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.

The Provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

Objective. To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). Methods. In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordce in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results. The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician`s global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent`s global assessment of patient`s well-being, 5) functional ability, and 6) health-related quality of life. Conclusion. The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European Leauge Against Rheumatism, propose a core set of criteria for the evaluation of response of therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

A quantitative and qualitative evaluation of reports of clinical trials published in six Brazilian dental journals indexed in the Scientific Electronic Library Online (SciELO)

INTRODUCTION: Open access publishing is becoming increasingly popular within the biomedical sciences. SciELO, the Scientific Electronic Library Online, is a digital library covering a selected collection of Brazilian scientific journals many of which provide open access to full-text articles.This library includes a number of dental journals some of which may include reports of clinical trials in English, Portuguese and/or Spanish. Thus, SciELO could play an important role as a source of evidence for dental healthcare interventions especially if it yields a sizeable number of high quality reports. OBJECTIVE: The aim of this study was to identify reports of clinical trials by handsearching of dental journals that are accessible through SciELO, and to assess the overall quality of these reports. MATERIAL AND METHODS: Electronic versions of six Brazilian dental Journals indexed in SciELO were handsearched at www.scielo.br in September 2008. Reports of clinical trials were identified and classified as controlled clinical trials (CCTs - prospective, experimental studies comparing 2 or more healthcare interventions in human beings) or randomized controlled trials (RCTs - a random allocation method is clearly reported), according to Cochrane eligibility criteria. CRITERIA TO ASSESS METHODOLOGICAL QUALITY INCLUDED: method of randomization, concealment of treatment allocation, blinded outcome assessment, handling of withdrawals and losses and whether an intention-to-treat analysis had been carried out. RESULTS: The search retrieved 33 CCTs and 43 RCTs. A majority of the reports provided no description of either the method of randomization (75.3%) or concealment of the allocation sequence (84.2%). Participants and outcome assessors were reported as blinded in only 31.2% of the reports. Withdrawals and losses were only clearly described in 6.5% of the reports and none mentioned an intention-to-treat analysis or any similar procedure. CONCLUSIONS: The results of this study indicate that a substantial number of reports of trials and systematic reviews are available in the dental journals listed in SciELO, and that these could provide valuable evidence for clinical decision making. However, it is clear that the quality of a number of these reports is of some concern and that improvement in the conduct and reporting of these trials could be achieved if authors adhered to internationally accepted guidelines, e.g. the CONSORT statement.

Effectiveness of sealing active proximal caries lesions with an adhesive system: 1-year clinical evaluation

The objective of this study was to evaluate the effectiveness of a therapeutic sealant to arrest non-cavitated proximal carious lesion progression. The study population comprised 44 adolescents who had bitewing radiographs taken for caries diagnosis. Non-cavitated lesions extending up to half of dentin thickness were included in the sample. In the experimental group (n = 33), the proximal caries-lesion surfaces were sealed with an adhesive (OptiBond Solo, Kerr) after tooth separation. The control group (n = 11) received no treatment, except for oral hygiene instructions including use of dental floss. Follow-up radiographs were taken after one year and were analyzed in comparison with baseline radiographs. In a blind study setting, visual readings were performed by two examiners, blinded to whether the examined radiograph was baseline or follow-up, and whether it concerned a test or control lesion. The efficacy of sealing treatment was evaluated by the McNemar test (0.05). About 22% of the sealed lesions showed reduction, 61% showed no change and 16% showed progression. For the control lesions, the corresponding values were 27%, 36% and 36% respectively. The number of lesions that showed reduction and no changes were merged and therefore 83.3% of the sealed lesions and 63.6% of the control lesions were considered clinically successful. No statistical significance was detected (p > 0.05). In the course of 1 year, sealing proximal caries lesions was not shown to be superior to lesion monitoring.

The anticancer drug tamoxifen is active against Trypanosoma cruzi in vitro but ineffective in the treatment of the acute phase of Chagas disease in mice

The activity of the antineoplastic drug tamoxifen was evaluated against Trypanosoma cruzi. In vitro activity was determined against epimastigote, trypomastigote and amastigote forms of CL14, Y and Y benznidazole resistant T. cruzi strains. Regardless of the strain used, the drug was active against all life-cycle stages of the parasite with a half maximal effective concentration ranging from 0.7-17.9 µM. Two experimental models of acute Chagas disease were used to evaluate the in vivo efficacy of treatment with tamoxifen. No differences in parasitemia and mortality were observed between control mock-treated and tamoxifen-treated mice.

Active Dendrites Enhance Neuronal Dynamic Range

Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range.

Revisiting clinical trials on glycemic control and cardiovascular risk

The most relevant clinical trials, assessing the role of glycemic control in reducing cardiovascular risk, are examined. The UKPDS was the first to address this issue. More recent trials (ACCORD, ADVANCE and VADT) are controversial and evidences did not support that strict glycemic control (reflected by normal glycated hemoglobin) exclusively is sufficient to reduce cardiovascular risk in complicated individuals with long-term type 2 diabetes mellitus. Some possible reasons for controversies are included.

On the mass determination of super-Earths orbiting active stars: the CoRoT-7 system

Context. Star activity makes the mass determination of CoRoT-7b and CoRoT 7c uncertain. Investigators of the CoRoT team proposed several solutions, but all but one of them are larger than the initial determinations of 4.8 +/- 0.8 M(Earth) for CoRoT-7b and 8.4 +/- 0.9 M(Earth) for CoRoT 7c. Aims. This investigation uses the excellent HARPS radial velocity measurements of CoRoT-7 to redetermine the planet masses and to explore techniques for determining mass and orbital elements of planets discovered around active stars when the relative variation in the radial velocity due to the star activity cannot be considered as just noise and can exceed the variation due to the planets. Methods. The main technique used here is a self-consistent version of the high-pass filter used by Queloz et al. (2009, A&A, 506, 303) in the first mass determination of CoRoT-7b and CoRoT-7c. The results are compared to those given by two alternative techniques: (1) the approach proposed by Hatzes et al. (2010, A&A, 520, A93) using only those nights in which two or three observations were done; (2) a pure Fourier analysis. In all cases, the eccentricities are taken equal to zero as indicated by the study of the tidal evolution of the system. The periods are also kept fixed at the values given by Queloz et al. Only the observations done in the time interval BJD 2 454 847-873 are used because they include many nights with multiple observations; otherwise, it is not possible to separate the effects of the rotation fourth harmonic (5.91 d = P(rot)/4) from the alias of the orbital period of CoRoT-7b (0.853585 d). Results. The results of the various approaches are combined to give planet mass values 8.0 +/- 1.2 M(Earth) for CoRoT-7b and 13.6 +/- 1.4 M(Earth) for CoRoT 7c. An estimation of the variation of the radial velocity of the star due to its activity is also given. Conclusions. The results obtained with three different approaches agree to give higher masses than those in previous determinations. From the existing internal structure models they indicate that CoRoT-7b is a much denser super-Earth. The bulk density is 11 +/- 3.5 g cm(-3), so CoRoT-7b may be rocky with a large iron core.

NGC 7097: THE ACTIVE GALACTIC NUCLEUS AND ITS MIRROR, REVEALED BY PRINCIPAL COMPONENT ANALYSIS TOMOGRAPHY

Three-dimensional spectroscopy techniques are becoming more and more popular, producing an increasing number of large data cubes. The challenge of extracting information from these cubes requires the development of new techniques for data processing and analysis. We apply the recently developed technique of principal component analysis (PCA) tomography to a data cube from the center of the elliptical galaxy NGC 7097 and show that this technique is effective in decomposing the data into physically interpretable information. We find that the first five principal components of our data are associated with distinct physical characteristics. In particular, we detect a low-ionization nuclear-emitting region (LINER) with a weak broad component in the Balmer lines. Two images of the LINER are present in our data, one seen through a disk of gas and dust, and the other after scattering by free electrons and/or dust particles in the ionization cone. Furthermore, we extract the spectrum of the LINER, decontaminated from stellar and extended nebular emission, using only the technique of PCA tomography. We anticipate that the scattered image has polarized light due to its scattered nature.

Comparison Between Single-Diode Low-Level Laser Therapy (LLLT) and LED Multi-Diode (Cluster) Therapy (LEDT) Applications Before High-Intensity Exercise

Background Data and Objective: There is anecdotal evidence that low-level laser therapy (LLLT) may affect the development of muscular fatigue, minor muscle damage, and recovery after heavy exercises. Although manufacturers claim that cluster probes (LEDT) maybe more effective than single-diode lasers in clinical settings, there is a lack of head-to-head comparisons in controlled trials. This study was designed to compare the effect of single-diode LLLT and cluster LEDT before heavy exercise. Materials and Methods: This was a randomized, placebo-controlled, double-blind cross-over study. Young male volleyball players (n = 8) were enrolled and asked to perform three Wingate cycle tests after 4 x 30 sec LLLT or LEDT pretreatment of the rectus femoris muscle with either (1) an active LEDT cluster-probe (660/850 nm, 10/30mW), (2) a placebo cluster-probe with no output, and (3) a single-diode 810-nm 200-mW laser. Results: The active LEDT group had significantly decreased post-exercise creatine kinase (CK) levels (-18.88 +/- 41.48U/L), compared to the placebo cluster group (26.88 +/- 15.18U/L) (p < 0.05) and the active single-diode laser group (43.38 +/- 32.90U/L) (p<0.01). None of the pre-exercise LLLT or LEDT protocols enhanced performance on the Wingate tests or reduced post-exercise blood lactate levels. However, a non-significant tendency toward lower post-exercise blood lactate levels in the treated groups should be explored further. Conclusion: In this experimental set-up, only the active LEDT probe decreased post-exercise CK levels after the Wingate cycle test. Neither performance nor blood lactate levels were significantly affected by this protocol of pre-exercise LEDT or LLLT.

Search for Active Neutrino Disappearance Using Neutral-Current Interactions in the MINOS Long-Baseline Experiment

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between nu(mu) and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of nu(mu) oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from nu(e) appearance at the current experimental limit is also presented.

Active to Sterile Neutrino Mixing Limits from Neutral-Current Interactions in MINOS

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07 x 10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 +/- 28(stat) +/- 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing nu(mu) that may transition to nu(s) is found to be less than 22% at the 90% C.L.

Finding Quasi-Optimal Network Topologies for Information Transmission in Active Networks

This work clarifies the relation between network circuit (topology) and behaviour (information transmission and synchronization) in active networks, e.g. neural networks. As an application, we show how one can find network topologies that are able to transmit a large amount of information, possess a large number of communication channels, and are robust under large variations of the network coupling configuration. This theoretical approach is general and does not depend on the particular dynamic of the elements forming the network, since the network topology can be determined by finding a Laplacian matrix (the matrix that describes the connections and the coupling strengths among the elements) whose eigenvalues satisfy some special conditions. To illustrate our ideas and theoretical approaches, we use neural networks of electrically connected chaotic Hindmarsh-Rose neurons.

Active waveguide effects from porous anodic alumina: An optical sensor proposition

We present in this paper an active waveguide effect observed in porous anodic alumina (PA), which can be applied in optical sensors. The spectral position, shape, and polarization effect of the narrow waveguide modes is described. An analytical test with a commercial pesticide was performed. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3447375]

Three-dimensional fabrication of optically active microstructures containing an electroluminescent polymer

Microfabrication via two-photon absorption polymerization is a technique to design complex microstructures in a simple and fast way. The applications of such structures range from mechanics to photonics to biology, depending on the dopant material and its specific properties. In this paper, we use two-photon absorption polymerization to fabricate optically active microstructures containing the conductive and luminescent polymer poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV). We verify that MEH-PPV retains its optical activity and is distributed throughout the microstructure after fabrication. The microstructures retain the emission characteristics of MEH-PPV and allow waveguiding of locally excited fluorescence when fabricated on top of low refractive index substrates. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3232207]