Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors

One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese. Thirty-one eumenorrheic women matched for BMI and age, with no evidence of hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in the PCOS group was twice that of the Control group (76.1% versus 32.25%). The most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C; 57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all subgroups of women with PCOS when compared to the subgroups of normal women. No significant differences were seen in the total cholesterol (p = 0.307), low-density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels among the subgroups. An independent effect on HDL-C was detected for glucose (p = 0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant impact on this abnormality.

Air Pollution and Mortality in Latin America The Role of Education

Background: People with less education in Europe, Asia, and the United States are at higher risk of mortality associated with daily and longer-term air pollution exposure. We examined whether educational level modified associations between mortality and ambient particulate pollution (PM(10)) in Latin America, using several timescales. Methods: The study population included people who died during 1998-2002 in Mexico City, Mexico; Santiago, Chile; and Sao Paulo, Brazil. We fit city-specific robust Poisson regressions to daily deaths for nonexternal-cause mortality, and then stratified by age, sex, and educational attainment among adults older than age 21 years (none, some primary, some secondary, and high school degree or more). Predictor variables included a natural spline for temporal trend, linear PM(10) and apparent temperature at matching lags, and day-of-week indicators. We evaluated PM(10) for lags 0 and I day, and fit an unconstrained distributed lag model for cumulative 6-day effects. Results: The effects of a 10-mu g/m(3) increment in lag 1 PM(10) on all nonextemal-cause adult mortality were for Mexico City 0.39% (95% confidence interval = 0.131/-0.65%); Sao Paulo 1.04% (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%. We found cumulative 6-day effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and Sao Paulo (1.38% [0.85%-1.91%]), but no consistent gradients by educational status. Conclusions: PM(10) had important short- and intermediate-term effects on mortality in these Latin American cities, but associations did not differ consistently by educational level.

The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila

The intracellular bacterium Legionella pneumophila induces a severe form of pneumonia called Legionnaires diseases, which is characterized by a strong neutrophil (NE) infiltrate to the lungs of infected individuals. Although the participation of pattern recognition receptors, such as Toll-like receptors, was recently demonstrated, there is no information on the role of nod-like receptors (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs. Here, we employed a murine model of Legionnaires disease to evaluate host and bacterial factors involved in NE recruitment to the mice lungs. We found that L. pneumophila type four secretion system, known as Dot/Icm, was required for NE recruitment as dot/icm mutants fail to trigger NE recruitment in a process independent of bacterial multiplication. By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice. In addition, Rip2-dependent responses were important for cytokine production and bacterial clearance. Collectively, these studies show that Nod1, Nod2, and Rip2 account for generation of innate immune responses in vivo, which are important for NE recruitment and bacterial clearance in a murine model of Legionnaires diseases. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that > 80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.

Delayed orbital hemorrhage after routine strabismus surgery

PURPOSE: To report a case of delayed rectus muscle hemorrhage after strabismus surgery. METHODS: Case report. RESULTS: Rectus muscle hemorrhage occurred 36 hours after strabismus surgery in a 26-year-old man, causing temporary loss of vision and reduced ocular motility. Urgent lateral cantholysis and orbital exploration to restore hemostasis were undertaken. Full recovery of vision occurred and a small residual motility disturbance was present 3 months postoperatively. CONCLUSION: Delayed rectus muscle hemorrhage post-strabismus surgery is rare but can have sight-threatening effects. When vision is threatened because of optic nerve compromise, urgent orbital exploration may allow full recovery of function. (Am J Ophthalmol 2001;131: 818-819, (C) 2001 by Elsevier Science Inc. All rights reserved.).

Twisting and planarization in push-pull ethylenes

As determined by X-ray crystallography, Meldrum's acid derivatives 8–19 feature dihedral angles around the central CC double bonds between 3 and 83°. Hydrogen bonds between substituents RHN and the carbonyl groups favour near-planarity. Sterically demanding substituents favour large dihedral angles and zwitterionic structures as in formula 20. AM1 calculations of the structures are in excellent agreement with the experimental X-ray data, provided a dielectric field is incorporated (?= 40). This can be ascribed to the highly polar (zwitterionic) nature of the molecules. It is further predicted that all these molecules, including those that are stabilised in a planar form by intramolecular hydrogen bonds, undergo rapid rotation about the central CC bonds at room temperature. DFT calculations incorporating a dielectric field model (PCM) are in excellent agreement with the near-perpendicular arrangement of the alkene moiety in 19.

Texto para discuss??o 11: governabilidade, governan??a e capacidade governativa: algumas notas

Prop??e para fins anal??ticos, o conceito capacidade governativa, definido de maneira ampla, de forma a englobar tanto os aspectos operacionais do aparelho do Estado ??? a?? inclu??dos os requisitos organizacionais e gerenciais ??? como suas dimens??es econ??mica e pol??tica. Indica, ainda, a ambi??ncia mais ou menos democr??tica do sistema pol??tico. Esse conceito operacional permite, assim, a an??lise da efici??ncia e efic??cia do Estado em ajustar a economia, redefinir seu tamanho e suas fun????es, resgatar a d??vida social e manter-se em ambiente democr??tico, desafios impostos e assumidos por todos os governantes do Brasil p??s-constituinte.

Influência dos estrativos na resistência ao apodrecimento de seis espécies de madeira

O presente trabalho teve como objetivo avaliar o efeito da extração da madeira de seis espécies, quatro nativas (candeia, cedro, cerejeira e jacarandá-caviúna) e duas exóticas (E. citriodora e E. gumifera), em diferentes solventes, na resistência ao apodrecimento causado pelo fungo da podridão-parda Gloeophyllum trabeum. O material foi ensaiado na forma de serragem, em face da maior facilidade para os procedimentos de extração. Dentre os resultados, pode-se destacar a baixa perda de massa ocorrida na madeira de cedro (Cedrela fissilis), evidenciando sua elevada resistência natural ao fungo testado e, ainda, à incapacidade dos solventes utilizados na retirada de compostos que conferem resistência ao apodrecimento. As madeiras de candeia (Vanillosmopsis erythropappa), cerejeira (Amburana cearensis), jacarandá-caviúna (Machaerium scleroxylon) e de eucaliptos (Corymbia citriodora e Eucalyptus gummifera) também apresentaram elevada resistência natural, em função da baixa perda de massa ocorrida, quando expostas ao fungo G. trabeum. Essas madeiras, quando totalmente extraídas, apresentaram elevados valores de perda de massa. No que diz respeito ao material extraído por diferentes solventes de forma isolada, observou-se, na candeia, que o solvente mais eficiente na retirada de substâncias que conferem resistência ao apodrecimento foi o diclorometano. Com relação ao cedro, o mais eficiente foi o metanol. Na cerejeira, por meio da mistura de etanol/tolueno retiraram-se mais substâncias, ao passo que no jacarandá-caviúna foi o metanol. Nas madeiras de eucaliptos, o metanol foi mais eficiente na retirada de componentes tóxicos ao fungo utilizado neste estudo, devendo destacar ainda, no E. gummifera, a eficiência da água quente na retirada de tais compostos. No C. citriodora, os valores de perda de massa, em razão das extrações em água fria, em água quente, em diclorometano e ao natural (não-extraída), foram muito baixos.

Identificação Química em Nível Molecular de Amostras de Maconha por ESI-FT-ICR MS

mais consumida no país, e proscrita pela Lei n° 11.343 de 23 de agosto de 2006 (chamada de “nova lei de droga”), onde todos os isômeros, sais, éteres e ésteres do ∆9-Tetrahidrocannabinol (THC), princípio ativo, foram proscritos. O método utilizado pela Polícia Civil do Estado do Espírito Santo para a identificação de cannabinóides é o teste colorimétrico, por meio de solução básica de Salt Fast Blue B, o qual apresenta resultados falsos negativos e falsos positivos. A técnica de espectrometria de massas de altíssima resolução e exatidão de massas (ESI(-)FTICR MS), permite detectar os principais cannabinóides na forma de molécula desprotonada, íon [M-H]-. Alguns íons que podem ser identificados são: [CBN - H]- de m/z 309 (CBN = cannabinol); [THC - H]- de m/z 313 (THC = tetrahidrocannabinol) e [CBD - H]- de m/z 313; [CBC - H]- de m/z 327 (CBC = cannabicromeno); [CBEA - H]- de m/z 345 (CBEA = ácido cannabielsóico); [CBNA - H]- de m/z 353 (CBNA = ácido cannabinólico); [THCA - H]- de m/z 357 (THCA = ácido tetrahidrocannabinólico); [8α, 11-Bis-hydroxy-∆9-THC-A - H]- de m/z 389); [∆9-THCA +C2H2O - H]- de m/z 357; e dímeros com m/z de 637, 653, 673, 681, 685 e 717. Foram encontrados adulterantes identificados como [M + N + H]+ : 491; [2M + N + H]+ : 819 e [3M + N + H]+ : 1147, onde M = OTHC (328Da C21H28O3) e N = Nicotina (162Da C10H14N2), além de lidocaína e cocaína. Ainda foram identificados alguns noncannabinóides como Cannflavino A e B e ácidos graxos como palmítico, oleico, linolênico e gama-linolênico nos extratos de sementes de Cannabis. Este estudo tem o objetivo de identificar o perfil químico de amostras de maconha, apreendidas pela Polícia Civil do Estado do Espírito Santo, por ESI(±)-FT-ICR MS.

Hand-held robotic device for laparoscopic surgery and training

Laparoscopic surgery (LS) has revolutionized traditional surgical techniques introducing minimally invasive procedures for diagnosis and local therapies. LSs have undeniable advantages, such as small patient incisions, reduced postoperative pain and faster recovery. On the other hand, restricted vision of the anatomical target, difficult handling of the surgical instruments, restricted mobility inside the human body, need of dexterity to hand-eye coordination and inadequate and non-ergonomic surgical instruments may restrict LS only to more specialized surgeons. To overcome the referred limitations, this work presents a new robotic surgical handheld system – the EndoRobot. The EndoRobot was designed to be used in clinical practice or even as a surgical simulator. It integrates an electromechanical system with 3 degrees of freedom. Each degree can be manipulated independently and combined with different levels of sensitivity allowing fast and slow movements. As other features, the EndoRobot has battery power or external power supply, enables the use of bipolar radiofrequency to prevent bleeding while cutting and allows plug-and-play of the laparoscopic forceps for rapid exchange. As a surgical simulator, the system was also instrumented to measure and transmit, in real time, its position and orientation for a training software able to monitor and assist the trainee’s surgical movements.

Revestimentos de piso de madeira aplicados por colagem

Neste trabalho é apresentado detalhadamente uma monografia sobre: revestimentos de piso de madeira aplicados por colagem, com referência à normalização aplicável; soluções construtivas e exigências funcionais de bases; revestimentos e materiais de fixação, assim como os procedimentos de aplicação em obra. Efectivamente trata-se de um material de revestimento amplamente utilizado e considerado como nobre pela sociedade civil, nomeadamente projectistas, construtores, imobiliárias e utentes em geral, quer pela tradição, de se assemelhar aos pavimentos antigos da construção tradicional portuguesa, quer pelo aspecto visual, do cheiro, do toque, conforto térmico, das qualidades de estabilidade, durabilidade e resistência superiores a outros tipos de pavimentos. Porém tem sido registado várias situações de deficiências construtivas, com os prejuízos inerentes e algumas desconfianças do consumidor final. Assim quer na construção nova ou na reabilitação em geral, os trabalhos devem ser executados escolhendo o tipo de madeira adequado ao local e respectiva funcionalidade, verificando as condições físicas das bases de assentamento, as prescrições técnicas dos materiais de revestimento e de colagem e respectivos processos construtivos, enquadrados pela normalização europeia e nacional existente além de que tais trabalhos devem serem executados por pessoal técnico especializado e credenciado por acções de formação contínua perante a panóplia de materiais existentes no mercado.

Multilingualism and interpreting: training for the EU

AGM and Conference in Mechelen 27 – 30 April 2010

Cluster Analysis of Business Data

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