A note on the SG(m) test

López et al. (Reg Sci Urban Econ 40(2–3):106–115, 2010) introduce a nonparametric test of spatial dependence, called SG(m). The test is claimed to be consistent and asymptotically Chi-square distributed. Elsinger (Reg Sci Urban Econ 43(5):838–840, 2013) raises doubts about the two properties. Using a particular counterexample, he shows that the asymptotic distribution of the SG(m) test may be far from the Chi-square family; the property of consistency is also questioned. In this note, the authors want to clarify the properties of the SG(m) test. We argue that the cause of the conflict is in the specification of the symbolization map. The discrepancies can be solved by adjusting some of the definitions made in the original paper. Moreover, we introduce a permutational bootstrapped version of the SG(m) test, which is powerful and robust to the underlying statistical assumptions. This bootstrapped version may be very useful in an applied context

Propagación del desgarro de tejido biológico empleado en la construcción de bioprótesis cardíacas en función de la forma y el tipo de sutura

En este trabajo hemos estudiado la fuerza necesaria para propagar un desgarro en un tejido de pericardio de avestruz, tejido alternativo y en estudio para la fabricación de bioprótesis cardiacas. Se analiza la influencia de dos de las suturas más empleadas en cirugía cardiovascular: Prolene® y Gore-Tex®, en este comportamiento mecánico. El tejido se suturó de dos formas distintas borde-borde y en solapa. Para los ensayos se utilizó un péndulo Elmendorf capaz de medir, la fuerza necesaria para propagar el desgarro de un tejido. Se analizaron 106 ensayos, tras aplicar criterios de selección morfológica habituales en estos ensayos y que homogenizaron las muestras por su espesor y las hicieron comparables. La serie de control, no suturada, necesitó 24 N, como valor medio, para propagar el desgarro en 1 cm, mientras que las series suturadas borde con borde, con Gore-Tex® y con Prolene®, necesitaron, para la misma propagación del d-esga-rro, 12.69 N (p=0.001) y 16.18 N respectivamente. Esta pérdida de resistencia no se observó en las series suturadas con solape de 1 cm de longitud, 29.73 N, como valor medio, en la serie suturada con Gore-Tex® y 42.56 N, como valor medio, en la serie suturada con Prolene® (p=0.000). La sutura de Prolene® mostró una mayor resistencia a la propagación del desgarro que la sutura de Gore-Tex®. Una sutura protegida, mediante una zona previa no rasgada, dificulta la propagación del desgarro y puede tener interés desde un punto de vista constructivo en el diseño de las formas de sutura de implantes o bioprótesis

Evaluación ingenieril, agronómica y económica de la labranza cero en Venezuela | Engineering, agronomical and economical evaluation of the non-tillage farming in Venezuela

Venezuela cuenta con alrededor de 300.000 ha bajo labranza conservacionista. La labranza convencional es prácticamenteinconveniente realizarla en el agro venezolano dado la problemática de friabilidad de los suelos en conjunto con los tiemposoportunos operacionales, el alto costo involucrado y los daños físicos, químicos biológicos y térmicos acarreados. Losobjetivos específicos son la evaluación de la labranza cero con el propósito de apreciar algunos parámetros (a) ingenieriles,(b) agronómicos y (c) económicos que rigen su proceso. Los ingenieriles evaluados fueron: peso, capacidad efectiva,eficiencia, ancho de corte teórico, potencia requerida y velocidad de operación. Los agronómicos: fertilización, pH, materiaorgánica y estructura del suelo. Los económicos: análisis incluyendo el coeficiente operacional agrícola (0,0002 día-1), elancho óptimo por máxima y mínimo, consumo energético, comparaciones con el arrendamiento, costos de adquisición,fertilización y mecanización convencional con relación al cultivo de maíz. Se aplicó el PERT (Program Evaluation ReviewTechnique), el Punto de Oportunidad Igual, análisis de costos y el análisis de regresión para interpretar la variancia entrealgunos parámetros. Entre los resultados de índole económicos se estableció el diagrama PERT usado en los procesos delabranza cero en Venezuela, costos fijos de 18652,33 USD/año, costos totales para la unidad tractor sembradora de27261,93 USD/año (34,42 USD/ha), tasa de arrendamiento para 742,25 ha/año de equilibrio, ancho óptimo de la labor entre4 y 10 m para un máximo de 5000 ha. Entre los ingenieriles: la capacidad efectiva promedio encontrada fue de 4,95 ha/h,velocidad de la labor de 11 km/h, el precio entre 5.648,91 – 10.119,85 USD/m y la eficiencia del 75%. Agronómicamentelos parámetros evaluados produjeron ventajas. Se concluye: (a) la labranza cero reduce los costos, (b) los problemas deltiempo oportuno de operación es altamente reducido, (c) la estructura del suelo es favorecida, (d) es más barato alquilar conmenos de 800 ha/año y (e) el proceso operacional del proceso productivo es minorado.Palabras Clave: Labranza cero, labranza convencional, arrendamiento versus adquisición, erosión, materia orgánica,cobertura, PERT, punto de equilibrio económico.ABSTRACTVenezuela counts with around 300.000 ha under no-tillage farming. It is practically impossible to carry out conventionaltillage in Venezuelan agriculture due to the problem of friability of the farm soils, together with timeliness factor, the highinvolved cost, physical, chemical, biological and thermal damages carried out. The specific objectives are the evaluation ofthe no-tillage with the purpose of appreciating some parameters: (a) engineering, (b) agronomic and (c) economic thatgoverns their process. The engineering factors valued were: weigh, efficiency, field capacity, width, power required andoperation speed. The agronomic: fertilization, pH, organic matter and soil structures. The economic: analysis including thetimeliness factor (0,0002 day-1), the optimum width by maxim and minimum, energy consumption, comparisons with thelease, costs of acquisition, fertilization and conventional mechanization with relationship to the cultivation of corn. It wasapplied the PERT, the point of same opportunity and the regression analysis to interpret the variance among costparameters. Among the economic results the PERT diagram was established for the processes of zero tillage in Venezuela,fixed costs of 18652,33 USD/year, total cost for the unit tractor-seeder of 27261,93 USD/year (34,42 USD/ha), equilibriumlease for 742,25 ha/year, optimum width between 4 and 10 m for of 5000 ha maximum. Among the engineering results, thefield capacity was of 4,95 ha/h, speed of 11 km/h, the price of the direct seeder between 5.648,91-10.119,85 USD/m and anefficiency of 75%. Agronomics: the evaluated parameters produced advantageous results. It is concluded: (a) the zerotillagereduced the costs, (b) the problems of the opportune time of operation are highly reduced, (c) the structure of the soilis favored, (d) it is cheaper to leasing and (e) the operational process of the productive process is lessened.Key Words: Non-tillage farming, Conventional tillage, lease versus acquisition, erosion, organic matter, covering, PERT,equilibrium economic point

Consensus of experts from the Spanish pharmacogenetics and pharmacogenomics society and the Spanish society of medical oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidinesThis project has been financed with SEOM and SEFF resource

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines

A simulational and theoretical study of the spherical electrical double layer for a size-asymmetric electrolyte: the case of big coions

Monte Carlo simulations of a spherical macroion, surrounded by a size-asymmetric electrolyte in the primitive model, were performed. We considered 1:1 and 2:2 salts with a size ratio of 2 (i.e., with coions twice the size of counterions), for several surface charge densities of the macrosphere. The radial distribution functions, electrostatic potential at the Helmholtz surfaces, and integrated charge are reported. We compare these simulational data with original results obtained from the Ornstein-Zernike integral equation, supplemented by the hypernetted chain/hypernetted chain (HNC/HNC) and hypernetted chain/mean spherical approximation (HNC/MSA) closures, and with the corresponding calculations using the modified Gouy-Chapman and unequal-radius modified Gouy-Chapman theories. The HNC/HNC and HNC/MSA integral equations formalisms show good concordance with Monte Carlo "experiments", whereas the notable limitations of point-ion approaches are evidenced. Most importantly, the simulations confirm our previous theoretical predictions of the non-dominance of the counterions in the size-asymmetric spherical electrical double layer [J. Chem. Phys. 123, 034703 (2005)], the appearance of anomalous curvatures at the outer Helmholtz plane and the enhancement of charge reversal and screening at high colloidal surface charge densities due to the ionic size asymmetry.Comment: 11 pages, 7 figure

Geodetic Research on Deception Island and its Environment (South Shetland Islands, Bransfield Sea and Antarctic Peninsula) During Spanish Antarctic Campaigns (1987-2007)

Since 1987, Spain has been continuously developing several scientific projects, mainly based on Earth Sciences, in Geodesy, Geochemistry, Geology or Volcanology. The need of a geodetic reference frame when doing hydrographic and topographic mapping meant the organization of the earlier campaigns with the main goals of updating the existing cartography and of making new maps of the area. During this period of time, new techniques arose in Space Geodesy improving the classical methodology and making possible its applications to other different fields such as tectonic or volcanism. Spanish Antarctic Geodetic activities from the 1987/1988 to 2006/2007 campaigns are described as well as a geodetic and a levelling network are presented. The first network, RGAE, was designed and established to define a reference frame in the region formed by the South Shetlands Islands, the Bransfield Sea and the Antarctic Peninsula whereas the second one, REGID, was planned to control the volcanic activity in Deception Island. Finally, the horizontal and vertical deformation models are described too, as well as the strategy which has been followed when computing an experimental geoid

Paediatricians provide higher quality care to children and adolescents in primary care: A systematic review

Aim: The number of primary care paediatricians is decreasing in Europe without a justifiable reason. We aimed to compare the clinical practice of paediatricians and family doctors attending children and adolescents in primary care. Methods: MEDLINE, Embase, CENTRAL, TRIP and Google Scholar were searched from December 2008 to February 2018. No language or study design restrictions were applied. Three reviewers assessed eligibility of the studies. Seven pairs of reviewers performed the data extraction and assessed the methodological quality independently. Discrepancies were resolved by consensus. Results: Fifty-four, out of 1150 studies preselected, were included. We found that paediatricians show more appropriate pharmacology prescription patterns for the illness being treated; they achieve higher vaccination rates and have better knowledge of vaccines and fewer doubts about vaccine safety; their knowledge and implementation of different screening tests are better; they prescribe psychoactive drugs more cautiously and more in line with current practice guidelines; their evaluation and treatment of obesity and lipid disorders follow criteria more consistently with current clinical practice guidelines; and they perform fewer diagnostic test, show a more suitable use of the test and request fewer referrals to specialists. Conclusion: According to published data, in developed countries, paediatricians provide higher quality care to children than family doctors

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial

Background: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. Patients and methods: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Results: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. Conclusions: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations

A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial)

Altres ajuts: Bayer HealthCare Pharmaceuticals Inc.Purpose: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. Patients and methods: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. Results: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. Conclusions: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. Clinicaltrials.gov identifier: NCT02835924