An extension of the continual reassessment method using decision theory

The primary goal of a phase I trial is to find the maximally tolerated dose (MTD) of a treatment. The MTD is usually defined in terms of a tolerable probability, q*, of toxicity. Our objective is to find the highest dose with toxicity risk that does not exceed q*, a criterion that is often desired in designing phase I trials. This criterion differs from that of finding the dose with toxicity risk closest to q*, that is used in methods such as the continual reassessment method. We use the theory of decision processes to find optimal sequential designs that maximize the expected number of patients within the trial allocated to the highest dose with toxicity not exceeding q*, among the doses under consideration. The proposed method is very general in the sense that criteria other than the one considered here can be optimized and that optimal dose assignment can be defined in terms of patients within or outside the trial. It includes as an important special case the continual reassessment method. Numerical study indicates the strategy compares favourably with other phase I designs.

Spin-Electron-Phonon Excitation in Re-based Half-Metallic Double Perovskites

A remarkable hardening (similar to 30 cm(-1)) of the normal mode of vibration associated with the symmetric stretching of the oxygen octahedra for the Ba2FeReO6 and Sr2CrReO6 double perovskites is observed below the corresponding magnetic ordering temperatures. The very large magnitude of this effect and its absence for the antisymmetric stretching mode provide evidence against a conventional spin-phonon coupling mechanism. Our observations are consistent with a collective excitation formed by the combination of the vibrational mode with oscillations of Fe or Cr 3d and Re 5d occupations and spin magnitudes.

Evaluación preliminar de insecticidas químicos, botánicos y biológicos en el control de la mosquita del sorgo (Contarinia sorguicola Coq) y los rendimientos de granos en la variedad pinolero - 1

Con el propósito de determinar el producto más eficaz en el control de la mosquita del sorgo (Contarinia sorghicola Coq). Se realizó un experimento en el periodo comprendido entre los meses de septiembre a diciembre de 1996, en el Centro Nacional de Investigación Agropecuaria (CNIA/INTA), cuyos suelos pertenecen a la serie Sabana Grande con drenaje moderadamente rápido y textura que varia de franco a franco arenoso. El disefto utilizado fue un bloque completo al azar con cuatro repeticiones y seis tratamientos. Los tratamientos estudiados fueron insecticidas a base de (deltametrina) Decis 2.5 EC, (metamidophos) MTD 60 SL, (azadiractina) Nim 20%,(azadhiractina) Nim 80%, EM-5 (microorganismos efectivos) y un testigo absoluto (sin aplicación). La variedad utilizada fue Pinolero-1. Los resultados demuestran que no se presentaron diferencias significativas para ninguna de las variables evaluadas por lo que no hubo efecto de los tratamientos evaluados. Sin embargo el análisis económico de los tratamientos refleja que el testigo absoluto (sin aplicación) presentó la mayor tasa de rentabilidad.

Uma Metodologia para Auxiliar no Processo de Conversão de Bases Cartográficas Utilizando o Padrão da Estrutura de Dados Geoespaciais Vetoriais.

Na década de 80, o surgimento de programas de computadores mais amigáveis para usuários e produtores de informação e a evolução tecnológica fizeram com que as instituições, públicas e privadas, se aperfeiçoassem em estudos sobre sistemas de produção cartográfica apoiados por computador, visando a implementação de Sistemas de Informação Geográfica (SIG). A pouca simultaneidade de forças entre órgãos interessados, resultou em uma grande quantidade de arquivos digitais com a necessidade de padronização. Em 2007, a Comissão Nacional de Cartografia (CONCAR) homologou a Estrutura de Dados Geoespaciais Vetoriais (EDGV) a fim de minimizar o problema da falta de padronização de bases cartográficas. A presente dissertação tem como foco elaborar uma metodologia de trabalho para o processo de conversão de bases cartográficas digitais existentes no padrão da Mapoteca Topográfica Digital (MTD), do Instituto Brasileiro de Geografia e Estatística (IBGE), para o padrão da EDGV, bem como suas potencialidades e limitações para integração e padronização de bases cartográficas digitais. Será feita uma aplicação da metodologia utilizando a carta topográfica de Saquarema, na escala de 1:50.000, vetorizada na Coordenação de Cartografia (CCAR) do IBGE e disponível na Internet. Como a EDGV foi elaborada segundo técnicas de modelagem orientada a objetos, foi necessário um mapeamento para banco de dados relacional, já que este ainda é utilizado pela maioria dos usuários e produtores de informação geográfica. Um dos objetivos específicos é elaborar um esquema de banco de dados, ou seja, um banco de dados vazio contendo todas as classes de objetos, atributos e seus respectivos domínios existentes na EDGV para que possa ser utilizado no processo de produção cartográfica do IBGE. Este esquema conterá todas as descrições dos objetos e de seus respectivos atributos, além de já permitir que o usuário selecione o domínio de um determinado atributo em uma lista pré definida, evitando que ocorra erro no preenchimento dados. Esta metodologia de trabalho será de grande importância para o processo de conversão das bases cartográficas existentes no IBGE e, com isso, gerar e disponibilizar bases cartográficas no padrão da EDGV.

半干旱区典型植物对气候变化与C02浓度升高的响应与适应

1.羊草对土壤水分的响应与适应 羊草生物量随着土壤水分含量的降低逐渐降低，后期的降低幅度远远大于前期。干旱促进鞘分配增加，增加了在处理初期的根的分配，但到后期则使之减少，表明羊草在经历较长期的持续干旱后通过增加根部的比重来提高抗旱性的能力逐渐降低。轻度(LD)、中度干旱(MD)对羊草叶片相对含水量(RWC)、气孔密度、光合参数、荧光猝灭参数和群体日交换速率无显著影响，但严重土壤干旱使它们显著降低。 羊草叶片的可溶性蛋白质以中度干旱的最高，严重干旱(SD)特别是极严重干旱(VD)使之显著降低，游离氨基酸含量(FAA)的变化与之相似。随着土壤水分含量的降低硝酸还原酶(NR)活性逐渐下降，而谷氨酰胺酶合成酶(GS)的活性变化则是LD和MD使之分别增加了25.75%和12.22%，SD和VD则分别减少了8.21%和28.72%，说明了NR的活性变化对土壤干旱较敏感，而GS的活性则对适度的干旱有一定程度的适应性。LD处理没有增加天冬酰胺酶(AE)和内肽酶(EP)两种酶的活性，但MD、SD和VD使两种水解酶的活性显著增加，说明轻度土壤干旱对蛋白质和氨基酸的分解作用有稍降低作用，但随着土壤干旱程度的加剧，又极大地促进了这个分解过程。严重和极严重土壤干旱显著降低了叶片的总核酸含量和RNA的含量，暗示严重程度的土壤水分胁追限制了核酸的合成代谢，加强了其分解代谢，严重土壤干旱还显著增加了丙二醛(MDA)的含量，说明提高了羊草叶片叶肉细胞的膜质过氧化水平。 2.羊草对土壤干旱和复水的响应与适应 羊草受到适当的干旱驯化可促进生长，但过长时间的干旱处理，复水后未能补偿损失的生物量和叶面积。羊草叶片的气孔密度以中度干旱持续期(Mtd)处理的最高，其次是短期干旱持续期( Std)，二者分别比没有经过土壤干旱的处理（对照）增加了14.90%和3.61%，但长期干旱持续期(Ltd)却使之减少了27.19%，气孔指数亦有类似的趋势。复水增加羊草叶片的光合速率、气孔导度、蒸腾速率，近期复水的激发效应明显大于前期，而对夜晚的呼吸作用影响不显著。水分利用率( WUE)的日变化动态呈“M”字型曲线，以Mtd的WUE值的峰值最大，以三次曲线拟合WUE的24小时日进程最佳。叶绿素荧光动力学的分析结果表明，复水，特别是最近的复水可显著改善羊草叶片的PS II性能，增加叶绿素a，b的含量及其比值，提高碳酸酐酶的活性。 羊草含氮量以叶片的最高(4.40%)，根部的最低(1.99%)，枯叶、茎鞘和根茎的含量差异较小(2.26～4.40%)。所有器官的含氨量对土壤水分处理的响应基本一致，以对照处理的最低，Std的最高。各器官的碳氮比都是以对照的最高，而其它土壤水分处理相差不显著，给于一定时间的土壤干旱处理可使羊草获得较强的氨代谢能力。Std的氮素总拥有量最多，和对照相比，绿叶、枯叶、茎鞘、根茎和根分别提高了35.58、26.88、23.49、31.66、40.75%，而Ltd的含氨总量呈下降趋势，说明短时间的土壤水分干旱处理可明显促进羊草各器官和植株的氮素积累，而较长时间的土壤干旱则不利于氮素的积累。羊草各器官氮素绝对量占整株的百分比从大到小依次为：绿叶(42.42-44.00%)、根茎(20.13—23.69%)、根(15.43～17.18%)、枯叶(10.07～11.30%)和茎鞘(7.27～8.67%)，表明叶片的氮素存量占植株的一半以上。Mtd处理增加了叶片的氮素贡献率，减少了茎鞘和根茎的贡献率，有利于加强叶片的光合性能。 以中度干旱持续期(Mtd)处理的叶片可溶性蛋白质含量、谷氨酰胺合成酶(GS)活性、RNA含量为最高，但中长期的土壤干旱处理再复水后则显著降低了羊草叶片内肽酶(EP)的活性和MDA的含量，说明给于一定时间的土壤干旱处理可使羊草叶片保持较高的蛋白质代谢水平，降低膜脂过氧化水平。 3.羊草对昼夜温差与土壤水分交互作用响应与适应 昼夜温差减少使单株羊草的生物量降低21.3%，分蘖和根的生物量减少，而鞘的生物量稍增加，显著降低了严重和极严重条件下的生物量。温差缩小降低了分蘖和根的投资比例，减少植株的地下部分生物量，而增加新叶、鞘和分蘖光合产物的比例，表明温差的减少将抑制光台产物向地下部分的转移。温差减少对充足土壤水分和轻度干旱处理的放射性比强影响较小，但减少了其它3种干旱处理的放射性比强。其原因主要是减少了植株鞘、根和根茎的放射性比强，显著增加了饲喂叶和心叶的放射性比强，表明温差的缩小阻止了“源”的光合产物向“库”的转移，降低对分蘖和根的投资，不利于羊草对干旱逆境的适应。 昼夜温差缩小使羊草叶片的气孔密度降低4.01%，而且减少了土壤干旱对气孔密度的影响。较高的昼夜温差和较低的昼夜温差相比，羊草叶片的光合速率和WUE分别增加了7.37%和20.09%;而气孔导度、胞间CO2浓度和蒸腾速率分别降低了14.03%、2.57%和10.80%。昼夜温差减少降低了土壤干旱的δ13C值，说明可能减少处在干旱条件下的植株WUE，暗示减小昼夜温差不利于增大羊草叶片对土壤水分亏缺的耐性。昼夜温差的缩小主要影响了下午羊草群体的CO2交换速率，增加了对照、LD和MD处理的夜间呼吸速率，降低了尤其是显著降低了在土壤缺水条件下的CO2昼夜净交换量，而在两个昼夜温差条件下都是以LD的最高。 昼夜温差缩小影响氮素含量在羊草各器官中的氮素分配，降低了叶片和茎鞘中的氮素百分比含量，但增加了根茎和根中的氮素含量。在较小的昼夜温差条件下，LD显著增加了叶片的氮素含量，但其它土壤水分处理影响不显著，在较大的昼夜温差条件下，亦是LD显著增加了叶片的氮素含量，但MD也使其显著增加。昼夜温差缩小增加了叶片和茎鞘的碳氮比，降低了根茎和根的碳氮比，使叶片在中度和严重土壤水分胁迫时无变化，降低了响应于土壤水分变化的调节弹性。 昼夜温差缩小使羊草叶片可溶性蛋白质降低了16.14%。LD和MD显著促进叶片可溶性蛋白质含量增加，SD和VD都显著地降低了羊草叶片的可溶性蛋白质含量。昼夜温差缩小有使羊草叶片游离氨基酸降低的趋势，主要是降低土壤干旱条件下的游离氨基酸含量，虽然昼夜温差缩小稍增加了可溶性耱的含量(4.68%)，但使土壤干旱激发效应变得不显著，表明温差的缩小降低了叶片中渗透调节物质的积累，不利于羊草抗旱性的提高。昼夜温差缩小显著降低了羊草叶片的NR、GS和谷氨酸脱氢酶(GDH)的活性，在较小昼夜温差条件下几乎看不出土壤水分降低的激发效应，而在高温差下则明显看出LD的激发效应。昼夜温差减少加强土壤干旱对天冬酰胺酶和内肽酶活性的影响，加强了蛋白质和关键氨基酸的分解作用，提高了叶片的膜脂过氧化水平，不利于羊草对干旱的适应性响应。 在土壤水分充足条件下，昼夜温差缩减对羊草叶片气孔形态的影响不明显，但可以看出温差较大时有较多的星状蜡质覆于气孔表面及其周围，这可能是由于夜间温度升高后植物为了减少水分的散失而采取的一种适应性策略。在本实验条件下，中度和严重土壤水分胁迫使气孔变得更加凹陷，气孔更加坚挺，体现了对土壤干旱的适应性反应。对羊草叶片叶肉细胞超微结构的观察表明，昼夜温差对土壤水分充足时的超微结构影响不显著，但在严重土壤干旱条件下，昼夜温差缩减似乎减少了叶绿体中的淀粉粒，加速了叶绿体和线粒体膜的裂解，表明昼夜温差缩减加大了严重土壤干旱对羊草叶片叶肉细胞超微结构的负面影响。 4.羊草对温度和土壤水分交互作用的响应与适应 温度升高使羊草叶片气孔导度和蒸腾速率增加，使光合速率(A)和水分利用率( WUE)降低。土壤干旱和高温均导致最大光化学效率、量子产额和光化学荧光猝灭系数降低，使非光化学荧光猝灭系数升高。土壤干旱减少了羊草幼苗的生物量，却显著增加了根的贡献率和根冠比，而高温使二者显著地降低。在本实验条件下，直到极端干旱才显著降低了羊草叶片的A和WUE，而其他的水分处理影响不显著。土壤干旱使得叶片中的含氮量显著降低：温度对叶片氮含量无显著影响，但却显著地降低了根中的氮含量，尤其显著增加根与叶片氮含量的比率。高温加强了干旱对光合性能的影响，表明高温降低了羊草对干旱的适应能力。 温度过低或过高都对叶片保持高水平的可溶性蛋白质不利，温度过高还削弱了土壤水分亏缺对叶片中游离氨基酸的激发作用。水分梯度对20℃时的GS活性无显著影响，但LD促使26℃和29'C下的GS活性增加，MD以上强度的土壤干旱都显著降低了23℃以上温度尤其是29℃和32℃时的GS活性，表明高温和干旱的协同效应对谷氨酰胺的合成不利。高温增加了AE和EP的活性，加强了土壤干旱对羊草叶片蛋白质和氨基酸分解的促进作用，在一定的土壤水分条件下，高温对RNA的合成作用增强，认为这是对高温胁迫的一种适应性响应。 随着温度的升高羊草叶片中的可溶性糖含量逐渐增加，土壤干旱亦增加了其可溶性糖的含量，但至极端干旱时则使之降低。在20℃下，土壤水分对羊草叶片的可溶性糖的含量无显著影响，在23—32℃温度条件下则是土壤干旱增加了其值，但至VD时则使之显著降低。不同温度条件下，土壤水分对羊草叶片的MDA影响不同，在20℃下，无显著影响，在23和26℃下，SD和VD使MDA稍升高，但在29和32℃条件下使之显著增加，说明温度升高加强了土壤干旱所引发的增加叶片膜质过氧化水平的负面影响。 5.柠条和杨柴对CO2浓度倍增和土壤水分交互作用的响应与适应 土壤干旱使拧条和杨柴的生物量在倍增CO2浓度条件下比在正常浓度条件下降低幅度更大。CO2浓度倍增较大地促进了充足水分条件下的植物生长，而对干旱条件下的生长促进作用则较小。无论在中度条件下还是在严重干旱条件下，两种优势植物均是在倍增CO2浓度条件下增加的根冠比幅度较大;无论在中度条件下还是在严重干旱条件下，且无论正常CO2浓度条件下还是在倍增CO2浓度条件下均是杨柴增加的幅度大。CO2浓度倍增主要增加了水分充足和MD的单位叶面积质量(LMA)，但反而降低了严重干旱的LMA。 CO2倍增使δ13C降低，但土壤干旱使之增加。用“库”（根）中的δ13C值对“源”（叶片）中的δ13C作图，可以用以评价碳分配以及“库”中新增生物量，两种沙生灌木叶片与根部的δ13C值呈极显著线性关系，杨柴的斜率大于柠条的，表明前者叶片与根部在光合产物分配上具有较高的可塑性，这和干旱条件下杨柴的根冠比增加相关联。杨柴的“源库”调节特性反映了对逆境具有较高的耐性。 CO2倍增使柠条和杨柴叶片含氮量分别降低了10.40%和5.06%，土壤干旱有使柠条叶片含氮量增加的趋势，但中度干旱没有增加羊柴叶片的含氮量。CO2倍增使叶片的碳氮比显著增加，而干旱使之降低。CO2浓度倍增降低叶肉细胞质膜的过氧化产物MDA的含量，干旱亦使叶片的MDA含量增加。叶片含氮量与MDA呈显著正相关，表明CO2倍增有保护叶片免受土壤干旱的作用，但干旱的负面影响是CO2倍增效应所难以弥补的。 CO2倍增降低了柠条叶片的可溶性蛋白质的含量，但在干旱条件下降低幅度较小，说明CO2浓度升高条件下可减轻干旱影响叶片中可溶性蛋白质的强度，体现了CO2浓度倍增对植物的抗旱性有利的一面。CO2浓度倍增使土壤水分充足条件下的柠条叶片中游离氨基酸含量降低17.24%，却使SD条件下增加10.78%，表明土壤干旱导致的叶片游离氨基酸含量的增加平衡了CO2升高造成的降低。在充足土壤水分和MD条件下，CO2浓度倍增对核酸总含量和RNA含量有稀释效应，但严重干旱条件下，CO2倍增提高了核酸总含量和RNA的含量。

云南文山黄牛和迪庆黄牛的遗传多样性比较研究

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该论文在褐藻多糖硫酸酯已有研究工作的基础上,参考中药治肾病领域有关文献,结合中医药理论,组方成治疗慢性肾衰复方海洋新药-复方褐藻多糖硫酸酯,并进行了复方褐藻多糖硫酸酯的部分药学、初步药效学和急性毒性试验的研究.

孔石莼多糖及其衍生物的研究

在中国，孔石莼应用于医药方面已有几千年的历史，其煎剂常被当地居民用来治疗中暑和泌尿方面的疾病。实验室以前所做的工作表明，孔石莼的水溶多糖具有很好的抗高血脂活性，本论文在此研究的基础上主要就多糖的长期毒性、一般药理、多糖的衍生化、不同分子量孔石莼多糖的抗氧化活性、衍生物的抗氧化活性和动物调血脂活性进行了研究。 水提醇沉制备多糖，多糖主要由糖醛酸、鼠李糖、木糖、葡萄糖和硫酸根组成，还含有微量的半乳糖、甘露糖和阿拉伯糖。多糖中主要的二糖重复单位为[β-D-Glcp A-(1->4)- α-L-Rhap 3S] 和 [α-L-Idop A-(1->4)- α-L-Rhap 3S]。急性毒性实验表明，KM小鼠对孔石莼多糖的最大耐受量(MTD)大于4000 mg/kg，其腹腔注射雌性小鼠的半致死量(LD50)为408.7 mg/kg，雄性动物为432.7 mg/kg。长期毒性（6个月）实验表明孔石莼多糖无毒反应剂量为1.2 g/kg。一般药理研究表明孔石莼多糖对小鼠中枢神经系统无明显影响，对麻醉犬心血管系统和呼吸系统均无明显影响。 采用过氧化氢降解的方法制备了不同分子量的孔石莼多糖，并且测定了体外抗氧化活性；制备了高硫酸根含量的孔石莼多糖、乙酰化和苯甲酰化孔石莼多糖衍生物，测定了体外抗氧化活性和动物调血脂试验。结果表明，不同分子量的孔石莼多糖其抗氧化活性是不同的，分子量低的孔石莼多糖表现出了较强的抗氧化活性。孔石莼多糖的衍生物其抗氧化活性要优于孔石莼多糖。调血脂动物试验表明，孔石莼多糖以及其衍生物都具有很好的调血脂效果。高硫酸根含量孔石莼多糖的中、低剂量组的调血脂活性要优于高剂量组（低剂量组降低低密度脂蛋白的能力要稍弱于原料），而且，中剂量组与原料组相比，小鼠血清TG明显降低（P＜0.05），LDL－C 明显降低（P＜0.01）。低剂量组乙酰化衍生物降低甘油三酯（TG）和低密度脂蛋白（LDL－C）的能力要优于中高剂量组。对于孔石莼多糖以及衍生物调血脂的机制还需进一步的研究。

Vertical transmission efficiency and insecticidal properties of Spodoptera exigua Nucleopolyhedrovirus (SeMNPV) genotypes for their use in biological control

El nucleopoliedrovirus de Spodoptera exigua (SeMNPV) es un patógeno natural de las poblaciones larvarias de S. exigua que constituye la base de un bioinsecticida comercializado en España para el control biológico de esta plaga en pimiento. Recientes estudios han demostrado que la transmisión del virus a la descendencia (transmisión vertical) se da con frecuencia y podría ser una característica deseable para su uso en aplicaciones de campo. En el presente trabajo se discute la conveniencia de utilizar una mezcla de dos genotipos SeAl1 (transmisión vertical) y SeG25 (transmisión horizontal) en determinadas proporciones para mejorar las características que cada uno de ellos presenta por separado y así explotar cada una de las vías de transmisión. La patogenicidad (CL50) del genotipo SeG25, y de cualquiera de las mezclas que contienen un 25, 50 o 75 % del mismo, fue más alta que la del aislado SeAl1. Sin embargo, en términos de virulencia (TMM) y productividad (OBs/larva) no se observaron diferencias significativas entre genotipos ni entre sus mezclas. Además se evaluó la capacidad de producir infecciones encubiertas de cada genotipo y sus mezclas sometiendo larvas de S. exigua a infecciones subletales del virus. Se encontraron transcritos del virus para el gen temprano ie0 mediante RT-PCR en los adultos supervivientes a infecciones provocadas por el genotipo SeG25 y todas las mezclas. También se testaron otros dos genes virales que se expresan de manera temprana y tardía en la infección de baculovirus (DNA-polimerasa y polihedrina) para los que en ningún caso se detectaron transcritos.

Selección de un aislado del nucleopoliedrovirus de Helicoverpa armigera (HearNPV) para su uso como base de un bioinsecticida

Helicoverpa armigera (Lepidoptera; Noctuidae), conocida como el taladro del tomate, es una especie polífaga y de amplia distribución, responsable de grandes pérdidas económicas en más de 60 cultivos a lo largo de las regiones tropicales y subtropicales del mundo. Estas plagas se controlan mayoritariamente con plaguicidas químicos, aunque existe un gran interés por desarrollar otros agentes de control biológico. Entre estos, se encuentra el nucleopoliedrovirus de Helicoverpa armigera (HearNPV, Baculoviridae), que por sus características de seguridad y eficacia, sería útil para impulsar los programas de gestión integrada de plagas que se fomentan desde la Directiva 2009/128/CEE. El objetivo de este trabajo fue realizar una caracterización bioquímica y biológica de varios aislados de HearNPV : un aislado silvestre español (Badajoz) HearNPV-SP1, un aislado chino HearSNPV-G4, tres aislados sudafricanos (HearNPV-Whl, HearNPV-Kzn, HearNPV-Alb) y la materia activa de un producto comercial en uso en Europa (HearNPV-Hx). El análisis con las enzimas de restricción determinó que la enzima BglII generaba perfiles similares pero con fragmentos característicos en todos los casos a excepción de los aislados HearNPV-Kzn y HearNPVAlb, que no pudieron ser diferenciados entre sí con ninguna de las enzimas probadas. El análisis filogenético, basado en las secuencias parciales de los genes poliedrina (polh), lef-8 y lef-9, donde se incluyeron las secuencias correspondientes a 18 genomas mostró que el aislado HearNPV-Whl es filogenéticamente próximo a las cepas de origen ibérico, mientras que los aislados HearNPV-Hx y HearNPV-Alb comparten la misma rama que los aislados asiáticos y australiano. La caracterización insecticida de los aislados HearNPV-SP1, HearNPV-Hx y HearNPV-G4 reveló que la virulencia (TMM) del aislado HearNPV-SP1 (104 h) fue significativamente menor que la de los aislados HearNPV-G4 (109 h) y HearNPV-Hx (111 h). En este trabajo, se determinó que el tiempo de acción del HearNPV-SP1 es menor al de otros bioinsecticidas en uso en Europa, por lo que se confirma la posibilidad de mejorar los productos activos en uno de los aspectos más sensibles de cara a su comercialización como es su tiempo de actuación.

An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.

An EORTC phase I study of capecitabine (Xeloda) in combination with fixed doses of cyclophosphamide and epirubicin (cex) as primary treatment for large operable or locally advanced/inflammatory breast cancer.

In breast cancer, chemotherapy regimens that include infusional 5-fluorouracil (5-FU) lead to high response rates, but require central venous access and pumps. To avoid these inconveniences, we substituted infusional 5-FU with capecitabine. The main objective of this study was to determine the maximum tolerated dose (MTD) of capecitabine when given in combination with fixed doses of epirubicin and cyclophosphamide (100 and 600 mg/m(2) day 1 every (q) 3 weeks) as primary treatment for large operable or locally advanced/inflammatory breast cancer without distant metastasis. Capecitabine was escalated from 750 mg/m(2) twice a day (bid) to 1250 mg/m(2) bid from day 1 to day 14 in four dose levels. Dose escalation was permitted if 0/3 or 1/6 patients experienced dose-limiting toxicity (DLT). A total of 23 patients were included and 117 courses were administered. At dose level 4, 2 of 2 patients presented DLTs defining the MTD. A high rate of capecitabine treatment modification was required with capecitabine 1050 mg/m(2) bid (dose level 3). 19 patients achieved an objective response (83%). In conclusion, we believe that capecitabine 900 mg/m(2) bid (dose level 2) is the recommended dose in combination with epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2). The acceptable toxicity profile and encouraging activity of this regimen warrant further evaluation.

An EORTC phase I study of epirubicin in combination with fixed doses of cyclophosphamide and infusional 5-fu (CEF-infu) as primary treatment of large operable or locally advanced/inflammatory breast cancer.

PURPOSE: The association of continuous infusion 5-fluorouracil, epirubicin (50 mg/m2 q 3 weeks) and a platinum compound (cisplatin or carboplatin) was found to be very active in patients with either locally advanced/inflammatory (LA/I) [1, 2] or large operable (LO) breast cancer (BC) [3]. The same rate of activity in terms of response rate (RR) and response duration was observed in LA/I BC patients when cisplatin was replaced by cyclophosphamide [4]. The dose of epirubicin was either 50 mg/m2 [ 1, 2, 3] or 60 mg/m2/cycle [4]. The main objective of this study was to determine the maximum tolerated dose (MTD) of epirubicin when given in combination with fixed doses of cyclophosphamide and infusional 5-fluorouracil (CEF-infu) as neoadjuvant therapy in patients with LO or LA/I BC for a maximum of 6 cycles. PATIENTS AND METHODS: Eligible patients had LO or LA/I BC, a performance status 0-1, adequate organ function and were <65 years old. Cyclophosphamide was administered at the dose of 400 mg/m2 day 1 and 8, q 4 weeks and infusional 5-fluorouracil 200 mg/m2/day was given day 1-28, q 4 weeks. Epirubicin was escalated from 30 to 45 and to 60 mg/m2 day 1 and 8; dose escalation was permitted if 0/3 or 1/6 patients experienced dose limiting toxicity (DLT) during the first 2 cycles of therapy. DLT for epirubicin was defined as febrile neutropenia, grade 4 neutropenia lasting for >7 days, grade 4 thrombocytopenia, or any non-haematological toxicity of CTC grade > or =3, excluding alopecia and plantar-palmar erythrodysesthesia (this toxicity was attributable to infusional 5-fluorouracil and was not considered a DLT of epirubicin). RESULTS: A total of 21 patients, median age 44 years (range 29-63) have been treated. 107 courses have been delivered, with a median number of 5 cycles per patient (range 4-6). DLTs on cycles I and 2 on level 1, 2, 3: grade 3 (G3) mucositis occurred in 1/10 patients treated at the third dose level. An interim analysis showed that G3 PPE occurred in 5/16 pts treated with the 28-day infusional 5-FU schedule at the 3 dose levels. The protocol was subsequently amended to limit the duration of infusional 5-fluorouracil infusion from 4 to 3 weeks. No G3 PPE was detected in 5 patients treated with this new schedule. CONCLUSIONS: This study establishes that epirubicin 60mg/m2 day 1 and 8, cyclophosphamide 400mg/m2 day 1 and 8 and infusional 5-fluorouracil 200 mg/m2/day day 1-21. q 4 weeks is the recommended dose level. Given the encouraging activity of this regimen (15/21 clinical responses) we have replaced infusional 5-fluorouracil by oral capecitabine in a recently activated study.

Multi-touch accceptance: perceived disorientation and consequences on task engagement

The research project takes place within the technology acceptability framework which tries to understand the use made of new technologies, and concentrates more specifically on the factors that influence multi-touch devices’ (MTD) acceptance and intention to use. Why be interested in MTD? Nowadays, this technology is used in all kinds of human activities, e.g. leisure, study or work activities (Rogowski and Saeed, 2012). However, the handling or the data entry by means of gestures on multi-touch-sensitive screen imposes a number of constraints and consequences which remain mostly unknown (Park and Han, 2013). Currently, few researches in ergonomic psychology wonder about the implications of these new human-computer interactions on task fulfillment.This research project aims to investigate the cognitive, sensori-motor and motivational processes taking place during the use of those devices. The project will analyze the influences of the use of gestures and the type of gesture used: simple or complex gestures (Lao, Heng, Zhang, Ling, and Wang, 2009), as well as the personal self-efficacy feeling in the use of MTD on task engagement, attention mechanisms and perceived disorientation (Chen, Linen, Yen, and Linn, 2011) when confronted to the use of MTD. For that purpose, the various above-mentioned concepts will be measured within a usability laboratory (U-Lab) with self-reported methods (questionnaires) and objective indicators (physiological indicators, eye tracking). Globally, the whole research aims to understand the processes at stakes, as well as advantages and inconveniences of this new technology, to favor a better compatibility and adequacy between gestures, executed tasks and MTD. The conclusions will allow some recommendations for the use of the DMT in specific contexts (e.g. learning context).