Journal articles on the topic 'Villa E.1027'

This paper describes the method employed for the restoration of the Maison La Roche and the Villa E-1027 buildings, considered emblematic for modern French architecture. The radical atten- tion to material conservation was the main objective, supported by substantial research of the archives and minute analysis of the existing buildings, the results of which are reported. Maison La Roche became a museum compliant with the requirements of a public utility building. A discussion is given of the study and restoration of the murals by Le Corbusier conserved at Villa E-1027, which has not yet found a new function.

Design, beauty, the ethical question, aesthetics: all these terms are present in the story of Le Corbusier's drawings on the walls of Eileen Gray's villa E1027. Seven drawings were painted by Le Corbusier on the interior and exterior walls without her knowledge. They are drawings of considerable size and in very vivid colours and the author is undoubtedly one of the people who changed the culture of the 20th century. On the other hand, Gray's villa is also considered today one of the masterpieces of modern architecture: it is essential in its lines and colours and every detail has been carefully thought out and designed. The situation that arose with the inclusion of Le Corbusier's wall paintings poses many questions for those involved in Restoration. According to some lines of thought every intervention is a trace and as such it has its own meaning it tells a piece of history and as such it deserves to be preserved. In this specific case, however, Le Corbusier's brightly coloured drawings completely change the perception of the villa's spaces. In this case the preservation of a trace, no matter how significant it may be, has the power to change and cause the loss of the basic idea of this villa: preservation causes loss. This story therefore brings an important reflection on the role of conservation, on the ethics of restoration and also on the power that a drawing on a wall can have.

Corrosion in reinforced concrete is generally attributed to either carbonation or chloride presence in the vicinity of the bars. But in the field of cultural heritage, especially for the most ancient monuments, it is not rare to encounter both carbonated and chloride polluted concrete, inducing heavy corrosion, as was the case in the Villa E-1027 in Roquebrune-Cap-Martin, on the French Mediterranean seashore. The villa was designed by Eileen Gray and Jean Badovici between 1926 and 1929. Due to aggressive environmental conditions and a period of dereliction, the concrete of the villa was quite heavily decayed and a deep restoration was led between 2000 and 2006. But after a little more than 10 years, and despite active maintenance, the villa is again facing corrosion induced decay. Prior to the definition of a new restoration protocol, to better evaluate the corrosion activity, in 2017 a permanent monitoring of moisture and temperature both in the air and in the concrete was installed. In the meantime, a series of instant electrochemical measurements was performed from 2017 to 2018. A first analysis of the results of the monitoring and the non-destructive tests clearly evidences that probably due to the conjunction of the carbonation of the concrete and external active chloride pollution, corrosion can happen at quite low moisture content.

Coincidiendo con el cincuenta aniversario del fallecimiento de Le Corbusier, Tim Benton escribió Le Corbusier, peintre à Cap-Martin (Éditions du Patrimonie, 2015), que fue objeto de una reedición seis años después, también en francés. Sobre esta villa también ha publicado Cap Moderne. Eileen Gray and Le Corbusier. Modernisme by the Sea (2022) y ha colaborado en la antología E1027. Restoring a House by the Sea (2022). Con esta nueva versión inglesa viene a completar la difusión de este valioso libro que incide en una reconsideración crítica de la figura de Le Corbusier.

The restoration of the paintings of Le Corbusier in the Villa E-1027 was preceded by an important study phase including systematic sampling of the paintings. One purpose of the study was to determine the presence of the original paintings under the global over-paint made by a local craftsman in the seventies. Four of the eight paintings have been rediscovered, in a much better condition than expected. These paintings are a fragile testimony of the particular use of “Ripolin” by Le Corbusier, in the context of its use by others famous artists as Picasso or Picabia in the same period.

El presente artículo está basado en la exposición de M. Michel Richard, en el 3rd International Architecture Workshop 2017: Tourisme et patrimoine. Le territoire de Roquebrune-Cap Martin, realizado por la Designing Heritage Tourism Landscape Network, en septiembre de 2017, en Francia. Como Presidente, entonces, de la Fundación Le Corbusier y experto en su obra y en el trabajo de preservación que esta implica, Michel Richard llama a reflexionar sobre los desafíos que la apertura al turismo de masas presupone para dichas obras. Tal es el caso de las que fueron tema del Workshop antes mencionado (el Cabanon, la Villa E-1027, las Unités de Camping, el estudio de Le Corbusier), y que fueron concebidas como espacios para la vida privada, como arquitecturas íntimas. Richard hace foco en las contradicciones entre la necesidad de hacer conocer el patrimonio (y los potenciales recursos que esta acción proporciona para la conservación del mismo) y la obligación de protegerlo, a su vez, de las consecuencias lógicas del acceso del público.

Reseña de: Dubois, Y.: Ornamentation et discours architectural de la villa romaine d’Orbe Boscéaz. (Cahiers d’Archéologie romande, 163, URBA II/1). Lausanne, 2016, 3 volúmenes. ISBN: 972-288028-163-2; ISSN: 1021-1713.

Acute appendicitis is the most common acute surgical infection during pregnancy. Although usually pyogenic in origin, parasitic infections account for a small percentage of cases. Despite the relatively high prevalence of acute appendicitis in our environment, it is not commonly associated with schistosomiasis. We report here the association of pregnancy and appendicitis caused by Schistosoma haematobium. Schistosomiasis is very common complication of pregnancy in hyperendemic areas. Schistosome egg masses can lodge throughout the body and cause acute inflammation of the appendix, liver and spleen. Congestion of pelvic vessels during pregnancy facilitates passage of eggs into the villi and intervillous spaces, causing an inflammatory reaction. Tourism and immigration make this disease a potential challenge for practitioners everywhere.

Para la sociedad actual es fundamental la correlación entre sociedad y educación, más aún si se toma en cuenta la influencia de las telecomunicaciones en los procesos humanos, lo cual ha reducido el contacto directo entre las personas. Asimismo, es un reto vigente de los procesos educativos en educación básica, el mejoramiento de las competencias lectoras, siendo el lenguaje una de las áreas primordiales en el desarrollo del ser humano en sociedad. En este contexto, se plantea el presente artículo con el objetivo de mostrar una propuesta pedagógica de integración socioeducativa para el mejoramiento de la comprensión lectora, denominada “PPECLE: Leer contigo, Leer conmigo”, la cual fungió como estrategia pedagógica en el marco de una investigación cuantitativa con diseño cuasi experimental y nivel explicativo, en la cual se trabajó con 320 sujetos, entre estudiantes y padres del sexto grado de la Institución Educativa La Frontera, municipio Villa del Rosario, Colombia. Como técnica de recolección de información se utilizaron: un test de comprensión lectora (post-test) para evidenciar el desempeño luego de la propuesta, y cuestionarios para padres y estudiantes para medir el impacto de la propuesta. Respecto al mejoramiento de la comprensión lectora a través de la propuesta diseñada, se obtuvo a través de la prueba de Mann Whitney, la demostración de cambio con un alto nivel de significancia (0,04) en el desempeño alcanzado respecto al pre-test que sirvió de base a la propuesta Al evaluar la eficacia de la propuesta como mecanismo pedagógico de integración socioeducativa para el trabajo lector, se encontraron resultados satisfactorios en los indicadores cumplimiento del objetivo (93%), ambiente propiciado (83%) y diseño (77%). Se concluye que la propuesta mejora la comprensión lectora e impacta positivamente el ambiente familiar, escolar y social, además del estado emocional de los estudiantes.

Emerging bacterial resistance to antibiotics increases the need for effective alternatives to control intestinal inflammation and thus gut disorders in piglets. This study evaluated the effects of including Saccharomyces cerevisiae (strain 1026) and Saccharomyces boulardii (CNCM I-1079) as antibiotic alternatives in the starter diets of pigs on the concentrations of ileal inflammatory markers (nuclear factor-κB (NF-κB)), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and interleukin-12 subunit p40 (IL-12p40), and villus height. Forty piglets were assigned to four experimental diets, namely basal diet (C−), basal diet with antibiotics (C+), basal diet with S. cerevisiae (Sc), and basal diet with S. boulardii (Sb). At 7 and 14 days post weaning, five piglets per diet group were euthanized to quantify the inflammatory markers and to measure villus height. The C− group exhibited the highest concentration of inflammatory markers and the most atrophied villi. The Sc group had intermediate values for both variables. The C+ group had the lowest values for inflammatory markers and the highest villus height was similar to that of the Sb group, which showed low concentrations of inflammatory markers, although not so low as those of the C+ group. Both yeasts could be used as antibiotic alternatives to reduce the use of antibiotics in pig starter diets. However, S. boulardii CNCM I-1079 supplementation controls inflammation and preserves intestinal mucosa more effectively than S. cerevisiae strain 1026.Keywords: cytokines, pigs, probiotic, Saccharomyces, weaning

Se consideró la variación estacional en el contenido isotópico e hidroquímico de 38 manantiales, dos pozos, tres norias y dos lagos ubicados principalmente en las zonas de recarga de la Cuenca de México. La tendencia quími­ca global de los iones principales señala un comportamiento del tipo HCO3-Ca y HCO3-Na+K, que de acuerdo con los resultados de Sólidos Totales Disueltos (STD) muestran un tiempo corto de residencia en zonas de rocas fracturadas, fundamentalmente andesitas y basaltos. Entre las anomalías químicas (STD en mg/1) se encuentran los manantiales del Peñón de los Baños (> 2500, muestra 1), Poza de Reyes (> 900, muestra 6), Copilco (> 540, muestra 4) y Pocito La Villa (>700, muestra 21), mientras que el resto de los aprovechamientos fluctúa en el in­tervalo de 13 - 460 mg/1. Existen dos anomalías térmicas detectadas en este estudio, que son: la muestra No. 1 correspondiente al Peñón de los Baños, con una temperatura de 45°C y la muestra No. 18, que corresponde a La Castañeda (>250 mg/1), con una temperatura máxima de 46°C. El promedio isotópico para los manantiales es de δ0= -10.7 y δD= -73, más ligero que los promedios reportados en pozos. Los resultados de lluvia se grafican congruentemente en la línea meteórica local de pendiente ≅8 y ordenada ≅12, reportada para la Sierra de las Cruces.

Organized 25th years ago laboratory was of the first relevant prenatal center in Russia. Originally elaborated methods for chromosome preparations from different embryonic tissue samples (chorionic & placenta villi, umbilical cord blood) and for molecular genetic analysis of common and most sever inherited disorders such as cystic fibrosis, haemophilia A and B, Deuchenn myodistrophy, spinal muscular atrophy, phenylketonuria, adreno-genital syndrome, myotonic dystrophy, Huntington chorea, Martin-Bell syndrome etc. as well as automatic programs for biochemical screening of embryonic marker proteins substantiated efficient prenatal diagnosis service launched in Saint-Petersburg and in North-West region of Russia. Altogether 14 000 invasive prenatal diagnostics were carried out so far with total 1029 fetuses with chromosomal (734) or genetic (295) disorders identified. Implication of QF-PCR method for detection of common chromosomal disorders, one-stop clinic algorithm, preimplantation diagnosis as well as non-invasive diagnostics of fetal sex and Rh-factor are currently at use in our prenatal diagnostics service. Array — CGH for submicroscopic rearrangements, non-invasive diagnostics of chromosomal and genetic disorders as well as implication of Genetic Form of Female Reproductive Health, elaborated in our laboratory for prevention of fetal and pregnancy complications are our close future

Biology of the lonicera whitefly, Aleyrodes lonicerae Walker (Aleyrodidae: Hemiptera) were studied on violet, Viola tricolor L. (Violaceae) plants. Whitefly adults were collected from Mercurialis annua L. (Euphorbiaceae) plants in Adana. The development duration of egg, first, second, third, fourth larval (pupa) stages of A. lonicerae on V. tricolor were 9.17, 6.33, 5.83, 4.00, 5.17 and 30.50 days for the females and 10.27, 5.91, 5.55, 4.82, 4.55 and 31.10 days for the males, respectively. The total development duration from egg to adult of female and males of A. lonicerae were 30.50 and 31.10 days. The mortality rate (%) of egg, 1., 2., 3. and 4. larva (pupae) stages on violet leaves were 22.45, 18.37, 12.25, 4.08 and 8.16, respectively. According to life table depending on pre-adult stages on violet plants, the biggest k value determined was for the first larvae stage (k=0.1174). At the same time, the k-values determined indicated the stage with the highest mortality rates. In the studies conducted for host plant preference, the average numbers of eggs deposited by the females of A. lonicerae were significantly different between rose (2.67/two leaves) and violet (15.83/two leaves) in the same experimental area. The study was conducted in a climate-controlled room in at 20±2°C, 40%±5 relative humidity.

The genus Corema D. Don (1826: 63) (Ericaceae Jussieu 1789: 159) comprises two species. Corema album (Linnaeus 1753: 1022) D. Don (1830: 460) (incl. C. febrifugum Boissier ex Willkomm & Lange 1877: 512) occurs on the west coast of the Iberian Peninsula (subsp. album) from Gibraltar to Finisterre (Willkomm & Lange 1877, Webb 1972, Cabezudo 1987, Villar 1993, Boratyński & Vera de la Puente 1994, López González 2001, Ruiz de la Torre 2006, Gil-López 2011), the Azores (subsp. azoricum Pinto da Silva 1966: 86), and the Mediterranean Basin (Spain, Alicante province, one population) (Solanas 1996, Solanas & Crespo 2001, Serra 2007, Aguilella et al. 2009). Corema conradii (Torrey 1837: 83) Torrey (1842: 1092) occurs on the eastern coast of North America from Newfoundland to New Jersey (Redfield 1884, McEwen 1894, Elisens 2009), and can be distinguished from C. album by its very small fruits which are devoid of fleshiness and covered with elaiosomes (oily appendages associated with ant dispersal) (Redfield 1884, McEwen 1894, Martine et al. 2005). Corema album subsp. azoricum exists on six of the nine islands of the Azores, and below 200 m (Franco 1984) this taxon has been recognized by some authors at the species level as C. azoricum [“azorica”] (Pinto da Silva 1966) Rivas Martínez, Lousã, Fernández Prieto, E. Días, J.C. Costa & C. Aguiar (in Rivas-Martínez, Fernández-González, Loidi, Lousã & Penas 2002: 700).

Background:Despite the advent of newer imaging techniques, temporal artery biopsy (TAB) retains a key role in the diagnosis of giant cell arteritis (GCA). The classical histological description of GCA is that of granulomatous lesions characterized by a transmural inflammatory infiltrate1. Giant cells are typically noted in the internal elastic lamina. Vascular remodeling and structural changes are also frequently described, with intimal hyperplasia or fragmentation, fibrosis and calcifications1.Objectives:To identify the type and location of the inflammatory lesions in TAB-positive cases of GCA.Methods:We conducted a retrospective analysis of all TABs undertaken at our unit between 2011- 2018 with clinical record review. TABs were performed by vascular, ophthalmology and ENT teams.Results:379 TABs were reviewed of which 68 (17.9%) were reported as positive and 10 (2.6%) were equivocal (presence of fragmentation and intimal thickening). Of the TAB-positive cases, 43 (63.2%) were greater than 1cm in keeping with the British Society for Rheumatology guidance and 65 (95.6%) were biopsies in patients on corticosteroids at the time of procedure. The following tables demonstrate the frequency of the type and location of the inflammatory lesions detected in TAB-positive cases of GCA.Type of inflammatory lesionFrequencyChronic inflammatory infiltrate (lymphocytes, macrophages, plasma cells)66Giant cells41Intimal thickening22Intimal fragmentation33Location of inflammatory infiltrateFrequencyFull thickness32Intima only7Intima and Media only3Media only7Media and Adventitia only8Adventitia only4Intima and Adventitia only3Not recorded4Conclusion:Only 60% of our TAB-positive biopsies had giant cells present. Although perhaps surprisingly low, this finding is similar to other studies1,2. It emphasises the need to review the body of a report as well the conclusion. Other non-giant cell features present in positive reported biopsies may suggest a less certain diagnosis and prompt clinical review. There was considerable variablity in the style of reporting. With no standardised scoring system in place, the variable spectrum of inflammation and differences in reporting, there is the potential for inconsistencies amongst pathologists in interpreting and recording TAB results. Consistent reporting templates and close collaboration between rheumatologists and pathologists is needed to help correlate clinical, laboratory and imaging findings.References:[1]Cavazza A, Muratore F, Boiardi L, Restuccia G, Pipitone N, Pazzola G, et al. Inflamed temporal artery: histologic findings in 354 biopsies, with clinical correlations. Am J Surg Pathol. 2014;38(10):1360-70.[2]Hernandez-Rodriguez J, Murgia G, Villar I, Campo E, Mackie SL, Chakrabarty A, et al. Description and Validation of Histological Patterns and Proposal of a Dynamic Model of Inflammatory Infiltration in Giant-cell Arteritis. Medicine (Baltimore). 2016;95(8):e2368.Disclosure of Interests:Soha Khaled Amar: None declared, Dimitrios Christidis: None declared, George Kousparos: None declared, MARK LLOYD Speakers bureau: £700 into department fund

Changes in the function of existing buildings with changes in load functions that exceed the design load cause structural failure. The impact of structural failure varies from light to moderate, to severe damage and collapse. Thus, structural failure requires efforts to strengthen the structure with good reinforcement methods that are easy to carry out on-site. The existing building studied is the Villa Minggu Seminyak building, which is located on Jl Kunti, Gg Mangga, Seminyak, Kuta, Badung, Bali. To get good and easy-to-do reinforcement results, an investigation is carried out to obtain data on damage to existing buildings, and then analysis and evaluation are carried out. Models and analyses were carried out in 3D using SAP2000 software. The purpose of this research is to determine the behavior of existing structures before and after strengthening. The strengthening method used for column structural components is the Concrete Jacketing method. The results of the analysis show that the capacity of the existing beams and columns is insufficient, where the existing beam B1 reinforcement area of 896.47mm2 is smaller than the required reinforcement area of 1023 mm2, the axial force capacity and ultimate moment of column K1 are outside the interaction diagram and the structure's vibration time is 1.193 seconds smaller than allowable vibration time of 0.351 seconds. Thus, strengthening of the beams and columns is required. The results of the analysis and design show that concrete jacketing reinforcement requires 10 cm thick concrete with 16D13 mm main reinforcement and Ø10-75 mm stirrup reinforcement. This reinforcement can increase the axial load capacity of the column by 314.5%. Strengthening the beam with the addition of WF Steel was able to increase the ultimate moment of the support by 38.7% and the ultimate moment of the field by 39.6%. The ultimate shear force increases by 121.4%. By strengthening the columns and beams, the vibration time of the structure has a shorter duration of 48%, so the structure becomes stiffer.

Objectif. - Cette étude a été menée pour décrire les caractéristiques épidémiologiques, cliniques, biologiques et radiologiques des patients atteints de COVID-19 pendant l'épidémie dans la ville de Kiffa, en Mauritanie.Patients et méthodes. –Il s'agit d'une étude rétrospective sur une période de deux mois (du 15 mai au 31 juillet 2020). Tous les patients atteints de syndrome grippal ou de syndrome de détresse respiratoire aiguë (SDRA), ainsi que les sujets asymptomatiques ayant des antécédents récents de contact avec des sujets atteints de COVID-19, ont été inclus. Le diagnostic a été confirmé par réaction en chaîne par polymérase transcriptase inverse (RT-PCR) et, dans le cas du SDRA, par scanner thoracique.Résultats. - Vingt-huit cas confirmés de COVID-19 ont été identifiés. L'âge moyen (écart type) était de 47,9 ans ± 15,8 ans (extrêmes: 22–75 ans). Les facteurs de risque comprenaient la manipulation des appareils d'hémodialyse (n = 15) contaminés par un technicien de Nouakchott et / ou le contact avec des patients atteints de COVID-19, confirmés ou non (n = 12), une historique de voyage récent (n = 1), et résidence dans une zone à risque où des cas de COVID-19 ont été diagnostiqués (n = 6). La majorité (78,6%) des cas de COVID-19 étaient nosocomiaux et 17,9% étaient d'origine communautaire. Le syndrome grippal était présent chez 14 (50%) patients. Trois (10,7%) patients ont présenté une forme sévère avec le SDRA. Deux patients sont décédés du SDRA. Parmi les patients guéris (n = 26), aucun n'a présenté de séquelles neurologiques ou respiratoires.Conclusions. –Il n'y a pas de traitement spécifique pour le COVID-19 et sa prise en charge est multidisciplinaire. La prévention, le dépistage et l'isolement des patients sont essentiels dans la gestion de la pandémie et doivent être mis en oeuvre dès les premiers stades de la maladie.

Abstract Prostate cancer is one of the leading causes of death among men worldwide and thus research on the genetic factors enabling the formation of treatment resistant cancer cells is crucial for improving patient outcomes. Here, we report a cell-line specific dependence on FANCI and related signaling pathways to counteract effects of DNA damaging chemotherapy in prostate cancer. Our results reveal that FANCI depletion results in significant downregulation of Fanconi anemia (FA) pathway members in prostate cancer cells indicating that FANCI is an important regulator of FA pathway. Furthermore, we found that FANCI silencing reduces proliferation in p53-expressing prostate cancer cells. This extends the evidence that inactivation of FANCI may convert cancer cells from a resistant to an eradicable state under the stress of DNA-damaging chemotherapy. Our results also indicate that high expression of FA pathway genes correlates with poorer survival in prostate cancer patients. Moreover, genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients; mutation and copy number information for the FA pathway genes in seven patient cohorts (N = 1732 total tumor samples) reveals that 1025 (59.2%) tumor samples have an alteration in at least one of the FA pathway genes, suggesting that genomic alteration of the pathway is a prominent feature in patients with the disease. Citation Format: Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijärvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola. FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A025.

Las excavaciones arqueológicas realizadas en Monte Molião permitieron la recogida de un importante conjunto de artefactos de hueso pulido, de la Edad del Hierro y de época Romana, que supone un total de 80 piezas. Están distribuidas por distintas categorías funcionales, relacionadas con el adorno personal, con la actividad textil, con el juego y con la escritura. Otros integran la categoría de complementos de muebles. El conjunto es revelador de la presencia, en el sur de Portugal, de individuos con costumbres y usanzas que siguen patrones estéticos y sociales del Mediterráneo romanizado.Palabras clave: Algarve romano, mundus muliebris, textiles, ludi, stiliTopónimo: PortugalPeriodo: Edad del Hierro, época romana ABSTRACTThe archaeological digs undertaken in in Monte Molião led to the discovery of 80 bone artefacts, dating from Iron Age and Roman times. They are divided into several functional categories, connected with personal adornment, textile activity, games, and writing. 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Abstract Introduction. This was a cross-sectional study of patients with hemoglobinopathies attending 13 Italian centers participating in the LICNET (Liver Iron Cutino Network) network promoted from Piera Cutino partnership and instituted by our center (Campus of Haematology Franco e Piera Cutino-A.O.O.R. Villa Sofia Cervello, Italy) on February 2013. LICNET is addressed to the diagnostics of iron overload in liver by R2 MRI (Ferriscan®) in patients with hemoglobinopathies. Ferriscan is a rapid scan method now available (10 minutes). This tool is crucial to have accurate and reliable measures for iron body burden control in hemoglobinopathies. Methods. Data included patients with β-thalassemia major (TM) (regularly transfused) (TX), β-thalassemia intermedia (TI) (both TX and non-transfused) (non-TX), and sickle cell disease (SCD) (both TX and non-TX). The main aim of the study was to evaluate how serum ferritin levels (SFLs) predict liver iron concentration (LIC) in different hemoglobinopathies, and to have valuable information about prognosis and response to therapy. In particular, to identify SFLs that best predict LIC thresholds of clinical significance (7 and 15 mg Fe/g dw) by identifying levels with highest sum of sensitivity and specificity was used the receiver operating characteristic (ROC) curve analysis. Results. A total of 363 patients were evaluated in this analysis, with a mean age of 35.6 ± 13.0 years (range: 6-76) and including 160 (44.1%) males. The underlying diagnosis were β-TM (n=204, 56.2), β-TI (n=102, 28.1%), and SCD (n=57, 15.7%). Among β-TI patients, 60 (58.8%) were on transfusion therapy. Similarly, in patients with SCD 34 (59.6%) were on transfusion therapy. The mean LIC in the study population was 7.8 ± 9.6 mg Fe/g dw and the median was 4.0 mg Fe/g dw. Across underlying diseases, LIC distribution was as follows: β-TM (mean: 9.0 ± 10.7, median: 4.9 mg Fe/g dw), TX β-TI (mean: 7.1 ± 7.3, median: 5.0 mg Fe/g dw), non-TX β-TI (mean: 5.1 ± 6.0, median: 3.2 mg Fe/g dw), TX SCD (mean: 8.5 ± 11.0, median: 4.5 mg Fe/g dw), and non-TX SCD (mean: 3.1 ± 1.9, median: 2.4 mg Fe/ g dw). It was apparent that TX patients irrespective of underlying diagnosis have a comparable proportion of patients with high LIC risk categories (>7 mg Fe/g dw) (p=0.627). Among chelated patients, LIC distribution was as follows: Deferoxamine (DFO) (mean: 7.3 ± 8.5, median: 4.7 mg Fe/g dw), Deferiprone (DFP) (mean: 11.6 ± 11.4, median: 8.4 mg Fe/g dw), Deferasirox (DFX) (mean: 7.8 ± 10.3, median: 3.2 mg Fe/g dw), DFO+DFP (mean: 8.2 ± 10.6, median: 4.5 mg/ Fe g dw), and other combinations (mean: 6.5 ± 4.0, median: 5.1 mg Fe/ g dw), with a statistically significant difference noted between groups (p =0.009) with the highest median among chelated patients noted in DFP treated patients and lowest median noted in DFX treated patients. For underlying disease groups, ROC curve analysis showed that SFLs that best predict LIC thresholds of 7 and 15 mg Fe/g dw varied, although patients with β-TI showed lowest SFLs to predict these thresholds especially non-TX patients (Fig. 1, Fig.2). Discussion. This study suggest as high values of LIC are present even in patients with TI or SCD, confirming that gastro-intestinal iron absorption is one of the main mechanism for secondary iron overloading. Moreover, close to 20% of patients with non-TX β-TI continue to have high LIC thresholds, while none of non-TX patients with SCD have LIC values > 7 mg Fe/g dw. The evidence that SFLs of 900 ng/mL are related in β-TI with LIC > 15 mg Fe/g dw (Fig. 2) suggests as chelation treatment could be reconsidered earlier in this cohort of patients. Finally, these findings suggest as LIC is predicted by different SFLs according to the different types of hemoglobinopathy. Figure 1. Receiver operating characteristic curve analysis of serum ferritin level for predicting LIC>7 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 1. Receiver operating characteristic curve analysis of serum ferritin level for predicting LIC>7 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 2. Receiver operating characteristic curve analysis of serum ferritin levels for predicting LIC>15 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Figure 2. Receiver operating characteristic curve analysis of serum ferritin levels for predicting LIC>15 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients. Disclosures No relevant conflicts of interest to declare.

BackgroundFor patients with RA who are refractory to biologic DMARDs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy.1 In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients.ObjectivesTo describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR).MethodsA post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND,2 -CHOICE,3 and -COMPARE.4 For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28(CRP), CDAI, and SDAI, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021.Results568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; cardiovascular (CV) risk factors were common among this refractory population (Table 1). ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND2 and CHOICE3 bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups (Figure 1). Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 patient-years (PY) of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND2 and CHOICE3 bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events, adjudicated venous thromboembolism (VTE), and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY.Table 1.Baseline characteristics of TNFi-IR patients treated with UPA 15 mgn (%), unless specifiedSELECT-BEYOND (n=146)SELECT-CHOICE (n=263)SELECT-COMPARE (ADA → UPA) (n=159)Female122 (83.6)219 (83.3)133 (83.6)Mean (SD) age, years56.6 (11.0)55.5 (11.1)53.9 (10.6)Mean (SD) duration of RA diagnosis, years13.2 (9.5)12.5 (9.4)8.2 (8.5)Concomitant csDMARDs MTX alone100 (70.4)195 (74.1)159 (100.0) MTX and other csDMARDs20 (14.1)25 (9.5)0 csDMARDs other than MTX22 (15.5)38 (14.4)0Concomitant oral steroids73 (50.0)140 (53.2)98 (61.6)1 prior bDMARD68 (46.6)172 (65.4)142 (89.3)2 prior bDMARDs40 (27.4)62 (23.6)17 (10.7)a≥3 prior bDMARDs38 (26.0)29 (11.0)0Failed ≥1 prior TNFi due to lack of efficacyb131 (89.7)223 (84.8)159 (100.0)History of VTE / CV event3 (2.1) / 28 (19.2)6 (2.3) / 20 (7.6)4 (2.5) / 14 (8.8)CV risk factors Hypertension72 (49.3)109 (41.4)68 (42.8) Diabetes mellitus22 (15.1)34 (12.9)17 (10.7) Smoking (current former past)68 (46.6)109 (41.5)55 (34.6) Elevated LDL-C (≥3.36 mmol/L)38 (26.0)52 (20.0)48 (30.2) Low HDL-C (≤1.55 mmol/L)80 (54.8)171 (65.0)88 (55.3)aThese patients received one bDMARD before entry into SELECT-COMPARE.bRemaining patients were intolerant to ≥1 prior TNFi.ConclusionIn this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program.References[1]Rendas-Baum R, et al. Arthritis Res Ther 2011;13:R25;[2]Genovese C, et al. Lancet 2018;391:2513–24;[3]Rubbert-Roth A, et al. NEJM 2020;383:1511–21;[4]Fleischmann R, et al. Ann Rheum Dis 2019;78:1454–62.AcknowledgementsAbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. No honoraria or payments were made for authorship. Medical writing support was provided by Amy Wilson, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsRoy M. Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Biosplice, Bristol-Myers Squibb, Flexion, Gilead, Horizon, Eli Lilly, Galvani, Janssen, Novartis, Pfizer, Sanofi-Aventis, Selecta, Teva, UCB, Viela, and Vorso, Louis Bessette Speakers bureau: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Consultant of: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Teva, and UCB, Jeffrey Sparks Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer, Stephen Hall Consultant of: AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Meyers Sqibb, Eli Lilly, Gilead, Janssen, Merck, Novartis, and UCB, Manish Jain Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, and Pfizer, Adriana Kakehasi Speakers bureau: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, and UCB, Yanna Song Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Sebastian Meerwein Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Ryan DeMasi Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Jessica Suboticki Shareholder of: AbbVie (may own stock or options), Employee of: AbbVie, Andrea Rubbert-Roth Consultant of: AbbVie, AbbVie Deutschland, Amgen, Bristol-Myers Squibb, Chugai Pharmaceuticals, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen Global Services, Novartis, and Sanofi Pasteur

(francuski) L??poque des Comnene (1081-1185) voit le glissement progressif du centre de l?Etat serbe, depuis l?ancienne Dioclee et les contr?es du littoral adriatique plus a l?int?rieur de l?arri?re-pays, c?est-a-dire sur le territoire de l?archev?ch? grec d?Ohrid. Celui-ci correspondait alors une vaste r?gion dont les limites avaient ?t? fix?es au d?but du XIe si?cle lorsque, sous le r?gne de Basile II (976-1025), Byzance a r?tabli son autorit? sur le territoire des Balkans. De tous les souverains serbes, le grand Joupan Vukan (fin du XIe - d?but du XIIe si?cle) est le premier a avoir alors ?tendu son autorit? sur la contr?e de Ras, autrement dit le territoire de l??v?ch? du m?me nom qui entrait dans le dioc?se Ohrid et dont les ?v?ques si?geaient alors depuis plusieurs si?cles dans l??glise Saint-Pierre-et-Paul (aujourd?hui Saint-Pierre pr?s de Novi Pazar). Dans ce travail l?auteur observe les relations entretenues par l?Etat serbe et l?Eglise grecque sur le sol de la Serbie du XIIe si?cle, lesquelles ?taient avant tout fonction des relations politiques entre ce m?me Etat et Byzance. Pour l??poque m?me du joupan Vukan nous n?avons aucune donn?e concernant l?activit? des ?v?ques de Ras. Le pr?sent texte accorde donc une attention plus particuli?re a la situation enregistr?e vers le milieu du XIIe si?cle, a savoir sous le r?gne de Stefan Nemanja, fondateur de la dynastie des Nemanjic. D??pres le syst?me de pouvoir alors en vigueur en Serbie, Stefan Nemanja s?est tout d?abord vu confier l?administration d?une partie de l?Etat serbe (1158-1159). Il s?agissait en l?occurrence des r?gions appel?es Ibar, Rasina, Toplica et Reke, c?est-a-dire les contr?es orientales du pays jouxtant directement le territoire sous l?autorit? directe de Byzance. Pour cette p?riode, les sources serbes notent tout particuli?rement l?engagement de ce prince en faveur de l??rection de monast?res (un premier place sous le vocable de saint Nicolas et un second consacre au culte de la Vierge). On sait aussi que ces deux ?tablissements ont ?t? ?riges avec le consentement de l??v?que de l?archev?ch? d?Ohrid, et ce, dans les deux cas, avant 1166, ann?e ou Stefan Nemanja a ?tendu son pouvoir sur l?ensemble du pays. Or, de nouvelles donn?es nous r?v?lent que durant toute cette ?poque (plus pr?cis?ment jusqu?en 1164) l?archev?que d?Ohrid Jean (Adrien) Comn?ne, fils du sebastocrator Isaac Comn?ne, fr?re tr?s influent de l?empereur Alexis Ier Comnene, a joue un r?le de premier plan dans les relations serbe-byzantines. En l?occurrence, il a acc?de a cette fonction en 1140 et l?a exerc?e jusqu?a sa mort, en 1164, soit pr?cis?ment durant les d?cennies ayant vu d?importants ?v?nements pour l?avenir de l?Etat serbe. Nous apprenons ainsi qu?il ?tait pr?sent a Nis durant l??t? 1163, lors de la rencontre entre Manuel Ier Comn?ne et Stefan Nemanja, a l?occasion de laquelle l?empereur a d?cerne au prince serbe un titre ?l?ve de rang imp?rial et lui a remis, a titre de bien h?r?ditaire, la r?gion de la Dubocica (a savoir la r?gion de l?actuelle ville de Leskovac). Et il apparait qu?avant m?me cette rencontre, il soutenait d?j? les entreprises de Stefan Nemanja, avant tout s?agissant de l??rection d??glises dans la r?gion de Toplica (a savoir les ?glises Saint-Nicolas et de la Sainte-Vierge d?j? nomm?es). Par ailleurs, nous apprenons que ce m?me archev?que a aussi participe, cette m?me ann?e 1163, a des discussions en mati?re de dogme avec l??v?que russe en exil Leon, lors de son s?jour, avec l?empereur Manuel Ier, a Belgrade. L?auteur note que c?est assur?ment a cette p?riode d?activit? de fondateur de Stefan Nemanja qu?appartient l??rection de l??glise Saint-Nicolas dans la Toplica qui, selon les crit?res largement admis, se range dans le groupe des ?difices monumentaux de l?architecture sacr?e byzantine de l??poque des Comn?ne, d?notant de fortes influences de l?architecture de la capitale.

BackgroundDue to geographic isolation and border controls, Aotearoa New Zealand attained high levels of population coronavirus disease-19 (COVID-19) vaccination before widespread community transmission of Omicron variant COVID-19 in early 2022. This provides a unique opportunity to examine outcomes in people with rheumatic diseases immunologically naive to COVID-19.ObjectivesThis study aims to describe the outcomes of Omicron variant COVID-19 infection in people with rheumatic diseases in Aotearoa New Zealand.MethodsWe conducted an observational study of people with inflammatory rheumatic disease and COVID-19 infection from centers in Aotearoa New Zealand between 1 February to 30 April 2022. Data were collected via the Global Rheumatology Alliance Registry, including demographic and rheumatic disease characteristics and COVID-19 vaccination and outcomes. Multivariable logistic regression was used to explore associations of demographic and clinical factors with COVID-19 hospitalisation and death.ResultsA total of 1599 cases were included, with 98% from three hospitals that systematically identified all patients from rheumatology clinics who had COVID-19 infection. At the time of COVID-19 infection, 1513 cases (94.6%) had received at least two COVID-19 vaccinations. Hospitalisation occurred for 104 (6.5%) cases, and 10 (0.6%) patients died. A lower frequency of hospitalisation was seen in cases who had received at least two vaccinations (5.9%), compared to cases who were unvaccinated (20.6%) or who received a single vaccine dose (10.7%). In multivariable adjusted models, people with gout (OR 2.2 95% CI 1.02, 4.77) or connective tissue diseases (CTD) (OR 2.78 CI 1.61, 4.80) had increased risk of the combined outcome of hospitalisation and death, compared to people with inflammatory arthritis. Glucocorticoid and rituximab use were associated with 3 to 6 times higher odds of hospitalization and/or death. All cases who died had three or more co-morbidities associated with a known higher risk of poor outcomes or were over 60 years old.ConclusionIn this cohort of people with inflammatory rheumatic diseases with high vaccination rates, severe outcomes from Omicron variant COVID-19 were infrequent. The hospitalisation rate during COVID-19 infection was higher in people who had not completed the primary vaccination course, had gout or CTD, and used glucocorticoids. These findings suggest that outcomes of Omicron variant COVID-19 infection among people with rheumatic disease who are vaccinated but immunologically naive to prior COVID-19 variant infections were favorable.AcknowledgementsThere was no specific funding for data collection. Data analysis was funded by the COVID-19 Global Rheumatology Alliance. The Global Rheumatology Alliance registries are supported by the American College of Rheumatology and European Alliance of Associations of Rheumatology but the views expressed here are of the authors.We thank our colleagues who entered patients to the cohort who include Ms J Heslett, Dr S Bourke, Dr E Chan, Dr S Jordan, Dr K Lindsay, Dr R Murdoch and Dr S Stebbings,Disclosure of InterestsJonathon Brooks: None declared, Anna Montgomery: None declared, Nicola Dalbeth Consultant of: Personal fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, all outside this abstract, Mark Sapsford: None declared, Amy Cooper: None declared, Rachel Ngan Kee: None declared, Vicki Quincey: None declared, Jean Liew Grant/research support from: Pfizer, outside this abstract, Suleman Bhana Shareholder of: Owns restricted stock units with Pfizer as a Pfizer employee, Consultant of: Honoraria from AbbVie, Horizon, Novartis, Pfizer, has received travel support from Pfizer, Employee of: Pfizer Inc, Monique Gore-Massy Consultant of: Patient consultant for Aurinia Pharmaceuticals, Boehringer Ingelheim, Johnson & Johnson, Bristol-Myers Squibb, all unrelated to this abstract. Receives honoraria from Aurinia Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, all unrelated to this abstract, Jonathan Hausmann Consultant of: Consulting fees from Novartis, Pfizer, Sobi and Biogen, all unrelated to this manuscript, Pedro Machado Speakers bureau: PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Paul Sufka: None declared, Emily Sirotich: None declared, Philip Robinson Speakers bureau: PR reports personal fees from Abbvie, Atom Biosciences, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Kukdong, Novartis, UCB, Roche, Pfizer;, Grant/research support from: Meeting attendance support from BMS, Pfizer and UCB and grant funding from Janssen, Novartis, Pfizer and UCB Pharma., Zachary Wallace Consultant of: Consulting fees from Zenas Biopharma, Horizon, Sanofi, Shionogi, Viela Bio, and MedPace, all outside this abstract., Grant/research support from: Research support from Bristol-Myers Squibb and Principia/Sanofi, all outside this abstract., Jinoos Yazdany Consultant of: Consulting fees from Astra Zeneca, Aurinia, Pfizer, all unrelated to this manuscript, Grant/research support from: Grants from Gilead, Astra Zeneca, BMS Foundation, all unrelated to this manuscript, Rebecca Grainger Speakers bureau: RG reports personal fees from AbbVie, Janssen, Cornerstones, Novartis; meeting attendance support from Pfizer.

BackgroundSLE is a heterogeneous disease with diverse clinical presentations, and up to 70–80% of patients develop skin manifestations.1–3 In SLE, plasmacytoid dendritic cells (pDCs), a major source of Type I interferon (IFN), accumulate in the skin.4 Treatment with BIIB059, a humanized monoclonal antibody targeting blood dendritic cell antigen 2 (BDCA2) that is expressed on pDCs, leads to rapid internalization of BDCA2 from the surfaces of pDCs and inhibits the production of Type I IFNs, pro-inflammatory cytokines, and chemokines.5 Part A of the randomized, two-part, Phase 2 LILAC study (NCT02847598) enrolled participants with SLE and active skin and joint disease. The primary endpoint was met, with a greater reduction in total active joint count at Week 24 in the BIIB059 treatment group vs placebo (PBO), and more participants achieved a ≥50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index – Activity (CLASI-A) score with BIIB059 vs PBO.6ObjectivesTo further evaluate the effect of BIIB059 vs PBO in reducing skin disease activity, as measured by various CLASI-A response thresholds.MethodsAdults with an SLE diagnosis according to the revised ACR 1997 SLE classification criteria, with ≥4 tender and ≥4 swollen joints (28-joint assessment), active skin disease (as defined by the SLE Disease Activity Index 2000 [SLEDAI-2K]), and positive anti-nuclear antibodies and/or anti-double-stranded DNA antibodies, were enrolled. Participants were randomized to receive BIIB059 450 mg or PBO, administered subcutaneously every 4 weeks with an additional dose at Week 2. Improvements in skin disease were assessed in participants with baseline CLASI-A score ≥8. The proportion of participants achieving a ≥7-point reduction from baseline in CLASI-A score was assessed at Week 24, and CLASI-20, -50, -70, and -90 responses were assessed over time. Achievement of CLASI-A scores of 0–1 was also assessed at Week 24. These analyses used non-responder imputation with logistic regression, without correction for multiplicity. The proportions of participants achieving CLASI-A scores of 0–3 and with resolution of SLEDAI-2K skin rash at Week 24 were evaluated ad hoc in the same population. Non-responder imputation was applied to visits post treatment failure and treatment discontinuation. Improvement from baseline in British Isles Lupus Assessment Group index (BILAG-2004) A or B mucocutaneous domains was similarly assessed at Week 24. P-values were calculated based on the odds ratios (ORs) for BIIB059 compared with PBO.ResultsAt Week 24, a significantly greater proportion of participants receiving BIIB059 (n=39) vs PBO (n=38) had a ≥7-point reduction in CLASI-A score from baseline to Week 24 (56.4% vs 34.2%, OR [95% confidence interval {CI}] 2.71 [1.03, 7.17], P=0.044). Numerically greater proportions of participants receiving BIIB059 vs PBO achieved CLASI-50, CLASI-70, or CLASI-90 responses (Figure 1). Similarly, the proportion of participants who achieved CLASI-A scores of 0–1 was greater in the BIIB059 group vs PBO (25.6% vs 13.2%), as was the proportion who achieved CLASI-A scores of 0–3 (48.7% vs 28.9%). A greater proportion of BIIB059- vs PBO-treated participants had resolution of SLEDAI-2K skin rash at Week 24 (28.6% vs 10.7%), with similar findings seen in the BILAG-2004 mucocutaneous domain.ConclusionNumerically greater reductions in skin disease activity were consistently observed with BIIB059 treatment vs PBO in participants with SLE and active skin disease, supporting a potential benefit of BIIB059 treatment for skin manifestations in SLE.References[1]Dörner T, Furie R. Lancet 2019;393:2344–2358[2]Patel J, et al. Curr Rheumatol Rep 2020;22:69[3]Grönhagen C, et al. Lupus 2010;19:1187–1194[4]Vermi W, et al. Immunobiology 2009;214:877–886[5]Pellerin A, et al. EMBO Mol Med 2015;7:464–476[6]Furie R, et al. Arthritis Rheumatol 2020;72(Suppl. 10):0935 (Abstract)AcknowledgementsThe authors thank the LILAC investigators for their valuable contributions to this study. This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Selene Medical Communications (Macclesfield, UK), funded by Biogen.Disclosure of InterestsRonald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB, Grant/research support from: BMS, GSK, UCB (research support; institutional grants); MSD, Pfizer, Roche (educational program support; institutional grants), Richard Furie Consultant of: AstraZeneca, Biogen, Grant/research support from: AstraZeneca, Biogen, Victoria Werth Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Aurinia, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Consultant of: OMass Therapeutics, Employee of: Biogen

BackgroundOlokizumab (OKZ) is an interleukin-6-inhibitor for treatment of RA. We present patient reported outcomes (PROs) reported in a long-term extension trial (OLE) (ClinicalTrials numberNCT03120949).ObjectivesTo assess long-term effect of OKZ treatment in patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), fatigue (FACIT-F) and health related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores).MethodsPatients (pts) who completed phase III core studies (within 24 weeks) were continued on OKZ 64 mg q2w or q4w, or were randomized 1:1 to receive OKZ 64 mg q2w or q4w following placebo (PL) or adalimumab (ADA) in RCTs with an OLE period of up to week 82. PROs through CORE and OLE phases are summarized as observed data by treatment groups using descriptive statistics.ResultsBaseline demographics and disease characteristics of 2104 enrolled pts were comparable between groups. The achieved improvement from CORE baseline to OLE baseline in PtGA, Pain, HAQ-DI, FACIT-F, SF-36 PCS, MCS and all domains under treatment with OKZ q2w and q4w was maintained over the full observation period of 106 weeks (Table 1, Figure 1). SF-36 improvements reported from OLE BL continued (in 5 domains) or increased (in 3 domains: PF, RE and RP) with OKZ until week 82.Table 1.Patient reported outcomes dynamicsMean (SD)OKZ q2w N= 745OKZ q4w N= 783Adalimumab → OKZ N= 462Placebo → OKZ N= 455Core BLOLE BLWeek 82Core BLOLE BLWeek 82Core BLOLE BLWeek 82Core BLOLE BLWeek 82PtGA-VAS (mm)67.6(19.6)32.3(21.4)31.4(24.0)67.4(19.5)32.0(21.4)30.7(22.6)66.7(21.0)31.3(22.7)29.5(23.3)68.8(18.6)42.7(22.3)32.6(23.3)Change from OLE BL-0.2[-2.1 -1.7]0.1[-1.8 -2.0]-0.1[-3.8 -1.4]-10.0[-13.1 -6.8]Pain-VAS (mm)68.6(19.6)30.4(22.3)29.4(25.0)67.6(20.1)29.9(21.6)28.5(22.7)66.8(21.5)30.5(23.1)27.7(23.6)67.6(20.0)41.2(23.2)30.0(23.3)Change from OLE BL-0.4[-2.4; 1.6]0.2[-2.1; 1.6]-2.0[-4.6; 0.5]-10.4[-13.7; -7.2]HAQ-DI1.74(0.55)1.03(0.64)0.99(0.67)1.70(0.58)1.02(0.62)0.94(0.66)1.72(0.57)1.03(0.67)0.95(0.68)1.74(0.58)1.29(0.67)1.03(0.67)Change from OLE BL-0.03[-0.1; 0.0]-0.04[-0.1; 0.0]-0.04[-0.1; 0.0]-0.24[-0.3; -0.2]SF-36 PCS score31.7(6.8)41.1(8.4)42.0(9.2)31.7(7.1)41.1(8.0)42.4(8.8)31.4(7.4)40.8(8.6)42.4(9.3)31.7(6.9)37.7(8.0)41.6(9.1)Change from OLE BL0.8[0.2; 1.5]1.0[0.4; 1.6]1.2[0.3;2.0]3.8[2.9;4.7]SF-36 MCS score43.1(11.6)49.1(10.1)48.7(10.3)43.5(11.1)49.7(9.8)49.4(10.0)44.1(11.4)49.8(10.1)50.1(9.9)42.8(10.2)46.4(10.8)46.2(10.7)Change from OLE BL0.5[-0.3; 1.2]0.3[-0.5; 1.0]-0.2[-1.2; 0.7]2.0[0.9;3.1]FACIT-F26.8(10.3)36.4(9.7)37.2(10.4)27.1(10.1)36.8(9.6)37.7 (10.2)27.4(11.3)36.7 (10.0)38.0(10.6)27.1 (9.6)33.0(10.3)37.2 (10.0)Change from OLE BL0.7[-0.1; 1.4]0.7[-0.03; 1.4]0.9[0.04; 1.8]3.6[2.5;4.7]EQ-5D43.8(21.5)67.8(20.5)70.1(22.3)44.7(21.4)68.6(19.8)70.3(21.0)45.2(22.1)68.7(20.9)72.6(21.2)44.4(22.8)59.7(21.6)69.7(20.4)Change from OLE BL2.1[0.1; 4.1]1.3[-0.5; 3.0]3.5[0.9; 6.0]9.7[6.9; 12.5][95% CI].Abbreviations: CI, confidence interval; EQ-5D, Health Questionnaire 5 Dimension; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire Disability Index; MCS, Mental Component Summary; PCS, Physical Component Summary; PtGA, Patient Global Assessment of disease activity; SD, standard deviation; SF-36, Short Form-36 Health Survey; VAS, visual analogue scale.Figure 1.SF-36 domain changes from baseline to week 82.AbbreviationsAGNorms, age- and gender-matched normative values; BL, baseline; BP, bodily pain; GH, general health; MH, mental health; OLE-open label extension; PF, physical functioning; q2w, every 2 week; q4w, every 4 week; RE, role emotional; RP, role physical; SF, social functioning; VT, vitality.ConclusionTreatment with OKZ resulted in sustained improvement of PROs in MTX and TNF-IR RA pts over a period of up to 106 weeks.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsVibeke Strand Consultant of: Abbvie, Alpine Immune Sciences, Alumis, Amgen, Aria, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celltrion, Endo, Equillium, Ermium, Genentech/Roche, Gilead, GSK, Horizon, Inmedix, Janssen, Kiniksa, Lilly, Merck, MiMedx, Novartis, Omeros, Pfizer, Regeneron, R-Pharm, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, Tonix, Urica;, Eugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Tatiana Lisitsyna Consultant of: R-Pharm, Alexander Lila Consultant of: Abbvie, Amgen, Bayer, Biotechnos, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, RPharm, Roche, Sanofi, Stada, Viatris and UCB, Grant/research support from: Novartis, Pfizer, Sofia Kuzkina Employee of: R-Pharm, Sofia Kuzkina Employee of: R-Pharm, Mikhail Samsonov Employee of: R-Pharm, Roy M. Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galvani, GlaxoSmithKlein (GSK), Janssen, Pfizer, Gilead, UCB, Novartis, Arthrosi, AstraZeneca, Flexion, Genentech, Horizon, Selecta, Viela, Vorso, Vyne.

Abstract Background The inflammatory bowel disease questionnaire (IBDQ) is a measure of health-related quality of life (QoL), with higher scores indicating greater QoL. In a prior phase 2 study (NCT02589665), mirikizumab, an anti-IL23p19 antibody, demonstrated efficacy and improvement in IBDQ scores in participants with moderately to severely active ulcerative colitis (UC). Purpose This analysis evaluated effect of mirikizumab (miri) vs placebo (PBO) on IBDQ scores in patients (pts) with moderately to severely active ulcerative colitis (UC) who had failed prior conventional or biologic therapy in a Phase 3, double-blind, 12-week (W) induction study (LUCENT-1) followed by a 40W maintenance study (LUCENT-2) for a total of 52W continuous therapy. Method Pts (N=1162) in LUCENT-1 were randomized 3:1 to receive 300mg miri or PBO intravenously once every four weeks (Q4W). 544 pts who achieved Modified Mayo Score Clinical Response to miri by W12 of induction were rerandomized 2:1 in LUCENT-2 to subcutaneous miri 200mg or PBO Q4W in maintenance period. Randomization was stratified by previous biologic therapy failure, baseline corticosteroid use, and region. LUCENT-1 stratification included baseline (BL) disease activity, and LUCENT-2 included LUCENT-1 clinical remission status. The least squares mean change from BL in IBDQ scores at W12 of induction and W40 of maintenance was determined using analysis of covariance models. BL was W0 of therapy and stratification factors and BL scores were used as covariates. The Minimal Clinically Important Difference (MCID) was defined as an improvement of ≥16 points in total IBDQ score (IBDQ response) and IBDQ remission as a total score ≥170 points. IBDQ response and remission were calculated using non-responder imputations. Treatments were compared using the common risk difference (risk diff). Result(s) Miri treatment resulted in significantly greater improvement from BL in IBDQ total and domain scores vs PBO at both W12 of induction and W40 of maintenance (52W treatment) (Table). The proportions of pts who achieved an IBDQ response was significantly greater for miri treated pts vs PBO at W12 (risk diff =17.1[95%CI:10.7, 23.5]) and W40 (29.5 [21.0, 37.9]). Significantly greater proportions of pts receiving miri achieved IBDQ remission at W12 (18.1 [11.8, 24.4]) and W40 (28.5 [20.1, 37.0]) vs PBO (all evaluations and timepoints: p<0.001). Image Conclusion(s) Pts reported significantly greater improvements in IBDQ scores at induction and maintenance with miri compared to PBO. Over 75% of pts achieved a clinically meaningful improvement in QoL, as measured by IBDQ response, at the end of the 52 weeks of miri treatment. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest B. Sands Consultant of: Abivax, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Eli Lilly and Company, Enthera, Evommune, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Kaleido Biosciences, Kallyope, MiroBio, Morphic Therapeutic, MRM Health, Pfizer, Progenity, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Q32 Bio, Surrozen, Takeda, Teva, TLL Pharmaceutical, USWM Enterprises, and Viela Bio, B. Feagan Shareholder of: Gossamer Bio, Consultant of: AbbVie, AdMIRx, AgomAb Therapeutics, Akebia Therapeutics, Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Avir Pharma, Azora Therapeutics, Boehringer Ingelheim, Boston Scientific, Celgene/Bristol Myers Squibb, Connect BioPharma, Cytoki Pharma, Disc Medicine, Ecor1 Capital, Eli Lilly and Company, Equillium, Everest Clinical Research, F. 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Schreiber Grant / Research support from: personal fees and/or travel support from: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Dr. Falk Pharma, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Gilead Sciences, I-MAB Biopharma, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Biopharma, and UCB Pharma, V. Jairath Consultant of: AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Protagonist Therapeutics, Reistone Biopharma, Roche, Sandoz, Second Genome, Shire, Takeda, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics, A. Armuzzi Consultant of: AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and TiGenix, J. Jones: None Declared

RESUMENNuestro conocimiento sobre las religiones protohistóricas se encuentra prejuiciado por categorías de pensamiento presentistas y el recurso a fuentes posteriores. Para lograr una caracterización mínima de la fenomenología de tales manifestaciones se propone una aproximación a partir de los materiales de la Edad del Hierro, con atención a los problemas y metodologías de la arqueología, que privilegie el estudio de casos particulares frente a la generalización céltica. A través del ejemplo de la cultura castreña, se examinará qué elementos constituyeron objeto de atención ritual y sobredimensión simbólica para una sociedad de la Edad del Hierro.PALABRAS CLAVE: Cultura Castreña, Edad del Hierro, protohistoria, ritual, arqueologíaABSTRACTOur knowledge of protohistoric religions is prejudiced by presentist ways of thinking and recourse to later sources. To achieve a minimum characterization of the phenomenology of such manifestations, I propose an approach based on Iron Age materials, being careful of the archaeological problems and methodologies, and favouring particular case studies rather than Celtic generalizations. Through the example of Castreño culture, I will examine which elements might have been the object of ritual attention and symbolic oversizing in an Iron Age society.KEY WORDS: Castro culture, Iron Age, Protohistory, ritual, archaeologyBIBLIOGRAFÍAAlmeida, C. A. F. (1980) “Dois Capacetes e tres copos, em Bronze, de Castelo de Neiva”, Gallaecia, 6, 245-257.Alonso Burgos, F. (2014): Estructura social y paisaje simbólico: las comunidades astures y el imperio romano. Tesis doctoral inédita, Universidad Complutense de Madrid.Angelbeck, B. y Grier, C. 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Introduction Relapses involving the central nervous system (CNSrel) occur in ~5% of patients (pts) with aggressive non-Hodgkin lymphoma (NHL) in the rituximab era (Ghose et al, Clin LML 2015) with rates exceeding 10% in high risk groups (Villa et al, Ann Onc 2010; Schmitz et al, JCO 2016). CNSrel are generally thought to occur in the first 4-6 months from diagnosis. Prophylaxis (PPx) administration, route, and frequency are not standardized, and the impact of PPx on CNSrel risk is incompletely understood. Methods We performed a multicenter retrospective analysis of pts with aggressive NHL (excluding Burkitt's) without known CNS involvement (inv) who received single-route CNS PPx with during front-line (FL) anthracycline-based therapy (tx) from 2013-2019 across 19 US academic institutions. Recipients of chemotherapy for prior CLL or indolent NHL were ineligible. Method, frequency, and outcomes of CNS PPx administration were evaluated, with significance assessed by various statistical methods via two-tailed P<0.05. Results 1030 patients were identified who met eligibility criteria. Clinical features included median age 61 years (yrs; range 16-86), 40.9% female, ECOG PS 0-1 82.8%, elevated LDH 65.3%, >1 extranodal (EN) site 42.3%, stage 3/4 disease 79.2%. NHL histologies included diffuse large B cell (DLBCL; 75.2%), high grade B cell (16.3%), transformed follicular lymphoma (5.6%) and 3% other; among pts with DLBCL, 46.4% had germinal center (GCB) subtype and 40.5% had non-GCB. 26.2% (n=210) of evaluable pts had double-hit lymphoma (DHL). Among pts with known HIV status, 7.2% (n=65) were HIV-positive. 85.7% had EN inv; common sites included bone (35.4%), liver (13.7%), gastrointestinal (12.7%), lung (11.8%), and marrow (11.5%). FL regimens included RCHOP (45.9%), REPOCH (46.5% total; 79.1% with dose-adjustment), 7.6% other. PPx was given intravenously (IV) in 20% of pts vs 77% intrathecally (IT), over a median 2.9 vs 4.1 doses respectively; see Table 1 for factors associated with PPx route. PPx was generally well-tolerated, with 10.7% PPx-related toxicity reported; see Table 2. CNSrel after FL tx was 5.3% overall without significant difference by PPx route (7% IV vs 5% IT, p=0.178). This lack of difference between PPx routes was observed in all subgroup analyses performed, including by: age, stage, histology, number of EN sites, individual EN site inv, elevated LDH, CNS-IPI, DHL status, HIV status, FL regimen, number of PPx doses. There was no significant difference in anatomic site(s) of CNSrel by PPx route. CNSrel occurred bimodally: 24% by end of FL tx vs 76% delayed (average 2.3 yrs, range 0.4-5.2 yrs). Rates of CNSrel were significantly higher with CNS-IPI high vs moderate risk (8.3 vs 4.1%, p=0.03; Figure 1), elevated LDH (6.9 vs 2.6%, p=0.007) and multiple inv EN sites (7.5% for 2+ vs 4% for 0-1, p=0.01); each additional EN site further increased risk (p=0.03 for trend; Figure 2). Increased CNSrel was noted in pts with testis (13.7 vs 5%, p=0.004) and liver inv (11.1 vs 4.6%, p=0.002) vs those without inv at respective sites. No significant difference was noted at other EN sites, including renal/adrenal (4.8 vs 5.6%, p=0.71), marrow (8.9 vs 5.1%, p=0.09), or lung (8.6 vs 5.1%, p=0.12). All EN site-CNSrel correlations were unchanged when accounting for PPx route. With median follow-up of 2.3 yrs, median PFS and OS for the overall group have not been reached; 2-yr PFS and OS were 70 and 85% respectively. PFS and OS were each predicted by CNS-IPI (p<0.0001) and maintained significance when separated by PPx route. 196 deaths were reported, including 122 disease-related and 34 tx-related (TRM). There was no significant difference in TRM by PPx route (1.9% IV vs 3.6% IT, p=0.24). Death due to progression was more common following IT PPx (13.3% vs 7.9% IV; HR 1.72, p=0.04), driven primarily by DH status (adjusted PPx HR: 1.54, p=0.11). In those with CNSrel, subsequent relapse and/or death was common (n=41, 74.5%) regardless of initial PPx route or salvage tx. Median survival after CNSrel diagnosis was poor (7.1 months, range 1 day-5.3 yrs) and was significantly inferior to those with non-CNSrel (HR 1.488, p=0.03). Conclusion Use of single-route ppx demonstrated similar CNSrel vs established outcomes for this population in the rituximab era, with no difference by PPx route. CNSrel remains a rare but devastating complication, with greater risk even after single-route PPx in those with higher EN burden and inv of key EN sites. Disclosures Kahl: Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Spinner:Notable Labs: Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Voorhees:AstraZeneca: Research Funding. Grover:Genentech: Research Funding; Tessa: Consultancy. Huntington:Genentech: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Bayer: Consultancy, Honoraria; DTRM: Research Funding; Astrazeneca: Honoraria; AbbVie: Consultancy. Spurgeon:Beigene: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy, Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding; Genmab: Research Funding; AstraZeneca: Research Funding; Acerta: Research Funding. Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding. Landsburg:Seattle Genetics: Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Triphase: Research Funding. Kamdar:Roche: Research Funding. Caimi:Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Verastem: Other: Advisory Board; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Celgene: Speakers Bureau. Karmali:Takeda: Research Funding; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Stephens:Pharmacyclics: Consultancy; Innate: Consultancy; Verastem: Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Research Funding; Arqule: Research Funding; Juno: Research Funding; MingSight: Research Funding; Acerta: Research Funding; Beigene: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Khan:Celgene: Research Funding; Pharmacyclics: Honoraria; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Honoraria. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Portell:Bayer: Consultancy; Xencor: Research Funding; BeiGene: Consultancy, Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding.

La investigación –cuantitativa, descriptiva, correlacional y transversal– pretendió conocer si las dimensiones del liderazgo directivo –transformacional, transaccional y laissez-faire– predicen significativamente el desempeño docente, de acuerdo con la percepción de 105 docentes de un grupo de nueve colegios privados salvadoreños, quienes respondieron (a) el Cuestionario Multifactorial (MQL), de 45 ítems, y (b) el Cuestionario de Autoevaluación Docente, para medir la variable desempeño docente, de 20 ítems. Se utilizó el análisis de regresión múltiple. De las tres dimensiones del liderazgo del director, el liderazgo transaccional mostró una correlación positiva con el desempeño docente. La predicción es significativa para todas las dimensiones del desempeño docente, excepto emocionalidad. Los docentes que laboran en colegios cuyos directores están en función por más de siete años mostraron un desempeño significativamente mejor en las dimensiones de capacidad pedagógica y emocionalidad. A la vez, demostraron una percepción del liderazgo transformacional más baja en términos de motivación por inspiración. Referencias Aguilar Ludeña, E. H. (2018). Liderazgo directivo y el desempeño docente en la institución educativa 1278, La Molina (Tesis de maestría). Universidad Nacional de Educación Enrique Guzmán y Valle, Perú. Alonso Ayala, O., Ávila Sánchez, M. y Sánchez López, M. (2016). Desempeño del profesional de enfermería en la atención a los pacientes con afecciones traumatológicas y ortopédicas. Revista Cubana de Tecnología de la Salud, 7(4), 30-35. Alzate Sánchez, A. y López Cortés, M. C. (2014). 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El suelo es el componente esencial para la producción de la ciudad. En Buenos Aires la oferta de suelo vacante adecuado para desarrollar proyectos inmobiliarios de alta rentabilidad depende, mayormente, de la incorporación al mercado de propiedades fiscales y suelo ocupado irregu­larmente en las urbanizaciones populares. Para ello interviene el Estado con dos orientaciones fundamentales: mercantilización y propiedad privada. Desde el año 2007 se concreta en dos políticas cuya finalidad es transferir (privatizar) suelo a los operadores inmobiliarios, tanto desde propiedades fiscales como por la incorporación al mercado de suelo ocupado irregularmente por sectores populares. El texto analiza el proceso de reurbanización de la Villa 31-31bis y las políticas de venta de suelo público.

Abstract The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal-fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (TPM > 0.66), with 10.7% stably expressed genes across gestation. Differentially expressed genes account for 86.7% of genes in the full cohort (FDR < 0.05). Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change>1.5), there remain 50.1% differentially expressed genes (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and stably expressed genes may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal-fetal health.

Abstract Background In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. Result The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. Conclusions These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.

Abstract Disclosure: O.C. Reyes: None. A. Sison: None. M. Villa: None. D. Dimayuga: None. Introduction: Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is a rare type of pancreatic neuroendocrine tumor that causes ectopic adrenocorticotropic hormone syndrome. Cushingoid manifestations and metabolic abnormalities can occur rapidly. High index of suspicion is required for early diagnosis. Case: A 31-year-old Filipino female presented with facial and ankle swelling that occurred 6 weeks before the visit. She also had acne, easy bruising, amenorrhea and frequent mood swings. There was reported weight gain of 3 kg a month prior. She had no history of hypertension and diabetes, and had no unusual family history. At the time of admission, vital signs were blood pressure of 130/80mmHg, pulse of 92/min, respiratory rate 20/min and body temperature of 37.2C. Her body mass index was 28kg/m2. She had muscle atrophy of the upper and lower extremities, facial flushing, posterior cervical fat pad, abdominal violaceous striae, and skin pigmentation. Her external genitalia was normal, Tanner Stage 5 consistent with adult pattern. Neurologic exam was unremarkable. She was examined for Cushing’s syndrome. On initial tests, glucose was 406 mg/dl, HbA1C 10.7%, thyroid stimulating hormone 0.122 (NV: 0.55-4.78), Free T3 0.77 (NV: 2.3-4.2), Free T4 0.58 (NV: 0.89-1.76). Creatinine was 0.86 mg/dL, sodium was 140 mEq/L, potassium was 2.1 mEq/L showing hypokalemia. There was leukocytosis on her blood count, white blood cells 15,310/mm3 (neutrophils 94%, lymphocytes 3%). In the low-dose dexamethasone suppression test (DST), the serum cortisol concentration was 991.03nmol/L. Her adrenocorticotrophic hormone (ACTH) level was elevated at 577pg/mL. After high-dose DST, the serum cortisol concentration was > 1750 nmol/L. No tumor was observed on pituitary magnetic resonance imaging. On abdominal computed tomography (CT), a large, lobulated, heterogeneously-enhancing mass arising from the pancreatic body and tail measuring 7.5cm x 10cm x 10.9cm was seen. The mass had infiltrated the gastric fundus, and encased the splenic artery. Multiple non-calcified subcentimeter pulmonary nodules were observed on chest CT. CT-guided biopsy of the pancreatic mass was done. On microscopic examination, numerous atypical cells arranged with small clusters and sheets and scattered singly were found in the tumor. The cells had small to enlarged, hyperchromatic, ovoid to round nuclei and scant to ample delicate cytoplasm. On immunohistochemical staining, the tumor cells were stained positive for synaptophysin and chromogranin A, which are both neuroendocrine markers, as well as ACTH. However, the patient died prior to any definitive management. Conclusion: ACTHoma is a very rare disease that causes hypercortisolemia. Reporting of similar cases will provide insight into its clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis. Presentation: Thursday, June 15, 2023

Preeclampsia is associated with maternal perinatal morbidity and mortality and a high risk of premature birth and intrauterine growth restriction. The apelin system is a novel pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We have previously reported that total apelin content is lower in human preeclamptic chorionic villi. In this study, we determined whether (Pyr1)-apelin-13 improves hypertension, proteinuria, fetal characteristics, uteroplacental hemodynamics, and the autonomic function in preeclamptic rats (TgA, female transgenic for human angiotensinogen mated to male transgenic for human renin). (Pyr1)-apelin-13 (2 mg/kg/day) (n=7) or saline (n=5) was infused in TgA via osmotic minipumps starting at day 13 of gestation, when blood pressure begins to increase in these animals. Pregnant SD (n=6) rats were used as controls. At the 20th day of pregnancy, TgA rats had higher MAP (138±6 vs. 79±3 mmHg in SD, p<0.001) which was reduced by (Pyr1)-apelin treatment to 119±2 mmHg vs. TgA, p<0.006. TgA rats also had impaired heart rate variability measured as root of mean successive differences (rMSSD) compared with SD (2.7±0.4 vs. 3.8±0.3 ms in SD, p<0.05). Apelin treatment normalized rMSSD to 3.6±0.3, p<0.05. Similarly, baroreflex sensitivity measured in the sequence domain was lower in TgA (0.7±0.1 vs. 2.6±0.5 ms/mmHg in SD, p<0.01) and normalized with (Pyr1)-apelin-13 to 2.0 ± 0.4 ms/mmHg, p<0.05. Proteinuria was greater in TgA (53±9 vs. 10±2 mg/kg/day, p<0.001), and normalized by (Pyr1)-apelin-13 (18±6, p<0.05). Pup (3.0±0.1 vs. 3.7±0.1 g, p<0.01) and placental weight (0.41±0.01 vs. 0.45±0.01 g, p<0.01), and pup number (10.7±1.1 vs. 14.0±0.8, p<0.01) were lower in TgA vs. SD; however they were not changed by (Pyr1)-apelin-13. Uterine artery peak systolic velocity was not different between SD and TgA, but increased with (Pyr1)-apelin-13 treatment (179.5±16.7 vs. 122.6±16.7 ml/min, p<0.05) with no change in resistance index. In conclusion, our findings suggest that (Pyr1)-apelin-13 may be beneficial for the treatment of preeclampsia due to its hemodynamic and renoprotective effects. We also report for the first time that these changes may involve central control of the cardiovascular system.

Abstract Background Limited data are currently available on protozoan parasites of the genus Sarcocystis that infect their avian hosts within the order Anseriformes (waterfowl). To date, no Sarcocystis species has been recorded in ducks in China. Methods Leg muscles were sampled from 26 domestic ducks (Anas platyrhynchos) in China in 2021. Morphological characteristics of sarcocysts detected in the muscle tissue were described using light microscopy (LM) and transmission electron microscopy (TEM). Genomic DNA was extracted from single sarcocysts obtained from different ducks, and three genetic markers, 18S ribosomal DNA (18S rDNA), 28S ribosomal DNA (28S rDNA) and mitochondrial (mt) cytochrome oxidase subunit 1 (cox1), were amplified and cloned for sequence analyses. Results Sarcocysts were observed by LM in only three of the 28 samples (10.7%). These sarcocysts had a thick cyst wall with numerous brush-like villar protrusions (vps) of 3.8–4.3 μm in length (n = 30) on the cyst surface. TEM observation showed that the sarcocysts had lanceolated vps. Each vps narrowed in the stalk and contained a bundle of microtubules that extended into the ground substance. Comparisons of the new sequences with those deposited in GenBank showed that the most similar sequences were those of Sarcocystishalieti in the great cormorant Phalacrocorax carbo and European starling Sturnus vulgaris, and Sarcocystis calchasi in the domestic pigeon (Columba livia) at the 18S rDNA (99.1% identity); Sarcocystiswenzeli from the domestic chicken Gallus gallus at the 28S rDNA (95.9–96.0% identity); and Sarcocystis speeri from the opossum at the mtcox1 (98.2% identity). The new 18S rDNA, 28S rDNA and mitochondrial cox1 sequences shared up to 99.0%, 95.6% and 97.7% identity, respectively, with those of Sarcocystis spp. obtained from Anseriformes avian hosts. Phylogenetic analysis inferred from the sequences of the three genetic markers placed the organism within a group of Sarcocystis spp. obtained from avian or carnivorous intermediate hosts and avian, marsupial or carnivorous definitive hosts. Based on the morphological observation and molecular analyses, the organism found in the Chinese domestic ducks was regarded as a new species and named Sarcocystis platyrhynchosi n. sp. Conclusions Based on morphology and sequence analyses, the microcysts diagnosed in the domestic ducks examined in this study were named as a new species. This is the first record of Sarcocystis spp. from waterfowl in China. Sarcocysts of similar morphology occur frequently in different Anseriformes birds, and the relationships among these species need to be further clarified in future studies using more molecular markers. Graphical Abstract

Platelet distribution width (PDW), a marker of platelet size heterogeneity used as a readout of processes leading to platelet production and destruction, was recently reported to tag platelet activation variability. As platelets participate in the pathogenesis of many acute and chronic diseases, we evaluated PDW as a predictor of all-cause and cause-specific mortality. Longitudinal analysis was performed on 17,334 participants (52% women, mean age 55.6±12 years) in the Moli-sani study cohort, without a history of hematological diseases. Baseline PDW measurements were categorized in tertiles, the lowest acting as the reference. A multivariable Cox-proportional hazard model was used to estimate the association between PDW and mortality. Over a median follow-up of 11.6 years (interquartile range 10.7-12.5), 1,535 deaths [37.7% cardiovascular disease (CVD) and 36.5% cancer] were ascertained. As compared to those in the first PDW tertile (14.6-16.0 fL), individuals within the highest tertile (16.6-20.4 fL) had an increased risk of all-cause [hazard ratios (HR):1.20; 95% CI: 1.04-1.37] and CVD mortality (HR:1.29; 1.03-1.62). No association between PDW and cancer mortality was found in the whole sample. Subgroup analyses by two age classes (35-65y, ≥65y) showed that the association of PDW with both all-cause and cancer mortality was more apparent in the elderly (HR:1.34; 1.14-1.58, P for interaction =0.028 and HR:1.37; 1.01-1.85, P for interaction =0.020, respectively). We conclude that PDW-associated increase in CVD mortality risk could be related to accelerated/altered activation, production, or destruction of platelets, leading to several clinical conditions and death. In the elderly, PDW involvement in all-cause and cancer mortality should be further investigated. *Moli-sani investigatorsSteering committee: Licia Iacoviello, Giovanni de Gaetano, Maria Benedetta Donati. Scientific secretariat: Marialaura Bonaccio, Americo Bonanni, Chiara Cerletti, Simona Costanzo, Amalia De Curtis, Augusto Di Castelnuovo, Alessandro Gialluisi, Francesco Gianfagna, Mariarosaria Persichillo, Teresa Di Prospero. Safety and ethical committee: Jos Vermylen, Renzo Pegoraro, Antonio Spagnolo. External event adjudicating committee: Deodato Assanelli, Livia Rago. Baseline and follow-up data management: Simona Costanzo, Marco Olivieri, Teresa Panzera. Data analysis: Augusto Di Castelnuovo, Marialaura Bonaccio, Simona Costanzo, Simona Esposito, Alessandro Gialluisi, Francesco Gianfagna, Sabatino Orlandi, Emilia Ruggiero, Alfonsina Tirozzi. Biobank, molecular and genetic laboratory: Amalia De Curtis, Sara Magnacca, Fabrizia Noro, Alfonsina Tirozzi. Recruitment staff: Mariarosaria Persichillo, Francesca Bracone, Teresa Panzera. Communication and press office: Americo Bonanni. Regional institutions: Direzione Generale per la Salute - Regione Molise; Azienda Sanitaria Regionale del Molise; Agenzia Regionale per la Protezione Ambientale del Molise; Molise Dati Spa; Offices of vital statistics of the Molise region. Hospitals: Presidi Ospedalieri ASReM: Ospedale A. Cardarelli, Campobasso; Ospedale F. Veneziale, Isernia; Ospedale San Timoteo, Termoli (CB); Ospedale Ss. Rosario, Venafro (IS); Ospedale Vietri, Larino (CB); Ospedale San Francesco Caracciolo, Agnone (IS); Casa di Cura Villa Maria, Campobasso; Ospedale Gemelli Molise, Campobasso; IRCCS Neuromed, Pozzilli (IS), Italy.

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