Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia

Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed

Proposal of low-cost housing modules for families of the socioeconomic level 'D': cCse study Arequipa-La Joya Project

This research work is aimed at developing a real estate project of an urbanization formed by single-family housing modules, located in a peri-urban area of the district of La Joya, province and region Arequipa. The property is characterized by having great potential due to the opportunity cost of the land price, which allows to carry out a project of this type. In recent years, in the sector, it has been giving urban habilitations destined, in its entirety, to houses of country for the socioeconomic levels A and B, bypassing to families of the socioeconomic level D; For this reason the project represents an interesting proposal by not having competition in the supply of the sector. This will begin with the urban habilitation of a field of 40896.00 m², resulting in a useful area of 25056.00 m², distributed in 261 lots of 96.00 m². In each of these lots a basic single-family housing module of 38.29 m² of covered area will be built. It also includes a market study that will mark the guidelines for the definition of the product appropriate to the preferences and needs of the target customer. The market study, even, presents an interesting deficit between the supply and demand of this type of housing in the population of the city of Arequipa, which is hoax by the project. The work also includes an analysis of different constructive systems taking into account the following indicators: efficiency, efficiency, market and regulation. Project planning is done by taking Lean Construction tools to ensure deadlines. The work culminates in a cash flow, which reflects, in its indicators, the academic appeal of the project for potential investors.Trabajo de investigaciónEl presente trabajo de investigación está orientado a desarrollar un proyecto inmobiliario de una urbanización conformada por módulos de vivienda unifamiliares, ubicada en una zona periurbana del distrito de La Joya, provincia de Arequipa. El predio se caracteriza por tener un gran potencial debido al costo oportunidad del precio del terreno, que permite realizar un proyecto de este tipo. En años recientes, en el sector, se ha venido dando habilitaciones urbanas destinadas, en su totalidad, a casas de campo para los niveles socioeconómicos A y B, soslayando a familias del nivel socioeconómico D; por esta razón el proyecto representa una interesante propuesta al no contar con competencia en la oferta del sector. Este se iniciará con la habilitación urbana de un terreno de 40 896.00 m², teniendo como resultado un área útil de 25 056.00 m², distribuidos en 261 lotes de 96.00 m². En cada uno de estos lotes se edificará un módulo de vivienda unifamiliar básico de 38.29 m² de área techada. Asimismo, comprende un estudio de mercado que marcará las pautas para la definición del producto adecuado a las preferencias y necesidades del cliente objetivo. El estudio de mercado, incluso, presenta un interesante déficit entre la oferta y demanda de este tipo de vivienda en la población de la ciudad de Arequipa, el cual es redituado por el proyecto. El trabajo incluye, además, un análisis de diferentes sistemas constructivos teniendo en cuenta los siguientes indicadores: eficiencia, eficacia, mercado y normatividad. El planeamiento del proyecto se realiza tomando herramientas de Lean Construction para asegurar el cumplimiento de plazos. El trabajo culmina con un flujo de caja, el cual refleja, en sus indicadores, el atractivo académico del proyecto para potenciales inversionistas

Iberoamerican Reviews

Reseñas IberoamericanasIberoamerican Review

Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia

Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed