Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate,duration), median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a) phytohemaglutinin-induced lymphocyte proliferation, b) prevalence of T-Regulatory (CD4+CD25+) cells and for specific immunity: a) lymphocyte proliferation induced by tumor-associated antigens (TAA) contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy) in response rate induced by the two treatments (39.0% and 35.0%) was not statistically significant. However, the response duration (22 and 31 weeks), the median survival time (32 and 44 weeks) and 1-year survival (33.3% and 39.1%) were statistically higher with chemoimmunotherapy. No difference in toxicity between both arms was demonstrated. A switch in the laboratory immunity profile, nonspecific and specific, was associated with the chemoimmunotherapy treatment: increase of proliferative lymphocyte response, decrease of tolerogenic T-regulatory cells and eliciting TAA-sensitization

Antiepileptic drugs for the treatment of neuropathic pain: a systematic review

Many therapies have been proposed for the management of neuropathic pain, and they include the use of different antiepileptic drugs. However, the lack of high quality studies indicates that results on the different neuropathic disorders under study do not recommend a particular drug treatment. This study makes a systematic review of the published literature on the use of several antiepileptic drugs to treat neuropathic pain, and has the objective of considering both its clinical characteristics and pharmacological use, which will depend on their level of scientific evidence and will follow the principles of evidence-based dentistry. The articles were stratified according to their scientific evidence using the SORT criteria (Strength of Recommendation Taxonomy), and it included those articles that only have level 1 or 2. Randomized clinical trials were stratified according to their level of quality using the JADAD scale, an instrument described by Jadad et al. (7). to assess the quality of clinical trials, while studies with a level below 3 were discarded. Recently, type A or B recommendations are given in favor or against the use of antiepileptic drugs to treat neuropathic pain on the basis of their scientific quality

Autopercepción de la salud, presencia de comorbilidades y depresión en adultos mayores mexicanos: propuesta y validación de un marco conceptual simple

Introduction: Self-rated health is an individual and subjective conceptualization involving the intersection of biological, social and psychological factors. It provides an invaluable and unique evaluation of a person’s general health status.Objective: To propose and evaluate a simple conceptual model to understand self-rated health and its relationship to multimorbidity, disability and depressive symptoms in Mexican older adults.Materials and methods: We conducted a cross-sectional study based on a national representative sample of 8,874 adults of 60 years of age and older. Self-perception of a positive health status was determined according to a Likert-type scale based on the question: “What do you think is your current health status?” Intermediate variables included multimorbidity, disability and depressive symptoms, as well as dichotomous exogenous variables (sex, having a partner, participation in decision-making and poverty). The proposed conceptual model was validated using a general structural equation model with a logit link function for positive self-rated health.Results: A direct association was found between multimorbidity and positive self-rated health (OR=0.48; 95% CI: 0.42-0.55), disability and positive self-rated health (OR=0.35; 95% CI: 0.30-0.40), depressive symptoms and positive self-rated health (OR=0.38; 95% CI: 0.34-0.43). The model also validated indirect associations between disability and depressive symptoms (OR=2.25; 95% CI: 2.01- 2.52), multimorbidity and depressive symptoms (OR=1.79; 95% CI: 1.61-2.00) and multimorbidity and disability (OR=1.98; 95% CI: 1.78-2.20).Conclusions: A parsimonious theoretical model was empirically evaluated, which enabled identifying direct and indirect associations with positive self-rated health.Introducción. La autopercepción de la salud es una concepción individual y subjetiva que resulta de la intersección entre factores biológicos, sociales y psicológicos, y proporciona una evaluación única e inestimable del estado general de salud de una persona.Objetivo. Proponer y evaluar un modelo conceptual simple para entender la autopercepción de la salud y su relación con la presencia de comorbilidades, discapacidad y síntomas depresivos en adultos mayores mexicanos.Materiales y métodos. Se hizo un estudio transversal basado en una muestra representativa nacional de 8.874 adultos de 60 y más años. Se determinó la autopercepción positiva de la salud mediante una escala de tipo Likert con la pregunta: “¿Cómo considera que es su estado actual de salud?”, así como de las variables intermedias de presencia de comorbilidades, discapacidad y síntomas depresivos, y variables exógenas dicotómicas (sexo, tener pareja, percepción de la participación en las decisiones del hogar y pobreza). Para validar el modelo conceptual propuesto, se diseñó un modelo generalizado de ecuaciones estructurales con función de enlace logit para la autopercepción positiva de la salud.Resultados. Se encontró una asociación de vías directas entre la presencia de comorbilidades y la autopercepción positiva de la salud (odds ratio, OR=0,48; IC95% 0,42-0,55), entre la discapacidad y la autopercepción positiva de la salud (OR=0,35; IC95% 0,30-0,40),y entre los síntomas depresivos y la autopercepción positiva de la salud (OR=0,38; IC95% 0,34-0,43). El modelo también validó asociaciones indirectas entre discapacidad y síntomas depresivos (OR=2,25; IC95% 2,01-2,52), presencia de comorbilidades y síntomas depresivos (OR=1,79; IC95% 1,61-2,00), y presencia de comorbilidades y discapacidad (OR=1,98; IC95% 1,78-2,20).Conclusiones. Se hizo la evaluación empírica de un modelo teórico parsimonioso, lo cual permitió determinar asociaciones directas e indirectas con la autopercepción positiva de la salud

The synergistic response of primary production in grasslands to combined nitrogen and phosphorus addition is caused by increased nutrient uptake and retention

Background and aimsA synergistic response of aboveground plant biomass production to combined nitrogen (N) and phosphorus (P) addition has been observed in many ecosystems, but the underlying mechanisms and their relative importance are not well known. We aimed at evaluating several mechanisms that could potentially cause the synergistic growth response, such as changes in plant biomass allocation, increased N and P uptake by plants, and enhanced ecosystem nutrient retention.MethodsWe studied five grasslands located in Europe and the USA that are subjected to an element addition experiment composed of four treatments: control (no element addition), N addition, P addition, combined NP addition.ResultsCombined NP addition increased the total plant N stocks by 1.47 times compared to the N treatment, while total plant P stocks were 1.62 times higher in NP than in single P addition. Further, higher N uptake by plants in response to combined NP addition was associated with reduced N losses from the soil (evaluated based on soil delta N-15) compared to N addition alone, indicating a higher ecosystem N retention. In contrast, the synergistic growth response was not associated with significant changes in plant resource allocation.ConclusionsOur results demonstrate that the commonly observed synergistic effect of NP addition on aboveground biomass production in grasslands is caused by enhanced N uptake compared to single N addition, and increased P uptake compared to single P addition, which is associated with a higher N and P retention in the ecosystem

Factores Pedagógicos que Favorecen el Éxito Escolar en Estudiantes de Enseñanza Postobligatoria

El foco del presente estudio ha sido el éxito escolar: la continuidad, la permanencia en el sistema educativo, lo cual implica transitar de forma adecuada por sus diversas etapas y modalidades formativas. En particular, hemos buscado conocer qué factores pedagógicos -vinculados a los procesos de enseñanza-aprendizaje y a la relación profesor/a-alumno/a- constituyen condiciones favorables para el éxito y la continuidad escolar de chicas y de chicos de enseñanza secundaria postobligatoria (Bachillerato y Ciclos Formativos). Hemos tratado de visibilizar el éxito escolar de chicos y de chicas en la educación secundaria, de analizar las experiencias y las trayectorias de estudiantes que, más allá del periodo obligatorio, dan continuidad a su vida escolar con éxito académico, de prestar atención a las diferencias entre estudiantes de Bachillerato y Ciclos Formativos y, por último, de analizar de forma diferenciada la experiencia de las chicas y de los chicos, indagando en los elementos de la construcción de la subjetividad en ambos sexos. Para ello, hemos trabajado con una muestra intencional de 26 estudiantes (12 chicas y 14 chicos), 16 de Bachillerato y 10 de Ciclos Formativos, seleccionados por sus docentes, en 12 centros urbanos y semiurbanos de Málaga, Sevilla, Granada, Cádiz y Almería. Los datos han sido recogidos a través de entrevistas semiestructuradas, con el apoyo de la técnica de foto-lenguaje y un cuestionario de contexto.Fundación Centro de Estudios Andaluces - [PRY031/11

Nitrogen but not phosphorus addition affects symbiotic N-2 fixation by legumes in natural and semi-natural grasslands located on four continents

Background and aims: The amount of nitrogen (N) derived from symbiotic N-2 fixation by legumes in grasslands might be affected by anthropogenic N and phosphorus (P) inputs, but the underlying mechanisms are not known.Methods: We evaluated symbiotic N-2 fixation in 17 natural and semi-natural grasslands on four continents that are subjected to the same full-factorial N and P addition experiment, using the N-15 natural abundance method.Results: N as well as combined N and P (NP) addition reduced aboveground legume biomass by 65% and 45%, respectively, compared to the control, whereas P addition had no significant impact. Addition of N and/or P had no significant effect on the symbiotic N-2 fixation per unit legume biomass. In consequence, the amount of N fixed annually per grassland area was less than half in the N addition treatments compared to control and P addition, irrespective of whether the dominant legumes were annuals or perennials.Conclusion: Our results reveal that N addition mainly impacts symbiotic N-2 fixation via reduced biomass of legumes rather than changes in N-2 fixation per unit legume biomass. The results show that soil N enrichment by anthropogenic activities significantly reduces N-2 fixation in grasslands, and these effects cannot be reversed by additional P amendment

The Iberian pig fed with high-fat diet: a model of renal disease in obesity and metabolic syndrome

The pathogenesis of renal disease in the context of overweight/obesity, metabolic syndrome, and insulin resistance is not completely understood. This may be due to the lack of a definitive animal model of disease, which limits our understanding of obesity-induced renal damage. We evaluated the changes in renal histology and lipid deposits induced by obesity in a model of insulin resistance: the Iberian swine fed with fat-enriched food.The IMBRAIN (CIBICAN) project (FP7-RE6-POT-2012-CT2012-31637-IMBRAIN) 329 funded under the 7th Framework Program (capacities); the Instituto de Salud Carlos 330 III (ISCIII) for the following grants: PI13/00342, PI, PI16/01814, the REDINREN RD16/0009 and PI10/02428; funding from the IRSIN (Instituto Reina Sofia de Investigacion), FEDER funds, SLL is a research fellow supported by the Instituto de Salud Carlos III (Grants for Río Hortega specialized healthcare post training contracts), ISCIII CM15/00214, Spain; EP is a Researcher of the Ramón y Cajal Program of the ISCIII.Peer reviewe

Strategies for GHG mitigation in Mediterranean cropping systems. A review

In this review we aimed to synthetize and analyze the most promising GHGs mitigation strategies for Mediterranean cropping systems. A description of most relevant measures, based on the best crop choice and management by farmers (i.e., agronomical practices), was firstly carried out. Many of these measures can be also efficient in other climatic regions, but here we provide particular results and discussion of their efficiencies for Mediterranean cropping systems. An integrated assessment of management practices on mitigating each component of the global warming potential (N2O and CH4 emissions and C sequestration) of production systems considering potential side-effects of their implementation allowed us to propose the best strategies to abate GHG emissions, while sustaining crop yields and mitigating other sources of environmental pollution (e.g. nitrate leaching and ammonia volatilization)

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO