Articles de revues sur le sujet « Laboratorio Nicola »

Nicolle (Jean-Marie), Le laboratoire mathématique de Nicolas de Cues. – Paris : Éditions Beauchesne, 2020. – 226 p. – (Le grenier à sel). – 1 vol. broché de 13,5 × 21,5 cm. – 19,00 €. – isbn 978-2-7010-2274-1.

Introducción: El síndrome de Nicolau también conocido como Embolia cutis medicamentosa o Dermatitis livedoide, es una patología infrecuente que se presenta como complicación de una inyección intramuscular, intraarterial o subcutánea, con grados variables de lesión tisular, incluyendo necrosis de la piel y tejidos blandos. La fisiopatogénia se desconoce, pero se cree que está relacionada a una lesión vascular inicial, con inflamación local, vasoconstricción arterial refleja, trombosis arterial local y oclusión vascular por microémbolos. El tratamiento consiste en la trombólisis y desinflamación. Con menor frecuencia las complicaciones podrían ser necrosis extensas, amputaciones e incluso la muerte. Objetivo: Describir un caso clínico enfocado en el síndrome de Nicolau, una patología infrecuente tras la administración de penicilina benzatínica. Material y métodos: Estudio descriptivo, retrospectivo, presentación de un caso clínico. Resultados: Se describe el caso clínico de un paciente masculino de 32 años de edad, sin antecedentes patológicos, acude por dolor intenso en glúteo derecho con limitación total al movimiento, de 24 horas de evolución, teniendo como causa aparente la autoadministación de penicilina benzatínica. Exploración física, en región glútea derecha se observa una placa violácea dolorosa a la palpación, miembro inferior derecho con ausencia de tono y arrefléctico. Pulso femoral y poplíteo disminuido, pedio ausente, con acrocianosis derecha. Laboratorio, leucocitos 24.470, dímero D 4292, LDH 837, CPK 1282, prueba rápida de COVID-19 negativa. Eco doppler de miembro inferior derecho con disminución del flujo sanguíneo. Tratamiento fibrinolítico y de soporte inmediato con evolución favorable. Luego de la valoración del paciente, se determinó un diagnóstico definitivo y su tratamiento médico inmediato, logrando evitar posteriores complicaciones. Como impresión diagnostica inicial se sospechó lesión inespecífica del nervio ciático. Al ser una patología poco frecuente, el diagnóstico final se llevó a cabo tras un análisis detallado del caso y exámenes complementarios. Conclusiones: El Síndrome de Nicolau es una patología poco frecuente, se necesitan exámenes de laboratorio e imagen para su diagnóstico definitivo. Puede presentarse tras la administración inadecuada de un medicamento de uso cotidiano, como la penicilina benzatínica

By the research and development (R&D) method designed by Nicolas Guichon (2007)), this scientific paper lists and describes the features of the free WhatsApp Messenger apps version 2.20.193.9 (released by WhatsApp Inc.) which is then analyzed using the theory of a language laboratory system made by Alfred S. Hayes for later analysis results are used to develop a virtual language laboratory manual. The purpose of this paper is to find out the features of the Whatsapp Messenger version 2.20.193.9 application that can be used for virtual language laboratories and also to develop its manual. Based on the results of the analysis that the author has done, the features that can be used for virtual language laboratories are the chat group, message, voice message, voice call, voice-video call, document delivery (voice document, video, text). The results of this study will be used for the development of the virtual language laboratories manual and are also expected to a topic of discussion among researchers and practitioners in the field of foreign language education and teaching.

Claude Roillet, professeur de lettres aux collèges de Bourgogne et de Boncourt, fit paraître en 1556 le recueil de ses oeuvres de poète et de dramaturge sous le titre Varia Poemata (Paris: Guillaume Julien). Cette collection contient notamment quatre tragédies latines, intitulées Philanira, Petrus, Aman et Catharina. De ces quatre pièces, seule la première, Philanira, devait faire l’objet d’une traduction française publiée en 1563 aux presses parisiennes de Richard Thomas, puis rééditée, toujours à Paris, chez Nicolas Bonfons en 1577. La présente étude examinera les détails de cette version française quant à (1) l’adaptation en vernaculaire des formes métriques latines variées dont use l’auteur et (2) l’équivalence des formulations lexicales, voire les stratégies d’imitation, dans un texte français qui fait preuve d’une tendance à l’amplification à partir de la composition latine originelle. In 1556, Claude Roillet, a literature professor at the Collège de Bourgogne and Collège de Boncourt, published a collection of his works as a poet and dramatist under the title Varia Poemata (Paris: Guillaume Julien). This collection notably contained four Latin tragedies, which were titled Philanira, Petrus, Aman, and Catharina. Of these four works, only the first, Philanira would become the subject of a French translation published in 1563 by the Parisian press of Richard Thomas, then republished—again in Paris—by Nicolas Bonfons in 1577. This paper will examine the particulars of this French version in terms of (1) the conversion into the vernacular of the various Latin metrical forms that the author uses and (2) the equivalency of lexical expressions, and even the strategies of imitation, in a French text that demonstrates a tendency to amplify the original Latin composition.

RésumésL’ouvrage collectif Le laboratoire des sciences sociales. Histoires d’enquêtes et revisites, coordonné par Gilles Laferté, Paul Pasquali et Nicolas Renahy, prend certaines grandes enquêtes de sciences sociales à la fois comme objets et expériences collectives à historiciser (« histoire d’enquêtes ») et comme matériaux pour de nouvelles recherches (« revisites ») ; il aborde ce faisant de manière empirique et originale, la question des archives produites par les sciences sociales et de leurs usages. À la différence des sources mobilisées par les historiens, qui consistent en des corpus clos, produits de différentes stratégies archivistiques et mémorielles, celles des contributeurs du Laboratoire des sciences sociales ont un statut plus ambigu du fait du raccourcissement temporel entre le moment de la production de l’enquête et celui de son histoire et de sa revisite, dont les effets doivent être analysés. Véritable laboratoire réflexif au carré, l’ouvrage plaide pour une réflexivité historienne comme pratique ordinaire et permet de reconsidérer un certain nombre de problèmes sous un nouveau jour. En s’interrogeant sur la distinction entre documents et archives, sur la nature cumulative du savoir archivé des sciences sociales et sur la différence entre les archives des enquêtes de sciences sociales et celles d’autres formes d’enquête pratiquées au cours du temps, cette note critique invite à la mise à l’épreuve du projet réflexif et historiciste qui se trouve au cœur de la redéfinition de la place des archives dans le travail historique.

El objetivo de este estudio fue evaluar los desoves espontáneos de la primera generación de corvina aguada (Cynoscion squamipinnis) criada en cautiverio con el fin de realizar programas de repoblamiento y proyectos de maricultura. Los juveniles obtenidos de desoves espontáneos de peces silvestres capturados en el Golfo de Nicoya fueron criados en el Laboratorio de Reproducción y Cultivo de Peces Marinos de la Estación de Biología Marina, Universidad Nacional, Puntarenas, Costa Rica. Los peces se mantuvieron en tanques de 18 t, con recambio de agua (100% diario), temperatura de 26.73 ± 1.15°C, salinidad de 32.60 ± 2.69 UPS y oxígeno disuelto de 6.20 ± 0.61 mg/L. Cada dos meses las corvinas fueron anestesiadas y examinadas para determinar su madurez sexual. En enero del año 2011, se comprobó mediante biopsias ováricas que una de las hembras estaba madura y se observaron ovocitos de 0.4-0.6 mm de diámetro, y mediante masaje abdominal se obtuvo semen fluido de los machos. En marzo del año 2011 comenzó un periodo de desoves espontáneos, sin realizar ningún estímulo ambiental u hormonal. En total se registraron 34 desoves de marzo a octubre del año 2011, obteniéndose un promedio de 85 996 huevos, con un máximo de 461 000 huevos y un mínimo de 4 500 huevos. El porcentaje de fertilización fue de 10-80%, con un promedio de 53.09 ± 26.97%. No se encontraron correlaciones significativas entre los desoves y las variables ambientales de la temperatura, la salinidad, el oxígeno disuelto, las mareas, las fases lunares y la precipitación.

Benedetta Castiglioni, Paesaggio e società. Una prospettiva geografica (Davide Papotti) – Giulio Iacoli, Davide Papotti, Giada Peterle, Lucia Quaquarelli (a cura di), Culture della mobilità: immaginazioni, rotture, riappropriazioni del movimento (Marcello Tanca) – Martina Tazzioli, Border Abolitionism: Migrants' Containment and the Genealogies of Struggles and Rescue (Lorenzo Mauloni) – Lorenza Pignatti, Cartografie radicali. Attivismo, esplorazioni artistiche, geofiction (Niccolò Cuppini) – Paola Minoia, Salla Jokela, Platform-Mediated Tourism. Social Justice and Urban Governance before and during Covid-19 (Barbara Brollo) – Alessandro Barile, Barbara Brollo, Sarah Gainsforth, Rossella Marchini, Dopo la gentrification. Un quartiere laboratorio dalla crisi economica all'abitare temporaneo (Samantha Cenere) – Marika Fior, Agim Kërçuku, Cristiana Mattioli, Gloria Pessina (a cura di), Fragilità nei territori della produzione (Daria Quatrida)

Abstract Context.—The investigation of high-profile fatalities poses special challenges to medical examiners and coroners. Most high-profile cases can be readily recognized early in the course of the investigation. Commonly encountered examples include police-related fatalities or deaths in custody, deaths of celebrities, and mass fatalities or clustered deaths (eg, serial killers). Medical examiner and coroner offices should have policies and procedures in place for adequately handling such cases. A rational approach to these high-profile cases includes activating medical examiner or coroner investigative teams, preplanning before the autopsy, using special autopsy techniques and toxicology procedures, skillful questioning of key witnesses, preparing detailed and comprehensive reports, and planning effective communication with the media. Objective.—The investigation of the sudden and unexpected death of Anna Nicole Smith, an entertainment personality, is presented as an example of how to address the challenging issues inherent in high-profile fatalities and how to adequately prepare for the forensic investigation of high-profile cases. Design.—This article presents a methodical approach to the investigation of high-profile deaths. Results.—A comprehensive, preplanned forensic investigation and autopsy (including use of adjunctive studies) following the death of Anna Nicole Smith resulted in the accurate determination of the cause and manner of her death while adequately convincing the public of the objectivity and reliability of the Medical Examiners Office with respect to its conclusions. Conclusion.—The forensic investigation of death in high-profile cases can be much more tedious and demanding than the investigation of routine cases. It requires more stringent safekeeping of the body and its evidence, more extensive and sophisticated dissection techniques on occasion, and exhaustive toxicologic analysis to exclude low-probability allegations. Procedures for honest, unbiased, and judicious communication with outside agencies and the media must be followed. Failure to follow such procedures might have serious consequences for the medical examiner, the family of the deceased, and the community at large. Adherence to these suggested guidelines may resolve most of the intricate problems involved in the investigation of these types of cases.

Se definieron las dosis más eficientes de aceite de eugenol Syzygium aromaticum para la sedación quirúrgica en juveniles de pargo manchado (Lutjanus guttatus) y se determinó el tiempo mínimo de exposición de no retorno, como una fuente de información para contar con un rango de tiempo seguro en la manipulación del pez durante labores de rutina. En el Laboratorio de Acuicultura y Biotecnología Marina del Parque Marino del Pacífico en el Golfo de Nicoya, se seleccionaron 76 juveniles de pargo manchado, producidos en enero del 2016, con un peso promedio 21.61± 2.0 g. Los juveniles fueron expuestos a concentraciones de eugenol 25, 100, 175 y 250 mg/L en tanques de 30 L, se vigiló los estados de inducción a la anestesia y su recuperación. Definida la dosis más eficiente, se procedió con ella a determinar el tiempo máximo de exposición; para este estudio se definieron cuatro tiempos de inducción en 4, 8, 12 y 16 min., y se establecieron 10 min., como umbral de recuperación. Se determinó que el eugenol es eficaz para la anestesia de juveniles de pargo con temperaturas entre 24.0 y 24.8°C. La concentración de 25 mg/L fue suficiente para la inducción parcial de los peces, apropiado para realizar actividades rutinarias menos complejas en el manejo de pargos, mientras que la concentración más eficiente fue de 100 mg/L, en tiempos de exposición no mayor a 8 minutos luego de la anestesia total.

AbstractWe would like to draw our readers‘ attention to the following three joint publications in this issue:· HAHN and SCHAUB (page 100)· ROEMER et al. (page 117)· INTORP et al. (page 139)The three papers are based on an initiative of the German regulative authorities who requested and initiated a research project to get more information concerning the influence of tobacco additives on the composition of cigarette mainstream smoke. Since up to now, most of the peer reviewed publications on the effects of additives originate from scientists based in the tobacco industry, in this case an independent regulative laboratory (Chemical and Veterinary Surveillance Agency Sigmaringen) was asked to evaluate the effects of the tobacco additives sucrose, cocoa powder and glycerol on the amounts of several selected compounds in cigarette mainstream smoke. The test cigarettes for these evaluations were manufactured in the pilot plant of BAT Germany and are described and characterized by HAHN and SCHAUB. This paper also contains the results of the regulatory laboratory on the effects of the three additives on mainstream smoke composition.The influence of these additives on cigarette mainstream smoke was also evaluated by ROEMER et al. and INTORP et al. using the identical test cigarettes as studied by HAHN and SCHAUB. While INTORP et al. in their three laboratory study analyzed the same mainstream smoke component as HAHN and SCHAUB, ROEMER et al. studied the effects of these tobacco ingredients on the levels of 39 different components in mainstream smoke of the test cigarettes and also on different endpoints of some selected toxicological in vitro assays. The chemical analytical work necessary for this evaluation was done by Labstat International, an independent contract laboratory; the in vitro tests were done by the Philip Morris Research Laboratories, Cologne, Germany. The results obtained by the participating laboratories showed no overall significant effects of the tested additives on the levels of the selected smoke constituents and the biological activity.Finally, we would like to inform our readers that Nicolas Baskevitch has decided to retire from the advisory board, being a member since 2006. We would like to thank him for his collaboration in improving the manuscripts submitted to the Journal.

Abstract This study investigates a custom 2Mb xGen Hyb panel designed against mutated gene targets implicated in several cancers using an end-to-end assay workflow on the Biomek NGeniuS platform. Automation in laboratories is advantageous to generate reproducible next generation sequencing (NGS) sample libraries, however, assay automation differs from instrument vendor to vendor but also from lab to lab with different deck layouts of the same instrument. These differences require a significant amount of optimization to design the workflow and begin generating NGS libraries. In addition to this optimization, some research, e.g., cancer research utilizes low input and/or degraded samples such as cfDNA from plasma or FFPE biopsies. Integrated DNA Technologies (IDT) and Beckman Coulter - Life Sciences together provide a walk away NGS automation solution for these research samples directly upon instrument installation with no optimization required by combining Beckman Coulter’s Biomek NGeniuS with IDT’s xGen cfDNA & FFPE DNA Library Prep kit and xGen Hybridization Capture. This trio provides a solution for laboratories to minimize technician hands-on time, error reduction, and rework while improving flexibility. IDT’s xGen cfDNA & FFPE DNA Library Prep kit utilizes novel chemistry to maximize sample input conversion, suppress adapter-dimer formation, and facilitate consensus analysis. IDT’s xGen Hybridization Capture products maintain high library diversity, obtain high on-target, and provide consistent and uniform sequencing coverage regardless of panel size. We demonstrate performance of this complete workflow with a custom 2Mb xGen Hyb panel yielding high library complexity, high on-target coverage, and capture uniformity. The combination of IDT’s xGen library preparation solutions on the NGeniuS Biomek platform provides a reliable and consistent solution that can be instantly downloaded from the portal straight to analysis of precious low input and degraded samples. Citation Format: Nicole Roseman, Laura Tucker, Francesco Criscuolo, Lynette Lewis, Li Liu, Tyler Buit, Jasmeen Mandair, Zachary Smith, Calvin Cortes. Automating next generation sequencing workflows for custom hyb panels: high quality library preparation and target enrichment on the Biomek NGeniuS System [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 263.

L’épigénétique concerne des variations d’accès au génome et de la régulation de son expression qui peuvent être induites par des facteurs environnementaux. Etant donnés que leur retentissement peut être comportementale, et que ce comportement chez le rongeur peut modifier les interactions inter-générationelles (condition d’élevage), des modifications épigénétiques peuvent être transmises d’une génération à l’autre, et donc mimer des effets plus directement génétiques (Meany et al., 2005). L’épigénétique fournit donc une hypothèse séduisante faisant le lien entre, d’une part, des facteurs de risque environnementaux (maltraitance infantile, qualité des interactions précoces…) et l’existence d’une héritabilité forte (entre 60 et 90 % pour schizophrénie, trouble bipolaire et autisme par exemple). Néanmoins, avant tout raccourci trop rapide et donc inapproprié, il est important pour tout psychiatre de comprendre ce dont il est question, au niveau technique comme au niveau théorique. Dans la lignée du symposium « le baclofène pour les nuls », nous proposons de faire un point compréhensible pour les non initiés, informatif pour les cliniciens, et utile pour tous ceux qui gèrent des patients ayant une maladie mentale (et leur entourage) qui peuvent interroger leur médecin sur les mécanismes de leur pathologie. Nicolas Ramoz, neurogénéticien travaillant dans un laboratoire Inserm dévolu aux troubles psychiatriques, fera un exposé didactique mais complet sur l’état des connaissances de l’approche épigénétique concernant la maladie mentale, afin que tout psychiatre puisse entendre (et répondre) à toute question concernant ce nouveau domaine de connaissance. Dans ce registre, un lexique sera donné, des exemples de travaux récents seront détaillés et l’importance de l’approche de l’épigénétique en psychiatrie sera critiquée.

Abstract Background CF acute pulmonary exacerbations are often caused by PSA, including multi-drug resistant strains. Optimal antibiotic therapy is required to return lung function and should be guided by in vitro susceptibility results. There are sparse data on the performance of Etest relative to reference broth microdilution (BMD) for many newer drugs against CF PSA. Herein, we describe Etest performance with 10 anti-PSA antibiotics against CF isolates. Methods Contemporary, clinical PSA (n=105) isolated during pulmonary exacerbation from patients with CF were acquired from 3 US hospitals. MICs were assessed by BMD (reference) and Etest for aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ceftazidime/avibactam (CZA), ceftolozane/tazobactam (C/T), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Each respective MIC was completed in at least triplicate using the same inoculum between methods. Modal MICs for each method were compared by rates of essential agreement (EA), categorical agreement (CA), minor error (miE), major error (ME), and very major error (VME) rates. All miE, ME and VME were adjusted if within EA. Results Of the 105 PSA, 46% had a mucoid phenotype. Results are summarized in the Table. Median modal Etest MICs read 0–1 dilution higher (IQR: 0–1) than BMD. CA and EA ranged from 64–93% and 63–86%, respectively. Single VMEs occurred for ATM (2.9%) and CAZ (4.2%). For CZA, 2 VMEs were observed and both were within EA. Major errors were ≤3% except for ATM (3.3%), MEM (3.3%), CZA (5.3% with adjusted ME 2.1%*), and FEP (13%). Minor error rates were < 10% except for TZP, CIP, LEV, TOB, and FEP (13–29%), for which majority of miE were within EA (3/14, 11/16, 10/18, 13/19, 20/31, respectively). Performance was similar for non-mucoid and mucoid populations. Etest Performance Conclusion Etest methods performed well for most antibiotics against this challenging collection of PSA from CF patients. Laboratories should be cautious of miE and ME that may occur with certain antibiotics. Furthermore, our observations suggest laboratories confirm CZA results for isolates with MICs near the breakpoint. Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials)) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)

Abstract Introduction: While the FDA has approved over 20 targeted therapies for non-small cell lung cancer (NSCLC), less than half of patients in the US undergo comprehensive biomarker testing to determine if they would benefit from these agents. This gap in testing is compounded in ex-US and minority populations. There are multiple barriers to access for biomarker testing, many of which stem from the complexity and high costs of current solutions, which limit testing to large, centralized laboratories. Alongside this, tissue requirements are high, turnaround times (TAT) for results typically take weeks, and reimbursement is uncertain. We demonstrate how ASPYRE can address these limitations by enabling ultra-sensitive biomarker testing using existing staff and widely available instrumentation. The technology is based on four enzyme steps (Silva et al 2020), the last of which is monitored on a real-time PCR instrument. ASPYRE-Lung targets 111 markers in 11 genes, including 77 DNA variants (substitutions and indels), and 34 RNA variants (fusions and exon skipping) across 24 wells, with a TAT of less than <4 hours from extracted nucleic acids to result. Experimental procedures: Four test sites were provided with ASPYRE reagents and contrived samples including Seracare ctDNA Mutation Mix v2 and a panel consisting of synthetic RNA oligonucleotides diluted in a background of normal lung RNA. The Seracare sample included variants in BRAF, EGFR, ERBB2, and KRAS at 0.25% variant allele fraction. The RNA sample included fusions in RET, ROS1 and NTRK1, with each fusion present at a mean of 6 copies in a background of 1 ng lung RNA. Operators from a range of educational backgrounds were provided a set of written Instructions for Use, with no additional training. Summary of data: The ASPYRE-Lung test was set up and performed at each test laboratory in as little as one day, using their existing real-time PCR instrument. The results demonstrated detection of the expected variants with consistent performance characteristics across the test sites and between users. Importantly, the sensitivity of detection was in line with, or superior to, the current gold standard. Conclusions: Biofidelity’s breakthrough ASPYRE technology enables a dramatic simplification of workflows, and the ultra-sensitive detection of actionable biomarkers using existing real-time PCR instruments. This work has demonstrated the ease with which independent laboratories can implement comprehensive multi-gene assays based on ASPYRE technology, utilizing their existing staff and infrastructure. This stands in stark contrast to alternative solutions, which typically require substantial investments in new instrumentation, skilled staff, IT infrastructure and bioinformatics. Taken together, ASPYRE promises to remove key barriers in cancer biomarker testing, enabling all patients to access the right treatment at the right time. Citation Format: Paulina Powalowska, Nicola Potts, Brandon A. Smith, Kala F. Schilter, Honey V. Reddi, Lan Beppu, Jerald Radich, Charles Massie, Quentin Vicentini, Tom Brown, Robert Osborne, Barnaby Balmforth. External user testing of Biofidelity’s ASPYRE-Lung assay demonstrates breakthrough capabilities and ease of use [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4105.

Abstract While there is no shortage of approved targeted therapeutics to address driver mutations in NSCLC, many patients are not tested for these alterations due to gaps in biomarker testing access. Challenges in NSCLC molecular testing include the need for assessment of multiple variants in both DNA and RNA, samples are often small specimens, cost, and clinical need for rapid turn-around time when patients are deteriorating and require timely treatment initiation. ASPYRE-Lung detects a targeted panel of 114 actionable genomic variants across 11 genes, covering NCCN treatment guideline-recommended biomarkers for samples that are associated with NSCLC. The assay simultaneously analyzes DNA and RNA with inputs of only 20 ng and 6 ng respectively. ASPYRE-Lung is easily adoptable by standard clinical laboratories, requiring only PCR and qPCR thermocyclers, with no specialist bioinformatics skills required for analysis and a run time of 2 days from specimen to result. We established the assay at two external sites and Biofidelity laboratories, with multiple operators at each site. We first determined that the assay had acceptable performance at each site, using a panel of contrived control samples. We then examined 56 matched DNA and RNA samples extracted from clinical FFPE lung tissue specimens. We also tested 29 unmatched samples derived from FFPE tissue (13), fine needle aspirate (FNA, 4), FNA rinse (5), peritoneal fluid (1), pleural effusion (1), pleural fluid (1) and fresh tissue (4), at all 3 sites. Data were analyzed using a simple cloud-based turnkey analysis solution. All samples yielded valid results across all runs. We assessed reproducibility (inter-run precision) using all 85 clinical samples, across new and experienced users, achieving a positive percent agreement (PPA) of 100% and negative percent agreement (NPA) of 99.99%. We then assessed concordance with NGS results, investigating any discrepancies. The 69 FFPE tissue-derived samples (56 matched DNA/RNA, 7 unmatched DNA, and 6 TNA) had PPA 96.55% and NPA 99.98%. The 16 cytopathology-derived samples had PPA 100% and NPA 99.96%. Together, these results demonstrate high concordance of ASPYRE-Lung and NGS across different types of clinical samples, alongside ease of adoption of the ASPYRE-Lung assay with simple training and no specialist expertise required. ASPYRE-Lung promises to enable all patients with NSCLC to start appropriate treatment in a cost-effective and timely manner. Citation Format: Sarah E. Herlihy, Caren Gentile, Samantha J. Scott, Brandon A. Smith, Kathryn A. Stoll, Kala F. Schilter, Justyna Mordaka, Rebecca Palmer, Christina Xyrafaki, Elizabeth Gillon-Zhang, Candace King, Ryan Evans, Amanda Green, Ana-Luisa Silva, Magdalena Stolarek-Januszkiewicz, Kristine von Bargen, Iyelola Turner, Chau Ha Ho, Alejandra Collazos, Nicola Potts, Dilyara Nugent, Jinsy Jose, Eleanor Gray, Elyse Shapiro, Wendy J. Levin, Aishling Cooke, Barnaby Balmforth, Robert Osborne, Honey V. Reddi, Vivianna M. Van Deerlin. Deployment of ASPYRE-Lung targeted variant panel across three sites and testing with FFPE tissue and cytology-derived nucleic acid samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5164.

Stone is turned into meat. This spectacular project entitled “Prometheus delivered” is an installation that Thomas Feuerstein stages as a fascinating laboratory of bubbling bioreactors, mysterious fluids, pumps and endless tubes which wind around a classicist marble sculpture of Prometheus and meander through the entire exhibition. It is the first major solo exhibition of the Austrian artist in Munich. At the center of the installation is a sculpture, a replica of the Prometheus statue by Nicolas-Sébastien Adam (1762), and features its gradual decomposition. The miraculous protagonists of this process of metabolism are stone-eating (chemolithoautotrophic) bacteria. They convert the marble into plaster and, in a further complex transformation, they themselves become the food of human liver cells. The cycle of destruction and re-creation inherent in the Prometheus myth is replicated in a biochemical process. Zeus chained Prometheus to a rock in the Caucasus as punishment for bringing fire to people and thus technology. An eagle rips his liver out of his body – but every night it grows back again. The final result of Thomas Feuerstein's “Prometheus delivered” is – by analogy to the myth – a bioreactor in which human hepatocytes grow and finally form a new three- dimensional liver sculpture. As in antiquity, the liver becomes the organ and a medium that looks into the future because Feuerstein’s installation gives us a glimpse into a time to come in which human beings no longer subsist on animals and plants, but possibly on their own body cells. The exhibition presents this narrative using drawings and objects, sets them to music that also incorporates a radio play, and performs them by means of biochemical processes. In addition to focusing on sound scientific facts, the show is also a science fiction story and a splatter movie on the brink of horror. Resumen La Piedra se convierte en carne. Este espectacular proyecto titulado “Prometeo liberado” es una obra que Thomas Feuerstein plantea como un laboratorio fascinante de biorreactores burbujeantes, fluidos misteriosos, surtidores y tubos sin fin que envuelven una escultura clásica de mármol de Prometeo y que serpentean por toda la exposición. Es la primera gran exposición en solitario del artista austríaco en Múnich. En el centro de la obra hay una escultura, una réplica de la estatua de Prometeo de Nicolas-Sébastien Adam (1762), y presenta su descomposición gradual. Los protagonistas milagrosos de este proceso son bacterias comedoras de piedra (quimiolitoautotróficas). Convierten el mármol en escayola y, en una transformación más compleja, ellas mismas se convierten en el alimento de células del hígado humano. El ciclo de destrucción y re-creación inherente al mito de Prometeo se replica en un proceso bioquímico. Zeus encadenó a Prometeo a una roca en el Cáucaso como castigo por llevar el fuego al hombre, y así, la tecnología. Un águila le arranca el hígado del cuerpo—pero cada noche vuelve a crecer. El resultado final del “Prometeo Liberado” de Thomas Feuerstein es—análogo al mito—un biorreactor en el que los hepatocitos humanos crecen y finalmente forman una nueva escultura tridimensional del hígado. Como en la antigüedad, el hígado se convierte en el órgano y en un medio que mira hacia el futuro porque la obra de Feuerstein nos permite ojear un tiempo venidero en el que los seres humanos ya no viven de animales y plantas, sino posiblemente de sus propias células. La exposición presenta esta narrativa usando dibujos y objetos, usa música que también incorpora una obra radiofónica, y los pone en funcionamiento mediante procesos bioquímicos. Además de centrarse en hechos científicos sobre el sonido, el espectáculo también es una historia de ciencia ficción y una película con salpicaduras al borde del terror.

Abstract Abstract 1619 Poster Board I-645 Background Quantitative PCR (qPCR) for fusion transcripts and overexpressed genes is a promising tool for following minimal residual disease (MRD) and detecting early relapse in patients with acute leukemia, and for identifying treatment failure in patients with chronic myeloid leukemia (CML). Its widespread use has, however, to some extent been hampered by differences in data analysis and in presentation. These issues constitute major challenges in the translation of these thoroughly pre-clinically validated assays into multicenter clinical trials. To address these problems we have designed an MRD reporting software package, in which data from the qPCR equipment can be imported, processed, and presented in a standardized fashion to generate a readily comprehensible report. Software The software builds upon a database with basic patient information and data imported from qPCR runs. The software is highly flexible, and data from a variety of qPCR platforms can be accommodated (Figure 1) when exported from the equipment as tab- or comma-separated files. MRD calculations may be based on both “relative” quantification, i.e. where a diagnostic sample or a cell line is used as reference, as well as “absolute” quantification, where plasmid standards are included as controls (Figure 2). Moreover, while a series of premade report types are available, individualized report generation is also possible. Report types include graphs detailing blood and bone marrow MRD either separately or simultaneously. Moreover, two or three target genes can be displayed within the same graph. QC Study To validate the software and provide proof of principle for applicability in multicenter studies we performed a quality control study involving analysis and reporting of multiple blinded leukemic samples by 8 laboratories. cDNA samples representing five consecutive samples from the same CML patient (BCR/ABL+), five from the same AML patient (MYH11/CBFá+, WT1+), as well as a K562 cell line sample were centrally prepared by the Aarhus laboratory. Samples were distributed to the test laboratories together with primer/probe kits from Ipsogen (Ipsogen, Marseilles, France) for the three target genes and the ABL control gene. Each laboratory performed qPCR using their in-house qPCR equipment (including ABI7500, ABI7900 (Applied Biosystems), Mx3000P (Stratagene), or LightCycler 480 (Roche)) and submitted 16 different reports as pdf files for comparison. The reports included relative quantification using the diagnostic sample as reference, relative quantification using cell line as reference, absolute quantification using plasmid standard curves, and lists of calculated MRD values and sensitivities. Excellent concordance in the quality of the reports was observed for all report types. Perspectives This software package, which has been distributed to members of the ELN MRD Workpackage, will shortly be made more widely available. The validation procedures outlined above should make this package suitable for general use in translational hematology allowing standardized reporting of MRD results (e.g. use of International Scale in CML trials) and facilitating comparison of results obtained between trial groups. Acknowledgment We thank Nicolas Maroc from Ipsogen for providing reagents for the QC Study and Karin Braendstrup and Lone Siig Mikkelsen for excellent technical assistance. Disclosures Grimwade: Ipsogen, Marseille, France: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: Systemic chemotherapy is used commonly in breast cancer and is associated with lymphopenia, potentially limiting efficacy of immune checkpoint blockade. The androgen receptor (AR) serves as a negative regulator of thymic function. AR antagonists, such as bicalutamide, may stimulate thymic production of naïve T-cells, which may help to restore lymphocyte diversity and augment immunotherapy response. The AR is expressed in 50% of hormone receptor negative (HR-) metastatic breast cancer (MBC) and >75% of HR+ MBC, and bicalutamide is clinically active with stable disease as best response. We hypothesize that bicalutamide could be combined with dual immune checkpoint blockade (anti-programmed death 1, nivolumab; plus anti-cytotoxic T-lymphocyte antigen 4, ipilimumab), stimulating T-cell production and resulting in durable clinical response. Methods: This is a phase II Simon 2-stage trial of nivolumab (240 mg IV q2w), ipilimumab (1 mg/kg IV q6w), and bicalutamide (150mg oral daily) for first- or second-line treatment of HER2-negative MBC (NCT03650894). The primary endpoint is iRECIST 24-week clinical benefit rate (CBR), evaluated separately for HR+ MBC (n=15) and AR+/HR- MBC (n=15). An optimum Simon 2-stage design (80% power, 5% one-sided alpha) is employed to evaluate an alternative hypothesis of >50% CBR compared to historical control of < 30% CBR for conventional chemotherapy, with expansion of each cohort planned if ≥6/15 responses are observed. Secondary outcomes include best overall objective response rate (ORR), progression-free and overall survival (PFS,OS), and safety. Exploratory endpoints include assessment of peripheral T-cell counts and T cell receptor excision circles (TREC PCR, Mayo Laboratories, a surrogate of thymic T-cell production) over time. Results: Durable responses were observed, with an ongoing complete response at 41+ months in a patient who discontinued due to toxicity (AR+/HR- cohort, PD-L1 CPS score 3%). Therapy was tolerated with a toxicity profile consistent with prior studies of ipilimumab & nivolumab, with five subjects (19%) requiring treatment discontinuation related to toxicity. Outcomes by cohort and PDL1 are summarized in Table 1. Using mixed effects linear models, therapy was associated with a significant expansion of CD8+ T cells (23/mcL/month, p< .01) but not CD3+ T cells (7/mcL/month, p=.59) or CD4+ T cells (4/mcL/month, p=.65). Baseline TREC counts were higher in younger participants (mean: < 50y 2156/mcL; 50-65y 961/mcL; >65y 311/mcL). TRECs did not increase globally, however TREC expansions were observed in several younger participants. Conclusions: The regimen of ipilimumab, nivolumab, plus bicalutamide is safe and clinically active in 1st/2nd-line HER2-negative MBC. Neither cohort crossed the Simon futility barrier for cohort expansion, however durable responses were observed including in PD-L1-negative patients, highlighting the unmet need for biomarkers to identify candidates for chemotherapy-sparing checkpoint blockade. Further research is indicated to evaluate the impact of AR antagonists on T-cell function and thymic stimulation in MBC. Acknowledgements: Drug and study support was provided by Bristol-Myers Squibb and The BMS International Immuno-Oncology Network (II-ON). Clinical outcomes XX XX HR: hormone receptor; AR: androgen receptor; CPS: PD-L1 combined positive score Citation Format: David Page, Alexander Hall, Krystle Collins, Nicole Moxon, Staci Mellinger, Tracy Kelly, Aysha Kelley, Nicole Fredrich, Amanda Seino, Gabriella Liberatore, Alison Conlin, Zheng Topp, Kelly Perlewitz, Sasha Stanton, Walter Urba, Yaping Wu, Maritza Martel, Zhaoyu Sun, Yoshinobu Kogushi, William Redmond, Tiffany Traina, Ayca Guculp. A phase II study of nivolumab plus ipilimumab and androgen receptor antagonist bicalutamide to stimulate thymic T cell generation in HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-09.

Background:Nailfold capillaroscopy (NVC), a non-invasive technique to assess microcirculation, is increasingly being incorporated into rheumatology routine clinical practice. Currently, the degree of description of NVC methods varies amongst research studies, making interpretation and comparison between studies challenging. In this field, an unmet need is the standardization of items to be reported in research studies using NVC.Objectives:To perform a Delphi consensus on minimum reporting standards in methodology for clinical research, based on the items derived from a systematic review focused on this topic.Methods:The systematic review of the literature on NVC methodology relating to rheumatic diseases was performed according to PRISMA guidelines (PROSPERO CRD42018104660) to July 22nd2018 using MEDLINE, Embase, Scopus. Then, a three-step web-based Delphi consensus was performed in between members of the EULAR study group on microcirculation in rheumatic diseases and the Scleroderma Clinical Trials Consortium. Participants were asked to rate each item from 1 (not appropriate) to 9 (completely appropriate).Results:In total, 3491 references were retrieved in the initial search strategy, 2862 were excluded as duplicates or after title/abstract screening. 632 articles were retrieved for full paper review of which 319 fulfilled the inclusion criteria. Regarding patient preparation before the exam, data were scarce: 38% reported acclimatization, 5% to avoid caffeine and smoking, 3% to wash hands and 2% to avoid manicure. Concerning the device description: 90% reported type of instrument, 77% brand/model, 72% magnification, 46% oil use, 40% room temperature and 35% software for image analysis. As regards to examination details: 76% which fingers examined, 75% number of fingers examined, 15% operator experience, 13% reason for finger exclusion, 9% number of images, 8% quality check of the images and 3% time spent for the exam. Then, a three-round Delphi consensus on the selected items was completed by 80 participants internationally, from 31 countries located in Australia, Asia, Europe, North and South America. Some items reached the agreement at the second round (85 participants), and other items were suggested as important to consider in a future research agenda (e.g. temperature for acclimatization, the impact of smoking, allergies at the application of the oil to the nailbed, significance of pericapillary edema, methods of reporting hemorrhages, ramified and giant capillaries). The final agreement results are reported below:Conclusion:On the basis of the available literature the description of NVC methods was highly heterogeneous and individual published studies differed markedly. These practical suggestions developed using a Delphi process among international participants provide a guidance to improve and to standardize the NVC methodology in future clinical research studies.Disclosure of Interests:Francesca Ingegnoli: None declared, Tommaso Schioppo: None declared, Ariane Herrick: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Francesca Bartoli: None declared, Nicola Ughi: None declared, John Pauling: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Abstract The MTHFD2 protein is consistently the most overexpressed enzyme when comparing cancer and normal cells and tissue. The protein regulates formate release from mitochondria and generation of nucleotides required for rapid cell growth. An additional role of MTHFD2 in DNA repair and genomic stability in cancer cells is also emerging. The MTHFD2 has been validated genetically as an anti-cancer target by numerous laboratories, but the enzyme has been notoriously difficult to target. Here, we describe first-in-class nanomolar MTHFD2 inhibitors, with protein co-crystal structures demonstrating binding in the active site of MTHFD2 and engaging with the target in cells and tumours. Because of the structural resemblance between MTHFD1, all MTHFD2 inhibitors were also found to inhibit MTHFD1, but no other folate-binding protein, kinases or other proteins. Here, we report that MTHFD1/2 inhibitors (MTHFD1/2i) reduce replication fork speed and induce replication stress, followed by S phase arrest, apoptosis and efficient killing of cancer cells in vitro and in vivo. Mechanistically, we find MTHFD1/2i prevent thymidine production leading to the misincorporation of uracil into DNA and replication stress. We show that TH9619 targets the nuclear MTHFD2 but not mitochondrial MTHFD2. Because of this, MTHFD1/2i lead to a unique folate trap, accumulation of 10-formyl-tetrahydrofolate, which depletes cells of tetrahydrofolate leading to thymidylate depletion and selective killing of MTHFD2-expressing cancer cells. Importantly, the folate trap is not generated in non-transformed cells that do not express MTHFD2. We also show that MTHFD1/2i target the DNA damage response (DDR), and the combined effect of targeting the DDR and generating a cancer-specific folate trap explains the unique > 1000-fold therapeutic index generated by these inhibitors. Furthermore, we show efficient haematological and solid cancer targeting in vitro and in vivo. Excitingly, we find potent anti-cancer efficacy and complete responses at low doses in vivo while demonstrating tolerability at 1000x fold higher doses, altogether underscoring the novelty of our approach. In conclusion, MTHFD1/2 inhibitors will offer a major new DDR inhibitor attack on cancer soon to be tested in clinical trials Citation Format: Petra Martilla, Alanna C Green, Nicole Kiweler, Christina Chalkiadaki, Elisée Wiita, Victoria Cookson, Antoine Lesur, Kim Eiden, François Bernhardin, Maeve Long, Ann-Sofie Jemth, Oliver Mortusewicz, Evert Homan, Nadilly Bonagas, Louise Ramos, Kumar Sanjiv, Emilio Guillén Mancina, Therese Pham, Ana Slipicevic, Martin Henriksson, Johannes Meiser, Thomas Helleday. MTHFD1/2 inhibitor TH9619 targets the DNA damage response and causes cancer-specific folate trapping with an unprecedented therapeutic window [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B109.

Abstract Background Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor under development for the treatment of gonorrhea and uncomplicated urinary tract infections (UTI). This study reports on the in vitro activity of gepotidacin and other oral antibiotics when tested against contemporary Escherichia coli and Staphylococcus saprophyticus clinical isolates collected from patients with UTIs for a gepotidacin uUTI global surveillance study as a part of the SENTRY Antimicrobial Surveillance Program. Methods A total of 3,562 E. coli and 344 S. saprophyticus isolates were collected between 2019 and 2020 from 92 medical centers located in 25 countries. Most isolates (68%) tested were cultured from urine specimens collected from patients seen in ambulatory, emergency, family practice, and outpatient medical services. Bacterial identifications were confirmed by MALDI-TOF. Isolates were tested for susceptibility by CLSI methods at a central laboratory (JMI Laboratories). MIC results for oral antibiotics licensed for the treatment of uUTI and drug-resistant subsets were interpreted per CLSI guidelines. Results Gepotidacin (MIC50/90, 2/2 mg/L) displayed good activity against 3,562 E. coli isolates, with 98.0% of all observed gepotidacin MICs ≤4 mg/L (Table). Susceptibility (S) rates for the other oral agents tested against these isolates were: amoxicillin-clavulanate (79.6% S), ampicillin (45.6% S), ciprofloxacin (72.5%S), fosfomycin (99.0% S), mecillinam (94.1%S), nitrofurantoin (97.3% S), and trimethoprim-sulfamethoxazole (68.2% S). When tested against the drug-resistant subsets, gepotidacin maintained similar MIC50/90 values (2/4 mg/L), except against isolates resistant to fosfomycin (2/8 mg/L). Against S. saprophyticus isolates, gepotidacin (MIC50/90, 0.06/0.12 mg/L) inhibited all isolates at ≤0.25 mg/L. Most oral agents showed S results of >97% against S. saprophyticus isolates, except for penicillin (3.5%S). Conclusion Gepotidacin demonstrated potent in vitro activity against contemporary E. coli and S. saprophyticus urine isolates. This activity was largely unaffected among isolates demonstrating drug-resistance to other oral standard of care antibiotics. Table Disclosures S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Deborah Butler, n/a, GlaxoSmithKline, LLC (Employee) Nicole Scangarella-Oman, MS, GlaxoSmithKline, LLC (Employee) Lindsey Paustian, BS (ASCP), GlaxoSmithKline, LLC (Research Grant or Support) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

Arbuscular mycorrhizal fungi (AMF) are ubiquitous underground symbiotic associations between most plants and fungi from the phylum Glomeromycota. From this symbiosis plants generally improve their capacity to obtain less mobile soil nutrients (like phosphorus) and increase resistance against biotic and abiotic stresses. Concomitantly the fungus has access to host carbon photosynthates. As obligate symbionts these fungi require always a host to survive, hence dual cultures is an obligatory laboratory requisite to maintain and multiply live Glomeromycota fungi. These cultures are mainly of three sorts: 1) Open pot cultures, 2) in vitro cultures with Ti DNA transformed root systems, 3) and in vitro cultures with L. cruciata, presented here. The internal mycelium of AMF usually assumes one or both of the morph-types named Arum (first described on Arum maculatum) and Paris (observed in Paris quadrifolia). The Paris-type morphology is characterized by hyphae with an intra-cellular growth, from cell-to-cell, forming coils and arbusculate coils. The Arum-type shows mainly intercellular hyphae growth, longitudinally between cells, with the arbuscules mounting upright on short intra-cellular branches.This study presents the first comparative morphologic characterization of 4 species of AMF grown in vitro with Lunularia cruciata (L.) Dumortier ex. Lindberg. Glomus clarum Nicol. & Schenck (CNPAB 005), G. intraradices Schenck & Smith (MUCL 43204), G. proliferum Dalpé & Declerck (MUCL 41827); and Gigaspora margarita Becker & Hall (CNPAB 001) internal hyphae share the same morph-type of L. cruciata colonization: the Paris-type. Stable and viable monoxenic cultures of AMF with L. cruciata were first presented by Fonseca and co-workers in 2006 for G. intraradices and G. proliferum on Petri dish (Fig. 1.1). In this work we bring two more species (G. clarum and Gi. margarita) cultured in vitro with L. cruciata, on bi-layer medium in flask containers (Fig. 1.2). The production of spores occurred mainly, among the rhizoids, between overlapping thallus and over the thallus (Fig. 1.3). Only the Glomus species produced spores within the medium.L. cruciata belongs to a group of complex thalloid liverworts with an internally differentiated anatomy: an upper epidermis forming air chambers where the chlorophyllous cells are located, a conspicuous vacuolated parenchyma, and the lower epidermis with its scales and rhizoids (Fig. 1.4). All four species show highly similar architecture of colonization with most fungi distributed in the thallus’ midrib parenchyma, and with internal mycelium architecture compatible with the Paris-type colonization (Figures 1.5 to 1.8). Although consistent the occurrence of Paris-type colonization among these four species, more species needed to be examined before a generalization can be given. The availability of AMF isolates for research at international fungi collections and laboratories is limited, and from these axenic isolates for in vitro culture are very few, which hinders the prove of the hypotheses that Paris-type colonization is the main pattern of hyphae colonization in L. cruciata mycothallus.

Abstract Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of this NatCUPMTB after 39 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and October 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and transcriptome analysis performed on the two PFMG2025 (French Genomic Medecine Plan 2025) national sequencing laboratories, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 244 pts were included. The median age at diagnosis was 60 yo, 53% were female, and the majority of patients had an OMS status <2. The median number of metastatic sites at diagnosis was 2, with a majority located in the lymph nodes (62%). The median time between diagnosis and first MTB presentation was 3 months (1-20). At the time of analysis, NatCUPMTB conclusions were available for 129 pts with a second MTB presentation. MTB investigations enabled to identify a likely primary origin in 89/129 (69%) pts, the most frequent being breast carcinoma (N=15), renal carcinoma (N=13) and lung carcinoma (N=13). The most frequently molecular alterations found were in TP53 (37%), KRAS (19%), CDKN2A (18%), NF2 (12%), KMT2C (10%), CDKN2B (9%), PBRM1 (9%) genes. MTB diagnoses were based on the combination of clinical, pathological and genomic investigations in 51/89 (59%) of pts. Importantly, a personalized therapeutic strategy was recommended by NatCUPMTB in 91/129 (71%) of pts. Among these recommendations, 72/91 (79%) were based on the diagnosis of tissue of origin (TOO), 9/91 (10%) on an actionable molecular alteration validated in the TOO indication, 8/91 (9%) on an actionable molecular alteration not validated in the TOO indication and 2/91 (2%) based on a druggable alteration only independently from the TOO. After a median follow-up of 1.5 months, the median overall survival (OS) was 17.7 months from the 2nd MTB presentation. Conclusion: NatCUPMTB provides significant diagnostic in 69% of pts with CUP and a therapeutic strategy recommendation for 71% of pts. Citation Format: Célia Dupain, Nicolas Jacquin, Isabelle Guillou, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle De La Fouchardière, Camille Tlemsani, Hélène Blons, Laëtitia Marisa, Anna Patrikidou, Fabienne Escande, Pierre Blanc, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Ivan Bièche, Maud Kamal, Christophe Le Tourneau, Sarah Watson. National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4637.

Abstract Introduction: With the increasing complexity of current diagnostic investigations, the integration of clinical, pathological and genomic characteristics is crucial for the management of patients (pts) with cancers of unknown primary (CUP). A national multidisciplinary tumor board (NatCUPMTB) was created in July 2020 in France to discuss the diagnostic and therapeutic management of CUP pts. The objective of this study was to evaluate the diagnostic, prognostic and therapeutic impact of this NatCUPMTB after 30 months of activity. Methods: This was a multicenter retrospective study with prospective follow-up. All pts discussed at least once in the NatCUPMTB between July 2020 and January 2023 were included. Pts and tumors characteristics, pathological and genomic analyses including WGS, WES and transcriptome analysis performed on the two PFMG2025 (French Genomic Medecine Plan 2025) national sequencing laboratories, multidisciplinary tumor board (MTB) conclusions, and follow-up after MTB were collected. Results: 151 pts were included. The median age at diagnosis was 58 yo, 55% were female, and the majority of patients had an OMS status <2. The median number of metastatic sites at diagnosis was 2, with a majority located in the lymph nodes (63%). The median time between diagnosis and first MTB presentation was 4 months (1-20). At the time of analysis, NatCUPMTB conclusions and long-term follow up (30 months) were available for 93 pts alive at the second MTB presentation. MTB investigations enabled to identify a likely primary origin in 62/93 (67%) pts, the most frequent being renal carcinoma (N=10), lung carcinoma (N=9) and breast carcinoma (N=8). The most frequently molecular alterations found were in TP53 (37%), KRAS (19%), CDKN2A (18%), NF2 (12%), KMT2C (10%), CDKN2B (9%), PBRM1 (9%) genes. MTB diagnoses were based on the combination of clinical, pathological and genomic investigations in 34/93 (37%) of pts. The others were based on pathological and genomic investigations in 15/93 pts (16%), genomic in 4/93 pts (4%), clinical and genomic in 3/93 pts (3%), clinical and pathological in 3/93 pts (3%) and pathological in 3/93 pts (3%). After a median follow-up of 11.2 months, the median overall survival (OS) was 11.9 months from the 2nd MTB presentation. Importantly, a personalized therapeutic strategy was recommended by NatCUPMTB in 79/93 (85%) of pts. Among these recommendations, 38/79 (49%) were based on the diagnosis of tissue of origin (TOO), 12/79 (15%) on an actionable molecular alteration, 24/79 (30%) on both the TOO and an actionable molecular alteration, and 5/79 (6%) were based on an unguided clinical trial. Conclusion: NatCUPMTB provides significant diagnostic and therapeutic benefit in 85% of pts with CUP. Early presentation of pts at NatCUPMTB as soon as CUP diagnosis is suspected should be recommended. Citation Format: Ivan Bieche, Maud Kamal, Nicolas Jacquin, Célia Dupain, Isabelle Guillou, Etienne Rouleau, Julien Masliah Planchon, Isabelle Soubeyran, Christelle De La Fouchardière, Camille Tlemsani, Hélène Blons, Laëtitia Marisa, Anna Patrikidou, Fabienne Escande, Pierre Blanc, Jennifer Wong, Pierre Saintigny, Sandrine Boyault, Adrien Buisson, Yves Allory, Anne Vincent-Salomon, Vincent Cockenpot, Janick Selves, Christophe Le Tourneau, Sarah Watson. National multidisciplinary tumor board improves diagnostic stratification and therapeutic management in cancers of unknown primary [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A113.

Abstract Background Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in Phase 3 clinical development for the treatment of gonorrhea and uncomplicated urinary tract infections (UTI). This study reports on interim results from a global surveillance program to monitor the in vitro activity of gepotidacin and comparator agents when tested against contemporary Escherichia coli (EC) and Staphylococcus saprophyticus (SSAP) clinical isolates collected from patients with UTIs worldwide as part of the SENTRY Antimicrobial Surveillance Program. Methods A total of 1,467 EC and 92 SSAP isolates were collected from 73 medical centers located in US (38), Europe (27), Asia-Pacific region (4), and Latin America (4). These isolates were tested for susceptibility by reference methods in a central laboratory (JMI Laboratories). MIC results for gepotidacin and comparators were interpreted as per US FDA and EUCAST criteria. Isolates were from UTIs, 70% of which were from ambulatory, outpatient, emergency, and family practice medical services. Results Gepotidacin (MIC50/90, 2/4 mg/L) displayed activity against 1,467 EC isolates with 98.2% of all observed MICs ≤ 4 mg/L. Susceptibility rates of trimethoprim-sulfamethoxazole (TMP-SMX; MIC50/90, ≤ .12/ > 16 mg/L), ciprofloxacin (MIC50/90, 0.015/ > 4 mg/L), and amoxicillin-clavulanate (MIC50/90, 8/16 mg/L) were 67.1%, 72.9%, and 78.7% (CLSI), respectively. Greater susceptibility against EC isolates was seen for fosfomycin (MIC50/90, 0.5/1 mg/L; 99.0%S), nitrofurantoin (MIC50/90, 16/32 mg/L; 97.4%S), and meropenem (≤ 0.015/0.03 mg/L; 100%S). An ESBL phenotype was observed in 15.3% of EC isolates; gepotidacin (MIC50/90, 2/4 mg/L) remained active against these isolates. Gepotidacin (MIC50/90, 0.06/0.12 mg/L) also was active against 92 SSAP isolates, with 100% of MICs ≤ 0.25 mg/L. Susceptibility of SSAP isolates to TMP-SMX, ciprofloxacin, or nitrofurantoin was greater than 98.8% (CLSI), while fosfomycin showed little activity (MIC50/90, 64/ > 256 mg/L; 98.9% R [EUCAST]). Conclusion Gepotidacin demonstrated potent activity against contemporary Escherichia coli, including ESBL-producing isolates and S. saprophyticus isolates collected worldwide. Table 1 Disclosures S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Deborah Butler, n/a, GlaxoSmithKline (Employee) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Background:The presence of rheumatoid factor (RF) in patients (pts) with rheumatoid arthritis (RA) is associated with higher disease activity,1and is regarded as a risk factor for more aggressive RA.1Most studies on anti-tumour necrosis factor (TNF) monoclonal antibodies such as infliximab, etanercept and adalimumab have shown better response in pts with negative versus positive and low versus high baseline RF titres.2-3Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF, has shown rapid and sustained reduction in signs and symptoms of moderate to severe RA, inhibition of radiographic progression and improvements in physical function in pts with an inadequate response to methotrexate (MTX).4–7The efficacy of CZP in pts with different baseline RF levels has not been studied.Objectives:To assess the efficacy of CZP, as measured by Disease Activity Score 28-erythrocyte sedimentation rate (DAS28[ESR]), in pts with active RA across baseline RF levels.Methods:In this post-hoc analysis, data were pooled from four clinical trials of CZP in RA: two global trials (RAPID 1,NCT00152386and RAPID 2,NCT00175877), a Japanese trial (J-RAPID,NCT00791999) and a Chinese trial (RAPID-C,NCT02151851). Pts ≥18 years with adult onset RA for ≥6 months (defined by ACR 1987 criteria), who received MTX for ≥6 months (≥3 months for RAPID-C) prior to baseline, were randomised 1:1 to receive placebo (PBO) every two weeks (Q2W)/CZP 400 mg Q2W/CZP 200 mg Q2W (CZP 400 mg at Weeks [Wks] 0/2/4) plus MTX for at least 24 Wks. Complete study design and pt characteristics were reported previously.4–7Here we include only pts who received CZP 200 mg Q2W (CZP 400 mg at Wks 0/2/4). RF titres were measured by validated assays in local hospital laboratories. Pts were stratified into quartiles based on pooled baseline RF levels: <25.0, <78.5, <207.0 and ≥207.0 IU/mL. DAS28(ESR) categories were adopted to stratify pts: remission (REM), DAS28(ESR) <2.6; low disease activity (LDA), DAS28(ESR) ≤3.2. Missing values were imputed using last observation carried forward.Results:Data were pooled from 1,017 and 504 pts in the CZP 200 mg Q2W and PBO Q2W groups, respectively. At baseline, mean [SD] DAS28(ESR) was similar with PBO vs CZP across RF quartiles (6.5 [0.9] – 7.0 [0.9] vs 6.6 [0.9] – 7.0 [0.9]). Compared with the PBO group, numerically higher DAS28(ESR) REM and LDA rates were observed for CZP 200 mg Q2W group at Wk 24 across RF quartiles (Figure 1). DAS28(ESR) REM and LDA responder rates increased to Wk 24 in pts treated with CZP. In general, LDA and REM rates were similar across RF quartiles at all timepoints (Figure 2).Conclusion:Over 24 Wks of treatment, trends showed steady efficacy of CZP across baseline RF quartiles in pts with active RA. In this pooled post-hoc analysis, efficacy of CZP appeared to be consistent and independent of RF levels; observed efficacy may be related to the unique molecular structure of CZP. CZP treatment in association with MTX may be a feasible option in pts with RA regardless of baseline RF status.References:[1]Aletaha D. Arthritis Research & Therapy 2015;17:229;[2]Bobbio-Pallavicini F. Ann Rheum Dis 2007;66:302–7;[3]Potter C. Ann Rheum Dis 2009;68:69–74;[4]Keystone E. Arthritis Rheum 2008;58:3319–29;[5]Smolen J. Ann Rheum Dis 2009;68:797–804;[6]Yamamoto K. Mod Rheumatol 2014;24:715–24;7.Bi L. Clin Exp Rheumatol 2019;37:227–234.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical, Singapore.Disclosure of Interests:Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Zhanguo Li: None declared, Nevsun Inanc: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche, Nicola Tilt Employee of: UCB Pharma, Carlos Cara Employee of: UCB Pharma, Carine Saadoun Employee of: UCB Pharma, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.

BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) and are chronic immune-mediated diseases characterised by joint inflammation and skin lesions which negatively impact patients’ health-related quality of life (HRQoL). Several previous comparative studies have focused on PsA patients with or without skin involvement. Better understanding of the impact of both PsO and PsA on HRQoL and work / activity impairment will improve understanding of the incremental burden of PsA compared to PsO, and may lead to more personalised treatment options.ObjectivesTo compare HRQoL, work impairment, and daily activity impairment of patients with a PsO diagnosis (dx) only, PsO dx with musculoskeletal (MSK) symptoms (sx), PsA dx with active skin sx, and PsA dx without active skin sx.MethodsData were drawn from the Adelphi PsO & PsA Disease Specific Programmes™ (DSP), real-world point-in-time surveys of rheumatologists, dermatologists and their consulting patients in the United States and Europe (France, Germany, Italy, Spain and UK); conducted in 2018/19. Patients were grouped according to their symptoms and confirmed diagnoses, comprising four groups:1. Patients with PsO dx only,2. Patients with PsO dx and with MSK sx,3. Patients with PsA dx and with active skin sx,4. Patients with PsA dx with no active skin sx,Multivariate linear regression analyses with marginal mean predictions examined differences in patient-reported outcome measures (PROMs) between the four groups. Measures included HRQoL (EuroQol 5-Dimension 5-Level [EQ-5D Utility] and EuroQoL Visual Analogue Scale [EQ-VAS]), work impairment, and daily activity impairment (Work Productivity and Activity Impairment Questionnaire [WPAI]). Analyses controlled for demographics (age, sex, BMI), comorbidities present in >10% of patients and current treatment class (biologics, csDMARDs, steroids & other).Results4491 patients were included: Group 1 (n=1833), Group 2 (n=91), Group 3 (n=2451), and Group 4 (n=116). 54% of patients were male, 89% of patients were white, with a mean age of 46.6 years. Demographics were consistent across all patient groups.The model-predicted EQ-5D-Utility was lower in Groups 2, 3 and 4, compared with Group 1 (p=0.003, p<0.001 and p=0.004 respectively). Similarly, predicted EQ-VAS was lower in Group 3 compared with Group 1 (p=0.006), Table 1.Table 1.Predictions of PROMs for PsO-PsA patient groupsPRO toolGroup [n]*Predicted PRO valuePopulation norm (MCID)Regression model p-value (vs. reference group)EQ-5D Utility score (n=1839)1 (ref) [743]0.9220.88 (0.07)2 [32]0.8160.0033 [1023]0.810<0.0014 [41]0.8500.004EQ-VAS (n=1882)1 (ref) [763]78.7878.2 (n/a)2 [36]70.560.0573 [1040]73.890.0064 [43]75.230.248WPAI % overall work impairment (n=1015)1 (ref) [422]15.36n/a (15.0)2 [14]17.860.5603 [558]22.16<0.0014 [21]26.090.014WPAI % work time missed (n=1028)1 (ref) [424]0.91n/a (n/a)2 [14]3.570.4863 [569]4.460.0024 [21]10.430.003WPAI % impairment while working (n=1153)1 (ref) [486]14.90n/a (20.0)2 [18]13.890.8463 [626]19.63<0.0014 [23]17.390.435WPAI % activity impairment (n=1818)1 (ref) [732]18.02n/a (20.0)2 [32]26.250.1223 [1012]26.14<0.0014 [42]25.240.044*n values provided for reference, but margins are predictions as a result of the model and not for the specific number of patients in each subgroup.(1) patients with PsO dx only(2) Patients with PsO dx and MSK sx(3) Patients with PsA dx and with active skin sx(4) Patients with PsA dx with no active skin sxOverall work impairment increased in Groups 3 and 4, compared with Group 1 (p<0.001 and p=0.014 respectively). Furthermore, Groups 3 and 4 missed more work compared with Group 1 (p=0.002 and p=0.003 respectively). Group 3 patients exhibited an increase in presenteeism and activity impairment compared with Group 1 (p<0.001), Table 1.ConclusionPatients experiencing PsA dx or MSK sx experienced an additional disease burden compared to patients with PsO sx alone, as measured by worse HRQoL and work impairment.Disclosure of InterestsJoseph F. Merola Consultant of: Merck Research Laboratories, Abbvie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, GSK, Almirall, Sun Pharma, Biogen, Pfizer, Incyte, Aclaris, and Leo Pharma, Lars Erik Kristensen Speakers bureau: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Consultant of: Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen Pharmaceuticals, Grant/research support from: Novo, UCB, Eli Lilly; Novartis and Abbvie, Feifei Yang Employee of: Employee of Janssen Pharmaceuticals, Steve Peterson Employee of: Employee of Janssen Pharmaceuticals, Rachel Teneralli Employee of: Employee of Janssen Pharmaceuticals, Nicola Massey Employee of: Adelphi Real World, Soumya D. Chakravarty Employee of: Employee of Janssen Pharmaceuticals, Megan Hughes Employee of: Adelphi Real World, May Shawi Employee of: Employee of Janssen Pharmaceuticals, Sarah Weatherby Employee of: Adelphi Real World, Christine Contre Employee of: Employee of Janssen Pharmaceuticals, Iris Lin Employee of: Employee of Janssen Pharmaceuticals, Fareen Hassan Employee of: Employee of Janssen Pharmaceuticals, M Elaine Husni Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Janssen, UCB, Pfizer, Regeneron, and BMS

BackgroundHigh levels of complete clearance of plaque psoriasis in high-impact areas such as the scalp, nails, palms and soles have been reported in patients (pts) after 1 year (yr) of bimekizumab (BKZ) treatment.[1]ObjectivesAssess scalp, nail and palmoplantar outcomes over 2 yrs from two BKZ phase 3 trials in moderate to severe plaque psoriasis.MethodsData were pooled over 2 yrs from the BE RADIANT phase 3b trial (NCT03536884), including Yr1 of its ongoing open-label extension (OLE), and the 1-yr BE SURE phase 3 trial (NCT03412747) with the ongoing OLE, BE BRIGHT (NCT03598790).[2,3]Pts included were randomised at baseline to BKZ 320 mg every 4 weeks (wks; Q4W) and then continued to receive BKZ Q4W or switched to BKZ every 8 wks (Q8W) at Wk16, and received the same dose on entering the OLE (Q4W/Q4W/Q4W or Q4W/Q8W/Q8W).Regional involvement was analysed using scalp Investigator’s Global Assessment (scalp IGA; 5-point scale [0–4]), modified Nail Psoriasis Severity Index (mNAPSI; total fingernail score, 0–130 scale) and palmoplantar (pp)-IGA (5-point scale [0–4]). We report proportions of pts who achieved complete regional clearance (scalp IGA 0, mNAPSI 0, pp-IGA 0) through Yr2 (OLE Wk48) among pts with moderate to severe regional involvement at baseline (scalp IGA ≥3, mNAPSI >10, pp-IGA ≥3). Missing data were imputed as non-response (NRI).ResultsOf pts who entered the OLEs from BE SURE and BE RADIANT, 303 and 323 received BKZ Q4W/Q4W/Q4W and Q4W/Q8W/Q8W, respectively. Of these, 209 (69.0%) and 241 (74.6%) had baseline scalp IGA ≥3; 43 (14.2%) and 44 (13.6%) had pp-IGA ≥3; 100 (33.0%) and 111 (34.4%) had mNAPSI >10.Among pts with baseline scalp IGA ≥3, 78.0% and 81.7% treated with BKZ Q4W/Q4W/Q4W and Q4W/Q8W/Q8W achieved scalp IGA 0 at Wk16, respectively; 80.4% and 79.3% achieved scalp IGA 0 at Yr2 (OLE Wk48) (Table 1).Of pts with baseline pp-IGA ≥3, 60.5% and 81.8% treated with BKZ Q4W/Q4W/Q4W and Q4W/Q8W/Q8W achieved pp-IGA 0 at Wk16, respectively; 83.7% and 81.8% achieved pp-IGA 0 at Yr2 (Table 1).Of pts with baseline mNAPSI >10, 51.0% and 58.6% treated with BKZ Q4W/Q4W/Q4W and Q4W/Q8W/Q8W achieved mNAPSI 0 at Wk32, respectively; 40.0% and 59.5% achieved mNAPSI 0 at Yr2 (Table 1).ConclusionA high percentage of BKZ-treated pts achieved complete clearance of scalp and palmoplantar psoriasis at Wk16, which was sustained over 2 yrs. Complete nail clearance continued to increase through Yr1, reflecting the longer timescale required for nail growth, and was generally sustained through Yr2. Proportions of pts achieving complete nail, scalp and palmoplantar clearance were generally comparable between BKZ Q4W/Q4W/Q4W and Q4W/Q8W/Q8W dosing regimens.Reference[1]Merola JF. Presented at EADV 2021;2.Reich K. N Eng J Med 2021;385(2):142–52;3.Warren RB. N Eng J Med 2021;385(2):130–41.Table 1.Complete regional clearance of scalp, nail, or palmoplantar psoriasis over 2 years (NRI)BKZ 320 mg Q4W/Q4W/Q4W n (%)BKZ 320 mg Q4W/Q8W/Q8W n (%)Scalp IGA ≥3 at baselineN=209N=241Scalp IGA 0 at Wk16163 (78.0)197 (81.7)Scalp IGA 0 at Yr1a186 (89.0)206 (85.5)Scalp IGA 0 at Yr2b168 (80.4)191 (79.3)mNAPSI >10 at baselineN=100N=111mNAPSI 0 at Wk32c51 (51.0)65 (58.6)mNAPSI 0 at Yr1a54 (54.0)79 (71.2)mNAPSI 0 at Yr2b40 (40.0)66 (59.5)pp-IGA ≥3 at baselineN=43N=44pp-IGA 0 at Wk1626 (60.5)36 (81.8)pp-IGA 0 at Yr1a35 (81.4)41 (93.2)pp-IGA 0 at Yr2b36 (83.7)36 (81.8)aWk48 of treatment;bOLE Wk48: BE RADIANT Wk96 and BE SURE/BE BRIGHT Wk104 of total treatment;cmNAPSI response initially reported at Wk32 due to the longer timescale required for nail growth vs skin clearance. Pts included had regional involvement at baseline and entered the OLE without switching maintenance dose. Treatment groups refer to BKZ dosing schedules in Wks: 0–16/16–48/OLE entry. BKZ: bimekizumab; IGA: Investigator’s Global Assessment; mNAPSI: modified Nail Psoriasis Severity Index; NRI: non-responder imputation; OLE: open-label extension; pp: palmoplantar; pts: patients; Q4W: every 4 wks; Q8W: every 8 wks; wk: week; yr: year.AcknowledgementsFunded by UCB Pharma. Medical writing support by Costello Medical.Disclosure of InterestsJoseph F. Merola Consultant of: Consultant and/or investigator for AbbVie, Amgen, Bayer, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB Pharma. Principal Investigator for Dermavant, LEO Pharma, and UCB Pharma., Alice B Gottlieb Speakers bureau: Honoraria as an advisory board member, non-promotional speaker or consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, DiCE Therapeutics, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and XBiotech (stock options for an RA project)., Consultant of: Honoraria as an advisory board member, non-promotional speaker or consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, DiCE Therapeutics, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and XBiotech (stock options for an RA project)., Grant/research support from: Research/educational grants from AnaptysBio, Bristol Myers Squibb, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai., Akimichi Morita Speakers bureau: Received research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharma, UCB Pharma, and Ushio., Consultant of: Received research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharma, UCB Pharma, and Ushio., Grant/research support from: Received research grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharma, UCB Pharma, and Ushio., Jose M Carrascosa Consultant of: Participated as Principal/Senior Investigator and/or consultant and/or advisor for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Sandoz, and UCB Pharma., Boni Elewski Consultant of: Consultant (honoraria) from Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, LEO Pharma, Menlo, Novartis, Pfizer, Sun Pharma, UCB Pharma, Valeant, and Verrica., Grant/research support from: Received research support as funding to Case Western Reserve University from AbbVie, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Incyte, LEO Pharma, Menlo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, Valeant, and Vanda., Nicola Tilt Shareholder of: Stockholder of GSK and UCB Pharma., Employee of: Employee of UCB Pharma., Susanne Wiegratz Shareholder of: Shareholder of UCB Pharma., Employee of: Employee of UCB Pharma., Krista Wixted Shareholder of: Shareholder of UCB Pharma., Employee of: Employee of UCB Pharma., Ulrich Mrowietz Consultant of: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr. Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi, and UCB Pharma., Grant/research support from: Served as advisor and/or clinical study investigator for, and/or received honoraria and/or grants from AbbVie, Almirall, Aristea, Boehringer Ingelheim, Celgene, Dr. Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Forward Pharma, Janssen, LEO Pharma, Medac, Novartis, Phi-Stone, Pierre Fabre, Sanofi, and UCB Pharma.

Presentación En septiembre de 2017, la Asociación Colombiana de Alergia, Asma e Inmunología (ACAAI) y la Organización Mundial de Alergia (WAO) celebraron conjuntamente en la Ciudad de Cartagena, Colombia, dos eventos únicos: el XI Congreso Colombiano de Alergia, Asma e Inmunología y el Simposio WAO “Alergia a ácaros: de la ciencia básica a las aplicaciones clínicas”. Los organizadores se esmeraron a fondo en ofrecer un programa de contenido novedoso e interesante, pero también en lograr una convocatoria numerosa y de calidad que motivara la presentación de trabajos libres. Para ello, se emprendió una ambiciosa gestión con el fin de lograr la publicación de los resúmenes en una revista de impacto para la especialidad, llegando a un acuerdo con la Revista de Alergia de México, líder en las áreas de la alergología y la inmunología en la región, y órgano oficial de la Sociedad Latinoamericana de Alergia, Asma e Inmunología (SLAAI). Alergología Presentación Carlos D. Serrano R. Adherence to pharmacotherapy improves school performance in children with rhinitis and asthma Jorge Mario Sánchez, Andrés Sánchez, Ricardo Cardona Adherencia a la inmunoterapia sublingual y subcutánea en los pacientes del servicio de alergología de una institución en salud. Medellín, Colombia Ana Milena Acevedo, Rosa Farfán, Ruth Ramírez, Ricardo Cardona Aerobiological study in Lima, Peru Silvia Uriarte,Óscar Calderón Aerobiological study in Peruvian cities Silvia Uriarte,Óscar Calderón Alergia al trigo en un adulto. Reporte de un caso Ricardo Cardona, Karen Hernández, Julián Londoño Alimentación complementaria antes de los 4 meses de edad y su relación con asma, rinitis y eccema Karol Cervantes De la Torre, Francisco Guillén-Grima Alta frecuencia de sensibilización a camarón entre pacientes con rinitis alérgica sin consumo previo María Angélica Muñoz, Estefanía Hernández Susana Diez, Jorge Sánchez Alteraciones psicosociales entre escolares y adolescentes con alergias respiratorias en Medellín, Colombia Juan José Yepes, Víctor Calvo, Ricardo Cardona Anafilaxia causada por cidra y yuca. Reporte de caso Emerson Daniel Amaya-Ruiz Anafilaxia en lactante alérgico a la proteína de la leche de vaca Ana María Calle-Álvarez, Carlos Fernando Chinchilla Anafilaxia perioperatoria. Reporte de un caso y revisión de la literatura María Clara Vásquez-Maya, Mónica Molina, Ricardo Cardona Anafilaxia tardía tras la ingesta de carnes rojas con sensibilización a alfa-gal. Reporte de caso María Beatriz García-Paba Asma alérgica infantil severa resistente que remite tras manejo con omalizumab. Reporte de caso Miguel Ángel Daza-Cruz, Andrés Felipe Mantilla-Santamaría Association of IgE profiles to micro-arrayed house dust mite allergens with allergic symptoms measured in a house dust mite challenge chamber Azahara Rodríguez-Domínguez, Yvonne Resch, Petra Zieglmayer, Rudolf Valenta, Susanne Vrtala Ausencia de reactividad cruzada entre aril propiónicos. Reporte de caso Julián Londoño, Ricardo Cardona Calidad de vida en población pediátrica con dermatitis atópica atendidos en una unidad especializada de alergología de Medellín, Colombia Ruth Ramírez-Giraldo, Iris Castelblanco-Arango, Víctor Calvo, Carlos Chinchilla-Mejía, Ricardo Cardona-Villa Caracterización clínica de pacientes con rinosinusitis crónica en un centro ambulatorio de alergología e inmunología en Bogotá Carlos Olmos-Olmos Clinical efficacy of cat or dog allergen A real-life study Silvia Uriarte, Joaquín Sastre Comparison of several combinations maintenance and reliever therapy for asthma patients Pablo Andrés Miranda-Machado Comportamiento de las gastroenteropatías eosinofílicas en la población pediátrica Carolina Gallego-Yepes, Luisa María Holguín-Gómez, Yuliana Toro-Colorado, Carlos Fernando Chinchilla-Mejía Conocimientos básicos en alergología en una cohorte de médicos generales que ingresan a residencia diferente de alergología Luis Fernando Ramírez-Zuluaga, Carlos Daniel Serrano-Reyes De anafilaxia por Culex a síndrome de activación mastocitaria en un paciente adulto Ricardo Cardona, Emerson Daniel Amaya-Ruiz, María Angélica Muñoz-Ávila Dermatitis de contacto no tan obvias: descripción de casos Carolina Gómez-García, Edison Morales-Cárdenas Desensibilización a quimioterápicos: nuestra experiencia David Baquero-Mejía, Alfredo Iglesias-Cadarso, María del Mar Goñi-Yeste, María del Mar Reaño-Martos, Marta Rodríguez-Cabrero, Matilde Rodríguez-Mosquera Desensibilización exitosa a ciclofosfamida. Reporte de un caso Diana Lucía Silva-Espinosa, Luis Fernando Ramírez-Zuluaga, Carlos Daniel Serrano-Reyes Desensibilización exitosa a hierro sacarosa endovenoso. Descripción de dos casos Edgardo Antonio Chapman-Ariza, Leidy Álvarez-Ricardo, Dalyla Leal, Mónica Duarte-Romero, Elizabeth García Desensibilización exitosa con tocilizumab. Reporte de un caso Luis Fernando Ramírez-Zuluaga, Diana Lucía Silva-Espinosa, Carlos Daniel Serrano-Reyes Diagnóstico molecular en alergia a camarón y langostino Diana Lucía Silva-Espinosa, Luis Fernando Ramírez-Zuluaga, Carlos Daniel Serrano-Reyes Eritrodermia recurrente que condujo al diagnóstico de síndrome hipereosinofílico Liliana María Tamayo-Quijano, Lina María Aguirre-Hernández ¿Es la levadura un alérgeno importante en la alergia a licores? Reporte de caso Yuliana Toro-Colorado Esofagitis eosinofílica en niños de una región intertropical Luisa Holguín-Gómez Experiencia de inmunoterapia con extractos no modificados durante un año en un centro ambulatorio de Bogotá Carlos Olmos-Olmos, Catalina Gómez-Parada Lizeth Florez Exposición y sensibilización a insectos en pacientes alérgicos en el trópico Jorge Mario Sánchez, Andrés Sánchez, Ricardo Cardona Exposure and sensitization to dust mites in Peruvian cities Silvia Uriarte, Óscar Calderón, Víctor Iraola Factores sociodemográficos y su relación con el nivel de control del asma en pacientes pediátricos del Instituto Nacional de Salud del Niño de Perú César Galván-Calle, Ricardo Muñoz-León, David García-Gomero, Edgar Matos-Benavides, Wilmer Córdova-Calderón, María López-Talledo Frecuencia de reacción alérgica a la triple viral en 94 pacientes con alergia a huevo Jorge Mario Sánchez, Ruth Ramírez, Ricardo Cardona Herramienta de orientación en casos de incertidumbre de intolerancia a AINE Ricardo Cardona, Julián Londoño, Felipe Arboleda, Víctor Calvo Hipersensibilidad a AINE en niños: lo que no se ajusta a la clasificación María Angélica Muñoz-Ávila, Ruth Helena Ramírez-Giraldo, Ricardo Cardona-Villa House dust mites as potential carriers for IgE sensitization to bacterial antigens Sheron Dzoro, Irene Mittermann, Yvonne Resch, Susanne Vrtala, Marion Nehr, Alexander M. Hirschl, Gustav Wikberg, Lena Lundeberg, Catharina Johansson, Annika Scheynius, Rudolf Valenta IgE serological tests based on natural house dust mite extracts underestimate allergen-specific IgE levels compared to recombinant allergen-based tests Huey-Jy Huang, Yvonne Resch-Marat, Kuan-Wei Chen, Renata Kiss, Rudolf Valenta, Susanne Vrtala IgE/IgG1 antibody responses to ubiquitin are associated with emergency room attendance due to asthma symptoms Juan Felipe López-Crespo, Dilia Mercado, Velky Ahumada-Contreras, Ronald Regino López, Josefina Zakzuk-Sierra, Luis Caraballo Impacto del uso de la herramienta “Reactividad cruzada entre betalactámicos” Ricardo Cardona, Julián Londoño, Felipe Arboleda, Víctor Calvo Inhibition of Orai-STIM coupling alleviates experimentally-induced airways remodeling changes Martina Sutovska, Sona Franova Más allá de la alergia a la yuca o mandioca Ricardo Cardona, María Angélica Muñoz-Ávila, Kenny Mauricio Gálvez-Cardenas Mastocitosis cutánea difusa. Reporte de un paciente pediátrico Rodrigo Alonso Gaviria-Rendón, Ricardo Cardona Miositis eosinofílica, parte del espectro del síndrome hipereosinofílico o diagnóstico Reporte de un caso Carlos Olmos-Olmos Modelo de ecuaciones estructurales en pacientes con urticaria crónica Ricardo Cardona, Susana Diez, Víctor Calvo Niveles séricos de cortisol matutino en niños atópicos con asma bronquial y su influencia en la respuesta inmune IgE. estudio piloto en comunidades pobres de la ciudad de Barranquilla Fernando Rafael De La-Cruz-López, Gloria Egea-Garavito, Nicole S. Pereira-Sanandres, Luis Fang-Mercado, Iván Stand-Niño, Sofía Moreno-Woo, Gloria Garavito-De Egea, Eduardo Egea-Bermejo Omalizumab como terapia adyuvante para la dermatitis atópica severa en niños: una serie de casos María Alejandra García-Chabur, Alejandro Durán, Edgardo Chapman, Elizabeth García Omalizumab en conjuntivitis vernal severa: a propósito de un caso Manuela Olaya-Hernández, Luis Fernando Ramírez, Carlos Daniel Serrano-Reyes Omalizumab más allá del asma y la urticaria crónica espontánea Luisa Holguín, Angélica Muñoz, Ricardo Cardona Patients living in urban areas require more pharmacotherapy and have lower remission of symptoms for asthma and rhinitis than patients in rural location Jorge Mario Sánchez, Andrés Sánchez, Ricardo Cardona Prevalence, incidence and mortality of anaphylaxis in Colombia Pablo Andrés Miranda-Machado Prueba de parches de flores, un acercamiento a la estandarización María Muñoz, Catalina Gómez, Susana Diez, Liliana Guevara, Carlos Chinchilla, Ricardo Cardona Pruebas in vivo e in vitro para el diagnóstico de alergia a metamizol en pacientes de un centro médico en Perú David García-Gomero, Daniel Mendoza-Quispe, Edgar Matos-Benavides, Rosario Inocente Malpartida, Marco Álvarez-Ángeles Remisión de urticaria solar posterior al uso de omalizumab. Reporte de caso Ana María Villa-Arango, María Angélica Muñoz-Ávila, Ricardo Cardona Reporte de un paciente con queratoconjuntivitis vernal controlada con omalizumab y recaída con su suspensión Jorge Sánchez, Luis Carlos Santamaría-Salazar ¿Requiere cambios la clasificación actual de urticaria crónica? July Ospina-Cantillo, Liliana Guevara-Saldaña, Ricardo Cardona Rhinitis symptoms, mattress covers and bedroom environmental control: a multicentred double blind randomized versus placebo-controlled trial Emeline Furon Safety of an ultra-rush subcutaneous immunotherapy using an infusion pump in real-life Silvia Uriarte, Joaquín Sastre Seguimiento a largo plazo de inmunoterapia oral con leche de vaca David Baquero-Mejía, Pedro Ojeda-Fernández, Peter Bae, Isabel Ojeda-Fernández, Gema Rubio-Olmeda, Rocío Mourelle-Aguado, Sandra Yago-Meniz Seguridad de la inmunoterapia por vía subcutánea con alergoides María Nelly Restrepo Sensibilización a aeroalérgenos en pacientes pediátricos con asma atendidos en un periodo de 4 años en un Hospital de Medellín, Colombia Estefanía Vásquez-Echeverri, J. H. Donado, M. P. Villar, S. I. Ramírez, Carlos Fernando Chinchilla-Mejía, J. E. García Sensibilización a contactantes en 2003 pacientes de Medellín, Colombia María Nelly Restrepo-Colorado, Edison Morales-Cárdenas E, Ana María Acevedo-Vásquez, Daniel Amaya-Ruiz, Paula Andrea Arango-Castaño, Rosa Remedios Farfán-Plata, Carolina Gómez-García, Ruth Mery Marín Franco, Margarita Olivares-Gómez, Rafael Alberto Pérez-Arango, Liliana María Tamayo-Quijano, Juan David Tobón-Franco, Liliana María Valencia-Gómez Sensitization to the mosquito allergens, Aed a 1 and Aed a 2 in patients with papular urticaria from two Colombian cities with different altitude Luis Miguel Henao, Juana Bustillo, Josefina Zakzuk, Luis Caraballo, Elizabeth García Simplificación del estudio alergológico en pacientes con sospecha de alergia a fármacos con riesgo bajo a moderado Diana Lucía Silva-Espinosa, Luis Fernando Ramírez-Zuluaga, Manuela Olaya-Hernández, Carlos Daniel Serrano-Reyes Síndrome DRESS por penicilina benzatínica. Primer reporte de caso en Latinoamérica Ana María Calle, Iris Castelblanco-Arango, Ricardo Cardona-Villa Síndrome de Frey como diagnóstico diferencial de alergia alimentaria July A. Ospina-Cantillo, Ruth Helena Ramírez-Giraldo, Iris Castelblanco-Arango, Ricardo Cardona Síndrome de Presentación de dos casos Liliana María Tamayo-Quijano, Lina María Aguirre-Hernández, Luz Marina Gómez-Vargas Superposición de reacciones graves por fármacos. Reporte de dos casos Diana Lucía Silva-Espinosa, Luis Fernando Ramírez-Zuluaga, Carlos Daniel Serrano-Reyes The efficiency of flavonols in the setting of experimentally induced allergic asthma Sona Fraková Tromboembolismo pulmonar como causa de exacerbaciones frecuentes en un paciente con asma de difícil control, aspergilosis broncopulmonar y uso de esteroides sistémicos Liliana M. Guevara-Saldaña, Libia Susana Díez-Zuluaga, Catalina Gómez-Henao, Ricardo Cardona Urticaria Reporte de un caso María Raigosa, Yuliana Toro, Jorge Sánchez Utilidad clínica del omalizumab en urticaria crónica inducible Ricardo Cardona Vitamina D y atopia en escolares pertenecientes a comunidades vulnerables de la ciudad de Barranquilla Luis Fang, Nicole Pereira-Sanandres, Fernando Rafael De la Cruz-López, Sofía Moreno-Woo, Nelly Lecompte, Lila Visbal, Gloria Garavito-De Egea, Eduardo Egea-Bermejo Inmunología Angioedema hereditario y lupus. Reporte de caso Catalina Gómez-Parada Características clínicas y de laboratorio en una cohorte de pacientes con ataxia telangiectasia en el Grupo de Inmunodeficiencias Primarias de la Universidad de Antioquía Lina Rocío Riaño, Jesús Armando Álvarez, Julio César Orrego, Dagoberto Cabrera, Carolina Gómez, Héctor Valderrama, Alexandra Sierra, Derly Carolina Hernández, José Luis Franco Cuantificación y análisis de citocinas proinflamatorias en pacientes con hallazgos coronariográficos de lesiones ateroscleróticas en la ciudad de Barranquilla, Colombia Franklin Torres, José Villarreal, Marcio de Ávila, Xavier Lastra, Edward Lozano, Martín Oviedo, Axel Tolstano Estudio de los polimorfismos de los antígenos leucocitarios humanos HLA y citocromos CYP en síndrome de Stevens-Johnson relacionado con fenitoína y carbamazepina en Colombia Nohemí Esther Santodomingo-Guerrero Estudio de una población barranquillera basada en los alelos DRB1 y DQB1 comparada con otras poblaciones suramericanas Carlos Hernando-Parga Evaluación de la adsorción de los alérgenos Blo t2 y Blo t3 y del proteoliposoma de Neisseria meningitidis al Al(OH)3 en formulaciones de una vacuna antialérgica adyuvada contra el ácaro Blomia tropicalis Yoskiel Laurencio-Lorca Exome sequencing reveals gain-of-function mutations in STAT1 conferring predisposition to chronic mucocutaneous candidiasis and tuberculosis in six Colombian patients Marcela Moncada-Vélez, Lucía Victoria Erazo-Borrás, Jesús Armando Álvarez-lvarez, Carlos Andrés Arango, Miyuki Tsumura, Satoshi Okada, Sara Daniela Osorio, Lorena Castro, Natalia González, Catalina Arango, Julio César Orrego, Lina Riaño, Juan Fernando Alzate, Felipe Cabarcas, Jean-Laurent Casanova, Jacinta Bustamante, Anne Puel, Andrés Augusto Arias, José Luis Franco Experiencia de una clínica de inmunodeficiencias primarias en un centro de atención nivel IV en Cali, Colombia Manuela Olaya-Hernández, Jaime Patiño, Diego Medina, Harry Pachajoa, Viviana Lotero, Paola Pérez Expression and immunological characterization a heat shock cognate-70 protein allergen, rAed a8, from the mosquito species Aedes aegypti José Fernando Cantillo, Leonardo Puerta, Enrique Fernandez-Caldas, José Luis Subiza, Irene Soria, Sylvie Lafosse-Marin, Barbara Bohle Gemelos idénticos con enfermedad granulomatosa crónica que se manifestó inicialmente como colitis alérgica. Reporte de caso Carlos Olmos-Olmos Genetic analysis of the SERPING1 gene in hereditary angioedema patients in Neiva, Colombia Jairo Antonio Rodríguez, Carlos Fernando Narváez Hyperimmunoglobulin E syndrome in three siblings of non-consanguineous healthy Egyptian family. Case report Rehab Zaki Elmeazawy, Nabil Elesawy, Ahmad Abdelrazik, Osama Toema, Mohamed Hamza, Amany Bararkat Local adverse reaction rates decreased over time during treatment with recombinant human hyaluronidase- facilitated subcutaneous infusion of immunoglobulin G (fSCIG) in patients with primary immunodeficiency diseases in the fSCIG phase 3 studies Lina Laguado, Mark Stein, Richard L Wasserman, Isaac Melamed, Sudhir Gupta, Lisa Kobrynski, Arye Rubinstein, Christopher J Rabbat, Werner Engl, Barbara McCoy, Heinz Leibl, Leman Yel Long-term adverse events, efficacy, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin in patients aged < 18 years with primary immunodeficiency diseases Lina Laguado, Richard L. Wasserman, Isaac Melamed, Lisa Kobrynski, Sudhir Gupta, Werner Engl, Heinz Leibl, Leman Yel Manifestaciones alérgicas en inmunodeficiencias primarias, ¿cómo diferenciar dermatitis atópica versus síndrome hiper-IgE? Reporte de casos Carlos Olmos-Olmos Immune response to multi-epitope Blomia tropicalis hybrid protein in mice Dalgys Martínez, Brenda Flam, Helber Herazo, Inés Benedetti, Narasaiah Kolliputi, Luis Caraballo, Richard F. Lockey Leonardo Puerta Next generation sequencing identifies mutations in Colombian patients with primary immunodeficiency diseases Carlos Andrés Arango-Franco, Marcela Moncada-Vélez, Alexander Franco-Gallego, Lucía Victoria Erazo, Catalina Martínez, Sebastián Gutiérrez, Jesús Armando Álvarez, , Manuela Molina, Diana Arboleda, Laura Naranjo, Juan Álvaro-López, Juan Fernando Alzate, Felipe Cabarcas, Claudia Milena Trujillo- Vargas, Julio César Orrego, Satoshi Okada, Anne Puel, Jacinta Bustamante, Jean-Laurent Casanova, Andrés Augusto Arias, José Luis Franco Niña con infección recurrente y severa de virus Epstein-Barr CD27 negativo. Reporte de caso Ana Ivette Mondragón-Pineda Non-interventional post-marketing safety study on the long-term safety of HyQvia (global) Lina Laguado, Katharina Fielhauer, Andras Nagy,2 Christopher J. Rabbat, Barbara McCoy, Heinz Leibl, Leman Yel Novel mutations in NCF4 gene confer non-classic chronic granulomatous disease with disseminated histoplasmosis in a Colombian child Carlos Andrés Arango-Franco, Alejandro Nieto-Patlán, Marcela Moncada-Vélez, Jesús Armando Álvarez, Carmen Oleaga-Quinta, Caroline Deswarte, Juan Fernando Alzate, Felipe Cabarcas, Carlos Garcés, Julio César Orrego, Susana Pamela Mejía, Luz Elena Cano, Jean-Laurent Casanova, Jacinta Bustamante, José Luis Franco, Andrés Augusto Arias Registro y caracterización de pacientes con inmunodeficiencia primaria en un centro ambulatorio de alergología e inmunología en Bogotá Catalina Gómez-Parada Relación entre la expresión del alelo HLA DRB1*08:02 y reacciones de hipersensibilidad al medicamento bucilamina en poblaciones amerindias colombianas Carlos Hernando Parga-Lozano Relación filogenética de alelos HLA con presencia de alergias en poblaciones amerindias Carlos Hernando Parga-Lozano, Nohemí Santodomingo Guerrero Reporte epidemiológico de inmunodeficiencias primarias en el Centro Jeffrey Modell de Colombia: 1987-2017 Lina Rocío Riaño-Cardozo, Natalia Correa-Vargas, Alejandro Gallón-Duque, Julio César-Orrego, José Luis Franco Respuesta IgE a extracto de Blomia tropicalis y Ascaris spp. en población proveniente de San Basilio de Palenque Andrés Merlano, Luis Fang, Beatriz Martínez, Catherine Meza, Luz Hernández, Eloína Zárate, Javier Marrugo Secuenciación completa del exoma como herramienta para el diagnóstico molecular de la enfermedad granulomatosa crónica Manuela Molina, Diana Marcela Arboleda, Marcela Moncada, Gabriel Vélez, Juan Fernando Alzate, Felipe Cabarcas, José Luis Franco, Andrés Augusto Arias-Sierra, Juan Álvaro-López The sigma-and omega-class members of the glutathione-S-transferase family from ascaris are IgE binding components with marked differences in the IgG1 and IgG4 response Ana Milena Lozano-Mendoza, Juana Bustillo, Juan López, Luis Caraballo, Josefina Zakzuk

In responding to our paper on the current limitations in influenza antiviral susceptibility testing in Europe, Ciancio and Nicoll criticise our suggestions for enhanced capacity in individual countries and favour a system that, as at present, relies on resistance monitoring by predefined central laboratories, as they consider this model most effective for clinical and public health purposes during a pandemic.

AbstractInsufficient operator training has been identified as an underlying root cause for many errors of point-of-care testing. However, while the need for operator training is beyond doubt, the practical solutions on how to train operators remain challenging. Therefore a multidisciplinary team of experts created the application guide VDE-AR-E 2411-2-101 “Schulung professioneller Anwender von patientennahen Tests” (Training of professional users of devices for near-patient testing). This work is based on the talk of Nicola Barabas during the POCT-Symposium in Munich 2017 and presents selected aspects of the application guide such as the role of the manufacturer, the learning path, the selection of training topics, the train-the-trainer concept and e-learning.

Background and aims: More than 15 million children worldwide are thought to have one or more congenital or acquired visual impairments. If their immune system is defective due to poor nutrition, children are more susceptible to eye infections and other eye disorders. The ongoing, intense war and disruption of social services have had a clear impact on the overall health and nutritional status of children and the entire population in Yemen. Therefore, the purpose of this study was to study bacterial conjunctivitis in malnourished children by identifying bacterial causes and associated factors and determining patterns of ocular antibiotic resistance in bacterial isolates. Subject and methods: A cross-sectional study was carried out in the three selected places (Alkhpt hospital in Al-Kapt district, Al-Khamis hospital in Al-Khamisdistrict, and Al-Joumhori hospital in Al-Mahwatt city), from November 2022 until June 2023. The first clinical investigations of malnutrition and conjunctivitis were done by doctors in the hospitals and recorded in the pre-designed questionnaire. Collected eye swabs were investigated for bacteriological agents and antibiotic susceptibility according to standard laboratory methods in the National Center of Public Health Laboratories Sana’a (NCPHL). Results:The study included 351 males (46.4%) and 406 females (53.6%). 143 children (18.9%) suffer from moderate acute malnutrition (MAM) and 55 (7.3%) from severe acute malnutrition (SAM), with total global acute malnutrition equal to 198 (26.2%).There was a highly significant association of bacterial conjunctivitis with MAM (OR=3.1, p<0.0001), SAM (OR=2.9, p<0.0001), and severe stunting (OR=2.2, p<0.0001). Conclusions: The severity of acute malnutrition was very high in the study area, reaching a critical phase and exceeding the emergency threshold. The commonest causative organisms of bacterial conjunctivitis were S. aureus and Branhamella catarrahalis. Since there isn't a single medication that can effectively treat these diverse species of bacteria, it's best to look into bacteriological culture and in vitro antibiotic sensitivity. Peer Review History: Received: 3 November 2023; Revised: 11 December; Accepted: 9 January 2024, Available online: 15 January 2024 Academic Editor: Dr. Amany Mohamed Alboghdadly, Ibn Sina National College for Medical Studies in Jeddah, Saudi Arabia, amanyalboghdadly@gmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Nkechi Obiofu Ezenobi, University of Port Harcourt, Nigeria, nkechi.ezenobi@uniport.edu.ng Dr. Nicola Micale, University of Messina, Italy, nmicale@unime.it

La Universidad Tecnológica Nacional Facultad Regional Buenos Aires (UTN.BA) ha organizado, junto a la Secretaría de Ciencia, Tecnología e Innovación Productiva, el Departamento de Electrónica, y el Laboratorio de NanoElectrónica (UTN-UIDI-CONICET) , la 2da edición del Simposio de Nanomateriales 2D, Grafeno, Dispositivos y Aplicaciones (https://nanomateriales2d.frba.utn.edu.ar/). El mismo se realizó íntegramente en formato virtual, dada las circunstancias de aislamiento que impone la pandemia de Covid-19. Este evento se dedicó al estudio de todos los materiales 2D que iniciaron con el descubrimiento del grafeno y su objetivo principal fue abordar las temáticas relativas a las propiedades físicas y químicas de los materiales 2D. A su vez se incluyeron las diversas aplicaciones de estos materiales, como ser la conformación de dispositivos, el almacenamiento y conversión de energía, el sensado y catálisis química, propiedades óptica y electrónica flexible entre otras más. El Simposio ha contado con las ponencias de más de 18 profesores distinguidos de EEUU, España, Chile y Argentina, que lideran la más amplia gama de investigaciones regionales, y en la mesa redonda participaron 4 especialistas del área de transferencia de conocimientos a la industria. Por otra parte, se han recibido diversos trabajos científicos y pósters , que fueron evaluados por los 10 miembros que componían el comité científico, y que participaron de la premiación al mejor Poster, mejor Video y al mejor Trabajo Finalista del simposio, y la concurrencia total al simposio superó las 100 visitas virtuales de diversos países entre los cuales cabe destacar diversas participaciones desde Brasil, Perú, Colombia, Chile y Argentina. Finalmente los vídeos del simposio se encuentran disponibles para su reproducción en la dirección: https://livestream.com/utnba/2dosimposionanomaterialesdia34. Desde el comité organizador agradecemos la participación de los asistentes del simposio y a cada uno de los que trabajaron arduamente para la realización de esta 2da edición del evento. Comité científicoProf. Dr. Felix Palumbo (Presidente / Chair)Prof. Dr. Francisco IbañezProf. Dra. Liliana ArracheaProf. Dra. Emilia HalacProf. Emérito Dr. Eduardo J. QuelProf. Dra. Mariela del GrossoProf. Dr. Hernan CalvoProf. Dr. Ricardo ArmentanoProf. Dr. Walter LegnaniProf. Dr. Julio Raba Comité OrganizadorDr. Francisco IbañezDr. Felix PalumboIng. Brenda RossiIng. Damian GranzellaIng. Emiliano BorghiIng. Cesar FuocoIng. Sebastián PazosIng. Fernando AguirreLic. Santiago BoyerasIng. Gabriel MaroliFranco CapraruloCarlos Nicolas AlanesSebastián FalconeAndrea MarquinezCristian De BonisDiego Gabriel AlboresDr. Hernan Giannetta (Presidente / Chair)

IntroductionStress is associated with disease and reduced leukocyte telomere length (LTL). The objective of this research is to determine if self-perceived stress is associated with telomere length in Costa Rican adults and the gender differences in this association. Findings may help explain how some populations in apparent socioeconomic disadvantage and with limited access to specialized medical services have a remarkably high life expectancy.MethodologyData come from the pre-retirement cohort of the Costa Rican Longevity and Healthy Aging Study (CRELES), a population based survey conducted in the households to 2,327 adults aged 53 to 66 years. The DNA to measure LTL was extracted from blood cells in laboratories of the University of Costa Rica whereas the Blackburn laboratory at the University of California performed the telomere length measurement applying the quantitative polymerase chain reaction (Q-PCR). The relationship between telomere length and perceived stress was measured using least-squares multiple regression. Perceived stress was measured by a set of questions about family, job, finances and, health reasons to be stressed. Models included the control variables: (1) age and sex of the participant, (2) whether he or she resides in the Nicoya area, a “blue zone” known for its high longevity, and (3) the aforementioned sociodemographic, health and lifestyles characteristics.ResultsStress perception and LTL are significantly different by sex. Women perceived higher stress levels than men in almost all aspects studied, except work. Women have significantly longer telomeres. Shorter telomeres are significantly associated with caregiving stress in men and with parental health concerns in women. Counter-intuitive telomere lengthenings were observed among women who feel stressed about caring for family members; and among men who feel stressed due to their family relationships as well as concerns about their own health.DiscussionResults confirm that people with self-perceived stress due to caregiving or health issues have shorter telomeres. The relationship between stress and telomere length differs between men and women. Gender relations exert a strong modifier effect on the relationship between stress and LTL: gender is related to perceived stress, telomere length, and apparently also to the way stress and LTL are related.

Abstract Background Gepotidacin is a novel, bactericidal, first-in-class triazaacenapthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and binding site and provides well-balanced inhibition of 2 different Type II topoisomerase enzymes. This study reports on the in vitro activity of gepotidacin and other oral antibiotics when tested against contemporary Escherichia coli and Staphylococcus saprophyticus clinical isolates collected from patients with UTIs for a gepotidacin uUTI global surveillance study. Methods A total of 1,001 E. coli and 92 S. saprophyticus isolates were collected during 2022 from 45 medical centers located within the United States. Most isolates (77%) tested were cultured from urine specimens collected from patients seen in ambulatory, emergency, family practice, and outpatient medical services. Bacterial identifications were confirmed by MALDI-TOF MS. Isolates were tested for susceptibility by CLSI methods at a central laboratory (JMI Laboratories). MIC results for oral antibiotics licensed for the treatment of uUTI and drug-resistant subsets were interpreted per CLSI guidelines. Results Gepotidacin (MIC50/90, 2/4 µg/mL) displayed good activity against 1,001 E. coli isolates as 98.8% of all observed gepotidacin MICs were ≤4 µg/mL (Table). Other oral agents tested against these isolates demonstrated the following rates of susceptibility (S): amoxicillin-clavulanate (85.2% S), ampicillin (55.6% S), ciprofloxacin (78.8%S), fosfomycin (99.3% S), mecillinam (93.5%S), nitrofurantoin (97.5% S), and trimethoprim-sulfamethoxazole (73.3% S). Gepotidacin maintained similar MIC50 values (ranging from 1 – 2 µg/mL) and MIC90 values (ranging from 2 – 4 µg/mL) against these drug-resistant subsets. Against S. saprophyticus isolates, gepotidacin (MIC50/90, 0.06/0.12 µg/mL) inhibited all isolates at ≤0.12 µg/mL. Most oral agents showed &gt;90% S against S. saprophyticus isolates, except for penicillin (7.6% S). Conclusion Gepotidacin demonstrated in vitro activity against contemporary E. coli and S. saprophyticus from US urine isolates. This activity remained unaffected by resistance to other oral standard-of-care antibiotics. Disclosures S J Ryan Arends, PhD, Cipla: Grant/Research Support|GSK: Grant/Research Support Renuka Kapoor, PhD, GSK: Grant/Research Support Didem Torumkuney, PhD, GSK: Grant/Research Support Nicole E. Scangarella-Oman, MS, GSK: Employee and shareholder Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support

Abstract Background Gepotidacin is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action that confers activity against most strains of target pathogens, such as Escherichia coli, Staphylococcus saprophyticus, and Neisseria gonorrhoeae, including those resistant to current antibiotics. This study reports on the in vitro activity of gepotidacin and other oral antibiotics tested against E. coli clinical isolates collected from patients with UTIs for a gepotidacin UTI global surveillance study as part of the SENTRY Antimicrobial Surveillance Program. Methods A total of 1,978 E. coli isolates were collected between 2019-2021 from 47 medical centers within the US. All isolates were cultured from urine specimens collected from patients seen in emergency and outpatient medical services representative of community-acquired infections. Bacterial identifications were confirmed by MALDI-TOF. Isolates were tested for susceptibility by CLSI methods at a central laboratory (JMI Laboratories). MIC results for oral antibiotics licensed for the treatment of uUTI, multidrug-resistant (MDR), and extended-spectrum β-lactamase (ESBL) subsets were interpreted per CLSI criteria. Results Gepotidacin (MIC50/90, 2/4 mg/L) displayed good activity against 1,978 E. coli isolates, with 98.3% of all observed gepotidacin MICs ≤4 mg/L (Table). Susceptibility (S) rates for other oral agents tested against these isolates were: amoxicillin-clavulanate (83.7%S), ampicillin (50.9%S), ciprofloxacin (79.1%S), fosfomycin (99.7%S), mecillinam (94.2%S), nitrofurantoin (98.2%S), and trimethoprim-sulfamethoxazole (71.3%S). When tested against the drug-resistant subsets, gepotidacin maintained similar MIC50/90 values (1-2/4 mg/L). Gepotidacin was also active against ESBL and MDR E. coli isolates, inhibiting 94.7% and 95.9%, respectively, at gepotidacin concentrations ≤ 4 mg/L. Conclusion Gepotidacin demonstrated potent in vitro activity against contemporary community-acquired E. coli urine isolates. This activity was maintained among isolates demonstrating resistance to other oral standard of care antibiotics including ESBL, FQ-R, and MDR E. coli. Disclosures SJ Ryan Arends, PhD, AbbVie: Grant/Research Support|GSK: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Shionogi: Grant/Research Support Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Lindsey Tholen, BS (ASCP), GSK: Board Member|GSK: work for hire|Shionogi: Grant/Research Support Jennifer M. Streit, BS, MT(ASCP), Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Shionogi: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

Background and Aims: Visceral leishmaniasis (VL) is a zoonotic and human disease caused by species of Leishmania. Parasites are transmitted to the vertebrate host by the bite of a sand fly female (Phlebotomus longipalpis), where the infected promastigotes transform into amastigotes; and this is deadly if left untreated. The purposes of the current research were to reveal the prevalence and potential risk factors for VL in adults in Sana’a city, Yemen. Subjects and methods: This cross-sectional study was performed during the period from January 2020 to November 2020. Individuals who come for a regular medical examination at Al-Zahrawi Medical Center, Althobhani Specialist Laboratories, Police Hospital, and University of Science and Technology Hospital. A target sample size of 300 was selected, and serum samples were collected from all subjects to determine the prevalence of anti-VL antibodies in human by immune-chromatographic assay using K39 recombinant antigen. Results: The ages of the participants' ranged from 18-65 years, with a mean of 29.8±8.2 years. The positive rate of antibodies against Leishmania species by immune-chromatographic dipstick strip (rK39) was 6.0%. There was statistically important association linking male gender and contracting VL (8.8%, OR=4.1, CI=1.2-14.4, P=0.01). There was a significant association (<0.001) between the presence of dogs, rats, and goats in or around live houses and positive VL antibodies with an OR equal to 8.8.7.3 and 8.4, respectively. There were significant risk factors for garbage around the living house, there was also a significant association between displacement and the incidence of VL (P<0.001) (OR=8.6, CI=2.8–27.2). Conclusion: Visceral leishmaniasis was highly prevalent in Sana'a city, and potential risk factors for VL were present with displacement, dogs, rats, goats, garbage, sleeping outside enclosed rooms, and sand flies in living houses. Further studies of human VL need to be conducted to clarify this issue in Yemen, to track and confirm potential reservoirs among canines and other animals, as well as to study vectors. Keywords: adults, immune-chromatographic assay, prevalence, potential risk factors, recombinant antigen K39, Sana’a city, visceral leishmaniasis, Yemen. Peer Review History: Received: 9 March 2022; Revised: 14 April; Accepted: 29 April, Available online: 15 May 2022 Academic Editor: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Tamer Elhabibi, Suez Canal University, Egypt, tamer_hassan@pharm.suez.edu.eg Dr. Nicola Micale, University of Messina, Italy, nmicale@unime.it Dr. Rawaa Souhil Al-Kayali, Aleppo University, Syria, rawah67@hotmail.com Similar Articles: PREVALENCE OF HEPATITIS G VIRUS AMONG PATIENTS WITH CHRONIC LIVER DISEASE AND HEALTHY INDIVIDUALS, SANA'A CITY-YEMEN

In 2008, Nicolas Eastaugh, founder and chief researcher at Art Discovery, a renowned London company for the analysis and research of artwork, discovered the presence of the white titanium (titanium dioxide) pigment in a painting attributed to the Dutch naturalized expressionist artist Heinrich Capendonk. The work had reached a record value of EUR 2.4 million at an auction in 2006. However, in 1915, the year in which the work was supposed to have been created, white titanium was not even available for use as a pigment, which would happen about 20 to 30 years later. The analytical result achieved by Eastaught revealed one of the biggest schemes of artwork forgeries ever discovered. The forger, Wolfgang Beltracchi, made a fortune, (under)estimated at EUR 30 million, built over 25 years acting in the art market. There are several cases of counterfeiting schemes involving artwork, large fortunes, renowned galleries, museums, collectors, specialists, and masterpieces. Cases like the one revealed by Eastaugh's analyses or the millionaire counterfeit scheme involving the century-old North American Knoedler Gallery are illustrative examples of how the art market is vulnerable to this kind of crime. The International Monetary Fund (IMF) and the United Nations Office on Drugs and Crime (UNODC) estimated the total annual trade in art and antiques in 2018 at around USD 70 billion, of which about USD 6 billion may have been due to illegal transactions related to theft, counterfeiting, smuggling, and organized crime. Still according to those institutions, half of that amount involved financial crimes and money laundering. In Brazil, within the scope of the Lava Jato Operation, the Federal Police seized 842 pieces of art and historical and cultural heritage, including paintings from different historical periods, sculptures, and other pieces, which add up to an estimated value of over BRL 33 million. All the pieces were related to investigations involving money laundering in cases of active and passive corruption. As other forms of money laundering resulting from various crimes have been curtailed by world authorities through specific legislation, the art market world has become increasingly attractive to crime. This scenario, combined with the great financial relevance of the legitimate art market, caused a very considerable increase in the demand for works by renowned authors and, as a direct consequence, a proportional increase in the number of forgeries and adulterations. As a result, the quality of counterfeits has also experienced a great improvement, requiring a proportional gain in technology and expertise in forensic analysis and authentication fields. Similarly, the high speculation in prices of artworks also increased the interest in new and advanced analytical techniques for determining authenticity, authorship, origin, and materials used by the authors. The refinement of counterfeiting and adulteration techniques has demanded a multidisciplinary and technological approach to the authentication process, and, at this point, we are faced with a considerable degree of complexity in the already difficult process of authenticating works of art. The authorship or authenticity determination of a painting is unavoidably based on a triangle formed by three disciplines: art history, preservation sciences, and materials sciences. The voices of our benches and equipment are unlikely to be able, on their own, to unequivocally conclude the authenticity of a work of art. Likewise, the most trained eyes of a professional connoisseur are no longer able to face the most astute counterfeiters. The best results of authenticity studies will always be achieved when these three distinct disciplines come together and complement each other in the search for comprehensive, technical, and artistic knowledge about the work. In addition to the historical study of the piece, the physical–chemical characterization of materials and components or elementary and multispectral imaging become powerful tools for fraud detection and even characterization and individualization of the authentic piece. The simplest techniques, generally used for initial documentation, to the more complex, analytical resources are used to extract the greatest amount of information from the different parts that make up a painting. In its diverse and complex layers, from the support to the final coating, paintings are composed of multilayers of heterogeneous mixtures of varied organic and inorganic compounds. A thorough investigation of this scenario always requires the use of advanced and combined techniques to better understand each case, depending on their nature. The analysis of the painting surface by a stereo-microscope will reveal genuine—or artificially produced—craquelure or brushwork patterns compatible with the artistic style proposed by the author of the work. Likewise, the UV fluorescence properties of the painting may differentiate between old and new additions of paint to the piece. However, it is in the deepest layers of an artwork that the most sophisticated analytical techniques contribute most incisively. X-ray radiography and infrared reflectography, coupled with ultra-sensitive charge-coupled devices (CCD), began to detect underdrawings that were invisible to the previously available methods. Several works have demonstrated the usefulness of tools such as synchrotron radiation, microimaging by X-ray fluorescence (XRF), and Raman or Fourier-transform infrared (FTIR) spectroscopies, combined with the versatility of portable spectrometric identification techniques, where pigment particles less than 1 micrometer in diameter can be analyzed. Even the power of pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) to identify novel synthetic organic polymers, which greatly assists in the analyses of pigments, coatings, binders, and other painting components, can, in many cases, reveal anachronisms present in the counterfeits. Other techniques such as laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), isotope-ratio mass spectrometry (IRMS), and accelerator mass spectrometry (AMS) allow for the determination of isotopic ratios of heavy and light elements, which are decisive to determining the geographical origin of some pigments and the age of a painting canvas or its wooden frame. Such techniques used in association with multivariate analysis tools, artificial intelligence, and machine learning help achieve increasingly conclusive results, requiring less time and effort from the entire team of researchers. Each of the analytical techniques, evaluated for their versatility, resolution power, type of information generated, portability, and employment, have the potential for greater use in combined and multimodal work. This approach makes the description of the artwork much more precise and richer in details since it individualizes not only its components, support, and coating materials, but also the context in which they were used. The wisdom in better bringing together the analytical resources available and performing the analyses required by each case determines the success of a forensic examination of a forgery or the authenticity of a work of art. It is not hard to see that it is unlikely that a single company or laboratory, whether public, private, academic, or not, will own all the technological resources to exhaust such an analysis. Furthermore, it is not uncommon for crimes involving works of art to be transnational. All this leads us to the last step of our range of complexity: laboratories, museums, forensic, and research institutes involved in examining the authenticity of artworks should operate on secure and integrated networks, generating data that is widely shared between partner institutions. Several institutes in the world already work in this way, such as INTERPOL, the INTERNATIONAL COUNCIL OF MUSEUMS (ICOM), the Federal Bureau of Investigation (FBI), UNODC, and the Integrated Platform for the European Research Infrastructure on Cultural Heritage (Iperion CH). This has proven to be one of the most effective ways to curb this type of crime, which, sneakily, erodes our history and cultural heritage.

In the years surrounding the turn of the millennium, there emerged an assemblage of American and Spanish horror films fixated on uncanny child characters. Caught in the symbolic abyss between death and life, these figures are central to the films’ building of suspense and Gothic frisson—they are at once familiar and unfamiliar, vulnerable and threatening, innocent yet unnervingly inscrutable. Despite being conceived and produced in two very different cultural climates, these films construct the child as an embodiment of trauma in parallel ways. In turn, these Gothic children express the wavering of narratives of progress which suffused the liminal moment of the millennial turn. Steven Bruhm suggests that there is “a startling emphasis on children as the bearers of death” (author’s emphasis 98) in popular Gothic fiction at the turn of the new millennium, and that this contemporary Gothic “has a particular emotive force for us because it brings into high relief exactly what the child knows ... Invariably, the Gothic child knows too much, and that knowledge makes us more than a little nervous” (103). A comparative analysis of trans-millennial American and Spanish supernatural horror films reveals the specifically threatening register of the Gothic child’s knowledge, and that the gradual revelation of this knowledge aestheticizes the mechanics of trauma. This “traumatic” aesthetic also entails a disruption to linear progress, exposing the ways in which Gothic representations of the child’s uncanny knowledge express anxieties about the collapse of temporal progress. The eeriness associated with the child’s knowledge is thus tied to a temporal disjuncture; as Margarita Georgieva explains, child-centred Gothic fiction meditates on the fact that “childhood is quickly lost, never regained and, therefore, outside of the tangible adult world” (191). American films such as The Sixth Sense (M. Night Shyamalan, 1999) and Stir of Echoes (David Koepp, 1999), and Spanish films The Nameless (Jaume Balagueró, 1999) and The Devil’s Backbone (Guillermo del Toro, 2001), and also American-Spanish co-productions such as The Others (Alejandro Amenábar, 2001) and Fragile (Jaume Balagueró, 2005), expose the tangle of contradictions which lurk beneath romanticised definitions of childhood innocence and nostalgia for an adult’s “lost” childhood. The child characters in these films tend to be either ghosts or in-between figures, seemingly alive yet acting as mediators between the realms of the living and the dead, the past and the present. Through this liminal position, these children wreak havoc on the symbolic coherence of the films’ diegetic worlds. In so doing, they incarnate the ontological wound described by Cathy Caruth in her definition of trauma: “a breach in the mind’s experience of time, self, and the world” caused by an event that “is experienced too soon, too unexpectedly, to be fully known and is therefore not available to consciousness until it imposes itself ... repeatedly ... in the nightmares and repetitive actions” (4) of those who have experienced trauma. The Gothic aesthetic of these children expresses the ways in which trauma is locatable not in the original traumatic past event, but rather in “the way it was precisely not known in the first instance”, through revealing that it is trauma’s unassimilated element which “returns to haunt the survivor later on” (Caruth, author’s emphasis 4). The uncanny frisson in these films arises through the gradual exposition of the child character’s knowledge of this unassimilated element. As a result, these children trouble secure processes of symbolic functioning, embodying Anne Williams’ suggestion that “Gothic conventions imply a fascination with … possible fissures in the system of the symbolic as a whole” (141). I suggest that, reflecting Bruhm’s assertion above, these children are eerie because they have access to memories and knowledge as yet unassimilated within the realm of adult understanding, which is expressed in these films through the Gothic resurfacing of past traumas. Through an analysis of two of the most transnationally successful and influential films to emerge from this trend—The Sixth Sense (1999) and The Devil’s Backbone (2001)—this article explores the intersecting but tellingly distinctive ways in which the American and Spanish horror films figure the child as a vessel for previously repressed trauma. In both films, the eeriness of the children, Cole and Santi respectively, is associated with their temporal liminality and subsequent ability to invoke grisly secrets of the past, which in turn unsettles solid conceptions of identity. In The Sixth Sense, as in other American ghost films of this period, it is an adult character’s subjectivity which is untethered by the traumas of the uncanny child; Bruhm suggests that the contemporary Gothic “attacks adult self-identity on multiple fronts” (107), and in American films the uncanny child tends to launch this traumatic assault from within an adult character’s own psyche. Yet in the Spanish films, the Gothic child tends not to threaten an individual adult figure’s self-identity, instead constituting a challenge to secure concepts of socio-cultural identity. In The Sixth Sense, Cole raises a formerly repressed trauma in the mind of central adult character Malcolm Crowe, while simultaneously disturbing the viewer’s secure grasp on the film’s narrative world. Ultimately, Cole raises Freudian-inflected anxieties surrounding childhood’s disruption to coherent adult subjectivity, functioning as a receptacle for the adult’s repressed secrets. Cole’s gradual exposure of these secrets simulates the effects of trauma for both Malcolm and the viewer via a Gothic unsettling of meaning. While The Sixth Sense is set in the present, The Devil’s Backbone is set during the Spanish Civil War (1936-39)—a violent and traumatic period of Spain’s history, the ramifications of which have been largely unexplored in Spanish popular culture until very recently as a result of forty years of strict censorship under General Franco, whose dictatorship eroded following his death in 1975. Unlike Cole, Santi does not arouse a previously submerged trauma within an adult character’s mind, instead serving to allegorically raise socio-cultural trauma. Santi functions as an incarnation of Gilles Deleuze’s “child seer”, a figure who Deleuze claims first emerged in Italian neo-realist films of the 1940s as a response to the massive cultural rupture of World War II (3). The child seer is characterised by his entrapment in the gap between the perception of a traumatic event, and the understanding and subsequent action required to move on from it. Thus, upon experiencing a disturbing event, he suffers a breach in comprehension which disrupts the typical sensory-motor chain of perception-understanding-action, rendering him physically and mentally unable to escape his situation. Yet in experiencing this incapacity, the seer gains a powerful insight beyond the limits of linear temporality. On becoming a ghost, Santi escapes coherent space-time, and invokes the repressed spectre of Spain’s violent Civil War past, inciting an eerie collision of past and present. This temporal disruption has deep allegorical implications for contemporary Spain through the child’s symbolic status as vessel for the future. Santi’s embodiment of cultural trauma ensures that Spain’s past, as constructed by the film, eerily folds into the nation’s extra-diegetic present. The Sixth Sense In The Sixth Sense, adult protagonist Malcolm Crowe is a child psychiatrist, thus unravelling the riddles of the child’s psyche is positioned as the central quest of the film’s narrative. The dramatic twist in the film’s final scene reveals that the analysis of the child Cole’s “phobia” has in fact exhumed dormant spectres within Malcolm’s own mind, exposing the Gothic mechanisms whereby the uncanny child becomes conflated with the adult’s repressed trauma. This impression is heightened by the narrative structure of The Sixth Sense, in which the twist in the final scene shifts the meaning of all that has happened before. Both the audience and Malcolm are led to assume that they have uncovered and come to terms with Cole’s secret once it becomes clear two-thirds into the film that he “sees dead people”. However, the climactic twist exposes that Cole has in fact been hiding another secret which is not so easily ameliorated: that Malcolm is one of these dead people, having died in the film’s opening sequence. If the film’s narrative “pulling the rug out” from under the audience functions as intended, at the climax of the film both Malcolm and viewer simultaneously become privy to a layer of Cole’s secret previously inaccessible to us, both that Malcolm has been dead all along and that, subsequently, the hidden quest underlying the surface narrative has been Malcolm’s journey to come to terms with this disturbing truth. Thus, the uncanny child functions as a symbolic stage for the adult protagonist’s unassimilated trauma, and the unsettling nature of this experience is extended to the viewer via the gradual exposure of Cole’s secret. Further intensifying the uncanny effects of this Gothic disruption to adult knowledge, Cole also functions like a reincarnation of the crisis which has undermined Malcolm’s coherent identity as a successful child psychiatrist: his failure to cure former patient Vincent. Thus, Cole is like uncanny déjà vu for Malcolm and the viewer, an almost literal re-evocation of Malcolm’s past trauma. Both Vincent and Cole have a patch of grey hair at the back of their head, symbolising their access to knowledge too great for their youth, and as Malcolm explains, “They’re both so similar. Same mannerisms, same expressions, same things hanging over their heads.” At the opening of the film, Vincent is depicted as a wretched madman. He appears crying and half naked in Malcolm’s bathroom, having broken into his house, before shooting Malcolm and then turning the gun on himself. Thus, Vincent is an abject image of Malcolm’s failure, and his taunting words expose a rupture in Malcolm’s paternalistic, professional identity by hinting at his lack of awareness. “You don’t know so many things” Vincent remarks, and sarcastically undermines Malcolm’s “saviour” status by taunting, “Don’t you know me, hero?”. Functioning as a repetition of this trauma, Cole provides Malcolm with an opportunity to discover the “so many things” that he does not know, and also to once again become a “hero”. Cole functions as a literalisation of Malcolm’s compulsion to repeat the trauma which has exposed a breach in his sense of self, and to gain mastery over it. On first viewing, the audience is led to believe that this narrative is the primary one in the film, and that the film is wrapped up when Malcolm finally achieves his goal and becomes Cole’s hero. However, the final revelation that Cole has been keeping yet another secret from Malcolm—that Malcolm has been dead all along—reveals that this trauma is actually irrevocable: Malcolm was in fact killed by Vincent at the beginning of the film, thus the adult’s subjective breach (symbolised by his gunshot wound, which he suddenly notices for the first time) cannot be filled or repaired. All Malcolm can do at the close of the film is disappear, as a close-up of his face fades into the mediated image of him, now his only form of existence in the world as we know it, on the home videotapes of his wedding which play as his wife sleeps. Thus, Cole evokes the experience of a violent, unassimilated trauma which is experienced “too soon, too unexpectedly to be fully known in the first instance” (Caruth 4), a breach in subjectivity which has only become consciously known to Malcolm through the “nightmare repetition” figured by Cole. This experience of a traumatic disruption to the wholeness and coherence of subjective reality is echoed by the viewer’s own experience of The Sixth Sense, if the twist-narrative functions as intended. While on first viewing we are led to believe that we are watching a straightforward ghost story about a paternalistic psychologist helping a young child with an uncanny gift, we learn in the final scene that there has been an underlying double reality haunting the surface narrative all along. Central to this twist is the recognition that Cole was always aware of this second reality, but has been concealing it from Malcolm—underscoring the ways in which Malcolm’s trauma is bound up largely with what he was unable to comprehend and assimilate when the traumatic event of his death first occurred. The eerie effects of Malcolm’s traumatic confrontation with the child’s Gothic knowledge is extended to the viewer via the film’s narrative structure. Erlend Lavik discusses The Sixth Sense and other twist films in terms of a particular relationship between the syuzhet (the way in which a story’s components are organized) and the fabula (the raw components which constitute the story). He explains that in such films, there is a “doubling of the syuzhet, where we are led to construct a fabula that initially seems quite straightforward until suddenly a new piece of information is introduced that subverts (or decentres) the fictional world we have created. We come to realize the presence of another fabula running parallel to the first one but ‘beneath’ it, hidden from view” (Lavik 56). The revelation that Malcolm has been a ghost all along shatters the fabula that most viewers construct upon first viewing the film. The impression that an eerie, previously hidden double of accepted reality has bubbled to the surface of our perceptions is deeply uncanny, evoking the experience of filmic déjà vu. This is of course heightened by the fact that the viewer is compelled to re-watch the film in order to construct the second, and more “correct”, fabula. In doing so, the viewer experiences a “narrative bifurcation whereby we come to notice how traces of the correct fabula were actually available to us the first time” (Lavik 59). The process of re-watching the film in an attempt to solve the riddles of Malcolm’s existence reveals the viewer’s compulsion to undergo their own “detective work” in a parallel of Malcolm’s analysis of Cole: the exposure of the child’s secret turns a mirror upon the protagonist and audience which exposes a fracture in the adult’s subjectivity. Discussing the detective story, Slavoj Žižek explains that “the detective's role is ... to demonstrate how ‘the impossible is possible’ ... that is, to resymbolize the traumatic shock, to integrate it into symbolic reality” (58). On first viewing, this detective work is realized through Malcolm’s quest to comprehend Cole’s secrets, and then to situate the abject ghosts the child sees into a secure framework whereby they disappear if Cole helps them. The compulsion to re-watch the film in order to better understand how Malcolm experiences time, consciousness and communication (or lack there-of) represents an analogous attempt to re-integrate the traumatic shock raised by the twist-ending by imposing more secure symbolic frameworks upon the film’s diegetic world: to suture the traumatic breach in meaning. However, there are many irremediable gaps in Malcolm’s experiences—we do not actually see him trying to pay for the bus, or meeting Cole’s mother for the first time, or pondering the fact that no other human being has spoken to him directly for six months apart from Cole—fissures which repeat viewings cannot repair. The Devil’s Backbone The Devil’s Backbone is set in the final years of the Civil War, a liminal period in which the advancement of Spain’s national narrative is disturbingly uncertain. The film takes place in an orphanage for young boys from Republican families whose parents have been killed or captured in the Civil War. In the middle of the orphanage’s courtyard stands an unexploded bomb, an ominous and volatile reminder of the war. As well as being haunted by this unexploded bomb, the orphanage is also haunted by a child ghost, Santi, a former inhabitant of the orphanage who disappeared on the same night that the bomb landed in the orphanage’s grounds. We learn mid-way through the film that Santi in fact drowned in the orphanage’s cavernous cistern: after being struck on the head by the angry groundskeeper, Santi was left unable to swim, and is shown sinking helplessly into the water’s murky depths. Thus, Santi’s death represents the ultimate extreme of the child seer’s traumatic entrapment between perceiving and understanding the traumatic event, and the physical action required to escape it. Both the ghostly Santi and the unexploded bomb exude an eerie power despite, and perhaps because of, their apparent physical incapacity. Such corporeal powerlessness is the defining feature of Deleuze’s “child seer”, as the breach in the sensory-motor chain comes to imbue the child who encounters trauma with a penetrating gaze which sees beyond temporal borders. Once he becomes a ghost, Santi escapes the bounds of linear time altogether, becoming forever fused to the moment of his drowning. Santi’s spectral presence warps the ether around him as if he is permanently underwater, and the blood from his head wound constantly floats upwards. The sensory-motor chain becomes completely severed in a cinematic moment which can be likened to Deleuze “crystal of time”. Like the dual layers of narrative in The Sixth Sense, this crystal of time sparks a moment of Gothic frisson as linear time collapses and dual modes of temporality are expressed simultaneously: the chronological moment of Santi’s death—a ‘dead’ present that has already passed—and the fractured, traumatic memories of this past which linger in the present—what Deleuze would call a ‘virtual’ past which “coincides with the present that it was” (79). The traumatic effect of this collapse of temporal boundaries is enhanced by the fact that the shot of Santi drowning is repeated multiple times throughout the film—including in the opening minutes, before the audience is able to comprehend what we are seeing and where this scene fits into the film’s chronology. Ultimately, this cinematic crystal symbolically ungrounds linear narratives of Spanish history, which position the cultural rupture of the Civil War as a remnant of Spain’s past which has successfully been overcome. Through uncanny repetition, Santi’s death refuses to remain lodged in an immobilized “historical” past—a present that has passed—but remains forever alongside the present as an ethereal past that “is”. Santi’s raising of Gothic knowledge incites the wavering of not an adult character’s self-identity, as in The Sixth Sense, but a trembling in conceptual models of linear cultural progress. As a ghost, Santi is visually constructed as a broken porcelain doll, with cracks visible all over his body, emphasising his physical fragility; however, in his ghostly form it is this very fragility which becomes uncanny and threatening. His cracked body fetishizes his status as a subject who is not fully formed or complete. Thus, the film presents the post-Civil War child as a being who has been shattered and broken while undergoing the delicate process of being formed: an eerie incarnation of a trauma that has occurred “too soon” to be properly integrated. Santi’s broken body visualises the mechanisms whereby the violent conditions and mentalities of war permeate the child’s being in irreversible ways. Because he is soldered to the space and time of his death, he is caught forever as an expression of trauma in the inescapable gap between perception, assimilation and action. His haunting involves the intrusion of this liminal space onto the solid boundaries and binaries of the diegetic present; his abject presence forces other characters, and viewers, to experience the frisson of this previously concealed traumatic encounter. In so doing, Santi allegorically triggers the irruption of a fissure in the progression of Spain’s socio-cultural narrative. He embodies the ominous possibility that Spain’s grisly recent past may return within the child mutated by wartime trauma to engulf the future. The final scene of the film ideates the threshold of this volatile future, as the orphaned children stand as a group staring out at the endless expanse of desert beyond the orphanage’s bounds, all the adult characters having killed each other in a microcosm of the Civil War. Ultimately, both Cole and Santi enforce an eerie moment of recognition that the previously unassimilated traumas of the past live on within the present: a Gothic drawing forth of buried knowledge that exposes cracks in coherent meaning. In The Sixth Sense, Cole reveals the extent to which trauma is located in “the way it was precisely not known in the first instance” (Caruth 4), haunting Malcolm with his previous failure before exposing the all-encompassing extent to which this past trauma has fractured Malcom’s subjectivity. Santi of The Devil’s Backbone alludes to the ways in which this process of eliding past trauma extra-diegetically haunts contemporary Spain, particularly because those who were children during the Civil War are now the adult filmmakers, political leaders and constituents of Spanish society. These disturbances of historical and personal progress are rendered particularly threatening emerging as they do at the millennial turn, a symbolic temporal threshold which divides the recent past and the “new” present. The Gothic child in these contexts points to the danger inherent in misrecognizing traumatic histories—both personal and socio-cultural—as presents that have long-since passed instead of pasts that are. ReferencesBruhm, Steven. “Nightmare on Sesame Street: or, The Self-Possessed Child.” Gothic Studies 8.2 (2006): 98-210. Caruth, Cathy. Unclaimed Experience: Trauma, Narrative and History. Baltimore: Johns Hopkins University Press, 1996. Deleuze, Gilles. Cinema 2: The Time-Image. 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