Torres Quevedo's mechanical calculator for second-degree equations with complex coefficients

Leonardo Torres Quevedo worked intensively in analogue calculating machines during the last years of the 19th century. The algebraic calculators were calculating machines in which numbers are represented by quantities of a given physical magnitude(s). The physical result is a magnitude of a physical quantity whose measurement in the coherent unit is the result of the algebraic equation. This article shows the three-dimensional (3D) modelling, virtual reconstruction and simulation of the first mechanical calculating machine for solving second-degree equations with complex coefficients, to prove that the functionality was correct and the machine could be built. Sketches of said machine provide enough information on the shape and mechanisms of the machine. By means of the simulation, it has been possible to prove its operation and feasibility of construction so that it is possible to replicate it as a real physical model. The mechanical calculator for second-degree equations with complex coefficients constituted a major milestone in the technological development of the time and helped to originate and improve the design of other algebraic calculators like the machine for solving eighth-degree equations

The 2011 submarine volcanic eruption in El Hierro (Canary Islands)

Forty years after the Teneguía Volcano (La Palma, 1971), a submarine eruption took place off the town of La Restinga, south of El Hierro, the smallest and youngest island of the Canarian Archipelago. Precursors allowed an early detection of the event and its approximate location, suggesting it was submarine. Uncertainties derived from insufficient scientific information available to the authorities during the eruption, leading to disproportionate civil protection measures, which had an impact on the island's economy-based primarily on tourism-while residents experienced extra fear and distress. © 2012 Blackwell Publishing Ltd, The Geologists' Association & The Geological Society of London.Peer Reviewe

The 2011 submarine volcanic eruption in El Hierro (Canary Islands)

Forty years after the Teneguía Volcano (La Palma, 1971), a submarine eruption took place off the town of La Restinga, south of El Hierro, the smallest and youngest island of the Canarian Archipelago. Precursors allowed an early detection of the event and its approximate location, suggesting it was submarine. Uncertainties derived from insufficient scientific information available to the authorities during the eruption, leading to disproportionate civil protection measures, which had an impact on the island's economy-based primarily on tourism-while residents experienced extra fear and distress. © 2012 Blackwell Publishing Ltd, The Geologists' Association & The Geological Society of London.Peer Reviewe

The ongoing volcanic eruption of El Hierro, Canary Islands

El Hierro, the youngest of the Canary Islands (Spain), is no stranger to hazards associated with volcanic activity or to efforts to minimize the effects of these hazards on local communities. As early as 1793, administrative records of El Hierro indicate that a swarm of earthquakes was felt by locals; fearing a greater volcanic catastrophe, the first evacuation plan of an entire island in the history of the Canaries was prepared. The 1793 eruption was probably submarine with no appreciable consequences other than that the earthquakes were felt [Carracedo, 2008]; over the next roughly 215 years the island was seismically quiet. Yet seismic and volcanic activity are expected on this youngest Canary Island due to its being directly above the presumed location of the Canary Island hot spot, a mantle plume that feeds upwelling magma just under the surface, similar to the Hawaiian Islands. Because of this known geologic activity, the Spanish Instituto Geogrfco Nacional (IGN) has managed geophysical monitoring of the island since the beginning of the 1990s.Peer Reviewe

Everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

Background and aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels <_ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation

Facer visible o invisible: habilidades para aprender dos e das escolares nos colexios rurais agrupados de Ourense

O presente estudo céntrase na descrición do funcionamento cognitivo, dos procesos lectores e dos procesos matemáticos do alumnado dos centros rurais agrupados (CRA) da provincia de Ourense escolarizados nas etapas de educación infantil e primaria, comparando o seu desempeño cos iguais en idade e nivel educativo pero escolarizados en centros educativos da cidade. Participaron un total de 114 escolares, 57 dos CRA e 57 de centos urbanos con idades comprendidas entre os 5 anos e 0 meses e os 7 anos e 11 meses, dos que 64 eran nenos e 50 nenas. Aos e ás participantes aplicóuselles de xeito individual unha proba de avaliación dos procesos cognitivos (D. N.: CAS), outra de avaliación dos procesos lectores en cada nivel educativo (BIL 3-6; PROLEC-R) e outra de avaliación dos procesos matemáticos (TEDI-MATH). A través de análises descritivas e de varianza dun só factor (ANOVA) obtívose que o alumnado participante ten un nivel medio no funcionamento cognitivo e nos procesos lectores e matemáticos acorde coa súa idade e nivel educativo. No contraste de puntuacións obtidas polo alumnado dos CRA e o do ámbito urbano atopáronse diferenzas estatisticamente significativas, tanto na etapa de educación infantil coma na de educación primaria, nas tarefas lectoras de rima, comprensión de textos, comprensión de oracións, comprensión oral, precisión da lectura de pseudopalabras e velocidade de igual-diferente. Nos procesos matemáticos as diferenzas manifestáronse nas tarefas de contar, operacións lóxicas e estimación do tamaño. Na maioría das tarefas lectoras e matemáticas o alumnado dos CRA obtivo significativamente máis puntuación ca o alumnado dos centros urbanos. Estes resultados positivos do alumnado dos CRA da provincia de Ourense poñen de manifesto o valor das prácticas pedagóxicas que se levan a cabo nese tipo de centros, así como os beneficios achegados pola contorna rural, tal e como se soporta noutras investigacións realizadas

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. Background: CMR is the reference tool for cardiac imaging but is time-consuming. Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine&#43;LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in less than 1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort. (J Am Coll Cardiol Img 2021;14:1742–1754)Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies

Background: Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course. Methods: We recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided. Results: We identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02). Conclusions: We show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.Supported by CERCA Programme/Generalitat de Catalunya, Health Department PERIS #SLT/002/16/00374, AGAUR-project #2017SGR1080; MCI/AEI/ERDF project #RTI2018-094049-B-I00; ERC EPIPHARM; Cellex Foundation; “la Caixa” Foundation (LCF/PR/GN18/51140001 and LCF/PR/GN18/50310007), RF-2016–02364388, Accelerator Award—Cancer Research UK/AIRC—INCAR Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) Project 5 × 1000 no. 9962, AIRC IG 2018 id. 21724, AIRC MFAG id. 21769 and id. 20450; MIUR (Grant PRIN 2017); and RCR-2019–23669115

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p <.001) and at 6 months (63.4% vs. 90.1%, p <.001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p =.001) and 6 months (p <.001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline