449 research outputs found

    Nutritional composition, antioxidant activity and isolation of scopoletin from Senecio nutans: support of ancestral and new uses

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    Continuing with our study characterising Senecio nutans Sch. Bip., we have isolated and identified a simple coumarin, scopoletin, that could be relevant for the biological properties of the species related with the ancestral medical uses. This is the first report of scopoletin from S. nutans. In addition, the extract was analysed for its antioxidant activity using the ABTS and FRAP method as well as providing the first nutritional analyses of this plant from northern Chile highlands

    Descentralización de la política de ciencia, tecnología e innovación: propuesta de diseño y gestión del Comité Regional de Innovación del Maule

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    50 p.Este estudio provee un análisis y recomendaciones respecto al proceso de regionalización de las políticas de ciencia, tecnología e innovación (CTI) en Chile, el cual requiere de múltiples acciones tendientes a lograr una adecuada coordinación con el nivel nacional, así como una sincronía con la estrategia regional de desarrollo país y las diversas políticas públicas entorno a la CTI. Un componente clave en este proceso será el Comité Regional de Ciencia, tecnología e Innovación (CCTI), indicado en la Ley 21074 de Fortalecimiento de la Regionalización del país (Artículo 68 bis) y en el cual, si bien se define su alcance, no se profundiza en su operacionalización ni en su gestión. En tal sentido, el presente trabajo busca proponer un Sistema de Gestión del CCTI del Maule, tomando referencia las experiencias internacionales y nacionales. La propuesta entrega términos de gobernanza, composición y propuestas de acción que permitan mejorar la capacidad de articulación entre niveles, sectores e intereses y, de esa forma, garantizar un mayor impacto de las políticas regionales de innovación. //ABSTRACT: This study provides an analysis and recommendations regarding the process of regionalization of science, technology, technology and innovation (STI) policies in Chile, which requires multiple actions aimed at achieving adequate coordination with the national level, as well as synchronization with the country's regional development strategy and policies on STI. A key component in this process will be the Regional Committee for Science, Technology and Innovation (CCTI), indicated in Law 21074 for strengthening the STI regionalization of the country (Art 68 bis) and in which, although its scope is defined, it does not its operationalization or management is deepened. This work proposes a Management System of the CCTI of Maule, taking into account international and national experiences. The proposal provides terms of governance, members and proposals for action to improve the articulation capacity between levels, sectors and interests and, thus, to guarantee a greater impact of regional innovation policies

    Diagnóstico del desempeño innovador de las Pymes en comparación con las grandes empresas en la región del Maule

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    35 p.Las capacidades de innovación son reconocidas hoy en día como unas de las fuentes centrales de la creación y mantenimiento de ventajas competitivas de las empresas. La mayor parte del aparato productivo las economías nacionales y locales, la componen las pequeñas y medianas empresas, lo que las posiciona como un actor clave que es necesario fortalecer para lograr mayores niveles de competitividad y bienestar. Sin embargo, las pymes por lo general tienden a lidiar con dificultades más severas para innovar que las grandes empresas, impidiendo su consolidación y crecimiento. El objetivo del trabajo es realizar un diagnóstico del desempeño innovador de las pymes ubicadas en la región del Maule usando la información reportada en la Encuesta Nacional e Innovación para Chile de 2017, así como plantear recomendaciones de política en base a los resultados encontrados. Entre los hallazgos es posible destacar que las Pymes muestran un desempeño innovador muy inferior al mostrado por las grandes empresas y las firmas ubicadas en otras regiones del país, que se expresan en limitadas capacidades para innovar, baja inversión en actividades de innovación, escasos flujos de conocimiento con otros actores del sistema de innovación, dificultades para obtener resultados innovadores y se encuentran más expuestas barreras externas a la innovación. // ABSTRACT: Innovation capabilities are recognized today as one of the central sources of the creation and maintenance of competitive advantages of companies. Most of the productive apparatus of national and local economies is made up of small and mediumsized enterprises, which positions them as a key player that needs to be strengthened to achieve higher levels of competitiveness and well-being. However, SMEs generally tend to deal with more severe difficulties in innovating than large companies, preventing their consolidation and growth. The objective of the work is to make a diagnosis of the innovative performance of SMEs located in the Maule region using the information reported in the 2017 National and Innovation Survey for Chile, as well as to propose policy recommendations based on the results found. Among the findings, it is posible to highlight that SMEs show an innovative performance that is much lower than that shown by large companies and firms located in other regions of the country, which is expressed in limited capacities to innovate, low investment in innovation activities, scarce cash flows. knowledge with other actors in the innovation system, difficulties in obtaining innovative results and external barriers to innovation are more exposed

    Identificación y caracterización de factores de transcripción del tipo C2H2-ZFP involucrados en el desarrollo del polen de Vitis vinifera

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    142 p.En la vid (Vitis vinifera L.) se ha sugerido que malformaciones generadas en el desarrollo del polen, reduce el potencial de germinación y la entrega de células espermáticas a los óvulos, aumentando la incidencia del desarrollo de frutos partenocárpicos (DFP), con un impacto negativo en la calidad del vino. Los mecanismos reguladores que controlan la formación de polen siguen siendo desconocidos en la vid. Sin embargo, en otras plantas se ha revelado una red que involucra varios tipos de factores de transcripción través del modelo (A)B(C) del desarrollo floral y se han asignado roles clave a los miembros de la familia de proteínas con dedos de zinc del tipo C2H2 (ZFP). Factores de este tipo han sido asociados a la regulación del desarrollo del polen en petunia, arabidopsis, y otras especies. El silenciamiento de algunos de estos genes provoca alteraciones morfológicas y funcionales en los granos de polen, en las diferentes etapas del desarrollo de estos. La identificación en el genoma de la vid tanto de genes homólogos a aquellos que regulan el desarrollo de anteras y polen en Arabidopsis thaliana, así como genes homólogos a la familia EPF de petunia, permite sugerir que los mecanismos moleculares similares a los descritos en estas especies modelo, regulan el desarrollo del polen en la vid. Basado en ello se planteó como hipótesis de trabajo: “La regulación del desarrollo del polen involucra la participación de proteínas factores de transcripción del tipo C2H2-ZFP en Vitis vinifera L.” Para comprender mejor el papel de las ZFP en el desarrollo del polen se realizó una búsqueda de genoma amplio identificando un grupo de 98 genes que codifican para ZFP (familia VviZFP), ampliamente distribuidos en el genoma de la vid. Luego de una caracterización general, se seleccionó un grupo de genes VviZFPs presumiblemente implicados en el desarrollo del polen, de acuerdo con su perfil de expresión in silico y homología con ZFP que regulan el desarrollo del polen, informado en otras plantas modelo. Posteriormente, se posicionaron eventos del desarrollo del polen dentro de la escala del desarrollo floral/frutal en vid (Sistema E-L), con análisis de microscopía y de expresión relativa de genes relacionados en el cultivar ‘Carmenere’. En este cultivar, la especificación de células madre del polen es visible a partir del estadio E-L13 y el desarrollo del polen ocurre entre el estadio E-L13 y E-L16. Luego, se determinó la expresión temporal de un set de genes VviZFP candidatos durante un periodo de la segunda temporada del desarrollo floral de la vid, se identificaron elementos de respuesta en las regiones promotoras de estos genes (2000 pb desde el codón de inicio de la transcripción) y finalmente se determinó la actividad órgano específica de la región promotora de VviZFP11 y VviZFP67. Todos los genes VviZFP seleccionados mostraron dinámicas de expresión a lo largo del desarrollo floral, lo que sugiere una posible participación de estos en el desarrollo de la vid. Las regiones promotoras presentaron diferentes niveles de enriquecimiento con elementos reguladores cis de respuesta a factores de transcripción, de señalización hormonal y elementos de expresión específicos del polen. Se observaron diferencias en la actividad espacio/temporal de los promotores entre VviZFP68 y el ortólogo propuesto PhMEZ1, sugiriendo roles diferentes para ambos genes. Por otro lado, el promotor del gen VviZFP13 presenta actividad similar a lo observado en AtDAZ1/2, además de actividad específica en tejido estigmático, haciéndolo interesante para estudios posteriores. Sin embargo, los perfiles de expresión indican que estos genes están siendo transcritos durante el momento del desarrollo del polen en vid. Finalmente, los resultados generados en esta tesis permiten generar una fuente de información importante que será útil a la hora de desarrollar trabajos posteriores que persigan comprender la participación de un grupo reducido de VviZFPs en eventos del desarrollo del polen en la vid. // ABSTRACT: In grapevine (Vitis vinifera L.) it has been suggested that malformations generated in the development of pollen, reduces the potential for germination and the delivery of sperm cells to the ovules, increasing the incidence of parthenocarpic fruit development (DFP), with an impact negative on the wine quality. The regulatory mechanisms that control pollen formation remains unknown in grapevine. However, in other plants a network involving various types of transcription factors has been revealed through the (A)B(C) model of flower development and key roles have been assigned to members of the C2H2 type zinc finger protein family (ZFP). Factors of this type have been associated with the regulation of pollen development in petunia, arabidopsis, and other species. The silencing of some of these genes causes morphological and functional alterations in pollen grains, at different stages of their development. The identification in the grapevine genome of genes homologous to those that regulate the development of anthers and pollen in Arabidopsis thaliana as well as genes homologous to the EPF family of petunia, allows us to suggest, that molecular mechanisms similar to those described in these model species regulate the pollen development in grapevine. Based on this, it is proposed as a working hypothesis: "The regulation of pollen development involves the participation of C2H2-ZFP-type transcription factor proteins in Vitis vinifera L." To better understand the role of ZFPs in pollen development, a genome-wide search was carried out identifying a group of 98 genes that code for ZFP (VviZFP family), widely distributed in the grapevine genome. After a general characterization, a group of VviZFPs genes presumably involved in pollen development was selected according to their in silico expression profile and homology with ZFP that regulate pollen development reported in other model plants. Subsequently, pollen development events were positioned within the scale of floral/fruit development in grapevine (E-L System), with microscopy analysis and relative expression of related genes in the ‘Carmenere’ cultivar. In this cultivar, the pollen stem cell specification is visible from stage E-L13 and pollen development occurs between stage E-L13 and E-L16. Then, the temporal expression of a set of candidate VviZFP genes were determined during a period of the second season of floral development in grapevines, response elements were identified in the promoter regions of these genes (2000 bp from the start codon) and finally the specific activity of the promoter region of VviZFP11 and VviZFP67 were determined. All the VviZFP genes showed these expression dynamics throughout flower development, suggesting a possible participation in grapevine development. The promoter regions present different levels of enrichment with cis regulatory elements of response to transcription factors, hormonal signaling, and pollen-specific expression elements. Differences in the spatial/temporal activity of the promoters are observed between VviZFP68 and the proposed PhMEZ1 ortholog, suggesting different roles for both genes. On the other hand, the promoter of the VviZFP13 gene presents activity similar to that observed in AtDAZ1/2, in addition to specific activity in stigmatic tissue, making it interesting for subsequent studies. However, the expression profiles indicate that these genes are being transcribed during the time of pollen development in grapevine. Finally, the results generated in this thesis allow generating an important source of information that will be useful when developing subsequent works that seek to understand the participation of a small group of VviZFPs in grapevine pollen development events

    Identificación de nuevas tecnologías para la elaboración de pellet destinado a calefacción

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    48 p.Hace un par de décadas comenzó a consolidarse el pellet como combustible en la calefacción, principalmente doméstica. Esto coincide con la creciente preocupación por el medio ambiente y los avances tecnológicos. Las propiedades del pellet hacen que este combustible sea considerado como sostenible, pues utiliza el concepto de economía circular, el cual consiste en crear producto utilizando los desechos de la industria, de esta forma se disminuye el impacto ambiental y aumentan las utilidades de la empresa. Se trata de un producto que se elabora normalmente en base a residuos (aserrín, ramas, astillas, etc.), ofrecido a un precio de venta muy competitivo, con porcentajes de humedad bajos, una mayor eficiencia en la combustión y menos emisiones de CO2. La creciente demanda del pellet enfrenta una reducción de la tradicional materia prima (desechos de madera), además de una industria peletizadora muy dependiente de la industria forestal. Por lo anterior, el presente proyecto buscó identificar y recomendar nuevas y mejores tecnologías de elaboración de pellet, a partir del uso de técnicas de vigilancia tecnológica y consultas a bases de datos de publicaciones científicas, patentes y proyectos internacionales. A partir de la información recopilada y su análisis, se identificaron seis espacios en los que la investigación aplicada, las patentes y los proyectos, confluyen y determinan posibles avances para la industria nacional o regional: la incorporación de nuevos componentes provenientes de la actividad agrícola, el uso de materia prima forestal o de jardín, el uso de material animal, el uso de desechos agroindustriales, la peletización móvil y aditivos y compuestos para mejorar el desempeño. //ABSTRACT: A couple of decades ago, pellets began to establish themselves as a heating fuel, mainly for domestic use. This coincides with the growing concern for the environment and technological advances. The properties of pellets mean that this fuel is considered sustainable, as it uses the concept of circular economy, which consists of creating a product using industrial waste, thus reducing the environmental impact and increasing the company's profits. It is a product that is normally made from waste (sawdust, branches, wood chips, etc.), offered at a very competitive selling price, with low humidity percentages, higher combustion efficiency and lower CO2 emissions. The growing demand for pellets faces a reduction of the traditional raw material (wood waste), in addition to a pelletising industry highly dependent on the forestry industry. The aim of this study is to identify and recommend new and improved pellet processing technologies, using technological surveillance techniques and consultation of scientific publications, patents and international projects databases. Based on the information collected and its analysis, six areas were identified in which applied research, patents and projects converge and determine possible advances for the national or regional industry: the incorporation of new components from agricultural activity, the use of forest or garden raw material, the use of animal material, the use of agro-industrial waste, mobile pelletisation and additives and compounds to improve performance

    Estimación de fracción de cobertura de dosel a partir de imágenes RGB capturadas desde un dron de bajo costo: caso de estudio en avellano europeo (Corylus avellana L.)

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    44 p.El avellano europeo (Corylus avellana L.) se ha convertido en un cultivo estratégico del desarrollo de las zonas agrícolas del valle central de Chile. El riego es una de las variables que interfieren en la productividad. Para precisar el consumo hídrico, se ha utilizado ampliamente la ecuación adaptada de la Fao-56, que involucra un coeficiente de cultivo (kc) referente a las características de las etapas fenológicas. El Kc se puede obtener a través de la fracción de cobertura (fc). Es por este motivo que se llevó a cabo un estudio durante las temporadas 2019-2020 y 2020-2021 con el objetivo de estimar el Kc utilizando imágenes de un UAV, en una planta de avellano europeo var. Tonda di Giffoni, en un huerto de la empresa Agrichile S.A, ubicado en la localidad de Camarico, Rio Claro, Maule, Chile (35° 18” 30 latitud Sur, 71°, 22 57 latitud oeste, 219 m.s.n.m). La fc se estimó a través de imágenes capturadas al medio día solar, utilizando 2 métodos diferentes. El primero, el conteo manual de una cuadricula a través de una fotografía digital y el segundo procesando las imágenes aéreas de un UAV Dji Mavic air en el programa QGIS para segmentar el suelo de planta. Además, a través de la ecuación para estima la evapotranspiración real, adaptada por Allen et, al., 1998, se calculó un coeficiente de corrección de riego (Kr), que fue multiplicado por el Kc de la literatura. Finalmente se realizó una regresión lineal entre ambos métodos que mostraron diferencias estadísticas entre las 2 temporadas. Se obtiene una relación muy baja entre la variable estimada y observada de (R2) de 0.0268, pendiente de 0.057377, MAE: 0.0711335%, RMSE: 0.00797239 para la temporada 2019-2020. Sin embargo, para la temporada 2020- 2021, existió una relación moderadamente fuerte entre fc observada y la fc estimada, con un R2= 0.76669 con pendiente de 0.641026, MAE: 0.0322436 % y RMSE: 0.00152509 %. Por medio de los resultados se concluye que el Kc se puede obtener a través de un Kr entregado por la fc capturadas por el UAV, sin embargo, se debe tener en cuenta factores climáticos y agronómicos. // ABSTRACT: The European hazelnut (Corylus avellana L.) has become a strategic crop for the development of agricultural areas in the central valley of Chile. Irrigation is one of the variables that interfere with productivity. To specify water consumption, the adapted equation of Fao-56, which involves a culture coefficient (kc) referring to the characteristics of the phenological stages, has been widely used. Kc can be obtained through the coverage fraction (fc). It is for this reason that a study was carried out during the seasons 2019-2020 and 2020-2021 with the aim of estimating the Kc using images of a UAV, in a European var hazel plant. Tonda di Giffoni, in an orchard of the company Agrichile S.A, located in the town of Camarico, Rio Claro, Maule, Chile (35° 18" 30 latitude South, 71°, 22 57 latitude West, 219 m.s.n.m). The fc was estimated through images captured at solar noon, using 2 different methods. The first, the manual counting of a grid through a digital photograph and the second processing the aerial images of a Dji Mavic air UAV in the QGIS program to segment the floor plan. In addition, through the equation for estimating actual evapotranspiration, adapted by Allen et al., 1998, an irrigation correction coefficient (Kr) was calculated, which was multiplied by the Kc of the literature. Finally, a linear regression was performed between both methods that showed statistical differences between the 2 seasons. We obtained a very low ratio between the estimated and observed variable of (R 2) of 0.0268, slope of 0.057377, MAE: 0.0711335%, RMSE: 0.00797239 for the 2019-2020 season. However, for the 2020-2021 season, there was a moderately strong relationship between observed and estimated fc, with an R 2= 0.76669 with a slope of 0.641026, MAE: 0.0322436 % and RMSE: 0.00152509 %. By means of the results it is concluded that the Kc can be obtained through a Kr delivered by the fc captured by the UAV, however it must take into account climatic and agronomic factors

    Understanding the adsorption process in ZIF-8 using high pressure crystallography and computational modelling

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    Understanding host–guest interactions and structural changes within porous materials is crucial for enhancing gas storage properties. Here, the authors combine cryogenic loading of gases with high pressure crystallography and computational techniques to obtain atomistic detail of adsorption-induced structural and energetic changes in ZIF-8

    Primary biliary cirrhosis

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    Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

    Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

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    Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme

    Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

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    BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038
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