Conditionally unbiased estimation in phase II/III clinical trials with early stopping for futility

Seamless phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages, with stage 1 used to answer phase II objectives such as treatment selection and stage 2 used for the confirmatory analysis, which is a phase III objective. Although seamless phase II/III clinical trials are efficient because the confirmatory analysis includes phase II data from stage 1, inference can pose statistical challenges. In this paper, we consider point estimation following seamless phase II/III clinical trials in which stage 1 is used to select the most effective experimental treatment and to decide if, compared with a control, the trial should stop at stage 1 for futility. If the trial is not stopped, then the phase III confirmatory part of the trial involves evaluation of the selected most effective experimental treatment and the control. We have developed two new estimators for the treatment difference between these two treatments with the aim of reducing bias conditional on the treatment selection made and on the fact that the trial continues to stage 2. We have demonstrated the properties of these estimators using simulations

A comparison of methods for constructing confidence intervals after phase II/III clinical trials

Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.

Grafisk profil för House of Sweden (Washington D.C.)

Detta examensarbete innefattar både en fördjupning och en praktisk del inom ämnet grafisk profilering och visuellt identitetsskapande. Den praktiska delen av examensarbetet har utförts parallellt med reklambyrån Cabesa Communication Sweden AB, Stockholm. Fördjupningsdelen behandlar områden som branding, företagsidentitet och grafisk profil. För att skapa ett starkt varumärke på en marknad krävs välplanerade, strategiska och originella reklamkampanjer samt en stark och enhetlig visuell identitet. Med hjälp av fördjupningen så har en kunskapsgrund lagts inom ämnet grafisk profilering och det praktiska arbetet har förenklats mycket.Den praktiska delen innehåller framtagning av en grafisk profil med tillhörande manual till House of Sweden, Sveriges nya ambassad, Event Center och lägenhetsbyggnad i Washington D.C., USA. Genom en kvalitativ och enhetlig grafisk profil ska House of Sweden kunna bli ett starkt och välkänt varumärke. Den grafiska profilen bygger på ett antal huvuddelar; logotyp, typsnitt, färger och bildspråk. Utifrån dessa delar har bland annat korrespondensprogram, annonser och profilartiklar tagits fram, allt sammanställt i en omfattandegrafisk manual.

Entomofauna visitante das flores de Cassia spectabilis (L.) D C. (Leguminosae)

Realizaram-se estudos sobre sistemas de reprodução de Cassia spectabilis (L.) D C. (Leguminosae) observando-se a diversidade, freqüência e constância dos insetos visitantes em diferentes horários. Também testou-se a influência dos fatores ambientais em relação às visitas. Os resultados de polinização manual sugerem que C. spectabilis é autocompatível, porém, a xenogamia é o sistema de reprodução predominante. As inflorescências foram visitadas por uma grande quantidade de insetos, havendo predominância de abelhas. O horário de maior ocorrência dos insetos nas flores de C. spectabilis foi das 8 às 14 h e de menor ocorrência entre 7 e 8 h e das 17 às 18 h. Quanto ao comportamento dos insetos em relação à flor de C. spectabilis, observou-se que Xylocopa frontalis Olivier, X. suspecta Camargo & Moure, Bombus morio Swederus e Centris scopipes Friese possuem comportamento e morfologia adequados aos polinizadores legítimos; C. similis F., Oxaea flavescens Klug e Epicharis rustica flava Cockerell foram considerados polinizadores ocasionais. Pseudaugochloropsis graminea (F.), Tetragonisca angustula Latreille e A. mellifera L. foram considerados pilhadores. A polinização por vibração é o método usado pelas abelhas para coleta de pólen.

Eram realmente pitagórico(a)s os homens e mulheres catalogado(a)s por Jâmblico em sua obra Vida de Pitágoras?

Pythagoras was one of the most important pre-Socratic thinkers, and the movement he founded, Pythagoreanism, influenced a whole thought later in religion and science. Iamblichus, an important Neoplatonic and Neopythagorean philosopher of the third century AD, produced one of the most important biographies of Pythagoras in his work Life of Pythagoras. In it he portrays the life of Pythagoras and provides information on Pythagoreanism, such as the Pythagorean religious community which resembled the cult of mysteries; the Pythagorean involvement in political affairs and in the government in southern Italy, the use of music by the Pythagoreans (means of purification of healing, use of theoretical study), the Pythagorean ethic (Pythagorean friendship and loyalty, temperance, self-control, inner balance); justice; and the attack on the Pythagoreans. Also in this biography, Iamblichus, almost seven hundred years after the termination of the Pythagorean School, established a catalog list with the names of two hundred and eighteen men and sixteen women, supposedly Pythagoreans of different nationalities. Based on this biography, a question was raised: to what extent and in what ways, can the Pythagoreans quoted by Iamblichus really be classified as Pythagoreans? We will take as guiding elements to search for answers to our central problem the following general objectives: to identify, whenever possible, which of the men and women listed in the Iamblichus catalog may be deemed Pythagorean and specific; (a) to describe the mystery religions; (b) to reflect on the similarities between the cult of mysteries and the Pythagorean School; (c) to develop criteria to define what is being a Pythagorean; (d) to define a Pythagorean; (e) to identify, if possible, through names, places of birth, life, thoughts, work, lifestyle, generation, etc.., each of the men and women listed by Iamblichus; (f) to highlight who, in the catalog, could really be considered Pythagorean, or adjusting to one or more criteria established in c, or also to the provisions of item d. To realize these goals, we conducted a literature review based on ancient sources that discuss the Pythagoreanism, especially Iamblichus (1986), Plato (2000), Aristotle (2009), as well as modern scholars of the Pythagorean movement, Cameron (1938), Burnet (1955), Burkert (1972), Barnes (1997), Gorman (n.d.), Guthrie (1988), Khan (1999), Mattéi (2000), Kirk, Raven and Shofield (2005), Fossa and Gorman (n.d.) (2010). The results of our survey show that, despite little or no availability of information on the names of alleged Pythagoreans listed by Iamblichus, if we apply the criteria and the definition set by us of what comes to be a Pythagorean to some names for which we have evidence, it is possible to assume that Iamblichus produced a list which included some Pythagoreans

Secagem do resíduo de acerola (Malphigia emarginata D.C.): estudo do processo e avaliação do impacto sobre o produto final

Brazil, one of the largest agricultural producers in the world, has managed in recent years to significantly improve its production. However, in response to this advance in the agro-industrial sector, the generation of agro-industrial residues has also increased. New technological alternatives have to be implemented in order to bring economic and rational use of this material and drying is one of the possible choices. Considering the great importance that bioactive compounds present for food science and technology, this research aims to evaluate the air-drying process of acerola residue in a tray convective drier under controlled temperature (60, 70 e 80ºC), air velocity (4.0, 5.0 e 6.0 m/s) and material width (0.5, 0.62 e 0.75 cm) by applying an experimental planning 23 + 3. Based on that, the impact on physical-chemical characteristics, color, bioactive compounds concentration and antioxidant activity of dried acerola waste was evaluated, having the in natura and freeze dried waste as control groups. Dried acerola residue presented natural pigments, mainly carotenoids (143.68 - 68.29 mg/g) and anthocyanins (290.92 - 90.11 mg/100 g), which explain the red and yellow instrumental color parameters observed. The acerola residue powder is also rich in phenolic compounds (3261.11 -2692.60 mgGAEeq/100g), proanthocyanidins (61.33-58.46 eq/100g), ascorbic acid (389.44 739.29 mg/100 g) and DPPH antioxidant activity (20.91 24.72 μg Trolox eq/g). Results show decreased concentration of phenolic compounds, anthocyanins, carotenoids, proanthocyanidins and ascorbic acid caused by the air-drying process. However, even after the observed drying losses, the acerola residue powder can be considered a high value food ingredient, considering the high bioactive compounds concentration found in the final product, as well as the colorimetric characterization and microbiological stability of the dried powder

Evaluation of the genotoxic and antigenotoxic potential of Brassica oleracea L. var. acephala D.C. in different cells of mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transient and d.c. analysis of the operation mechanism of light-emitting electrochemical cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O gênero Vaucheria D.C. (Vaucheriaceae, Xanthophyceae) no sul do Brasil: aspectos taxonômicos e ecológicos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Florescimento e frutificação do maracujazeiro silvestre Passiflora setacea D. C. cultivado em Jaboticabal, SP

Muitas espécies de Passiflora apresentam comportamento florífero diferente durante o ano e, consequentemente, com variações nas produções e períodos de colheitas, como observado para o maracujazeiro-amarelo (Passiflora edulis sims). Estudo com espécies silvestre constitui-se numa importante alternativa para usos de novos genótipos no melhoramento das espécies cultivadas comercialmente, em especial, a Passiflora setacea, devido ao grande potencial de mercado; contudo, essa espécie é pouco estudada, principalmente em relação à propagação, germinação, floração e condições de armazenamento. Assim, o objetivo deste trabalho foi avaliar o florescimento e a frutificação do maracujazeiro silvestre Passiflora setacea cultivado em Jaboticabal-SP. A floração e a frutificação foram avaliadas pelo percentual de frutificação através da polinização natural e artificial das flores, realizado no período de agosto a outubro. As características físicas dos frutos foram avaliadas através dos seguintes parâmetros: a) massa do fruto (g); b) diâmetro longitudinal do fruto (cm); c) diâmetro transversal do fruto (cm); d) espessura da casca (cm); e) rendimento de polpa (%). A característica química foi determinada por meio do teor de sólidos solúveis (SS). Verificou-se que a Passiflora setacea apresentou precocidade de floração em relação ao maracujazeiro-amarelo, com florescimento durante o ano todo, nas condições de Jaboticabal-SP. Observou-se que essa espécie possui bom nível de tolerância às doenças foliares, resistência à morte precoce e apresenta diferentes níveis de compatibilidade entre as plantas, possibilitando a essas características serem utilizadas em programas de melhoramento genético. Constatou-se ainda que as características físicas encontradas nos frutos atendem às exigências da indústria.

Aspects of the sexual reproduction of the Brazilian arnica (Solidago chilensis Meyen var. megapotamica (D.C.) Cabrera - Asteraceae)

The species is a very popularly used plant as woundwort. Leaves, top flowers and rhizomes are used. The objective of this work is a contribution to the germination study, photoblastism and more adequate temperature for reproduction of the species. The best temperature for the germination was found to be 20°C and no seeds germinated under continuous darkness, within 14 days; therefore, the seeds are positive photoblastics. The seed germination percentage was low, in relation to the mass of the achene produced, varying from 8,2 to 20,0%. The alternated temperatures of 20° and 30°C did not influence the seed germination and the average of the weight of 100 seeds was 0,026 1 g.