Butanol production in a first-generation Brazilian sugarcane biorefinery: Technical aspects and economics of greenfield projects

AbstractThe techno-economics of greenfield projects of a first-generation sugarcane biorefinery aimed to produce ethanol, sugar, power, and n-butanol was conducted taking into account different butanol fermentation technologies (regular microorganism and mutant strain with improved butanol yield) and market scenarios (chemicals and automotive fuel). The complete sugarcane biorefinery with the batch acetone–butanol–ethanol (ABE) fermentation process was simulated using Aspen Plus®. The biorefinery was designed to process 2million tonne sugarcane per year and utilize 25%, 50%, and 25% of the available sugarcane juice to produce sugar, ethanol, and butanol, respectively. The investment on a biorefinery with butanol production showed to be more attractive [14.8% IRR, P(IRR>12%)=0.99] than the conventional 50:50 (ethanol:sugar) annexed plant [13.3% IRR, P(IRR>12%)=0.80] only in the case butanol is produced by an improved microorganism and traded as a chemical

Dusquetide: Reduction in Oral Mucositis Associated with Enduring Ancillary Benefits in Tumor Resolution and Decreased Mortality in Head and Neck Cancer Patients

Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.Fil: Marullo, Rossella. Cornell University; Estados UnidosFil: Castro, Monica. Universidad de Buenos Aires; ArgentinaFil: Yomtoubian, Shira. Cornell University; Estados UnidosFil: Nieves Calvo Vidal, M.. Cornell University; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krumsiek, Jan. Cornell University; Estados UnidosFil: Nicholas, Andrew P.. Cornell University; Estados UnidosFil: Cresta Morgado, Pablo. Universidad de Buenos Aires; ArgentinaFil: Yang, ShaoNing. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Roth, Berta María Cristina. Universidad de Buenos Aires; ArgentinaFil: Bonomi, Marcelo. Ohio State University; Estados UnidosFil: Keshari, Kayvan R.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Mittal, Vivek. Cornell University; Estados UnidosFil: Navigante, Alfredo Hugo. Universidad de Buenos Aires; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC The Phase 2 CONDOR Randomized Clinical Trial

IMPORTANCE: Dual blockade of programmed death ligand 1(PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. OBJECTIVE :To assess safety and objective response rate of durvalumab combined with tremelimumab. DESIGN, SETTING, AND PARTICIPANTS: The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. INTERVENTIONS: Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. MAIN OUTCOMES AND MEASURES: Safety and tolerability and efficacy measured by objective response rate. RESULTS: Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%1339%) in the combination arm (n =129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. CONCLUSIONS AND RELEVANCE: In patients with R/M HNSCC and low or no PD-Lt tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way

Notariaalse testamendi vormistuslikud nõuded

http://tartu.ester.ee/record=b2659036~S1*es

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PURPOSE: The number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. METHODS: The XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine-Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). CONCLUSIONS: Single-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients

De promessa a realidade: como o etanol celulósico pode revolucionar a indústria da cana-de-açúcar: uma avaliação do potencial competitivo e sugestões de política pública

Bibliografia: p. 286-289Anexos: p. 289-294Após um longo período de desenvolvimento tecnológico em nível mundial, o etanol celulósico ou de segunda geração (E2G) atingiu o estágio de plantas comerciais. O Brasil, por conta dos projetos fomentados pelo Plano Conjunto BNDES-Finep de Apoio à Inovação Tecnológica Industrial dos Setores Sucroenergético e Sucroquímico (PAISS), tem atualmente uma capacidade instalada de produção de E2G de cerca de 140 milhões de litros por ano. Contudo, tal volume ainda pode ser considerado pequeno quando comparado à demanda interna de combustíveis, hoje suprida com volumes relevantes de gasolina importada. Assim, com o objetivo de fomentar a implementação de mecanismos de política pública que acelerem os investimentos em novas plantas de E2G, este artigo apresenta, baseado em premissas discutidas com diversas empresas e especialistas, estimativas sobre o potencial de melhoria de eficiência e redução de custos de produção do E2G em diferentes cenários tecnológicos. Se bem-sucedidas, tais políticas ajudariam a alterar o atual paradigma tecnoeconômico da indústria da cana-de-açúcar, resgatando sua competitividade

Construcción de conocimiento y evaluación en los procesos de elaboración de Trabajos Finales de Grado desde una perspectiva ecosistémica comunicacional

El presente trabajo es un informe final de un proyecto que tuvo como finalidad ahondar en las líneas teóricas del proceso de construcción de conocimiento y evaluación integral en el Nivel Superior Universitario de la enseñanza en el marco de la asignatura Taller de Elaboración de Trabajo Final de la carrera de Comunicación Social de la UNLaM. Concretamente, se buscó validar nuevos instrumentos de evaluación para los trabajos finales de graduación que permitan incluir los procesos subjetivos de producción del conocimiento. Para esto, la investigación se encuadró en la perspectiva metodológica cualitativa pero con la complementación de análisis cuantitativo en tanto herramienta para la síntesis de parte de la información. Asimismo, se llevó a cabo el método de análisis de contenido y se empleó la técnica de fichaje documental en el caso del análisis del discurso académico formal. Por otra parte, se aplicó la técnica de entrevistas en profundidad en el caso de los discursos académicos de los docentes y alumnos las cuales se realizaron luego de la culminación de su trabajo. En tanto, se utilizó la observación para el análisis de los posters presentados por los alumnos en su instancia de coloquio. Respecto de los resultados obtenidos, en el saber teórico-temático en el discurso formal la mayoría de los casos planteó correctamente el marco teórico y todos presentaron la tarea de análisis acompañada con ilustraciones, cuadros y citas textuales de acuerdo a la metodología que empleó cada uno. La mayoría realizó un entrecruzamiento adecuado entre el marco teórico y los resultados. En cuanto al discurso informal la mayoría de los entrevistados, tanto alumnos como tutores, coincidieron con lo expresado en los trabajos escritos. Si bien reconocieron que en la redacción hubo cohesión y coherencia, algunos alumnos mencionaron inconvenientes en la argumentación. En cuanto al aspecto metodológico, tanto en el discurso formal como en el informal todos los casos establecieron conjetura aunque no derivaron de forma adecuada variables y observables empíricos; la selección del corpus en todos los casos fue adecuada y significativa al planteo de investigación. También fue correcta la forma de obtención de la información. En relación a la dimensión escritural la mayoría discriminó tema y problema, y la redacción en general fue adecuada, simple y completa en todos los casos. En cuanto a la dimensión oralidad en la categoría estrategias de resolución de dificultades cuestiones no presentes en lo formal, las dificultades más mencionadas fueron con relación a enfrentar al jurado en la defensa y a exponer una síntesis conceptual del trabajo en el tiempo requerido para esta instancia. Asimismo, en el rol del tutor se mencionó la importancia del seguimiento del docente no sólo para la corrección de la redacción, sino también para el acompañamiento al alumno en la toma de decisiones pertinentes al marco teórico y metodológico. Finalmente en las conclusiones se corroboraron los objetivos y metas propuestos que incluyeron la modificación de los instrumentos de Evaluación de la cátedra de “Taller de Trabajo Final” como son: la Evaluación de Proceso, la Evaluación de Producto y la Evaluación de Coloquio. El análisis y estudio de estos últimos será profundizado en la investigación que la sucede sobre la Evaluación de Trabajos Finales en el Nivel Superior en el contexto de los nuevos lenguajes multimedia.Fil: Santorsola, María Victoria. Universidad Nacional de La Matanza; Argentina.Fil: Luján Acosta, Fernando Darío Ernesto. Universidad Nacional de La Matanza; Argentina.Fil: Chiavetta, Vanina Cecilia. Universidad Nacional de La Matanza; Argentina.Fil: Pidoto, Adriana. Universidad Nacional de La Matanza; Argentina.Fil: Giuliano, Mónica. Universidad Nacional de La Matanza; Argentina.Fil: Herrero, María Eugenia. Universidad Nacional de La Matanza; Argentina.Fil: Gordo Díaz, Daniel. Universidad Nacional de La Matanza; Argentina.Fil: Carrasana, Laura. Universidad Nacional de La Matanza; Argentina.Fil: Del Valle, Juan Martín. Universidad Nacional de La Matanza; Argentina.Fil: Larocca, María Adela. Universidad Nacional de La Matanza; Argentina.Fil: Magarola, Oscar. Universidad Nacional de La Matanza; Argentina.Fil: Sbresso Lagadari, María Sol. Universidad Nacional de La Matanza; Argentina.Fil: Antelo, María Valeria. Universidad Nacional de La Matanza; Argentina.Fil: Beccaría, Mariana. Universidad Nacional de La Matanza; Argentina.Fil: Turriaga, Lorena. Universidad Nacional de La Matanza; Argentina.Fil: Barberis, Sergio Horacio. Universidad Nacional de La Matanza; Argentina.Fil: Sartori, Marcelo. Universidad Nacional de La Matanza; Argentina.Fil: Csome, Diego. Universidad Nacional de La Matanza; Argentina.Fil: Bonomi, Facundo. Universidad Nacional de La Matanza; Argentina.Fil: Cosenza, Julián. Universidad Nacional de La Matanza; Argentina

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception