Efficacy of Anamorelin, a novel non-peptide ghrelin analogue, in patients with advanced non-small cell lung cancer (NSCLC) and Cachexia—Review and expert opinion

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy. The most beneficial approach is to target underlying systemic mechanisms, an approach where the novel non-peptide ghrelin analogue anamorelin has the advantage of stimulating appetite and possibly food intake, as well as promoting anabolism and significant muscle mass gain. In the ROMANA studies, compared with placebo, anamorelin significantly increased lean body mass in non-small cell lung cancer (NSCLC) patients. Body composition analysis suggested that anamorelin is an active anabolic agent in patients with NSCLC, without the side effects of other anabolic drugs. Anamorelin also induced a significant and meaningful improvement of anorexia/cachexia symptoms. The ROMANA trials have provided unprecedented knowledge, highlighting the therapeutic effects of anamorelin as an initial, but significant, step toward directly managing cancer cachexia

LIGO End-to-End simulation Program

A time-domain simulation program has been developed to provide an accurate description of interferometric gravitational wave detectors. This is being utilized to build a model of LIGO with the aim of aiding in the shakedown and integration of the interferometer subsystems, and ultimately the optimization of detector sensitivity

Rare radiative B decay to the orbitally excited K_2^*(1430) meson

The exclusive rare radiative B meson decay to the orbitally excited tensor K_2^*(1430) meson is investigated in the framework of the relativistic quark model based on the quasipotential approach in quantum field theory. The calculated branching ratio BR(B --> K_2^*(1430)\gamma)=(1.7\pm 0.6)\times 10^{-5} as well as the ratio BR(B --> K_2^*(1430)\gamma)/BR(B --> K^*(892)\gamma)=0.38\pm 0.08 is found in a good agreement with recent experimental data from CLEO.Comment: 10 pages, RevTe

Value of thrombin-antithrombin III complexes in major orthopedic surgery: relation to the onset of venous thromboembolism.

This study evaluated (a) the possible changes of plasma levels of thrombin-antithrombin III complexes during hospitalization to predict venous thromboembolism in patients undergoing elective total hip replacement and (b) the sensitivity and specificity of thrombin-antithrombin III complexes in the late incidence of deep vein thrombosis when these patients are discharged from the hospital. In 50 consecutive patients (18 men, mean age = 63 ± 8 years) a venous blood sample was obtained from each patient before surgery and postsurgery on days 5 ± 2, 9 ± 2, and 45 to evaluate the thrombin-antithrombin III complexes by the enzyme-linked immunosorbent assay as a part of a larger surveillance program. Six of 50 patients devel oped deep vein thrombosis, diagnosed by phlebography on the 45th day postsurgery. From the day before until the ninth day after surgery, mean values of the thrombin-antithrombin III complexes increased to a greater extent in patients with deep vein thrombosis than in those without, although the differences were not significant (from 14.8 ± 11.2 ng/mL to 36.2 ± 19.1 ng/mL in the former group and from 13.6 ± 3.3 ng/mL to 22.4 ± 5.1 ng/mL in the latter, p = NS). On the 45th day after surgery the mean value of the thrombin-antithrombin III com plexes reduced less in patients with deep vein thrombosis (up to 9.9 ± 1.9 ng/mL and to 25.2 ± 17.2 ng/mL, respectively, p = NS). In addition, thrombin-antithrombin III complexes re mained over the level reached on the fifth day only in the patients who developed deep vein thrombosis. On the 45th day after surgery, thrombin-antithrombin III complexes exhibited a sensitivity of 17%, a specificity of 86%, and an accuracy of 78% in differentiating the presence and absence of deep vein thrombosis as compared with phlebography. We conclude that after total hip replacement (a) serial measurement of the throm bin-antithrombin III complexes does not appear helpful in pre dicting venous thromboembolism during hospitalization, and (b) measurement of thrombin-antithrombin III complexes has a low diagnostic accuracy in diagnosing delayed deep vein thrombosis. However, the greater and persistent increase of thrombin-antithrombin III complexes level in patients who de veloped deep vein thrombosis may deserve further investiga tions

The impact of next and back buttons on time to complete and measurement reliability in computer-based surveys

To assess the impact of including next and back buttons on response burden and measurement reliability of computer-based surveys. A sample of 807 participants (mean age of 53; 64% women, 83% non-Hispanic white; 81% some college or college graduates) from the YouGov Polimetrix panel was administered 56 items assessing performance of social/role activities and 56 items measuring satisfaction with social/role activities. Participants were randomly assigned to either (1) automatic advance to the next question with no opportunity to go back (auto/no back); (2) automatic advance to the next questions with an opportunity to go back (auto/back); (3) next button to go to the next question with no opportunity to go back (next/no back); or (4) next button to go to the next question with an opportunity to go back (next/back). We found no difference in missing data, internal consistency reliability, and domain scores by group. Time to complete the survey was about 50% longer when respondents were required to use a next button to go on. Given the similarity in missing data, reliability and mean scale scores with or without use of the next button, we recommend automatic advancement to the next item with the option to go back to the previous item

Quantifying Protein Copy Number in Super-Resolution Using an Imaging Invariant Calibration

The use of super-resolution microscopy in recent years has revealed that proteins often form small assemblies inside cells and are organized in nanoclusters. However, determining the copy number of proteins within these nanoclusters constitutes a major challenge because of unknown labeling stoichiometries and complex fluorophore photophysics. We previously developed a DNA-origami-based calibration approach to extract protein copy number from super-resolution images. However, the applicability of this approach is limited by the fact that the calibration is dependent on the specific labeling and imaging conditions used in each experiment. Hence, the calibration must be repeated for each experimental condition, which is a formidable task. Here, using cells stably expressing dynein intermediate chain fused to green fluorescent protein (HeLa IC74 cells) as a reference sample, we demonstrate that the DNA-origami-based calibration data we previously generated can be extended to super-resolution images taken under different experimental conditions, enabling the quantification of any green-fluorescent-protein-fused protein of interest. To do so, we first quantified the copy number of dynein motors within nanoclusters in the cytosol and along the microtubules. Interestingly, this quantification showed that dynein motors form assemblies consisting of more than one motor, especially along microtubules. This quantification enabled us to use the HeLa IC74 cells as a reference sample to calibrate and quantify protein copy number independently of labeling and imaging conditions, dramatically improving the versatility and applicability of our approach

Rare radiative B decays to orbitally excited K mesons

The exclusive rare radiative B meson decays to orbitally excited axial-vector mesons K_1^*(1270), K_1(1400) and to the tensor meson K_2^*(1430) are investigated in the framework of the relativistic quark model based on the quasipotential approach in quantum field theory. These decays are considered without employing the heavy quark expansion for the s quark. Instead the s quark is treated to be light and the expansion in inverse powers of the large recoil momentum of the final K^{**} meson is used to simplify calculations. It is found that the ratio of the branching fractions of rare radiative B decays to axial vector K^*_1(1270) and K_1(1400) mesons is significantly influenced by relativistic effects. The obtained results for B decays to the tensor meson K_2^*(1430) agree with recent experimental data from CLEO.Comment: 17 pages, revte