Assessment of bronchodilator responsiveness in preschool children using forced oscillations

BACKGROUND: The forced oscillation technique (FOT) requires minimal patient cooperation and is feasible in preschool children. Few data exist on respiratory function changes measured using FOT following inhaled bronchodilators (BD) in healthy young children, limiting the clinical applications of BD testing in this age group. A study was undertaken to determine the most appropriate method of quantifying BD responses using FOT in healthy young children and those with common respiratory conditions including cystic fibrosis, neonatal chronic lung disease and asthma and/or current wheeze. METHODS: A pseudorandom FOT signal (4-48 Hz) was used to examine respiratory resistance and reactance at 6, 8 and 10 Hz; 3-5 acceptable measurements were made before and 15 min after the administration of salbutamol. The post-BD response was expressed in absolute and relative (percentage of baseline) terms. RESULTS: Significant BD responses were seen in all groups. Absolute changes in BD responses were related to baseline lung function within each group. Relative changes in BD responses were less dependent on baseline lung function and were independent of height in healthy children. Those with neonatal chronic lung disease showed a strong baseline dependence in their responses. The BD response in children with cystic fibrosis, asthma or wheeze (based on both group mean data and number of responders) was not greater than in healthy children. CONCLUSIONS: The BD response assessed by the FOT in preschool children should be expressed as a relative change to account for the effect of baseline lung function. The limits for a positive BD response of -40% and 65% for respiratory resistance and reactance, respectively, are recommended.

Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics

PURPOSE To explore whether population-related pharmacogenomics contribute to differences in patient outcomes between clinical trials performed in Japan and the United States, given similar study designs, eligibility criteria, staging, and treatment regimens. METHODS We prospectively designed and conducted three phase III trials (Four-Arm Cooperative Study, LC00-03, and S0003) in advanced-stage, non-small-cell lung cancer, each with a common arm of paclitaxel plus carboplatin. Genomic DNA was collected from patients in LC00-03 and S0003 who received paclitaxel (225 mg/m(2)) and carboplatin (area under the concentration-time curve, 6). Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism. Results were assessed by Cox model for survival and by logistic regression for response and toxicity. Results Clinical results were similar in the two Japanese trials, and were significantly different from the US trial, for survival, neutropenia, febrile neutropenia, and anemia. There was a significant difference between Japanese and US patients in genotypic distribution for CYP3A4*1B (P = .01), CYP3A5*3C (P = .03), ERCC1 118 (P < .0001), ERCC2 K751Q (P < .001), and CYP2C8 R139K (P = .01). Genotypic associations were observed between CYP3A4*1B for progression-free survival (hazard ratio [HR], 0.36; 95% CI, 0.14 to 0.94; P = .04) and ERCC2 K751Q for response (HR, 0.33; 95% CI, 0.13 to 0.83; P = .02). For grade 4 neutropenia, the HR for ABCB1 3425C-->T was 1.84 (95% CI, 0.77 to 4.48; P = .19). CONCLUSION Differences in allelic distribution for genes involved in paclitaxel disposition or DNA repair were observed between Japanese and US patients. In an exploratory analysis, genotype-related associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. This common-arm approach facilitates the prospective study of population-related pharmacogenomics in which ethnic differences in antineoplastic drug disposition are anticipated.

(Table 1) Age of Cretaceous seamounts in the Western Pacific

Dynamics of the Pacific Plate is recorded in the systematic variation of location and the 40Ar-39Ar age of seamounts in the Western Pacific from 120 to 65 Ma ago. The seamounts are grouped into three linear zones as long as 5000 km. The seamounts become younger in the southeastern direction along the strike of these zones. Correlation between age and location of seamounts allows to divide the history of their formation into three stages. Rate of seamount growth was relatively low (2-4 cm/yr) during the first and the third stages within intervals of 120-90 and 85-65 Ma, whereas during the second stage (90-85 Ma), the seamounts were growing very fast (80-100 cm/yr). In the midst of this stage, at ~87 Ma ago, magmatic activity increased abruptly. Dynamics of seamount building is in good agreement with (1) pulses in development of the Ontong Java, Manihiki, and Caribbean-Colombian oceanic plateaus; (2) age of spreading acceleration in the mid-Cretaceous; and (3) a short period when the Izanagi Plate ceased to exist and the Kula Plate was formed. Variation in seamounts' age and location are in consistence with the hypothesis of diffuse extension of the Pacific Plate in course of its motion with formation of impaired zones of decompression melting. Direction of extension (325°-340° NW) calculated from the strike of seamount zones is consistent with the path of the Pacific Plate (330° NW) in the Late Cretaceous. Immense perioceanic volcanic belts were formed at that time along the margin of the Asian continent. The Okhotsk-Chukchi Peninsula Belt extends at a right angle to the compression vector. Three stages of this belt's evolution are synchronous with the stages of seamount formation in the Pacific Plate. Delay in origination of the East Sikhote-Alin Volcanic Belt and its different orientation were caused by counterclockwise rotation of the vector of convergence of oceanic and continental plates in the mid-Cretaceous. At the same time, i.e. 95-85 Ma ago, volcanic activity embraced the entire continental margin and tin granites were emplaced everywhere in the Eastern Asia. This short episode (90+/-5 Ma) corresponds to the mid-Cretaceous maximum of compression of the continental margin, and its age fits well a culmination in extension of the Pacific Plate.

Description and geochemical composition of tephra layers from ODP Hole 186-1150A and Site 186-1151

The sediments collected at Sites 1150 and 1151 during Leg 186 included many tephra layers and volcaniclastic detritus. In order to identify these tephras, the major oxide compositions of individual glass shards were determined by electron probe microanalyzer. The uppermost four tephras in sediments from Hole 1150A are correlated with the Towada-Hachinohe tephra (To-H; Tohoku district), Shikotsu Daiichi (1st) tephra (Spfa-1; Hokkaido district), Narugo-Yanagisawa tephra (Nr-Y; Tohoku district), and Aso-4 tephra (Kyushu district), respectively. The uppermost tephra in Hole 1151C is correlated with To-H tephra. To-H, Spfa-1, and Aso-4 tephras are also present in piston core KH94-3, LM-8, collected between Sites 1150 and 1151. Eruptive ages of To-H and Spfa-1 estimated from the oxygen isotopic Stages of core KH94-3, LM-8 are between 14.9-15.3 and 39.5-40.1 ka.

Parque eólico offshore en San Pedro de Alcántara

El principal motivo de implantar un parque eólico de estas características es responder a una necesidad palpable en el ámbito mundial como es el crecimiento en la demanda energética unido a un agotamiento de los recursos petrolíferos. Si a esto le sumamos la tendencia actual que han adquirido muchos países de oponerse al desarrollo de nuevas centrales nucleares tras el desastre ocurrido en Fukushima (Japón), y el aumento de los niveles de contaminación en las principales ciudades europeas, así como la sobreexplotación de los parques eólicos onshore en la Península Ibérica, configuran un marco perfecto para el despegue definitivo de la energía eólica offshore como alternativa perfecta al resto de fuentes de energía. Desde el punto de vista particular a nuestra localización, existe una demanda energética considerable, dado el carácter turístico de nuestro emplazamiento, que queda de manifiesto en el Plan General de Ordenación Urbana de Marbella, por lo que el objetivo de este proyecto será abastecer energía a San Pedro Alcántara y las poblaciones vecinas, a fin de que no se produzca ninguna carencia energética a lo largo de los periodos estivales, que serán los momentos de mayor demanda solicitada.

Descontaminación y recuperación de áreas contaminadas

Tras el accidente de Fukushima, se han puesto en marcha una serie de actividades de caracterización y descontaminación de las zonas contaminadas alrededor de la central, destinadas a facilitar su habitabilidad. A partir de la experiencia de Japón, que el ponente conoce de cerca como miembro de la red europea NERIS-TP y tras participar en una reciente misión a Fukushima, en este curso se abordaron las técnicas más actuales que se utilizan para diseñar y proponer estrategias de cara a la recuperación de grades superficies contaminadas.

Estudio de la refrigeración de una piscina de combustible gastado con un código CFD

Tras el accidente nuclear de Fukushima se demostró que las piscinas de combustible gastado en las centrales nucleares ven comprometida su refrigeración a largo plazo en caso de una pérdida total de energía eléctrica (SBO), ya que si experimentan un SBO de larga duración no existen a priori sistemas para mantener la refrigeración de los elementos combustibles que no dependan de los diésel de emergencia o de la red externa. En este trabajo se ha estudiado la refrigeración de una piscina de combustible gastado con el programa CFD STAR-CCM+, tanto en condiciones normales como en caso de pérdida del sistema de refrigeración. Posteriormente se ha evaluado la misma mediante el empleo de sistemas pasivos que permiten refrigerar los elementos combustibles durante cierto tiempo tras la pérdida del sistema de refrigeración y de una manera pasiva. De esta manera se consigue cierto margen antes de la entrada en ebullición del agua de la piscina, mejorándose por tanto la refrigeración de la misma. ABSTRACT. After the Fukushima nuclear accident, it was proved that the cooling of the current spent fuel pools are not sure for long term in case of a Station Blackout (SBO) Accident. If a long lasting blackout SBO occurs there are no systems available to keep cooling the spent fuel assemblies that do not rely on diesel generators or the external grid. During this thesis, the author has studied the spent fuel pool cooling, in ordinary conditions and if the spent fuel pool loses its cooling system, using the CFD program STAR-CCM+. Afterwards, the spent fuel pool cooling has been studied through the use of passive systems. Those two systems are able to cool the spent fuel assemblies in a passive way during a certain period of time after losing the cooling system. As a consequence, the pool´s water would boil later and the spent fuel pools safety would be enhanced.

Analysis of the damage domains of sbo sequences with rcp passive thermal shutdown

The integrated Safety Assessment (ISA) methodology, developed by the Spanish Nuclear Safety Council (CSN), has been applied to a thermal-hydraulic analysis of PWR Station Blackout (SBO) sequences in the context of the IDPSA (Integrated Deterministic-Probabilistic Safety Assessment) network objectives. The ISA methodology allows obtaining the damage domain (the region of the uncertain parameters space where the damage limit is exceeded) for each sequence of interest as a function of the operator actuations times. Given a particular safety limit or damage limit, several data of every sequence are necessary in order to obtain the exceedance frequency of that limit. In this application these data are obtained from the results of the simulations performed with MAAP code transients inside each damage domain and the time-density probability distributions of the manual actions. Damage limits that have been taken into account within this analysis are: local cladding damage (PCT>1477 K); local fuel melting (T>2499 K); fuel relocation in lower plenum and vessel failure. Therefore, to every one of these damage variables corresponds a different damage domain. The operation of the new passive thermal shutdown seals developed by several companies since Fukushima accident is considered in the paper. The results show the capability and necessity of the ISA methodology, or similar, in order to obtain accurate results that take into account time uncertainties.

Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior

Although extracellular application of lysophosphatidic acid (LPA) has been extensively documented to produce a variety of cellular responses through a family of specific G protein-coupled receptors, the in vivo organismal role of LPA signaling remains largely unknown. The first identified LPA receptor gene, lpA1/vzg-1/edg-2, was previously shown to have remarkably enriched embryonic expression in the cerebral cortex and dorsal olfactory bulb and postnatal expression in myelinating glia including Schwann cells. Here, we show that targeted deletion of lpA1 results in approximately 50% neonatal lethality, impaired suckling in neonatal pups, and loss of LPA responsivity in embryonic cerebral cortical neuroblasts with survivors showing reduced size, craniofacial dysmorphism, and increased apoptosis in sciatic nerve Schwann cells. The suckling defect was responsible for the death among lpA1(−/−) neonates and the stunted growth of survivors. Impaired suckling behavior was attributable to defective olfaction, which is likely related to developmental abnormalities in olfactory bulb and/or cerebral cortex. Our results provide evidence that endogenous lysophospholipid signaling requires an lp receptor gene and indicate that LPA signaling through the LPA1 receptor is required for normal development of an inborn, neonatal behavior.

A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid

Extracellular lysophosphatidic acid (LPA) produces diverse cellular responses in many cell types. Recent reports of several molecularly distinct G protein-coupled receptors have raised the possibility that the responses to LPA stimulation could be mediated by the combination of several uni-functional receptors. To address this issue, we analyzed one receptor encoded by ventricular zone gene-1 (vzg-1) (also referred to as lpA1/edg-2) by using heterologous expression in a neuronal and nonneuronal cell line. VZG-1 expression was necessary and sufficient in mediating multiple effects of LPA: [3H]-LPA binding, G protein activation, stress fiber formation, neurite retraction, serum response element activation, and increased DNA synthesis. These results demonstrate that a single receptor, encoded by vzg-1, can activate multiple LPA-dependent responses in cells from distinct tissue lineages.

Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guérin vector candidate vaccine for human immunodeficiency virus type 1 in small animals.

A recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vector-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to the epitope and prevent the viral infection. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein and established the principal neutralizing determinant (PND)-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide, followed by passive transfer of the DTH by the systemic route. Further, immunization of mice with the rBCG resulted in induction of cytotoxic T lymphocytes. The guinea pig immune antisera showed elevated titers to the PND peptide and neutralized HIVMN, and administration of serum IgG from the vaccinated guinea pigs was effective in completely blocking the HIV infection in thymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutralize primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear cell-based virus neutralization assay. The data support the idea that the antigen-secreting rBCG system can be used as a tool for development of HIV vaccines.

Otimização do método lignina brometo de acetila na determinação do teor de lignina em plantas forrageiras e comparação com os métodos lignina detergente ácido e lignina Klason

Técnicas analíticas empregadas para a quantificação do teor de lignina em plantas forrageiras, atualmente em uso, são questionáveis quanto às suas acurácias. O método lignina detergente ácido (LDA), que é um dos métodos mais utilizado em Ciência Animal e Agronomia, apresenta algumas falhas, particularmente devido à parcial solubilização da lignina durante a preparação da fibra em detergente ácido (FDA). A lignina Klason (LK), outro método muito usado, apresenta o inconveniente de mensurar a proteína da parede celular como sendo lignina. Em ambos os procedimentos recomenda-se também mensurar cinzas nos resíduos de lignina. A quantificação da concentração de lignina pelo método espectrofotométrico lignina brometo de acetila (LBA) vem ganhando interesse de pesquisadores no Brasil e no exterior. Nesta metodologia, a lignina da planta contida na preparação parede celular (PC) é solubilizada numa solução a 25% de brometo de acetila em ácido acético e a absorbância mensurada é com luz UV a 280 nm. O valor da absorbância é inserido numa equação de regressão e a concentração de lignina é obtida. Para que esta técnica analítica seja mais aceita pelos pesquisadores, ela deve ser, obviamente, convincente e atrativa. O presente trabalho analisou alguns parâmetros relacionados à LBA em 7 gramíneas e 6 leguminosas, em dois estádios de maturidade. Dentre as diferentes temperaturas de pré-secagem, os resultados indicaram que os procedimentos de 55°C com ventilação e liofilização podem ser utilizados com a mesma eficácia. As temperaturas de 55°C sem ventilação e 80°C sem ventilação não são recomendadas, pois aumentaram os valores de FDA e LDA, possivelmente devido ao surgimento de artefatos de técnica como os compostos de Maillard. No método LBA os valores menores das amostras de leguminosas chamaram a atenção e colocaram em questão se a lignina destas plantas seria menos solúvel no reagente brometo de acetila. Dentre algumas alterações na metodologia da técnica LBA, a utilização do moinho de bolas (para diminuir o tamanho particular) nas amostras de PC não mostrou efeito; a hipótese era melhorar a solubilização da lignina usando partículas menores. O uso de um ultrasonicador, que aumenta a vibração das moléculas e assim, facilitaria a solubilização da lignina no reagente brometo de acetila, melhorou a solubilização da lignina em cerca de 10%, tanto nas gramíneas como nas leguminosas. Foi acoplado um ensaio biológico como referência, a degradabilidade in vitro da matéria seca (DIVMS); e como a lignina está intimamente associada à estrutura fibrosa da parede celular, também foi feito um ensaio de degradabilidade in vitro da fibra em detergente neutro (DIVFDN). Os resultados confirmaram o efeito da maturidade, reduzindo a degradabilidade nas plantas mais maduras, e que o teor de lignina de leguminosas é realmente inferior ao de gramíneas. Os resultados de degradabilidade apresentaram coeficientes de correlação mais elevados com o método LBA, quando foi empregada a técnica do ultrasom; o método LK mostrou os menores coeficientes. Também testou-se, com sucesso, a utilização da FDN, como preparação fibrosa, ao invés de PC. A razão é simples: enquanto que a FDN é amplamente conhecida, a preparação PC não o é. Inquestionável que esta manobra facilitará substancialmente a divulgação desse método, tornando-a mais aceitável pela comunidade científica

Las catástrofes nucleares y el desplazamiento

Las enseñanzas que podemos extraer del accidente nuclear de Fukushima en 2011 parece que son las mismas que en Chernóbil veinticinco años antes, pese a ser entornos políticos diferentes. Por lo visto no hemos aprendido mucho.

Germany's energy transformation: difficult beginnings. OSW Report, March 2013

Initiated in May 2011, several months after the Fukushima nuclear disaster, Germany’s energy transformation (Energiewende) has been presented as an irrevocable plan, and – due to the speed of change required – it represents a new quality in Germany’s energy strategy. Its main objectives include: nuclear energy being phased out by 2022, the development of renewable energy sources (OZE), the expansion of transmission networks, the construction of new conventional power plants and an improvement in energy efficiency.The cornerstone of the strategy is the development of renewable energy. Under Germany's amended renewable energy law, the proportion of renewable energy in electricity generation is supposed to increase steadily from the current level of around 20% to approximately 38% in 2020. In 2030, renewable energy is expected to account for 50% of electricity generation. This is expected to increase to 65% in 2040 and to as much as 80% in 2050. The impact of the Energiewende is not limited to the sphere of energy supplies. In the medium and long term, it will change not only to the way the German economy operates, but also the functioning of German society and the state. Facing difficulties with the expansion of transmission networks, the excessive cost of building wind farms, and problems with the stability of electricity supplies, especially during particularly cold winters, the federal government has so far tended to centralise power and limit the independence of the German federal states with regard to their respective energy policies, justifying this with the need for greater co-ordination. The Energiewende may also become the beginning of a "third industrial revolution", i.e. a transition to a green economy and a society based on sustainable development. This will require a new "social contract" that will redefine the relations between the state, society and the economy. Negotiating such a contract will be one of the greatest challenges for German policy in the coming years.