Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia

Purpose Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition. Once-daily treatment resulted in less toxicity, suggesting that toxicity results from continuous inhibition of unintended targets. Here, a dose-and schedule-optimization study is reported. Patients and Methods In this open-label phase III trial, 670 patients with imatinib-resistant or -intolerant CP-CML were randomly assigned 1: 1: 1: 1 between four dasatinib treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. Results With minimum follow-up of 6 months (median treatment duration, 8 months; range, = 1 to 15 months), marked and comparable hematologic (complete, 86% to 92%) and cytogenetic (major, 54% to 59%; complete, 41% to 45%) response rates were observed across the four groups. Time to and duration of cytogenetic response were similar, as was progression-free survival (8% to 11% of patients experienced disease progression or died). Compared with the approved 70-mg twice-daily regimen, dasatinib 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). Conclusion Dasatinib 100 mg once daily retains the efficacy of 70 mg twice daily with less toxicity. Intermittent target inhibition with tyrosine kinase inhibitors may preserve efficacy and reduce adverse events.

Race modeling: An effective cognitive strategy for the 100 m sprinter?

The purpose of this study was to investigate the effects of a specific cognitive race plan on 100 m sprint performance, Twelve elite sprinters (11 male and 1 female) performed 100 m time trials under normal (control) conditions and then under experimental conditions (use of race cues). In the experimental condition, participants were asked to think about specific thought content in each of three segments of the 100 m. A multiple baseline design was employed. A mean improvement of 0.26 s was found. Eleven of the 12 participants showed improvement using the specific cognitive race plan (p < .005). Participants also produced more consistent sprint performances when using the cues (p < .01). Subjective evaluations made by the participants unanimously supported the use of the race plan for optimizing sprint performance. Environmental conditions, effort, and practice effects were considered as possible influences on the results.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Gravitational waves : a 100-year tool applied to the dark energy problem

Recent observations from type Ia Supernovae and from cosmic microwave background (CMB) anisotropies have revealed that most of the matter of the Universe interacts in a repulsive manner, composing the so-called dark energy constituent of the Universe. Determining the properties of dark energy is one of the most important tasks of modern cosmology and this is the main motivation for this work. The analysis of cosmic gravitational waves (GW) represents, besides the CMB temperature and polarization anisotropies, an additional approach in the determination of parameters that may constrain the dark energy models and their consistence. In recent work, a generalized Chaplygin gas model was considered in a flat universe and the corresponding spectrum of gravitational waves was obtained. In the present work we have added a massless gas component to that model and the new spectrum has been compared to the previous one. The Chaplygin gas is also used to simulate a L-CDM model by means of a particular combination of parameters so that the Chaplygin gas and the L-CDM models can be easily distinguished in the theoretical scenarios here established. We find that the models are strongly degenerated in the range of frequencies studied. This degeneracy is in part expected since the models must converge to each other when some particular combinations of parameters are considered.

Aplicação da versão em português do instrumento de avaliação de qualidade de vida da Organização Mundial da Saúde (WHOQOL-100)

INTRODUÇÃO: O Grupo de Qualidade de Vida da OMS desenvolveu um instrumento de avaliação de Qualidade de Vida, o WHOQOL-100 que está traduzido para 20 idiomas (WHOQOL GROUP, 1998). A aplicação do instrumento na versão em português é o objetivo do trabalho. MÉTODOS: Foram aplicados em 250 pacientes provenientes de quatro grandes áreas médicas (psiquiatria, clínica, cirurgia e ginecologia) de um hospital de clínicas de Porto Alegre, RS, e em 50 voluntários-controles o Instrumento de Avaliação de Qualidade de Vida da OMS (WHOQOL-100), o Inventário de Beck para a depressão (BDI) e a Escala de Desesperança de Beck (BHS). RESULTADOS E CONCLUSÕES:O Instrumento mostrou bom desempenho psicométrico com características satisfatórias de consistência interna, validade discriminante, validade de critério, validade concorrente e fidedignidade teste-reteste. Concluiu-se que o instrumento está em condições de ser usado no Brasil, sendo importante avaliar seu desempenho em outras regiões e em diferentes amostras de indivíduos.

Estrutura de capital e a rendibilidade das 100 maiores empresas dos Açores

Dissertação de Mestrado, Ciências Económicas e Empresariais, 8 de Janeiro de 2015, Universidade dos Açores.

Especulação em mercado bolsista : análise técnica : o caso Nasdaq-100 perante a crise subprime

Mestrado em Controlo de Gestão e dos Negócios

100 Años de desarrollo de la teoría financiera : situación actual y previsible evolución tras la crisis : resumen de la ponencia

"Las Finanzas, como disciplina académica, nacen a caballo entre los siglos XIX y XX. Sin duda el importante desarrollo industrial de la época y la necesidad de empresas de mayores dimensiones llevaron a un creciente interés por las concentraciones empresariales como fusiones y adquisiciones. También aumentó el interés por los mercados donde se financiaban estas empresas cada vez mayores. Y esto, aunque sucedía en diversas partes del mundo, estaba ocurriendo de forma especial en Estados Unidos, de manera que allí fue donde nacieron las finanzas, y donde se han seguido desarrollando. De esta manera, desde un comienzo, las finanzas tienen un claro sello anglosajón." [introdução]

Matemática 100 stress: um projeto aberto no IPP

A Era Tecnológica em que nos vemos inseridos, cujos avanços acontecem a uma velocidade vertiginosa exige, por parte das Instituições de Ensino Superior (IES) uma atitude proactiva no sentido de utilização dos muitos recursos disponíveis. Por outro lado, os elementos próprios da sociedade da informação – flexibilidade, formação ao longo da vida, acessibilidade à informação, mobilidade, entre muito outros – atuam como fortes impulsionadores externos para que as IES procurem e analisem novas modalidades formativas. Perante a mobilidade crescente, que se tem revelado massiva, a aprendizagem tende a ser cada vez mais individualizada, visual e prática. A conjugação de várias formas/tipologias de transmissão de conhecimento, de métodos didáticos e mesmo de ambientes e situações de aprendizagem induzem uma melhor adaptação do estudante, que poderá procurar aqueles que melhor vão ao encontro das suas expetativas, isto é, favorecem um processo de ensino-aprendizagem eficiente na perspetiva da forma de aprender de cada um. A definição de políticas estratégicas relacionadas com novas modalidades de ensino/formação tem sido uma preocupação constante na nossa instituição, nomeadamente no domínio do ensino à distância, seja ele e-Learning, b-Learning ou, mais recentemente, “open-Learning”, onde se inserem os MOOC – Massive Open Online Courses (não esquecendo a vertente m-Learning), de acordo com as várias tendências europeias (OECD, 2007) (Comissão Europeia, 2014) e com os objetivos da “Europa 2020”. Neste sentido surge o Projeto Matemática 100 STRESS, integrado no projeto e-IPP | Unidade de e-Learning do Politécnico do Porto que criou a sua plataforma MOOC, abrindo em junho de 2014 o seu primeiro curso – Probabilidades e Combinatória. Pretendemos dar a conhecer este Projeto, e em particular este curso, que envolveu vários docentes de diferentes unidades orgânicas do IPP.

Coarctação Isolada da Aorta: Experiência em 100 Doentes Consecutivos

INTRODUCTION: Coarctation of the aorta (CoA) is a stenosis usually located in the descending aorta. Treatment consists of surgical or percutaneous removal of the obstruction and presents excellent immediate results but significant residual problems often persist. OBJECTIVES: To describe the presentation, treatment and long-term evolution of a population of 100 unselected consecutive patients with isolated CoA in a single pediatric cardiology center. METHODS: This was a retrospective study of all patients with isolated CoA treated during4 the last 21 years (1987-2008). RESULTS: The patients (n=100, 68.3% male) were diagnosed at a median age of 94 days (1 day to 16 years). The clinical presentation differed between patients aged less or more than one year, the former presenting with heart failure and the latter being asymptomatic with evidence of hypertension (88 and 63%, respectively; p < 0.01). Treatment, a median of 8 days after diagnosis, was surgical in 79 cases (20 end-to-end anastomosis, 31 subclavian flap, 28 patch) and percutaneous in the remaining 21 (15 balloon angioplasty, 6 with stenting). The mean age of surgical patients was younger than in those treated percutaneously (3.4 vs. 7.5 years; p < 0.01). Immediate mortality was 2% and occurred in the surgical group. There was no late mortality, in a mean follow-up of 7.2 +/- 5.4 years. Recoarctation occurred in 8 patients (6 surgical, 2 percutaneous). There are 46 patients who currently have hypertension (19 at rest, 27 with effort), their median age at diagnosis being older than the others (23 vs. 995 days; p < 0.01). CONCLUSIONS: Isolated CoA has an excellent short-term prognosis but a significant incidence of long-term complications, and should thus no longer be seen as a simple obstruction in the descending aorta, but rather as a complex pathology that requires careful follow-up after treatment. Its potentially insidious presentation requires a high level of clinical suspicion, femoral pulse palpation during physical examination of newborns and older children being particularly important. Delay in treatment has an impact on late morbidity and mortality. Taking into account the data currently available on late and immediate results, the final choice of therapeutic technique depends on the patient's age, associated lesions and the experience of the medical-surgical team. Hypertension should be closely monitored in the follow-up of these patients, as well as its risk factors and complications.

Desenvolvimento de padrão gravimétrico de medição de caudal de fluidos entre 10 mL/min e 100 nL/min

Dissertação para obtenção do Grau de Mestre em Engenharia Mecânica

Inquérito hematológico em 100 crianças da Fundação Romão de Mattos Duarte, Estado da Guananabara

Os AA. relatam os achados hematológicos em 100 crianças, 96 das quais se apresentavam com anemia de diversos graus, sendo 79% ferropênicas, 2% macrocíticas e 15% normocrômicas, a maioria das quais associadas à hipoproteinemia, havendo concomitância no aumento da eritrossedimentação em 45%. No quadro leucocitário, 38% apresentaram entre 10.000 e 20.000 leucócitos por mm3. As eosinofilias atingiram 89% dos exames, senão 44% de Grau II e 15% de Grau III.