Assessing the Performance of Design Variations of a Thermoacoustic Stirling Engine Combining Laboratory Tests and Model Results.

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A pooled subgroup analysis of glucarpidase treatment in 86 pediatric, adolescent, and young adult patients receiving high-dose methotrexate therapy in open-label trials

Acute kidney injury; Glucarpidase; MethotrexateLesió renal aguda; Glucarpidasa; MetotrexatLesión renal aguda; Glucarpidasa; MetotrexatoBackground Delayed methotrexate elimination can occur in patients undergoing high-dose methotrexate cancer treatment. Effectiveness of glucarpidase for rapidly reducing methotrexate concentrations was shown in compassionate-use trials in patients aged 0–84 years. Methods We performed post hoc analyses of infants (≥28 days to <2 years), children (≥2 to <12 years), adolescents (≥12 to <15 years), and young adults (≥15 to <25 years) from four multicenter, open-label, single-arm, glucarpidase compassionate-use trials. Patients had toxic methotrexate levels due to delayed methotrexate elimination and/or renal dysfunction, and received glucarpidase (50 U/kg). The primary endpoint was clinically important reduction (CIR) in plasma methotrexate (methotrexate ≤1 μmol/L at all post-glucarpidase measurements) based on high-performance liquid chromatography. Results Among 86 patients included in efficacy analyses, CIR was achieved by zero of one infant (0.0%), five of 16 children (31.3%), seven of 24 adolescents (29.2%), and 26/45 young adults (57.8%). Median methotrexate reduction was 98.7% or higher in each group 15 minutes post-glucarpidase. Patients with pre-glucarpidase methotrexate less than 50 μmol/L (35/42, 83.3%) were more likely to achieve CIR than those with methotrexate 50 μmol/L or higher (1/37, 2.7%). The most common treatment-related adverse event was paresthesia, occurring in three adolescents (4.5%) and six young adults (5.2%). No other treatment-related adverse event occurred in 5% or higher of any age group. Conclusion After accounting for pre-glucarpidase methotrexate levels, glucarpidase efficacy at inducing CIR in pediatric/young adult patients was consistent, with efficacy observed in the overall study population (i.e., patients aged 0–84), and no unexpected safety findings were observed. These findings demonstrate glucarpidase (50 U/kg) is an effective and well-tolerated dose for pediatric, adolescent, and young adult patients

Femtosecond Infrared Spectroscopy Resolving the Multiplicity of High-Spin Crossover States in Transition Metal Iron Complexes

Tuning the photophysical properties of iron-based transition-metal complexes is crucial for their employment as photosensitizers in solar energy conversion. For the optimization of these new complexes, a detailed understanding of the excited-state deactivation paths is necessary. Here, we report femtosecond transient mid-IR spectroscopy data on a recently developed octahedral ligand-field enhancing [Fe(dqp)2]2+ (C1) complex with dqp = 2,6-diquinolylpyridine and prototypical [Fe(bpy)3]2+ (C0). By combining mid-IR spectroscopy with quantum chemical DFT calculations, we propose a method for disentangling the 5Q1 and 3T1 multiplicities of the long-lived metal-centered (MC) states, applicable to a variety of metal–organic iron complexes. Our results for C0 align well with the established assignment toward the 5Q1, validating our approach. For C1, we find that deactivation of the initially excited metal-to-ligand charge-transfer state leads to a population of a long-lived MC 5Q1 state. Analysis of transient changes in the mid-IR shows an ultrafast sub 200 fs rearrangement of ligand geometry for both complexes, accompanying the MLCT → MC deactivation. This confirms that the flexibility in the ligand sphere supports the stabilization of high spin states and plays a crucial role in the MLCT lifetime of metal–organic iron complexes

Construcción de una explotación de porcino de cebo con capacidad para 2.000 plazas, en el término de Peñalba (Huesca).

Este proyecto tiene como objeto determinar las características técnicas, constructivas y presupuestarias para la nueva construcción de una explotación ganadera de porcino de cebo con una capacidad de 2.000 plazas en el T.M. de Peñalba (Huesca), adecuándose a las normativas municipales, autonómicas, estatales y comunitarias. Dicha explotación se situará en el término municipal de Peñalba, Polígono 604, parcela 90. La explotación se gestionará mediante una integración vertical. La empresa integradora suministrará cerdos, pienso, medicamentos, asesoría, veterinario, etc., y establecerá su propia normativa de funcionamiento. El promotor aportará el terreno, las instalaciones, gastos (luz, agua, gas oil, mantenimiento y mano de obra). Esta explotación tendrá una capacidad para 2.000 plazas y se funcionará con el sistema “todo dentro, todo fuera” lo que permitirá hacer vacíos sanitarios, limpieza y desinfección de las naves. Los animales entrarán con un peso vivo de unos 16 - 20 kg y saldrán con un peso vivo de entorno a unos 95 - 100 kg. Para alcanzar estos pesos cada lote permanecerá en la granja unos 120 días más 7 días de vacío sanitario, limpieza y desinfección. Con estos datos obtenemos 2, 87 ciclos al año. Contamos además con unas bajas del 3,5%, por lo que en cada partida calcularemos 1.930 cerdos de media. Al año contaremos con una producción de 5.539 cerdos enviados a matadero. En el tema de la construcción, la explotación constará de dos naves paralelas de medidas exteriores 60,25 m de largo por una anchura de 15 m cada una, con una altura en arranque de la cumbrera de 3,50 m y una altura máxima en cumbrera de 5,43m. La cubierta será a dos aguas (con pendiente del 25%) de panel sándwich. La distancia entre pórticos es de 6 m. Se instalarán 9 pórticos centrales completos (jácena + pilares) y 2 pilares hastiales en cada lateral de las naves y en las esquinas. Los cerramientos de las paredes se harán con termoarcilla. Cada nave aloja en su interior 80 celdas, de las cuales 3 serán lazaretos y 77 serán celdas de engorde. El suelo de las celdas se compondrá de zona slats y zona de descanso. Cada celda contará con una tolva y 2 bebederos. Las naves contarán con sistema de ventilación y sistema de calefacción. Además de las 2 naves principales, la explotación contará con otras construcciones necesarias para el manejo: caseta (baños, motor, caldera, baterías, cuadro general de mando y protección…) muelle de carga, balsa de purín, balsa de agua y fosa de cadáveres. Todo el recinto de la explotación se encontrará vallado. Este proyecto constará de las siguientes partes: 1 Memoria, 2 Anejos, 3 Planos, 4 Presupuesto, 5 Pliego de condiciones, 6 Estudio de Seguridad y Salud. Se ha redactado siguiendo en todo momento la normativa vigente

El Ecocidio como crimen internacional

Por medio del presente trabajo se trata de que los lectores reparen en la necesidad de regulación de un crimen ecológico internacional. Para ello comenzaré hablándoles acerca de la la etiología del desastre actual, fruto de la acción antrópica del ser humano moderno. Para continuar con las propuestas que abogan por la necesidad de criminalizar el ecocidio en tiempos de paz; la propuesta de considerar el ecocidio como el quinto crimen contra la paz por medio de su inclusión en el Estatuto de Roma y la Iniciativa Ciudadana Europea: acabemos con el Ecocidio en Europa, una iniciativa para dar derechos a la tierra. Para continuar con Ley de Derechos de la Madre Tierra de Bolivia. Todo ello antecedido de la definición legal del término Ecocidio, sus modalidades,la severidad del término empleado, su naturaleza jurídica y el bien jurídico que este protege, además, de la regulación ya existente que contempla el Ecocidio en tiempos de guerra. Para finalizar relatándoles los impactantes 10 lugares de ecocidio más graves del planeta, que demuestran la necesidad de que tales prácticas no queden impune

Educació 2018-2020. Reptes, tendències i compromisos

La recerca i la innovació s’han convertit en una peça clau en l’assoliment d’una educació que impulsi el desenvolupament humà, econòmic i social i es converteixi en un instrument real de millora del benestar individual i col·lectiu. L’IRE-UB (Institut de Recerca en Educació de la Universitat de Barcelona) s’ha creat, recentment, amb la finalitat de fomentar la investigació d’excel·lència en educació. Entre les seves finalitats, destaquen les de reforçar la investigació en educació, crear sinèrgies entre investigadors, aconseguir i optimitzar recursos i obrir camí als joves investigadors. Tot això, sense descuidar la seva clara vocació social centrada en posar-se al servei de l’entorn educatiu i en transferir de forma efectiva els resultats de la investigació. L’IRE-UB s’origina, doncs, amb la missió de contribuir a donar resposta als reptes educatius actuals, com poden ser el de millorar l’accés i la qualitat de l’educació, disminuir l’abandonament prematur, fomentar l’aprenentatge i la formació al llarg de la vida o afavorir els processos d’innovació educativa. Amb l’afany de concretar aquests reptes, sorgeix la primera publicació, impulsada des d’aquest institut, per a la qual alguns dels seus membres reflexionen sobre els reptes i les tendències en educació per al proper bienni, apuntant els seus propis compromisos en les qüestions que s’aborden. Mitjançant articles curts, els autors i les autores tracten aspectes com les característiques i la identitat de la formació universitària, així com les seves implicacions en el desenvolupament de la societat; les noves tendències en metodologies d’investigació educativa; l’orientació que adquireix la formació dels docents; la formació en disciplines educatives específiques; els valors en educació davant la responsabilitat social..

A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors

BACKGROUND The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors. METHODS T-VEC was delivered by intralesional injection at 10$^{6}$ plaque-forming units (PFU)/ml on the first day, followed by 10$^{8}$ PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST). RESULTS Fifteen patients were enrolled into two cohorts based on age: cohort A1 (n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 (n = 2) 2 to <12 years old (melanoma, n = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response. CONCLUSIONS T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed. TRIAL REGISTRATION ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845

Incidence and management of patients with methotrexate delayed elimination in the clinical practice : A Delphi study

High-dose methotrexate (HDMTX) is administered for the treatment of some cancers. HDMTX is usually safe but may crystallize in renal tubules causing acute kidney injury (AKI). Consequently, MTX elimination is delayed, resulting in a severe and life-threatening condition. No studies have been published about the impact of MTX toxicity in Spain. This study aims to estimate the incidence and management of MTX delayed elimination and toxicity. A two-round Delphi study was performed to reach consensus between 10 medical experts on haemato-oncology and paediatric oncology with experience in the management of HDMTX treated patients from leading Spanish hospitals. An online questionnaire was developed based on national and international guidelines and previous evidence regarding HDMTX-related toxicity. Consensus was established at 80% agreement. Median and interquartile ranges were calculated, and incidence data were extrapolated to the Spanish general population. Out of 1.475 patients estimated to receive HDMTX treatment annually in Spain, 27.5% present MTX delayed elimination and 11.6% develop HDMTX-induced AKI (35.4% with severe systemic toxicities (>grade 3) and 18.8% develop chronic renal disease). Mortality is estimated in 4.2%. Immuno-enzymatic assay is used in most of the hospitals (90%) for MTX serum level monitoring. All experts use increased supportive care and high leucovorin as first-line treatment. Available treatments in experts' hospitals in case toxicity persists are haemodialysis (90% of hospitals), glucarpidase (60%) and hemofiltration (50%). Most prevalent non-renal systemic toxicities are haematologic and mucositis (21-40% of patients). Patients with HDMTX-induced AKI require from intensive care (5% of patients), more than 3 sessions and 4 days of dialysis, and about 8.5 days of hospitalization (non-ICU patients) and 12 days in case of patients requiring ICU. These results are the first evidence regarding HDMTX-induced AKI in Spain. Incidence and mortality results are in line with previous studies. Clinical management is based on preventive measures and the treatment depend on the availability in the hospital. The need for effective, safe and rapid treatment for the reduction of MTX toxic levels and the improvement of monitoring methods were noted by experts as urgent needs. Further observational studies to validate these results would be needed