A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma.

BACKGROUND: Immunotherapy has demonstrated an improved overall survival (OS) and progression-free survival (PFS) as second-line treatment and subsequent lines compared with chemotherapy. MATERIALS & METHODS: This was a retrospective review among eight medical centers comprising 100 patients with a confirmed diagnosis of non-small-cell lung carcinoma, in their second-line treatment or beyond with immune checkpoints inhibitors treatment. The current study aimed to analyze effectiveness of immunotherapy in second-line treatment or further in the Mexican population, using PFS rate, OS rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. RESULTS: In total, 100 patients met the criteria for enrollment in the current study. From the total study population, 49 patients (49.0%) were male and 51 (51.0%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the study. A total of 61 patients (61.0%) had partial response; 11 (11.0%) stable disease; 2 (2.0%), complete response, 4 (4.0%), progression; and 22 (22.0%) were nonevaluable. We found a median PFS of 4 months (95% CI: 3.2-4.7 months) and an OS of 9 months (95% CI: 7.2-10.7 months). CONCLUSION: The response to immunotherapy is similar, with an improvement in OS and PFS, independent of which drug is used. Patients using nivolumab had a better survival, although that was not statistically significant.

Thermal Energy Storage by the Encapsulation of Phase Change Materials in Building Elements-A Review.

The energy sector is one of the fields of interest for different nations around the world. Due to the current fossil fuel crisis, the scientific community develops new energy-saving experiences to address this concern. Buildings are one of the elements of higher energy consumption, so the generation of knowledge and technological development may offer solutions to this energy demand, which are more than welcome. Phase change materials (PCMs) included in building elements such as wall panels, blocks, panels or coatings, for heating and cooling applications have been shown, when heating, to increase the heat storage capacity by absorbing heat as latent heat. Therefore, the use of latent heat storage systems using phase change materials (PCMs) has been investigated within the last two decades. In the present review, the macro and micro encapsulation methods for construction materials are reviewed, the former being the most viable method of inclusion of PCMs in construction elements. In addition, based on the analysis of the existing papers on the encapsulation process of PCMs, the importance to pay more attention to the bio-based PCMs is shown, since more research is needed to process such PCMs. To determine its thermophysical and mechanical behavior at the micro and macro levels, in order to see the feasibility of substituting petroleum-based PCMs with a more environmentally friendly bio-based one, a section devoted to the excellent PCM with lightweight aggregate (PCM-LWA concrete) is presented due to the lack of description given in other reviews.

Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR-mutated lung adenocarcinoma.

BACKGROUND: A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR-mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. METHODS: This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR-mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. RESULTS: EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response (P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression-free survival (P = 0.025 and P = 0.030). CONCLUSIONS: The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.

Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma.

PURPOSE: The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS: This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS: After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION: Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

Expression of estrogen receptor beta (ERß) and its prognostic value in pleural mesothelioma.

BACKGROUND: Overexpression of estrogen receptors in malignant pleural mesothelioma has shown an independent relation with a better prognosis of survival, and the use of selective estrogen receptor beta (ERß) agonists increases the susceptibility to antitumor treatment. METHODS: This was a retrospective single center study that analyzed the response of malignant pleural mesothelioma with an expression of ERß to first-line chemotherapy. The study included patients with pleural mesothelioma pathologically confirmed between 2013 and 2016 at the National Institute for Respiratory Disease (INER), who underwent an immunohistochemistry assay for ERß (mouse monoclonal antibody PPG5/10). The primary endpoint was the response to chemotherapy based on RECIST 1.1 according to the ERß expression; secondary outcomes were the overall survival (OS) and progression-free survival (PFS). RESULTS: We included 22 patients, regarding the expression of ERß, 17 (77.2%) patients had high or moderate degree, while 5 (22.7%) had low degree or null expression. The response to treatment as by RECIST 1.1, 12 (54.5%) had partial response, 5 (22.7%) had stable disease, and 3 (13.6%) had progression. None of the patients had a complete response. Of those who had a partial response, 9 (75%) had a high or moderate degree of ERß expression in tumor cells, and 3 (25%) had a low or null degree of expression. CONCLUSIONS: High and moderate expression of ERß group with advanced clinical stage malignant pleural mesothelioma was associated with a tendency of higher OS and better response to chemotherapy treatment resulting in longer PFS although statistical significance was not achieved.

Two independent and primitive envelopes of the bilobate nucleus of comet 67P.

The factors shaping cometary nuclei are still largely unknown, but could be the result of concurrent effects of evolutionary and primordial processes. The peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of the fusion of two objects that were once separate or the result of a localized excavation by outgassing at the interface between the two lobes. Here we report that the comet's major lobe is enveloped by a nearly continuous set of strata, up to 650 metres thick, which are independent of an analogous stratified envelope on the minor lobe. Gravity vectors computed for the two lobes separately are closer to perpendicular to the strata than those calculated for the entire nucleus and adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov-Gerasimenko is an accreted body of two distinct objects with 'onion-like' stratification, which formed before they merged. We conclude that gentle, low-velocity collisions occurred between two fully formed kilometre-sized cometesimals in the early stages of the Solar System. The notable structural similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate that the early-forming cometesimals experienced similar primordial stratified accretion, even though they formed independently.

Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse.

Pits have been observed on many cometary nuclei mapped by spacecraft. It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments and models cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts. Alternative mechanisms like explosive activity have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

Cometary science. The morphological diversity of comet 67P/Churyumov-Gerasimenko.

Images of comet 67P/Churyumov-Gerasimenko acquired by the OSIRIS (Optical, Spectroscopic and Infrared Remote Imaging System) imaging system onboard the European Space Agency's Rosetta spacecraft at scales of better than 0.8 meter per pixel show a wide variety of different structures and textures. The data show the importance of airfall, surface dust transport, mass wasting, and insolation weathering for cometary surface evolution, and they offer some support for subsurface fluidization models and mass loss through the ejection of large chunks of material.

Cometary science. On the nucleus structure and activity of comet 67P/Churyumov-Gerasimenko.

Images from the OSIRIS scientific imaging system onboard Rosetta show that the nucleus of 67P/Churyumov-Gerasimenko consists of two lobes connected by a short neck. The nucleus has a bulk density less than half that of water. Activity at a distance from the Sun of >3 astronomical units is predominantly from the neck, where jets have been seen consistently. The nucleus rotates about the principal axis of momentum. The surface morphology suggests that the removal of larger volumes of material, possibly via explosive release of subsurface pressure or via creation of overhangs by sublimation, may be a major mass loss process. The shape raises the question of whether the two lobes represent a contact binary formed 4.5 billion years ago, or a single body where a gap has evolved via mass loss.

Cometary science. Dust measurements in the coma of comet 67P/Churyumov-Gerasimenko inbound to the Sun.

Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(-5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 ± 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion. The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails.

Envelhecimento populacional e mudanças no padrão de consumo e na estrutura produtiva brasileira / Envejecimiento Poblacional y Cambios en el Estándar de Consumo: impactos en la estructura productiva de Brasil / Aging of Population and Changes in Consumption Patterns: impacts on the production structure in Brazil

Este trabalho objetiva analisar como o envelhecimento populacional pode afetar a estrutura produtiva brasileira, dadas as mudanças previstas no padrão de consumo da população no período 2005-2050. Para tanto, utilizou-se a análise insumo-produto em conjunto com informações da Pesquisa de Orçamentos Familiares (POF) de 2008-2009, da Pesquisa Nacional por Amostra de Domicílios (PNAD) de 2005 e da projeção da população do Brasil, por sexo e idade, para 1980-2050. Entre os principais resultados, observou-se que os produtos com maior consumo em favor das famílias idosas foram intermediação financeira e seguros, saúde mercantil, serviços domésticos e produtos farmacêuticos, enquanto para as famílias não idosas os destaques foram educação mercantil, vestuário, calçados e produtos do couro, transporte de passageiros e serviços de alojamento e alimentação. Quando comparada a produção necessária para satisfazer o consumo das famílias nos anos analisados, verificou-se que os setores com maior crescimento devem ser aqueles responsáveis pelos produtos com maior consumo pelas famílias idosas, com destaque para os setores produtos farmacêuticos, saúde mercantil, intermediação financeira e seguros, outros serviços, aparelho/instrumento médico-hospitalar, medida e óptico e serviços imobiliários e aluguel, ao passo que os setores com menor crescimento de sua produção devem ser educação mercantil, vestuário, calçados e produtos do couro, serviços de alojamento e alimentação, produtos do fumo, veículos automotores, peças e equipamentos. Por fim, apesar dessas diferenças observadas no crescimento dos setores, a estrutura produtiva brasileira pouco deve se alterar dadas as mudanças no consumo causadas pelo envelhecimento populacional.

The main objective of this paper is to analyze how the aging of the population could affect the Brazilian production structure, given the expected changes in consumption patterns of the population between 2005 and 2050. To achieve this objective an input-output analysis was used together with information from the 2008-2009 Consumer Expenditure Survey (POF), the 2005 National Household Sample Survey (PNAD) and a projection of Brazil’s population by sex and age between 1980 and 2050. The most important results were that: a) the products most heavily consumed in elderly households were Financial Intermediation and Insurance, the Health Market, Domestic Services, and Pharmaceutical Products, whereas in non-elderly families more was spent on Private Education, Clothing, Footwear and Leather Products, Passenger Transport, and Lodging and Food; b) when the production required to satisfy household consumption in the years analyzed was compared, it was found that the sectors with the highest growth rates are likely to be those responsible for products with higher consumption among elderly families, especially the areas of Pharmaceutical Products, Health Care, Financial Intermediation and Insurance, Other Services, Medical and Hospital Devices and Instruments, Measurement and Optical, and Real Estate and Rental Services. In contrast, sectors with lower growth in production will probably include Private Education, Clothing, Footwear and Leather Products, Lodgings and Food, Tobacco Products, Motor Vehicles, Parts and Equipment, and, finally, c) despite the differences in the growth of the sectors, the Brazilian production structure is not likely to change greatly as the result of changes in the consumption caused by the aging of the population.

Este trabajo tuvo como principal objetivo analizar cómo el envejecimiento poblacional puede afectar la estructura productiva brasileña en función de los cambios previstos en el estándar de consumo de la población entre los años 2005- 2050. Para alcanzar dicho objetivo se utilizó el análisis insumoproducto en conjunto con informaciones de la Pesquisa de Orçamentos Familiares (POF) (Investigación de Presupuestos Familiares) de 2008-2009, de la Pesquisa Nacional por Amostra de Domicílios (PNAD) (Investigación Nacional por Muestreo de Domicilios) de 2005 y de la proyección de la población de Brasil por sexo y edad para el periodo de 1980-2050. Entre los resultados se destacan los siguientes: a) los productos con mayor consumo en favor de las familias mayores fueron Intermediación Financiera y Seguros, Salud Mercantil, Servicios Domésticos y Productos Farmacéuticos, mientras que para el caso de las familias non mayores los destaques fueron Educación Mercantil, Vestimenta, Calzados y Productos de Cuero, Transporte de pasajeros y Servicios de alojamiento y alimentación; b) cuando se compara la producción necesaria para satisfacer el consumo de las familias en los años analizados, se verifica que los sectores que presentan mayor crecimiento deben ser aquellos responsables por los productos más consumidos por las familias mayores, con destaque para los sectores Productos Farmacéuticos, Salud Mercantil, Intermediación Financiera y Seguros, Otros Servicios, Aparatos/ Instrumentos Médico-Hospitalario, Medida y Óptico, y Servicios Inmobiliarios y Alquiler, al paso que los sectores que presentan menor crecimiento de su producción deben ser Educación Mercantil, Vestimenta, Calzados y Productos de Cuero, Servicios de Alojamiento y Alimentación, Productos de Tabaco, Vehículos Automotores, Repuestos y Equipos; c) por fin, a pesar de tales diferencias observadas en el crecimiento de los sectores, la estructura productiva brasileña debe alterarse poco debido a los cambios en el consumo ocasionados por el envejecimiento poblacional.

A collision in 2009 as the origin of the debris trail of asteroid P/2010 A2.

The peculiar object P/2010 A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010 A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.

Crystal structure characterization of nautilus shell at different length scales.

In this work, we studied the shell structure of the Nautilus pompilius Linnaeus by using analytical techniques of scanning (SEM) and transmission electron microscopy (TEM) and X-ray diffraction. The main objective of this study is the structural characterization of Nautilus shell at different length levels, from micron to nano-scale. The results were also used to try to determine the shell structure mechanism of formation. The information obtained in this work will place our particular knowledge a closer step to understand how self-assembly works in nature, and will increase the opportunities of using this information in the future synthesis of new advanced materials.

A large dust/ice ratio in the nucleus of comet 9P/Tempel 1.

Comets spend most of their life in a low-temperature environment far from the Sun. They are therefore relatively unprocessed and maintain information about the formation conditions of the planetary system, but the structure and composition of their nuclei are poorly understood. Although in situ and remote measurements have derived the global properties of some cometary nuclei, little is known about their interiors. The Deep Impact mission shot a projectile into comet 9P/Tempel 1 in order to investigate its interior. Here we report the water vapour content (1.5 10(32) water molecules or 4.5 10(6) kg) and the cross-section of the dust (330 km2 assuming an albedo of 0.1) created by the impact. The corresponding dust/ice mass ratio is probably larger than one, suggesting that comets are 'icy dirtballs' rather than 'dirty snowballs' as commonly believed. High dust velocities (between 110 m s(-1) and 300 m s(-1)) imply acceleration in the comet's coma, probably by water molecules sublimated by solar radiation. We did not find evidence of enhanced activity of 9P/Tempel 1 in the days after the impact, suggesting that in general impacts of meteoroids are not the cause of cometary outbursts.

Deep Impact observations by OSIRIS onboard the Rosetta spacecraft.

The OSIRIS cameras (optical, spectroscopic, and infrared remote imaging system) onboard the European Space Agency's Rosetta spacecraft observed comet 9P/Tempel 1 for 17 days continuously around the time of NASA's Deep Impact mission. The cyanide-to-water production ratio was slightly enhanced in the impact cloud, compared with that of normal comet activity. Dust particles were flowing outward in the coma at >160 meters per second, accelerated by the gas. The slope of the brightness increase showed a dip about 200 seconds after the impact. Dust Afrho values before and long after the impact confirm the slight decrease of cometary activity. The dust-to-water mass ratio was much larger than 1.