The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, 'Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients'.

BACKGROUND: The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged. RESULTS: Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E's impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms. CONCLUSIONS: Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E's excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.

Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer.

PURPOSE: Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. PATIENTS AND METHODS: Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. RESULTS: Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. CONCLUSION: Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

On the role of molecular clustering on infrared absorption line shapes of acetylene in a supersonic expansion

A supersonic expansion containing acetylene seeded into Ar and produced from a circular nozzle is investigated using CW/cavity ring down spectroscopy, in the 1.5 μm range. The results, also involving experiments with pure acetylene and acetylene-He expansions, as well as slit nozzles, demonstrate that the denser central section in the expansion is slightly heated by the formation of acetylene aggregates, resulting into a dip in the monomer absorption line profiles. Acetylene-Ar aggregates are also formed at the edge of the circular nozzle expansion cone. © 2008 Elsevier B.V. All rights reserved.

Investigation of the shape of the R(0) absorption line in ν3, N2O recorded from an axisymmetric supersonic free jet expansion

The hydrodynamic structure of an axisymmetric supersonic expansion can be regarded as a series of concentric divergent cones, with decreasing particle densities as the cone angle increases. Different groups of molecules therefore contribute to high-resolution absorption line shapes when optically probing the expansion in a direction perpendicular to the jet axis. These groups are distinguished by the cone angle, inducing a specific Doppler shift, and by the particle density, contributing a specific weight to the absorption intensity. As a result different broader line profiles are observed compared to room temperature spectra. This effect is investigated here selecting as the working example the R(0), ν3 absorption line in N2O recorded using a Fourier transform interferometer. Independent impact pressure and quadrupole mass spectrometric measurements are performed leading to two complementary maps of the expansion, allowing the recorded absorption line shape to be quantitatively modeled. © 2006 Elsevier Ltd. All rights reserved.

Water vapor line parameters in the 13 000-9250 cm-1 region.

info:eu-repo/semantics/published

Scientific writing: a randomized controlled trial comparing standard and on-line instruction.

BACKGROUND: Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in researcher education, ultimately determining the success and long-term sustainability of their careers. Despite the growing popularity of e-learning, we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing. METHODS: Forty eight participants from a medical, nursing and physiotherapy background from US and Brazil were randomly assigned to two groups (n = 24 per group): An on-line writing workshop group (on-line group), in which participants used virtual communication, google docs and standard writing templates, and a standard writing guidance training (standard group) where participants received standard instruction without the aid of virtual communication and writing templates. Two outcomes, manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure, and satisfaction scores with Likert scale were evaluated. To control for observer variability, inter-observer reliability was assessed using Fleiss's kappa. A post-hoc analysis comparing rates of communication between mentors and participants was performed. Nonparametric tests were used to assess intervention efficacy. RESULTS: Excellent inter-observer reliability among three reviewers was found, with an Intraclass Correlation Coefficient (ICC) agreement = 0.931882 and ICC consistency = 0.932485. On-line group had better overall manuscript quality (p = 0.0017, SSQSavg score 75.3 +/- 14.21, ranging from 37 to 94) compared to the standard group (47.27 +/- 14.64, ranging from 20 to 72). Participant satisfaction was higher in the on-line group (4.3 +/- 0.73) compared to the standard group (3.09 +/- 1.11) (p = 0.001). The standard group also had fewer communication events compared to the on-line group (0.91 +/- 0.81 vs. 2.05 +/- 1.23; p = 0.0219). CONCLUSION: Our protocol for on-line scientific writing instruction is better than standard face-to-face instruction in terms of writing quality and student satisfaction. Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different languages.

Reference groups and product line decisions: An experimental investigation of limited editions and product proliferation

Some luxury goods manufacturers offer limited editions of their products, whereas some others market multiple product lines. Researchers have found that reference groups shape consumer evaluations of these product categories. Yet little empirical research has examined how reference groups affect the product line decisions of firms. Indeed, in a field setting it is quite a challenge to isolate reference group effects from contextual effects and correlated effects. In this paper, we propose a parsimonious model that allows us to study how reference groups influence firm behavior and that lends itself to experimental analysis. With the aid of the model we investigate the behavior of consumers in a laboratory setting where we can focus on the reference group effects after controlling for the contextual and correlated effects. The experimental results show that in the presence of strong reference group effects, limited editions and multiple products can help improve firms' profits. Furthermore, the trends in the purchase decisions of our participants point to the possibility that they are capable of introspecting close to two steps of thinking at the outset of the game and then learning through reinforcement mechanisms. © 2010 INFORMS.

Far-field analysis of axially symmetric three-dimensional directional cloaks.

Axisymmetric radiating and scattering structures whose rotational invariance is broken by non-axisymmetric excitations present an important class of problems in electromagnetics. For such problems, a cylindrical wave decomposition formalism can be used to efficiently obtain numerical solutions to the full-wave frequency-domain problem. Often, the far-field, or Fraunhofer region is of particular interest in scattering cross-section and radiation pattern calculations; yet, it is usually impractical to compute full-wave solutions for this region. Here, we propose a generalization of the Stratton-Chu far-field integral adapted for 2.5D formalism. The integration over a closed, axially symmetric surface is analytically reduced to a line integral on a meridional plane. We benchmark this computational technique by comparing it with analytical Mie solutions for a plasmonic nanoparticle, and apply it to the design of a three-dimensional polarization-insensitive cloak.

Expression of the Ets transcription factor Erm is regulated through a conventional PKC signaling pathway in the Molt4 lymphoblastic cell line.

Erm, a member of the PEA3 group within the Ets family of transcription factors, is expressed in murine and human lymphocytes. Here, we show that in the human Molt4 lymphoblastic cell line, the erm gene expression is regulated by the conventional PKC (cPKC) pathway. To better characterize the molecular mechanism by which cPKC regulates Erm transcription in Molt4 cells, we tested proximal promoter deletions of the human gene, and identified a specific cPKC-regulated region between positions -420 and -115 upstream of the first exon.

Absolute line intensities for formic acid and dissociation constant of the dimer

Absolute line intensities in the v6 and v8 interacting bands of trans-HCOOH, observed near 1105.4 and 1033.5 cm -1, respectively, and the dissociation constant of the formic acid dimer (HCOOH)2 have been measured using Fourier transform spectroscopy at a resolution of 0.002 cm-1. Eleven spectra of formic acid, at 296.0(5) K and pressures ranging from 14.28(25) to 314.0(24) Pa, have been recorded between 600 and 1900 cm-1 with an absorption path length of 19.7(2) cm. 437 integrated absorption coefficients have been measured for 72 lines in the v6 band. Analysis of the pressure dependence yielded the dissociation constant of the formic acid dimer, k p=361(45) Pa, and the absolute intensity of the 72 lines of HCOOH. The accuracy of these results was carefully estimated. The absolute intensities of four lines of the weak v8 band were also measured. Using an appropriate theory, the integrated intensity of the v6 and v 8 bands was determined to be 3.47 × 1017 and 4.68 × 10-19 cm-1/(molecule cm-1) respectively, at 296 K. Both the dissociation constant and integrated intensities were compared to earlier measurements. © 2007 American Institute of Physics.

On-line algorithms for single machine scheduling with family setup times

The paper considers an on-line single machine scheduling problem where the goal is to minimize the makespan. The jobs are partitioned into families and a setup is performed every time the machine starts processing a batch of jobs of the same family. The scheduler is aware of the number of families and knows the setup time of each family, although information about a job only becomes available when that job is released. We give a lower bound on the competitive ratio of any on-line algorithm. Moreover, for the case of two families, we provide an algorithm with a competitive ratio that achieves this lower bound. As the number of families increases, the lower bound approaches 2, and we give a simple algorithm with a competitive ratio of 2.