A pharmacometrics model to define docetaxel target in early breast cancer

Aims: We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure. Methods: A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles followed by 4 cycles of docetaxel 75-100 mg/m2 infused every 21 days. Individual Bayesian estimates of docetaxel PK parameters were obtained using a nonparametric population PK model developed with data from patients with metastatic breast cancer who received dose-intensified docetaxel (300-350 mg/m2 ). Docetaxel area under the curve (AUC) and maximum concentration (Cmax) in each cycle and total cumulative AUC (AUCcum) were calculated and related to the incidence of adverse effects and tumour recurrence. Results: Docetaxel clearance showed no change over the 4 treatment cycles, but a gradual increase in the volume of distribution was observed. One third of the patients had at least 1 dose reduction of docetaxel due to toxicity. The mean AUC, AUCcum and Cmax in patients showing docetaxel-associated adverse events were significantly higher than in patients free of toxicity (P 4.5 mg*h/L and 3.5 mg/L, respectively, were risk factors for docetaxel toxicity, while an AUC <4.5 mg*h/L was associated with tumour recurrence. Conclusion: We report for the first time a relation between docetaxel exposure and toxicity and recommend specific targets of drug exposure with implications for the clinical management of early breast cancer patients

Identification of non-host resistance genes in wheat to barley yellow rust

Yellow rust, caused by Puccinia striiformis West., is an important foliar disease of wheat and barley throughout the world, and the development of resistant cultivars is the most economical and environmentally friendly method of control. Breeding for resistance to yellow rust has, for decades, been based on the use of race-specific resistance genes, which have shown to be short-lived. Non-host resistance has been studied as a possible source of durable resistance. Two major genes, as well as an undetermined number of minor genes, for non-host resistance to the barley attacking form of yellow rust, P. striiformis f. sp. hordei, have been previously detected in the wheat cultivar ‘Lemhi’. The present study aimed at quantifying and mapping those genes using QTL (quantitative trait loci) mapping procedures. For that purpose, an F2 population of 114 individuals resulting from the cross of resistant ‘Lemhi’ with ‘Chinese 166’, a wheat cultivar susceptible to barley yellow rust, was used as the mapping population. QTL effects and significance were estimated by means of interval mapping and MQM mapping procedures. A map for the F2 population was constructed which included 116 DNA markers (14 SSRs and 102 AFLPs). Two major QTLs have been mapped to chromosome arms 1DS (Psh1) and 2BL (Psh2), with significant LOD values. These two QTLs account for 76.7% of the phenotypic variance for resistance to barley yellow rust. Two other QTLs, with a minor effect, were mapped to chromosome arms 5AL (Psh3) and 6AL (Psh4), explaining 5.1% and 10.9% of the phenotypic variation, respectively. The QTL on 5A was derived from the susceptible variety, ‘Chinese 166’. In all cases the resistance towards P. striiformis f.sp. hordei was associated with a visual chlorosis/necrosis response typical of race-specific, host resistance

Simulation of the Dynamics of Pulsed Pumped Lasers Based on Cellular Automata

Laser dynamics is traditionally modeled using differential equations. Recently, a new approach has been introduced in which laser dynamics is modeled using two-dimensional Cellular Automata (CA). In this work, we study a modified version of this model in order to simulate the dynamics of pulsed pumped lasers. The results of the CA approach are in qualitative agreement with the outcome of the numerical integration of the laser rate equations

Bridging Sustainable Development Goals and Land Administration: The Role of the ISO 19152 Land Administration Domain Model in SDG Indicator Formalization

This study illustrates the linkages between the ISO’s Land Administration Domain Model (LADM) and the UN’s sustainable development goals (SDGs), highlighting the role of the LADM in promoting effective land administration suitable for efficient computation of land/water (space)-related SDG indicators. The main contribution of this study is the formalization of SDG indicators by using the ISO standard LADM. This paper proposes several SDG-indicator-related extensions to the multi-part LADM standard that is currently under revision. These extensions encompass the introduction of new procedures for calculating indicators, the integration of blueprints for external classes to fulfil additional information needs and the design of interface classes for presenting indicator values across specific countries and reporting years. In an innovative approach, this paper introduces the Four-Step Method—a powerful framework designed to formalize SDG indicators within the LADM framework. Detailed attention is devoted to specific indicators, including 1.4.2 (secure land rights), 5.a.1 (women’s agricultural land rights), 14.5.1 (protected marine areas) and 11.5.2 (valuation as a basis for direct economic loss). In short, the Four-Step Method is pivotal in eliminating ambiguities, enhancing the efficiency of indicator computation and securing more accurate indicator values that more truly reflect the progress towards SDG realization. This approach is also expected to work with other (ISO) standards for other SDG indicators

Enzyme-controlled sensing-actuating nanomachine based on Janus Au-mesoporous silica nanoparticles

[EN] Novel Janus nanoparticles with Au and mesoporous silica faces on opposite sides were prepared using a Pickering emulsion template with paraffin wax as the oil phase. These anisotropic colloids were employed as integrated sensing-actuating nanomachines for enzyme-controlled stimuli-responsive cargo delivery. As a proof of concept, we demonstrated the successful use of the Janus colloids for controlled delivery of tris(2,2'-bipyridyl) ruthenium(II) chloride from the mesoporous silica face, which was grafted with pH-sensitive gatelike scaffoldings. The release was mediated by the on-demand catalytic decomposition of urea by urease, which was covalently immobilized on the Au face.R. V. acknowledges a Ramon & Cajal contract from the Spanish Ministry of Science and Innovation. Financial support from the Spanish Ministry of Science and Innovation CTQ2011-24355, CTQ2009-12650, CTQ2009-09351, MAT2009-14564-C04-01, MAT2012-38429-C04-01 and Comunidad de Madrid S2009/PPQ-1642, programme AVANSENS, is gratefully acknowledged. The Generalitat Valencia (project PROMETEO/2009/016) is also acknowledged.Villalonga, R.; Díez, P.; Sánchez, A.; Aznar, E.; Martínez-Máñez, R.; Pingarrón, J. (2013). Enzyme-controlled sensing-actuating nanomachine based on Janus Au-mesoporous silica nanoparticles. Chemistry - A European Journal. 19(24):7889-7894. https://doi.org/10.1002/chem.201300723S788978941924Perro, A., Reculusa, S., Ravaine, S., Bourgeat-Lami, E., & Duguet, E. (2005). Design and synthesis of Janus micro- and nanoparticles. Journal of Materials Chemistry, 15(35-36), 3745. doi:10.1039/b505099eJiang, S., Chen, Q., Tripathy, M., Luijten, E., Schweizer, K. S., & Granick, S. (2010). Janus Particle Synthesis and Assembly. Advanced Materials, 22(10), 1060-1071. doi:10.1002/adma.200904094Lattuada, M., & Hatton, T. A. (2011). Synthesis, properties and applications of Janus nanoparticles. Nano Today, 6(3), 286-308. doi:10.1016/j.nantod.2011.04.008Tang, J. L., Schoenwald, K., Potter, D., White, D., & Sulchek, T. (2012). Bifunctional Janus Microparticles with Spatially Segregated Proteins. Langmuir, 28(26), 10033-10039. doi:10.1021/la3010079Kim, J.-W., Lee, D., Shum, H. C., & Weitz, D. A. (2008). Colloid Surfactants for Emulsion Stabilization. Advanced Materials, 20(17), 3239-3243. doi:10.1002/adma.200800484Synytska, A., Khanum, R., Ionov, L., Cherif, C., & Bellmann, C. (2011). Water-Repellent Textile via Decorating Fibers with Amphiphilic Janus Particles. ACS Applied Materials & Interfaces, 3(4), 1216-1220. doi:10.1021/am200033uHowse, J. R., Jones, R. A. L., Ryan, A. J., Gough, T., Vafabakhsh, R., & Golestanian, R. (2007). Self-Motile Colloidal Particles: From Directed Propulsion to Random Walk. Physical Review Letters, 99(4). doi:10.1103/physrevlett.99.048102YOSHIDA, M., ROH, K., & LAHANN, J. (2007). Short-term biocompatibility of biphasic nanocolloids with potential use as anisotropic imaging probes. Biomaterials, 28(15), 2446-2456. doi:10.1016/j.biomaterials.2007.01.048Salem, A. K., Searson, P. C., & Leong, K. W. (2003). Multifunctional nanorods for gene delivery. Nature Materials, 2(10), 668-671. doi:10.1038/nmat974Zhang, L., Zhang, F., Dong, W.-F., Song, J.-F., Huo, Q.-S., & Sun, H.-B. (2011). Magnetic-mesoporous Janus nanoparticles. Chem. Commun., 47(4), 1225-1227. doi:10.1039/c0cc03946bLee, J. E., Lee, N., Kim, T., Kim, J., & Hyeon, T. (2011). Multifunctional Mesoporous Silica Nanocomposite Nanoparticles for Theranostic Applications. Accounts of Chemical Research, 44(10), 893-902. doi:10.1021/ar2000259Casasús, R., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Ruiz, E. (2008). Dual Aperture Control on pH- and Anion-Driven Supramolecular Nanoscopic Hybrid Gate-like Ensembles. Journal of the American Chemical Society, 130(6), 1903-1917. doi:10.1021/ja0756772Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dCandel, I., Bernardos, A., Climent, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Parra, M. (2011). Selective opening of nanoscopic capped mesoporous inorganic materials with nerve agent simulants; an application to design chromo-fluorogenic probes. Chemical Communications, 47(29), 8313. doi:10.1039/c1cc12727fZhao, Y., Trewyn, B. G., Slowing, I. I., & Lin, V. S.-Y. (2009). Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP. Journal of the American Chemical Society, 131(24), 8398-8400. doi:10.1021/ja901831uFeng, Y., He, J., Wang, H., Tay, Y. Y., Sun, H., Zhu, L., & Chen, H. (2012). An Unconventional Role of Ligand in Continuously Tuning of Metal–Metal Interfacial Strain. Journal of the American Chemical Society, 134(4), 2004-2007. doi:10.1021/ja211086yChen, T., Chen, G., Xing, S., Wu, T., & Chen, H. (2010). Scalable Routes to Janus Au−SiO2and Ternary Ag−Au−SiO2Nanoparticles. Chemistry of Materials, 22(13), 3826-3828. doi:10.1021/cm101155vHong, L., Jiang, S., & Granick, S. (2006). Simple Method to Produce Janus Colloidal Particles in Large Quantity. Langmuir, 22(23), 9495-9499. doi:10.1021/la062716zPerro, A., Meunier, F., Schmitt, V., & Ravaine, S. (2009). Production of large quantities of «Janus» nanoparticles using wax-in-water emulsions. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 332(1), 57-62. doi:10.1016/j.colsurfa.2008.08.027Rodríguez-Fernández, D., Pérez-Juste, J., Pastoriza-Santos, I., & Liz-Marzán, L. M. (2012). Colloidal Synthesis of Gold Semishells. ChemistryOpen, 1(2), 90-95. doi:10.1002/open.201200002Jana, N. R., Gearheart, L., & Murphy, C. J. (2001). Seeding Growth for Size Control of 5−40 nm Diameter Gold Nanoparticles. Langmuir, 17(22), 6782-6786. doi:10.1021/la0104323FRENS, G. (1973). Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions. Nature Physical Science, 241(105), 20-22. doi:10.1038/physci241020a0Ghosh, S. K., & Pal, T. (2007). Interparticle Coupling Effect on the Surface Plasmon Resonance of Gold Nanoparticles:  From Theory to Applications. Chemical Reviews, 107(11), 4797-4862. doi:10.1021/cr0680282Jaroniec, C. P., Kruk, M., Jaroniec, M., & Sayari, A. (1998). Tailoring Surface and Structural Properties of MCM-41 Silicas by Bonding Organosilanes. The Journal of Physical Chemistry B, 102(28), 5503-5510. doi:10.1021/jp981304zJaroniec, C. P., Gilpin, R. K., & Jaroniec, M. (1997). Adsorption and Thermogravimetric Studies of Silica-Based Amide Bonded Phases. The Journal of Physical Chemistry B, 101(35), 6861-6866. doi:10.1021/jp964002aInnocenzi, P., Kozuka, H., & Yoko, T. (1997). Fluorescence Properties of the Ru(bpy)32+Complex Incorporated in Sol−Gel-Derived Silica Coating Films. The Journal of Physical Chemistry B, 101(13), 2285-2291. doi:10.1021/jp970004zStefanescu, M., Stoia, M., & Stefanescu, O. (2006). Thermal and FT-IR study of the hybrid ethylene-glycol–silica matrix. Journal of Sol-Gel Science and Technology, 41(1), 71-78. doi:10.1007/s10971-006-0118-5Ammam, M., & Easton, E. B. (2012). Novel organic–inorganic hybrid material based on tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate and Dawson-type tungstophosphate K7[H4PW18O62]·18H2O as a bifuctional hydrogen peroxide electrocatalyst for biosensors. Sensors and Actuators B: Chemical, 161(1), 520-527. doi:10.1016/j.snb.2011.10.070Leff, D. V., Brandt, L., & Heath, J. R. (1996). Synthesis and Characterization of Hydrophobic, Organically-Soluble Gold Nanocrystals Functionalized with Primary Amines. Langmuir, 12(20), 4723-4730. doi:10.1021/la960445uSahoo, B., Sahu, S. K., & Pramanik, P. (2011). A novel method for the immobilization of urease on phosphonate grafted iron oxide nanoparticle. Journal of Molecular Catalysis B: Enzymatic, 69(3-4), 95-102. doi:10.1016/j.molcatb.2011.01.00

Sexual Dimorphism and Breed Characterization of Creole Hens through Biometric Canonical Discriminant Analysis across Ecuadorian Agroecological Areas

Despite Ecuador having a wide biodiversity of zootechnical species, characterization studies of these genetic resources are scarce. The objective of this research was to perform the biometric characterization of the Creole hen population through 14 quantitative zoometric measures. We evaluated 207 hens and 37 roosters from Ecuador’s three agro-ecological regions: the Sierra (highlands) region (Bolivar, Chimborazo, Tungurahua and Cotopaxi provinces); the Costa (coastal) region (Guayas); and the Oriente Amazonian region (Morona Santiago). Sexual dimorphism was assessed using one-way analysis of variance (ANOVA). Body dimensions were generally significantly higher for males (p < 0.05), especially for length of head, beak, neck, dorsum, tarsus, thigh, leg, and middle finger. Then, individuals were biometrically clustered into populations after a stepwise canonical discriminant analysis (CDA) computing interpopulation Mahalanobis distances. Agroecologically-based structured populations were identified when zoometrical criteria were used to classify the animals. Cotopaxi and Tungurahua provinces were reported to be the most distant from the rest, with a slight differentiation of the Morona Santiago province population from those in Guayas, Chimborazo and Bolívar. Conclusively, Ecuadorian Creole hens were higher than longer contrasting light hen breeds, which favors their dual-purpose aptitude. Hence, the development of selection programs aimed at Ecuadorian differentiated entity of production of eggs and meat across agro-ecological areas is feasible

Immunoparasitological Diagnosis Of Strongyloides Stercoralis In Garbage Collectors In Uberlândia, Mg, Brazil

The objective of this study was to determine the presence of Strongyloides stercoralis in urban garbage collectors through the use of immunological and parasitological methods. A total of 92 individuals were evaluated from August, 1997, to June, 1998. For the parasitological diagnosis Baermann and Lutz' methods were applied. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and the enzyme-linked immunosorbent assay (ELISA) to detect specific IgG antibodies. Of the 92 workers examined, six (6.5%) were infected with larvae of S. stercoralis. The IFAT detected 19 (16.3%) and the ELISA 17 (18.5%) positive serum samples. The differences between the results of parasitological and immunological methods were statistically significant (p<0.05). These results demonstrate that there is a need to improve the health conditions of this category of city employees.6203/04/15180182CONCHA, R., HARRINGTON, J.R.W., ROGERS, A.L., Intestinal strongyloidiasis: Recognition, management and determinants of outcome (2005) J Clin Gastroenterol, 39, pp. 203-211SIDDIQUI, A.A., BERK, S.L., Diagnosis of Strongyloides stercoralis infection (2001) Clin Infect Dis, 33, pp. 1040-1047FERREIRA, M., Strongyloidiasis and acquired immunodeficiency syndrome (2003) Enf Emerg, 5, pp. 18-26VADLAMUDI, R.S., CHI, D.S., KRISHANASWAMY, G., Intestinal strongyloidiasis and hyperinfection syndrome (2006) Clin Mol Allergy, 4, pp. 1-13BAERMANN G. Eine Einfache methode zur auffindung von Ankylostomum (Nematoden) larven in Erdproben. Mededeel mit h. Geneesk Lab Weltvreden Feestbundel, Batavia, 1917, p. 41-7LUTZ, A.V., Schistosoma mansoni e a schistosomose, Segundo observações feitas no Brasil. (1919) Mem Inst Oswaldo Cruz, 11, pp. 121-125COSTA-CRUZ, J.M., BULLAMAH, C.B., GONÇALVEZ-PIRES, M.R.F., Cryo-microtome sections of coproculture larvae of Strongyloides stercoralis and Strongyloides ratti as antigen sources for the immunodiagnosis of human strongyloidiasis (1997) Rev Inst Med Trop São Paulo, 39, pp. 313-317MACHADO, E.R., UETA, M.T., GONÇALVES-PIRES, M.R.F., Strongyloides venezuelensis alkaline extract for the diagnosis of human strongyloidiasis by enzyme-linked immunosorbent assay (2003) Mem Inst Oswaldo Cruz, 98, pp. 849-853MACHADO, E.R., COSTA-CRUZ, J.M., Strongyloides stercoralis and other enteroparasites in children at Uberlândia City, state of Minas Gerais, Brazil (1998) Mem Inst Oswaldo Cruz, 93, pp. 161-164PAULA, F.M., CASTRO, E., GONÇALVES-PIRES, M.R.F., Parasitological and immunological diagnoses of strongyloidiasis in immunocompromised and nonimmunocompromised children at Uberlândia City, state of Minas Gerais, Brazil (2000) Rev Inst Med Trop São Paulo, 42, pp. 51-55OLIVEIRA, L.C.M., RIBEIRO, C.T., MENDES, D.M., Frequency of Strongyloides stercoralis in alcoholics (2002) Mem Inst Oswaldo Cruz, 97, pp. 119-121LINDO, J.F., CONWAY, D.J., ATKINS, N.S., Prospective evaluation of enzyme-linked immunosorbent assay and immunoblot methods for the diagnosis of endemic Strongyloides stercoralis infection (1994) Am J Trop Med Hyg, 51, pp. 175-179CLARK, C.S., LINNEMANN Jr, C.C., CLARK, J.G., Enteric parasites in workers occupationally exposed to sewage (1984) J Occup Med, 26, pp. 273-275SCHLOSSER, O., RALL, D., LAURECEAU, M.-N., Intestinal parasite carriage in workers exposed to sewage (1999) Eur J Epidemiol, 15, pp. 261-265GOMES, T.C., ALMEIDA, M.F., MUIRA, L.A., Helmintoses intestinais em população de rua da cidade do Rio de Janeiro. (2002) Rev Soc Bras Med Trop, 35, pp. 531-53

Association Of Inflammation, Dyslipidemia, Obesity And Physical Activity Status In Children

The aim of this study was to verify the association between inflammatory biomarkers, dyslipidemia, obesity and physical activity status in 10-years old children. Ninety-four children participated in this study and were classified into eutrophic (n=36), overweight (n=34) or obese (n=24) according to their body mass index (BMI). The genic expression of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and chemokine C-C motif ligand 2 (CCL-2) mRNA; the serum concentration of high-density lipoprotein cholesterol (HDL-c) and triglycerides; BMI, percentage of body fat (% BF) and waist circumference; and the number of steps per day were determined. The expression of IL-6, TNF-α and CCL-2 were associated (p 0.05) between pro-inflammatory biomarkers and number of steps per day was found.222182

Greenhouse effect gases emission implications on sustainability of the Campus of Vegazana, University of León

En este trabajo se presentan los resultados del estudio de emisiones de CO2, uno de los gases más importantes de efecto invernadero, debido a la actividad desarrollada en el Campus de Vegazana de la Universidad de León, para el año 2006. El estudio se enmarca en un proyecto más amplio de cálculo del indicador Huella Ecológica (HE), desarrollado para conocer en qué medida se alcanzan los objetivos de sostenibilidad establecidos para el Campus, así como para el desarrollo de propuestas encaminadas a la reducción de las emisiones de CO2. Los resultados obtenidos reflejan como el área de superficie biológicamente productiva necesaria para absorber las emisiones del Campus constituyen cerca del 99% del área total de HE. La mayor parte de estas emisiones proceden del gasto energético para electricidad (38%) y uso térmico (24%, seguido del transporte (19%) y la construcción del propio complejo universitario (16%, el cual hace referencia únicamente al año 2006, considerando una vida útil de 27 años para los edificios e instalaciones del Campus, inaugurado en 1979. Una vez analizadas cualitativa y cuantitativamente las emisiones producidas, se ha buscado conocer el total de superficie forestal necesaria para absorber dichas emisiones, considerando los datos del Tercer Inventario Forestal Nacional (2003) sobre cobertura de las masas forestales para el territorio nacional, y los aportados por Bravo (2007) en relación a las tasas de fijación del gas por parte de éstas. Como conclusión, puede estimarse que del total de la superficie forestal de la provincia de León, un 0.46% es necesaria como depósito y sumidero del CO2 emitido por el Campus de Vegazana (8.470.168 toneladas. Esta estimación se ha realizado considerando que las masas forestales son las únicas depositarias de CO2, tarea compartida en la naturaleza, no obstante, con el suelo, el agua y los cultivosIn this work, we present the results obtained about the CO2 emissions, one of the most important greenhouse gases, due to the normal activity developed in the Campus of Vegazana of the University of León for the year 2006. This study is all part of a wider project for evaluating the Fingerprint ecological indicator (HE, initially developed for assessing if the sustainability objectives established by the University policies for the Campus of Vegazana have been achieved, as well as the development of proposals and ideas directed towards the reduction of the emissions of CO2. Results obtained showed that the biologically productive area necessary for absorbing all emissions are close to the 99% of the total value of HE. The majority of these emissions come from the energy consumed for producing electricity (38%) and heating (24%), followed by the transport (19%) and the constructions of the buildings and infrastructures of the University (16%, which related just for the year 2006, considering a living period of 27 years as it was inaugurated in 1979. Once analyzed qualitatively and quantitatively the emissions produced, it was developed a method for estimating the total area covered necessary for absorbing them by considering data available from the Third National Forestry Inventory of Spain (2003), related with the forest cover of the territory, and data provided by Bravo(2007, about the absorption rate of the tree species. As a conclusion, we estimated that form the total area covered by forests of the Province of León, a 0.46% is necessary as sink of the CO2 produced in the Campus of Vegazana (8.470.168 ton. This assessment has been achieved considering that forests are the only warehouse of CO2, when actually soil, water and crops are in nature.Peer Reviewe