A Comparison of the Environmental Impact of Different AOPs: Risk Indexes

Today, environmental impact associated with pollution treatment is a matter of great concern. A method is proposed for evaluating environmental risk associated with Advanced Oxidation Processes (AOPs) applied to wastewater treatment. The method is based on the type of pollution (wastewater, solids, air or soil) and on materials and energy consumption. An Environmental Risk Index (E), constructed from numerical criteria provided, is presented for environmental comparison of processes and/or operations. The Operation Environmental Risk Index (EOi) for each of the unit operations involved in the process and the Aspects Environmental Risk Index (EAj) for process conditions were also estimated. Relative indexes were calculated to evaluate the risk of each operation (E/NOP) or aspect (E/NAS) involved in the process, and the percentage of the maximum achievable for each operation and aspect was found. A practical application of the method is presented for two AOPs: photo-Fenton and heterogeneous photocatalysis with suspended TiO2 in Solarbox. The results report the environmental risks associated with each process, so that AOPs tested and the operations involved with them can be compared

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

Abstract Background Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling. Methods To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. Results We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. Conclusions We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165).https://deepblue.lib.umich.edu/bitstream/2027.42/148212/1/40425_2018_Article_493.pd

Palynological evidence for environmental and climatic change in the lower Guadiana valley, Portugal, during the last 13 000 years

Pollen analysis of a 48 m AMS radiocarbon-dated sediment sequence from the Guadiana estuary provides the first record of Lateglacial and Holocene vegetation history in the Algarve province of Portugal. This paper focuses on the record of terrestrial pollen taxa, which document a series of forest expansions and declines during the period 13 000 cal. BP to 1600 cal. BP and provide insights into climate evolution in southwestern Iberia. The main vegetation phases identified in the Guadiana valley are (1) Lateglacial interstadial (Allerød) forest with Quercus and Pinus under a temperate, moist, continental climate; (2) a Younger Dryas forest decline (Quercus) and expansion of pinewoods, xeric scrub and open ground habitats (with Juniperus, Artemisia, Ephedra distachya type, Centaurea scabiosa type) under arid and cold conditions; (3) an early Holocene forest/scrub/open-ground vegetation mosaic developing under a warm, dry and continental climate; (4) a maximum of Quercus forest and thermomediterranean evergreen taxa (Olea, Phillyrea, Pistacia) reflecting a warm, moist oceanic climate between c. 9000 cal. BP and c. 5000 cal. BP; and (5) the expansion of shrublands with Cistaceae and Ericaceae under a drier climatic regime and increasing anthropogenic activity since c. 5000 cal. BP. Holocene episodes of maximum climatic aridity are identified in the record of xerophytic taxa (Juniperus, Artemisia, Ephedra distachya type) centred around 10 200 cal. BP, 7800 cal. BP, 4800 cal. BP, 3100 cal. BP and 1700 cal. BP. Regional comparisons suggest a correlation of arid phases across southern Iberia and northwest Africa, which can be related to abrupt North Atlantic coolings (Bond events).Research Council studentship for WJF (NERC/S/A/2001/06109), with the support of Trinity College and the Department of Geography, University of Cambridg

Qualitative aspects and validation of a screening method for pesticides in vegetables and fruits based on liquid chromatography coupled to full scan high resolution (Orbitrap) mass spectrometry

The analytical capabilities of liquid chromatography with single-stage high-resolution mass spectrometry have been investigated with emphasis on qualitative aspects related to selective detection during screening and to identification. The study involved 21 different vegetable and fruit commodities, a screening database of 556 pesticides for evaluation of false positives, and a test set of 130 pesticides spiked to the commodities at 0.01, 0.05, and 0.20 mg/kg for evaluation of false negatives. The final method involved a QuEChERS-based sample preparation (without dSPE clean up) and full scan acquisition using alternating scan events without/with fragmentation, at a resolving power of 50,000. Analyte detection was based on extraction of the exact mass (±5 ppm) of the major adduct ion at the database retention time ±30 s and the presence of a second diagnostic ion. Various options for the additional ion were investigated and compared (other adduct ions, M + 1 or M + 2 isotopes, fragments). The two-ion approach for selective detection of the pesticides in the full scan data was compared with two alternative approaches based on response thresholds. Using the two-ion approach, the number of false positives out of 11,676 pesticide/commodity combinations targeted was 36 (0.3 %). The percentage of false negatives, assessed for 2,730 pesticide/commodity combinations, was 13 %, 3 %, and 1 % at the 0.01-, 0.05-, and 0.20-mg/kg level, respectively (slightly higher with fully automated detection). Following the SANCO/12495/2011 protocol for validation of screening methods, the screening detection limit was determined for 130 pesticides and found to be 0.01, 0.05, and ≥0.20 mg/kg for 86, 30, and 14 pesticides, respectively. For the detected pesticides in the spiked samples, the ability for unambiguous identification according to EU criteria was evaluated. A proposal for adaption of the criteria was made

Reactivity of neonicotinoid insecticides with carbonate radicals

“NOTICE: this is the author’s version of a work that was accepted for publication in Water Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in WATER RESEARCH, [VOL46, ISSUE11, jul 2012] DOI10.1016/j.watres.2012.03.051¨ ©IWA Publishing 2012. The definitive peer-reviewed and edited version of this article is published in Water Research 46 11 3476-3489 2012 10.1016/j.watres.2012.03.051 and is available at www.iwapublishing.comThe reaction of three chloronicotinoid insecticides, namely Imidacloprid (IMD), Thiacloprid (THIA) and Acetamiprid (ACT), with carbonate radicals (CO3 center dot-) was investigated. The second order rate constants (4 +/- 1) x 10(6), (2.8 +/- 0.5) x 10(5), and (1.5 +/- 1) x 10(5) M-1 s(-1) were determined for IMD, THIA and ACT, respectively. The absorption spectra of the organic intermediates formed after CO3 center dot- is approximately equal to attack to IMD is in line with those reported for alpha-aminoalkyl radicals. A reaction mechanism involving an initial charge transfer from the amidine nitrogen of the insecticides to CO3 center dot- is proposed and further supported by the identified reaction products. The pyridine moiety of the insecticides remains unaffected until nicotinic acid is formed. CO3 center dot- radical reactivity towards IMD, ACT, and THIA is low compared to that of HO center dot radicals, excited triplet states, and O-1(2), and is therefore little effective in depleting neonicotinoid insecticides. (C) 2012 Elsevier Ltd. All rights reserved.This research was financially supported by Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Agencia Nacional de Promocion Cientifica y Tecnologica (Argentina, project PICT 2007 number 00308), and Agencia Espanola de Cooperacion Internacional (project A/8199/07). M.L.D. thanks CONICET for a graduate studentship. M.C.G. is a research member of CONICET. D.O.M. is a research member of Comision de Investigaciones Cientificas de la Provincia de Buenos Aires (CIC), Argentina. L.S.J. acknowledges Ministerio de Ciencia e Innovacion for his Juan de la Cierva scholarship.Dell'arciprete, ML.; Soler Escoda, JM.; Santos-Juanes Jordá, L.; Arques Sanz, A.; Martire, DO.; Furlong, JP.; González, MC. (2012). Reactivity of neonicotinoid insecticides with carbonate radicals. Water Research. 46(11):3476-3489. https://doi.org/10.1016/j.watres.2012.03.051S34763489461

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. MethodsA total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. ResultsSecond-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and & GE;3 concomitant medications. ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Tendencias de la investigación en Ingeniería Ambiental

Esta obra incluye las memorias del Simposio “Tendencias de la Investigación en Ingeniería Ambiental”, organizado por el Grupo de Investigaciones y Mediciones Ambientales (GEMA), realizado en la Universidad de Medellín en agosto de 2007. El texto está conformado por 14 capítulos agrupados en cuatro partes. En la primera se agrupan los trabajos relacionados con la calidad y alternativas de tratamiento del agua e hidráulica ambiental (capítulos 1 al 4). La segunda trata temas relacionados con la contaminación atmosférica y calidad del aire (capítulos 5 al 6). La tercera está relacionada con las tecnologías ambientales para la recuperación y conservación de suelos (capítulos 7 al 10) y la cuarta y última comprende las temáticas asociadas con la sostenibilidad ambiental del territorio (capítulos 11 al 14). En este sentido, estamos convencidos del valioso aporte que el libro dará a la comunidad científica, por ser este un documento de divulgación de resultados de investigación en ingeniería ambiental.PRÓLOGO............13 PRESENTACIÓN.............15 PRIMERA PARTE CALIDAD Y ALTERNATIVAS DE TRATAMIENTO DEL AGUA HIDRÁULICA AMBIENTAL Capítulo 1 PRETRATAMIENTO DE AGUAS RESIDUALES INDUSTRIALES MEDIANTE FOTO-FENTON SOLAR A ESCALA INDUSTRIAL ACOPLADO A BIOTRATAMIENTO CON FANGOS ACTIVOS INMOVILIZADOS Manuel Ignacio Maldonado, Isabel Oller, Wolfgang Gernjak, Sixto Malato 1.1 INTRODUCCIÓN............19 1.2 MATERIALES Y MÉTODOS.............21 1.2.1 Reactivos............21 1.2.2 Determinaciones analíticas.............22 1.2.3 Dispositivo experimental.............23 1.3 R ESULTADOS Y DISCUSIÓN............ 27 1.3.1 Tratamiento foto-Fenton solar............27 1.3.2 Biotratamiento mediante fangos activos inmovilizados.............33 1.3.3 Sistema combinado foto-Fenton solar-biológico aeróbico............35 1.4 CONCLUSIONES............. 42 Capítulo 2 DEGRADACIÓN DE LA ATRAZINA EN SOLUCIÓN ACUOSA USANDO RADIACIÓN UV Y PROCESOS DE OXIDACIÓN AVANZADA Margarita Hincapié, Gustavo Peñuela, Manuel I. Maldonado, Sixto Malato 2.1 INTRODUCCIÓN..............47 2.2 SECCIÓN EXPERIMENTAL..............53 2.2.1 Materiales.............53 2.2.2 Metodología...............53 2.2.3 Determinación analítica..............55 2.2.4 Determinación de la toxicidad...............55 2.3 R ESULTADOS Y DISCUSIÓN...............56 2.3.1 Hidrólisis..............56 2.3.2 Fotólisis y fotocatálisis con TiO2 Degussa P25.............56 2.3.3 Efecto de los agentes oxidantes peróxido de hidrógeno y persulfato de sodio en la fotocatálisis..............59 2.3.4 Proceso foto Fenton..............63 2.3.5 Evaluación de los aniones inorgánicos durante los dos tratamientos.............66 2.3.6 Cuantificación e identificación de los productos de degradación...............68 2.3.7 Evaluación de la toxicidad...............71 2.4 CONCLUSIONES...............74 Capítulo 3 HUMEDALES ARTIFICIALES PARA EL TRATAMIENTO DE AGUAS RESIDUALES Nazly E. Sánchez P., Gustavo A. Peñuela M., Juan C. Casas Z. 3.1 INTRODUCCIÓN...............81 3.2 MARCO TEÓRICO...............83 3.2.1 Humedales construidos para el tratamiento de aguas residuales..............84 3.2.2 Clasificación de los humedales.............85 3.2.3 Ventajas y desventajas de los humedales subsuperficiales..............87 3.2.4 Aspectos a considerar en los humedales subsuperficiales..............88 3.3 MATERIALES Y MÉTODOS.................89 3.3.1 Diseño y construcción de los humedales a escala piloto..............89 3.3.2 Componentes del agua residual sintética................90 3.3.3 Siembra y aclimatación de plantas............... 90 3.3.4 Muestreos............91 3.4 R ESULTADOS Y DISCUSIÓN..............91 3.4.1 pH..............91 3.4.2 Demanda bioquímica de oxígeno (DBO5)..............92 3.4.3 Carbono orgánico total (COT)................94 3.5 CONCLUSIONES................95 Capítulo 4 DESCRIPCIÓN DE LA DINÁMICA OCEANOGRÁFICA DEL GOLFO DE URABÁ UTILIZANDO MEDICIONES DE CAMPO Luis Javier Montoya Jaramillo, Francisco Mauricio Toro Botero 4.1 INTRODUCCIÓN...............103 4.2 DATOS Y MÉTODOS................107 4.3 DISCUSIÓN..............118 4.4 CONCLUSIONES............. 120 SEGUNDA PARTE CONTAMINACIÓN ATMOSFÉRICA Y CALIDAD DEL AIRE Capítulo 5 IMPACTO DE LAS MOTOCICLETAS EN LA CALIDAD DEL AIRE. ESTUDIO DE CASO: MONTERÍA Carlos Alberto Echeverri Londoño 5.1 INTRODUCCIÓN.................127 5.2 MATERIALES Y MÉTODOS...............131 5.2.1 S elección de los sitios de medición...............131 5.2.2 Período de medición................131 5.2.3 Parámetros seleccionados...............132 5.2.4 Equipos y materiales utilizados..............132 5.2.5 Índices de calidad del aire..............133 5.2.6 Legislación.............. 138 5.2.7 Inventario de emisiones..............141 5.3 RESULTADOS...............142 5.3.1 Calidad del aire y calidad acústica................142 5.3.2 Emisiones vehiculares.............150 5.3.3 Inventario de emisiones.............155 5.4 CONCLUSIONES.............. 158 5.5 RECOMENDACIONES............. 160 Capítulo 6 ROMPIMIENTO DE LA INVERSIÓN TÉRMICA EN EL VALLE DE ABURRÁ Ángela M. Rendón, José F. Jiménez, Carlos Palacio 6.1 INTRODUCCIÓN...............163 6.2 MEDICIÓN DE VARIABLES ATMOSFÉRICAS..............164 6.3 CAMPAÑAS DE MEDICIÓN.............165 6.4 RESULTADOS..............166 6.5 CONCLUSIONES................170 TERCERA PARTE TECNOLOGÍAS AMBIENTALES PARA LA RECUPERACIÓN Y CONSERVACIÓN DE SUELOS Capítulo 7 ESTRUCTURA MODELO DE LA PARTÍCULA FUNDAMENTAL DEL COMPOST Carlos E. Arroyave M., Carlos A. Peláez J. 7.1 INTRODUCCIÓN..............177 7.2 MATERIALES Y EQUIPOS.............178 7.2.1 Materias primas y planta de compostaje............178 7.2.2 Obtención de fracciones............. 182 7.2.3 Análisis estadístico.............184 7.3 RESULTADOS Y DISCUSIÓN.............184 7.3.1 Caracterización fisicoquímica del material de RSUsf...........184 7.3.2 Tamaño de partícula.............185 7.3.3 Análisis instrumental................187 7.3.4 Modelo de partícula..............194 7.4 CONCLUSIONES..............195 Capítulo 8 DEGRADACIÓN DE HEXACLOROCICLOHEXANO (HCH) CON HONGOS DE PODREDUMBRE DE LA MADERA Juan Carlos Quintero Díaz, Gumersindo Feijoo, Juan Manuel Lema 8.1 INTRODUCCIÓN..............199 8.2 MATERIALES Y MÉTODOS..............204 8.2.1 Microorganismos.............204 8.2.2 Ensayos de selección de los hongos de podredumbre de la madera.............204 8.2.3 Ensayos de degradación de HCH en medio líquido.............205 8.2.4 Ensayos de degradación de HCH en sobre suelo contaminado.............205 8.2.5 Extracción y análisis de los isómeros de HCH.............208 8.3 RESULTADOS Y DISCUSIÓN..............209 8.3.1 Selección de los microorganismos.............209 8.3.2 Degradación de HCH en medio líquido.............210 8.3.3 Degradación de HCH en fase sólida.............212 8.4 CONCLUSIONES.............. 220 Capítulo 9 AVANCES EN LA PROPAGACIÓN ASIMBIÓTICA IN VITRO DE ORQUÍDEAS CON ESPECIAL ÉNFASIS EN EL GÉNERO CATTLEYA Liliana R. Botero, María A. Jaramillo, Óscar O. Ossa R., Tatiana Saldarriaga F., Estefanía Ortiz R. 9.1 INTRODUCCIÓN...............227 9.2 MATERIALES Y MÉTODOS...............231 9.2.1 Evaluación de la metodología de desinfección de cápsulas de orquídeas.............231 9.2.2 Evaluación del efecto de un abono comercial y un suplemento comercial de banano............239 9.3 R ESULTADOS Y DISCUSIÓN..............242 9.3.1 Ensayos de desinfección...............242 9.3.2 Resultados del efecto de un abono comercial y un suplemento de banano comercial....246 9.4 CONCLUSIONES..............254 Capítulo 10 MOVILIDAD DEL BRAVONIL 720 (CLOROTALONILO) A TRAVÉS DE LA ZONA NO SATURADA Y SATURADA DE UN ACUÍFERO LIBRE SIMULADO Idalia Jacqueline López Sánchez, Gustavo Antonio Peñuela Mesa 10.1 INTRODUCCIÓN...............259 10.2 MATERIALES Y MÉTODOS...............261 10.3 RESULTADOS Y DISCUSIÓN..............269 10.4 CONCLUSIONES..............292 CUARTA PARTE SOSTENIBILIDAD AMBIENTAL DEL TERRITORIO Capítulo 11 LA RESPONSABILIDAD SOCIAL EMPRESARIAL COMO COMPONENTE DE SOSTENIBILIDAD AMBIENTAL John Fredy López Pérez 11.1 INTRODUCCIÓN...............299 11.2 UNA LECTURA DE LA SOSTENIBILIDAD AMBIENTAL DESDE UN PUNTO DE VISTA SOCIAL..............300 11.3 EL CONCEPTO DE LA RESPONSABILIDAD SOCIAL EMPRESARIAL...............303 11.4 LA RESPONSABILIDAD SOCIAL COMO ESPACIO PARA L A SOSTENIBILIDAD AMBIENTAL.............309 11.5 ESBOZOS DE UN CASO: EL SECTOR ELÉCTRICO COLOMBIANO..............311 11.6 CONCLUSIONES..............319 Capítulo 12 DETERMINACIÓN ESPACIAL DE ÁREAS DE IMPORTANCIA ESTRATÉGICA El caso de microcuencas abastecedoras de acueductos veredales del municipio de Medellín Joaquín Hincapié, Álvaro Lema 12.1 INTRODUCCIÓN................323 12.2 LA NOCIÓN DE ÁREA DE IMPORTANCIA ESTRATÉGICA...............325 12.3 LA IDEA DE LOS SERV ICIOS AMBIENTALES..............328 12.4 ESTRATEGIA METODOLÓGICA EN LA IDENTIFICACIÓN Y DETERMINACIÓN DE LAS ÁREAS DE IMPORTANCIA ESTRATÉGICA............332 12.5 L OS RESULTADOS DEL MODELO...............359 12.6 CONCLUSIONES............. 361 Capítulo 13 LA EDUCACIÓN AMBIENTAL EN LA TRANSFORMACIÓN DE LA CULTURA Luz Ángela Peña Marín, Alba Miriam Vergara Vargas 13.1 INTRODUCCIÓN..............369 13.2 APROXIMACIÓN CONCEPTUAL...............370 13.2.1 La reflexividad...............372 13.2.2 La construcción del otro...............374 13.2.3 El discurso.............. 372 13.2.4 La autonomía y la participación..............375 13.2.5 La educación ambiental y el desarrollo humano..............378 13.2.6 Base conceptual de la educación ambiental..............380 13.2.7 Contexto sociocultural..............382 13.2.8 Diagnóstico de la educación ambiental y la administración de los recursos naturales..............392 13.2.9 Criterios corporativos de educación ambiental.............394 13.3 CONCLUSIONES...............398 Capítulo 14 ENFOQUE CONCEPTUAL DE UN SISTEMA DE INDICADORES AMBIENTALES PARA LA EVALUACIÓN DE LOS POT: municipios del Valle de San Nicolás Oriente Antioqueño Carolina Arias Muñoz, Diana Elizabeth Valencia Londoño, Boris Puerto López 14.1 INTRODUCCIÓN...............401 14.2 ENFOQUE CONCEPTUAL DEL SISTEMA DE INDICADORES..............406 14.2.1 Primera aproximación: el enfoque de impacto ambiental..............406 14.2.2 Enfoque sistémico: de la sostenibilidad ambiental..............408 14.3 PROPUESTA FINAL DE INDICADORES E ÌNDICE DE SOSTENIBILIDAD AMBIENTAL DEL POT ISAPOT.............424 14.4 R EFLEXIONES FINALES..............42

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFβ antibody to promote durable rejection and immunity in squamous cell carcinomas

BACKGROUND: Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFβ signaling. METHODS: To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFβ or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. RESULTS: We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFβ monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFβ, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFβ antibody administration attenuates these effects. We show that α-TGFβ acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFβ acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. CONCLUSIONS: We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFβ-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFβ combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFβ/α-PD-1 combination therapy (NCT02947165)

A review of combined advanced oxidation technologies for the removal of organic pollutants from water

Water pollution through natural and anthropogenic activities has become a global problem causing short-and long-term impact on human and ecosystems. Substantial quantity of individual or mixtures of organic pollutants enter the surface water via point and nonpoint sources and thus affect the quality of freshwater. These pollutants are known to be toxic and difficult to remove by mere biological treatment. To date, most researches on the removal of organic pollutants from wastewater were based on the exploitation of individual treatment process. This single-treatment technology has inherent challenges and shortcomings with respect to efficiency and economics. Thus, application of two advanced treatment technologies characterized with high efficiency with respect to removal of primary and disinfection by-products in wastewater is desirable. This review article focuses on the application of integrated technologies such as electrohydraulic discharge with heterogeneous photocatalysts or sonophotocatalysis to remove target pollutants. The information gathered from more than 100 published articles, mostly laboratories studies, shows that process integration effectively remove and degrade recalcitrant toxic contaminants in wastewater better than single-technology processing. This review recommends an improvement on this technology (integrated electrohydraulic discharge with heterogeneous photocatalysts) viz-a-vis cost reduction in order to make it accessible and available in the rural and semi-urban settlement. Further recommendation includes development of an economic model to establish the cost implications of the combined technology. Proper monitoring, enforcement of the existing environmental regulations, and upgrading of current wastewater treatment plants with additional treatment steps such as photocatalysis and ozonation will greatly assist in the removal of environmental toxicants