Entorno de simulación de la gestión de una FPGA bidimensional, parte de un sistema computador de propósito general basado en HW

FPGA Simulator 1.0 simula el comportamiento de una FPGA bidimensional dinámicamente reconfigurable. La simulación consiste en la gestión de una cola de tareas de tamaño rectangular (simple), con la posibilidad de multitarea, lo que permite ejecutar simultáneamente varias de estas tareas. La ubicación de las tareas dentro de la FPGA se lleva a cabo mediante un algoritmo previamente implementado que gestiona el espacio libre en la FPGA. Este algoritmo gestiona las tareas en espera de ejecución, las que están ejecutándose actualmente en la FPGA y las que han terminado de ejecutar. Nuestra solución FPGA Simulator 1.0 permite gestionar tanto la FPGA como la lista de tareas en espera a través de una sencilla e intuitiva interfaz gráfica. El algoritmo encargado de la ubicación de las tareas también puede ser configurado manualmente. Entre la diversidad de algoritmos existentes (p.e. First-Fit (FF), Best-Fit (BF), First-Fit-Decreasing (FFD) y Best-Fit-Decreasing (BFD)), el algoritmo utilizado en nuestra solución es el Bin Packing MER, que ubica las tareas en el MER (Maximun Empty Rectangle) o Máximo Rectángulo Vacío. Trabajar con distintas FPGAs y listas de tareas se convierte en una tarea sencilla gracias a la exportación de estos elementos a ficheros de texto, que permite tanto abrir y guardar como modificar los elementos involucrados en la simulación. A parte, el uso de ficheros incrementa la versatilidad del producto, permitiendo la exportación de elementos a otros ordenadores. FPGA Simulator 1.0 permite además guardar la configuración de una simulación concreta de manera que se pueda reproducir en cualquier momento. Dado el carácter determinista de los algoritmos utilizados, una misma configuración desemboca en un mismo resultado, de forma que el almacenamiento de resultados se simplifica con el uso de un fichero de texto absolutamente independiente, que también es completamente portable. A parte de la creación de un entorno de simulación, FPGA Simulator 1.0 proporciona además una idea general del comportamiento de la simulación por medio de métricas. Estas métricas, que deben ser utilizadas de manera orientativa, se basan en la utilización del espacio libre de la FPGA, y consisten en la ocupación media y la ocupación instantánea (en porcentaje) del espacio de la FPGA. La comparación de estas métricas como resultado de la ejecución de diferentes algoritmos sobre un mismo entorno de simulación nos puede dar un acercamiento al comportamiento real de los algoritmos. La versión actual de FPGA Simulator 1.0 sólo está disponible para plataformas Windows (windows 95, 98, NT, 2000 y XP) Implementando en Borland C++ Builder, este software presenta una gran estabilidad y rapidez de ejecución, al igual que un mínimo consumo de recursos de sistema. La posibilidad de incorporar manualmente nuevos algoritmos de ejecución convierte este producto en un software de gran utilidad en el campo de la investigación. [Abstract] FPGA Simulator 1.0 simulates the behavior of a dynamically reconfigurable bidimensional FPGA. Simulation consists of a rectangular task queue managemente (simple tasks) with a multitask posibility, which implies the simultaneous execution of several tasks. The task allocation within the FPGA is done through a previously programmed algorithm, which manages the free space in the FPGA. The task management involves the waiting for execution tasks, currently executing, and already finished ones. Our solution FPGA Simulator 1.0, enables the management of both the FPGA and the task queue throug an easy and intuitive graphic interface. The algorithm used to allocate the tasks con also be manually configured. Between many other existing ones (p.e. First-Fit (FF), Best-Fit (BF), First-Fit-Decreasing (FFD) y Best-Fit-Decreasing (BFD)),Bin Packing MER was the final algorithm used in our product. Bin Packing MER allocates tasks in the Maximum Empty Rectangle available at a given moment. The exportation of elements such as FPGAs and task queues to text files translates into a clear enhancement of the working capabilities, specially when working with different types of these kind of elements. The use of text files increases the product's versatility, as these elements can be exported to other copmputers with a minimum amount of space expense. FPGA Simulator 1.0 allows saving concrete simulatin configurations for later execution Given that the algorithms used are deterministic, two identical configurations imply same results. Thus, results storage is simplified by the use of absolutely independent text files, wich are also portable. Apart from creating a simulation environment, FPGA Simulator 1.0 offers a general view of the algorithms behavior trough the metrics. These metrics, which should be used only in an orientative way, are based on the available free space in the FPGA. The two metrics used are the current occupation and the average occupation (in percentage). The comparison of the metrics obtained out of the execution of different algorithms over the same simulation environment can give us an approximate idea of the real behavior of th algorithms. The current version of FPGA Simualtor 1.0 is only supported under Windows platforms (Windows 95, 98, NT, 2000 and XP). Programmed under Borland C++ Builder, this software displays a great stability and execution time, at the same time as it consumes a minimum amount of system resources. The possibility of adding manually new algorithms provides this software with a great utility withing the scope of investigation

Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma

Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P= 2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those re-ceiving tisa-cel. Efficacy was not significantly different between both products

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p <= 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P =0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P =0.003, and 42% vs. 16%, P <0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P =0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P =0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P =0.195), 51% and 47% (P =0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lympho-depletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor

Temporal patterns of active fire density and its relationship with a satellite fuel greenness index by vegetation type and region in Mexico during 2003-2014

Background: Understanding the temporal patterns of fire occurrence and their relationships with fuel dryness is key to sound fire management, especially under increasing global warming. At present, no system for prediction of fire occurrence risk based on fuel dryness conditions is available in Mexico. As part of an ongoing national-scale project, we developed an operational fire risk mapping tool based on satellite and weather information. Results: We demonstrated how differing monthly temporal trends in a fuel greenness index, dead ratio (DR), and fire density (FDI) can be clearly differentiated by vegetation type and region for the whole country, using MODIS satellite observations for the period 2003 to 2014. We tested linear and non-linear models, including temporal autocorrelation terms, for prediction of FDI from DR for a total of 28 combinations of vegetation types and regions. In addition, we developed seasonal autoregressive integrated moving average (ARIMA) models for forecasting DR values based on the last observed values. Most ARIMA models showed values of the adjusted coefficient of determination (R2 adj) above 0.7 to 0.8, suggesting potential to forecast fuel dryness and fire occurrence risk conditions. The best fitted models explained more than 70% of the observed FDI variation in the relation between monthly DR and fire density. Conclusion: These results suggest that there is potential for the DR index to be incorporated in future fire risk operational tools. However, some vegetation types and regions show lower correlations between DR and observed fire density, suggesting that other variables, such as distance and timing of agricultural burn, deserve attention in future studiesAntecedentes: Una adecuada planificación del manejo del fuego requiere de la comprensión de los patrones temporales de humedad del combustible y su influencia en el riesgo de incendio, particularmente bajo un escenario de calentamiento global. En la actualidad en México no existe ningún sistema operacional para la predicción del riesgo de incendio en base al grado de estrés hídrico de los combustibles. Un proyecto de investigación nacional actualmente en funcionamiento, tiene como objetivo el desarrollo de un sistema operacional de riesgo y peligro de incendio en base a información meteorológica y de satélite para México. Este estudio pertenece al citado proyecto Resultados: Se observaron en el país distintas tendencias temporales en un índice de estrés hídrico de los combustibles basado en imágenes MODIS, el índice “dead ratio” (DR), y en las tendencias temporales de un ìndice de densidad de incendios (FDI), en distintos tipos de vegetación y regiones del país. Se evaluaron varios modelos lineales y potenciales, incluyendo términos para la consideración de la autocorrelación temporal, para la predicción de la densidad de incendios a partir del índice DR para un total de 28 tipos de vegetación y regiones. Se desarrollaron además modelos estacionales autoregresivos de media móvil (ARIMA en inglés) para el pronóstico del índice DR a partir de los últimos valores observados. La mayoría de los modelos ARIMA desarrollados mostraron valores del coeficiente de determinación ajustado (R2 adj) por encima de 0.7 to 0.8, sugiriendo potencial para ser empleados para un pronóstico del estrés hídrico de los combustibles y las condiciones de riesgo de ocurrencia de incendio. Con respecto a los modelos que relacionan los valores mensuales de DR con FDI, la mayoría de ellos explicaron más del 70% de la variabilidad observada en FDI. Conclusiones: Los resultados sugirieron potencial del índice DR para ser incluido en futuras herramientas operacionales para determinar el riesgo de incendio. En algunos tipos de vegetación y regiones se obtuvieron correlaciones más reducidas entre el índice DR y los valores observados de densidad de incendios, sugiriendo que el papel de otras variables tales como la distancia y el patrón temporal de quemas agrícolas debería ser explorado en futuros estudiosFunding for this work was provided by CONAFOR-CONACYT Project 252620 “Development of a Fire Danger System for Mexico.” This work was also cofinanced by the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria and European Social Fund (Dr. E. Jiménez grant)S

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial

Spanish Sleep Network.[Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.[Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.[Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.[Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction

Peabody Picture Vocabulary Test-III: Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Peabody Picture Vocabulary Test-III (PPVT-III) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Honduras, Guatemala, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the PPVT-III as part of a larger neuropsychological battery. PPVT-III scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age in all countries, such that scores increased linearly as a function of age. In addition, age2 had a significant effect in all countries, except Guatemala and Paraguay. Models showed that children whose parent(s) had a MLPE >12 years obtained higher scores compared to children whose parent(s) had a MLPE ≤12 years in all countries, except for Cuba, Peru, and Puerto Rico. Sex affected scores for Chile, Ecuador, Guatemala, Mexico, and Spain. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate interpretation of the PPVT-III when used in pediatric populations

Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome

Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess risk factors that may be involved in the pathogenesis of PH in untreated OHS.Peer reviewe