may falsify this hypothesis. Here we explore the use of galaxy cluster counts as a probe of a large-scale inhomogeneity, which is a novel approach for the study of inhomogeneous models, and to determine the precision with which future galaxy cluster surveys will be able to test the cosmological principle. We present forecast constraints on the inhomogeneous Lema\^{\i}tre-Tolman-Bondi (LTB) model with a cosmological constant and cold dark matter, from a combination of simulated data according to a compilation of `Stage-IV' galaxy surveys following a methodology that involves the use of a mass function correction from numerical $N$-body simulations of an LTB cosmology. When considering the \lcdm fiducial model as a baseline for constructing our mock catalogs, we find that our combination of the forthcoming cluster surveys, will improve the constraints on the cosmological principle parameters as well on the FLRW parameters by about $50\%$ with respect to previous similar forecasts performed using geometrical and linear growth of structure probes, with $\pm20\%$ variations depending on the level of knowledge of systematic effects.These results indicate that galaxy cluster abundances are sensitive probes of inhomogeneity, and that next-generation galaxy cluster surveys, will thoroughly test homogeneity at cosmological scales, tightening the constraints on possible violations of the cosmological principle in the framework of $\Lambda$LTB scenarios. (Abridged), Comment: 9 pages, 5 figure, accepted as is and published in A&A journal after adding Fig. 1 for illustrative purposes

Published
2023

26. H2CN/H2NC abundance ratio: a new potential temperature tracer for the interstellar medium

Author

Andrés, David San, Colzi, Laura, Rivilla, Víctor M., de la Concepción, Juan García, Melosso, Mattia, Martín-Pintado, Jesús, Jiménez-Serra, Izaskun, Zeng, Shaoshan, Martín, Sergio, and Requena-Torres, Miguel A.

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The ${\rm H_2NC}$ radical is the high-energy metastable isomer of ${\rm H_2CN}$ radical, which has been recently detected for the first time in the interstellar medium towards a handful of cold galactic sources, besides a warm galaxy in front of the PKS 1830-211 quasar. These detections have shown that the ${\rm H_2CN}$/${\rm H_2NC}$ isomeric ratio, likewise the HCN/HNC ratio, might increase with the kinetic temperature ($T_{\rm kin}$), but the shortage of them in warm sources still prevents us to confirm this hypothesis and shed light about their chemistry. In this work, we present the first detection of ${\rm H_2CN}$ and ${\rm H_2NC}$ towards a warm galactic source, the G+0.693-0.027 molecular cloud (with $T_{\rm kin} > 70 \, {\rm K}$), using IRAM 30m observations. We have detected multiple hyperfine components of the $N_{K_\text{a}K_\text{c}} = 1_{01} - 0_{00}$ and $2_{02} - 1_{01}$ transitions. We derived molecular abundances with respect to ${\rm H_2}$ of (6.8$\pm$1.3)$\times 10^{-11}$ for ${\rm H_2CN}$ and of (3.1$\pm$0.7)$\times 10^{-11}$ for ${\rm H_2NC}$, and a ${\rm H_2CN}$/${\rm H_2NC}$ abundance ratio of 2.2$\pm$0.5. These detections confirm that the ${\rm H_2CN}$/${\rm H_2NC}$ ratio is $\gtrsim$2 for sources with $T_{\rm kin} > 70 \, {\rm K}$, larger than the $\sim$1 ratios previously found in colder cores ($T_{\rm kin}\sim10 \, {\rm K}$). This isomeric ratio dependence with temperature cannot be fully explained with the currently proposed gas-phase formation and destruction pathways. Grain surface reactions, including the ${\rm H_2NC} \rightarrow {\rm H_2CN}$ isomerization, deserve consideration to explain the higher isomeric ratios and ${\rm H_2CN}$ abundances observed in warm sources, where the molecules can be desorbed into the gas phase through thermal and/or shock-induced mechanisms., Comment: 12 pages, 5 figures, 3 tables, 2 appendix - Accepted for publication in Monthly Notices of the Royal Astronomical Society

Published
2023
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27. A sequential acid-base (SAB) mechanism in the interstellar medium: The emergence of cis formic acid in dark molecular clouds

Author

de la Concepción, Juan García, Jiménez-Serra, Izaskun, Corchado, José Carlos, Molpeceres, Germán, Martínez-Henares, Antonio, Rivilla, Victor M., Colzi, Laura, and Martín-Pintado, Jesús

Subjects
Astrophysics - Astrophysics of Galaxies, Physics - Chemical Physics
Abstract

The abundance ratios between isomers of a COM observed in the ISM provides valuable information about the chemistry and physics of the gas and eventually, the history of molecular clouds. In this context, the origin of an abundance of c-HCOOH acid of only 6% the isomer c-HCOOH abundance in cold cores, remains unknown. Herein, we explain the presence of c-HCOOH in dark molecular clouds through the destruction and back formation of c-HCOOH and t-HCOOH in a cyclic process that involves HCOOH and highly abundant molecules such as HCO+ and NH3. We use high-level ab initio methods to compute the potential energy profiles for the cyclic destruction/formation routes of c-HCOOH and t-HCOOH. Global rate constants and branching ratios were calculated based on the transition state theory and the master equation formalism under the typical conditions of the ISM. The destruction of HCOOH by reaction with HCO+ in the gas phase leads to three isomers of the cation HC(OH)2+. The most abundant cation can react in a second step with other abundant molecules of the ISM like NH3 to form back c-HCOOH and t-HCOOH. This mechanism explains the formation of c-HCOOH in dark molecular clouds. Considering this mechanism, the fraction of c-HCOOH with respect t-HCOOH is 25.7%. To explain the 6% reported by the observations we propose that further destruction mechanisms of the cations of HCOOH should be taken into account. The sequential acid-base (SAB) mechanism proposed in this work involves fast processes with very abundant molecules in the ISM. Thus, HCOOH very likely suffers our proposed transformations in the conditions of dark molecular clouds. This is a new approach in the framework of the isomerism of organic molecules in the ISM which has the potential to try to explain the ratio between isomers of organic molecules detected in the ISM.

Published
2023
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29. Molecular precursors of the RNA-world in space: new nitriles in the G+0.693-0.027 molecular cloud

Author

Rivilla, Víctor M., Jiménez-Serra, Izaskun, Martín-Pintado, Jesus, Colzi, Laura, Tercero, Belén, de Vicente, Pablo, Zeng, Shaoshan, Martín, Sergio, de la Concepción, Juan García, Bizzocchi, Luca, Melosso, Mattia, Rico-Villas, Fernando, and Requena-Torres, Miguel A.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Earth and Planetary Astrophysics
Abstract

Nitriles play a key role as molecular precursors in prebiotic experiments based on the RNA-world scenario for the origin of life. These chemical compounds could have been partially delivered to the young Earth from extraterrestrial objects, stressing the importance of establishing the reservoir of nitriles in the interstellar medium. We report here the detection towards the molecular cloud G+0.693-0.027 of several nitriles, including cyanic acid (HOCN), and three C$_4$H$_3$N isomers (cyanoallene, CH$_2$CCHCN; propargyl cyanide, HCCCH$_2$CN; and cyanopropyne (CH$_3$CCCN), and the tentative detections of cyanoformaldehyde (HCOCN), and glycolonitrile (HOCH$_2$CN). We have also performed the first interstellar search of cyanoacetaldehyde (HCOCH$_2$CN), which was not detected. Based on the derived molecular abundances of the different nitriles in G+0.693-0.027 and other interstellar sources, we have discussed their formation mechanisms in the ISM. We propose that the observed HOCN abundance in G+0.693-0.027 is mainly due to surface chemistry and subsequent shock-induced desorption, while HCOCN might be mainly formed through gas-phase chemistry. In the case of HOCH$_2$CN, several grain-surface routes from abundant precursors could produce it. The derived abundances of the three C$_4$H$_3$N isomers in G+0.693-0.027 are very similar, and also similar to those previously reported in the dark cold cloud TMC-1. This suggests that the three isomers are likely formed through gas-phase chemistry from common precursors, possibly unsaturated hydrocarbons (CH$_3$CCH and CH$_2$CCH$_2$) that react with the cyanide radical (CN). The rich nitrile feedstock found towards G+0.693-0.027 confirms that interstellar chemistry is able to synthesize in space molecular species that could drive the prebiotic chemistry of the RNA-world., Comment: Accepted in Frontiers in Astronomy and Space Sciences

Published
2022

30. Hydrogen abstraction reactions in formic and thioformic acid isomers by hydrogen and deuterium atoms. Insights on isomerism and deuteration

Author

Molpeceres, Germán, Jiménez-Serra, Izaskun, Oba, Yasuhiro, Nguyen, Thanh, Watanabe, Naoki, de la Concepción, Juan García, Maté, Belén, Oliveira, Ricardo, and Kästner, Johannes

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The isomerism of molecules in the interstellar medium and the mechanisms behind it are essential questions in the chemistry of organic molecules in space. In particular, for the simple formic and thioformic acids, the low temperatures found in molecular clouds indicate that cis-trans isomerization in the gas-phase must be impeded. Reactions happening on top of interstellar dust grains may explain the isomer interconversion at low temperatures. We studied the isomerization processes of formic and thioformic acid susceptible to happen on the surface of interstellar dust grains and initiated by H abstraction reactions. Similarly, deuterium enrichment of the acids can occur by the same mechanism. Our objective is to shed light on both topics to increase our understanding of key precursors of organic molecules in space., Comment: Accepted for publication in Astronomy and Astrophysics

Published
2022
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32. Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study

Author

Eugenia García Montemayor, Victoria, Salgueira Lazo, Mercedes, Mazuecos Blanca, Auxiliadora, Jiménez Salcedo, Tamara, José Espigares Huete, María, Araceli Jiménez Vibora, Elena, Álamo Caballero, Concepción, Banegas Deras, Eduardo J., Alonso Bethencourt, Alejandro, Rodríguez García, Alejandra, Fernández Granados, Saulo, Fernández Fresnedo, Gema, Calle García, Leonardo, Martín García, Jesús, Estifan Kasabji, Jorge, Jesús Izquierdo, María, Mouzo Mirco, Ricardo, García Agudo, Rebeca, de Arriba de la Fuente, Gabriel, Facundo Molas, Carme, Xipell Font, Marc, Yugueros González, Alejandra, Antóns, Paula, Ibernon Vilaro, Meritxell, de la Fuente Fernández, Vanessa, González Galván, Yussel, Cabezas, Antonio, Castro Alonso, Cristina, Juan García, Isabel, Garín Cascales, Eduardo, Sebastiá Morant, Josepa, Luna Complejo, Enrique, María Díaz Campillejo, Rosa, González Sanchidrián, Silvia, Cao Vilariño Complejo, Mercedes, Sierra Carpio, Milagros, Ortega Díaz, Mayra, Sánchez Hernández, Rosa, Ossorio González, Marta, Vega Martínez, Almudena, Teresa López Picasso, María, Goma, Elena, Giorgi, Martín, Martínez Miguel, Patricia, Gutiérrez Martínez, Eduardo, Paraíso Cuevas, Vicente, Echarri, Rocío, Martínez, Víctor, Pérez Arnedo, Mario, Juliana Castañeda Infante, Laura, Antonio Menacho Miguel, Jose, Blasco, Miquel, Quiroga, Borja, García-Aznar, José M., Castro-Alonso, Cristina, Fernández-Granados, Saulo J., Luna, Enrique, Ossorio, Marta, Izquierdo, María Jesús, Sanchez-Ospina, Didier, Castañeda-Infante, Laura, Mouzo, Ricardo, Cao, Mercedes, Besada-Cerecedo, María L., Pan-Lizcano, Ricardo, Torra, Roser, Ortiz, Alberto, and de Sequera, Patricia

Published
2024
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33. Precursors of the RNA-world in space: Detection of ($Z$)-1,2-ethenediol in the interstellar medium, a key intermediate in sugar formation

Author

Rivilla, Víctor M., Colzi, Laura, Jiménez-Serra, Izaskun, Martín-Pintado, Jesús, Megías, Andrés, Melosso, Mattia, Bizzocchi, Luca, López-Gallifa, Álvaro, Martínez-Henares, Antonio, Massalkhi, Sarah, Tercero, Belén, de Vicente, Pablo, Guillemin, Jean-Claude, de la Concepción, Juan García, Rico-Villas, Fernando, Zeng, Shaoshan, Martín, Sergio, Requena-Torres, Miguel A., Tonolo, Francesca, Alessandrini, Silvia, Dore, Luca, Barone, Vincenzo, and Puzzarini, Cristina

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Earth and Planetary Astrophysics, Physics - Chemical Physics
Abstract

We present the first detection of ($Z$)-1,2-ethenediol, (CHOH)$_2$, the enol form of glycolaldehyde, in the interstellar medium towards the G+0.693-0.027 molecular cloud located in the Galactic Center. We have derived a column density of (1.8$\pm$0.1)$\times$10$^{13}$ cm$^{-2}$, which translates into a molecular abundance with respect to molecular hydrogen of 1.3$\times$10$^{-10}$. The abundance ratio between glycolaldehyde and ($Z$)-1,2-ethenediol is $\sim$5.2. We discuss several viable formation routes through chemical reactions from precursors such as HCO, H$_2$CO, CHOH or CH$_2$CHOH. We also propose that this species might be an important precursor in the formation of glyceraldehyde (HOCH$_2$CHOHCHO) in the interstellar medium through combination with the hydroxymethylene (CHOH) radical., Comment: Accepted for publication in The Astrophysical Journal Letters

Published
2022
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34. Ionise hard: interstellar PO$^{+}$ detection

Author

Rivilla, Víctor M., de la Concepción, Juan García, Jiménez-Serra, Izaskun, Martín-Pintado, Jesús, Colzi, Laura, Tercero, Belén, Megías, Andrés, López-Gallifa, Álvaro, Martínez-Henares, Antonio, Massalkhi, Sara, Martín, Sergio, Zeng, Shaoshan, De Vicente, Pablo, Rico-Villas, Fernando, Requena-Torres, Miguel A., and Cosentino, Giuliana

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Earth and Planetary Astrophysics
Abstract

We report the first detection of the phosphorus monoxide ion (PO$^{+}$) in the interstellar medium. Our unbiased and very sensitive spectral survey towards the G+0.693$-$0.027 molecular cloud covers four different rotational transitions of this molecule, two of which ($J$=1$-$0 and $J$=2$-$1) appear free of contamination from other species. The fit performed, assuming Local Thermodynamic Equilibrium conditions, yields a column density of $N$=(6.0$\pm$0.7)$\times$10$^{11}$ cm$^{-2}$. The resulting molecular abundance with respect to molecular hydrogen is 4.5$\times$10$^{-12}$. The column density of PO$^{+}$ normalised by the cosmic abundance of P is larger than those of NO$^{+}$ and SO$^{+}$, normalised by N and S, by factors of 3.6 and 2.3, respectively. The $N$(PO$^{+}$)/$N$(PO) ratio is 0.12$\pm$0.03, more than one order of magnitude higher than those of $N$(SO$^{+}$)/$N$(SO) and $N$(NO$^{+}$)/$N$(NO). These results indicate that P is more efficiently ionised in the ISM than N and S. We have performed new chemical models that confirm that the PO$^+$ abundance is strongly enhanced in shocked regions with high values of cosmic-ray ionisation rates (10$^{-15}-$10$^{-14}$ s$^{-1}$), as occurs in the G+0.693$-$0.027 molecular cloud. The shocks sputter the interstellar icy grain mantles, releasing into the gas phase most of their P content, mainly in the form of PH$_3$, which is converted into atomic P, and then ionised efficiently by cosmic rays, forming P$^+$. Further reactions with O$_2$ and OH produce PO$^{+}$. The cosmic-ray ionisation of PO might also contribute significantly, which would explain the high $N$(PO$^{+}$)/$N$(PO) observed. The relatively high gas-phase abundance of PO$^{+}$ with respect to other P-bearing species stresses the relevance of this species in the interstellar chemistry of P., Comment: Accepted in Frontiers in Astronomy and Space Sciences

Published
2022

35. Impact of species hybridization on the clinical management of schistosomiasis: A prospective study

Author

Salas-Coronas, Joaquín, Bargues, M. Dolores, Fernández-Soto, Pedro, Soriano-Pérez, Manuel J., Artigas, Patricio, Vázquez-Villegas, José, Villarejo-Ordoñez, Antonio, Sánchez-Sánchez, José C., Cabeza-Barrera, María I., Febrer-Sendra, Begoña, De Elías-Escribano, Alejandra, Crego-Vicente, Beatriz, Fantozzi, María C., Diego, Juan García-Bernalt, Castillo-Fernández, Nerea, Borrego-Jiménez, Jaime, Muro, Antonio, and Luzón-García, María P.

Published
2024
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46. Revision of the Most Harmful Organic Compounds Present in Sewage and Sludge

Author

Jiménez, Javier Canas, Rodríguez, Juan García, Mendioroz, Blanca Hermana, Ismael Águeda Maté, V., Álvarez-Torrellas, Silvia, Barceló, Damià, Series Editor, de Boer, Jacob, Editorial Board Member, Kostianoy, Andrey G., Series Editor, Garrigues, Philippe, Editorial Board Member, Hutzinger, Otto, Founding Editor, Gu, Ji-Dong, Editorial Board Member, Jones, Kevin C., Editorial Board Member, Knepper, Thomas P., Editorial Board Member, Negm, Abdelazim M., Editorial Board Member, Newton, Alice, Editorial Board Member, Nghiem, Duc Long, Editorial Board Member, Garcia-Segura, Sergi, Editorial Board Member, Núñez-Delgado, Avelino, editor, and Arias-Estévez, Manuel, editor

Published
2023
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