Effect of Application and Intensity of Bevacizumab-based Maintenance After Induction Chemotherapy With Bevacizumab for Metastatic Colorectal Cancer: A Meta-analysis

BACKGROUND: The administration and intensity of bevacizumab-based maintenance therapy after induction treatment with bevacizumab is still a matter of debate. Thus, the present meta-analysis and an indirect comparison were performed to clarify these issues. PATIENTS AND METHODS: Trials evaluating a separately defined "maintenance phase," with randomization after the induction phase, were selected. Three trials of maintenance with bevacizumab with or without a fluoropyrimidine (CAIRO3, SAKK 41/06, and AIO KRK 0207) were analyzed regarding the effect on progression-free survival (PFS) and overall survival (OS) of any maintenance therapy compared with observation alone and different maintenance intensities (bevacizumab with or without fluoropyrimidine) compared with observation alone and between each other. RESULTS: Maintenance with bevacizumab with or without fluoropyrimidine after bevacizumab-based induction treatment for 4 to 6 months significantly improved PFS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.75; P = .0004) and showed a trend toward prolonged OS (HR, 0.89; 95% CI, 0.78-1.02; P = .09) compared with observation alone. The effect on PFS increased with the intensity of the maintenance regimen (HR, 0.72; 95% CI, 0.60-0.85 for single-agent bevacizumab vs. HR, 0.45; 95%, CI 0.39-0.51 for combination therapy, both compared to observation alone). In contrast, the HRs for OS remained in the same range. A similarly improved PFS (HR, 0.63; 95% CI, 0.50-0.79) was shown for the more intensive maintenance therapy (bevacizumab and fluoropyrimidine) compared with bevacizumab alone. CONCLUSION: Bevacizumab-based maintenance therapy after induction chemotherapy with bevacizumab significantly improves PFS and showed a trend toward prolonged OS and should thus be considered, in particular, in patients with a response to induction treatment

Inertia compensation while scanning screw threads on coordinate-measuring machines

Usage of scanning coordinate-measuring machines for inspection of screw threads has become a common practice nowadays. Compared to touch trigger probing, scanning capabilities allow to speed up measuring process while still maintaining high accuracy. However, in some cases accuracy drasticaly depends on the scanning speed. In this paper a compensation method is proposed allowing to reduce the influence of some dynamic effects while scanning screw threads on coordinate-measuring machines

Can natural flavorings enhance the flavor of low-fat ground beef?

Natural flavorings were evaluated for use in low-fat ground beef, which frequently lacks flavor intensity. Three lean sources, A-maturity (young), E-maturity (mature cow), and imported (cow) beef round muscles, were used to formulate 7% and 25% fat ground beef. A-maturity fat was added to adjust fat levels. Controls (no added flavors) were prepared for each lean source. No additives were used in 25% fat controls, but 7% fat controls contained water (10%), carrageenan (.5%), and encapsulated salt (.38%). Four natural flavorings; Dried Cream Extract (DCE, Cumberland Packing Co., Inc.); Natural Prime Beef Base WONF #224545 and #224546 (224545, 224546, Tastemaker); and Hydrolyzed Vegetable Protein (HVP, A.C. Legg, Inc.) were added to 7% fat ground beef at recommended levels. A- and E-maturity domestic 25% fat controls were scored higher (P\u3c.05) for ground beef flavor intensity and lower (P\u3c.05) for off-flavors than 25% fat patties from imported beef. The 7% fat patties from imported lean had greater (P\u3c.05) beef flavor intensity and reduced off-flavors (P\u3c.05) when flavorings 224545, 224546, and HVP were added. These flavorings also enhanced the beef flavor intensity of low-fat patties from A-maturity lean to a level similar to that of the 25% fat control. Beef flavor intensity after a 60-min holding period was not enhanced by the natural flavorings, except when 224546 was added to E-maturity domestic lean. Therefore, the natural flavorings were most beneficial with imported lean

Solar neutrino-electron scattering as background limitation for double beta decay

The background on double beta decay searches due to elastic electron scattering of solar neutrinos of all double beta emitters with Q-value larger than 2 MeV is calculated, taking into account survival probability and flux uncertainties of solar neutrinos. This work determines the background level to be [1-2]E-7 counts /keV/kg/yr, depending on the precise Q-value of the double beta emitter. It is also shown that the background level increases dramatically if going to lower Q-values. Furthermore, studies are done for various detector systems under consideration for next generation experiments. It was found that experiments based on loaded liquid scintillator have to expect a higher background. Within the given nuclear matrix element uncertainties any approach exploring the normal hierarchy has to face this irreducible background, which is a limitation on the minimal achievable background for purely calorimetric approaches. Large scale liquid scintillator experiments might encounter this problem already while exploring the inverted hierarchy. Potential caveats by using more sophisticated experimental setups are also discussed

Myocardial T(1) and T(2) mapping at 3 T: reference values, influencing factors and implications

BACKGROUND: Myocardial T1 and T2 mapping using cardiovascular magnetic resonance (CMR) are promising to improve tissue characterization and early disease detection. This study aimed at analyzing the feasibility of T1 and T2 mapping at 3 T and providing reference values. METHODS: Sixty healthy volunteers (30 males/females, each 20 from 20--39 years, 40--59 years, 60--80 years) underwent left-ventricular T1 and T2 mapping in 3 short-axis slices at 3 T. For T2 mapping, 3 single-shot steady-state free precession (SSFP) images with different T2 preparation times were acquired. For T1 mapping, modified Look-Locker inversion recovery technique with 11 single shot SSFP images was used before and after injection of gadolinium contrast. T1 and T2 relaxation times were quantified for each slice and each myocardial segment. RESULTS: Mean T2 and T1 (pre-/post-contrast) times were: 44.1 ms/1157.1 ms/427.3 ms (base), 45.1 ms/1158.7 ms/411.2 ms (middle), 46.9 ms/1180.6 ms/399.7 ms (apex). T2 and pre-contrast T1 increased from base to apex, post-contrast T1 decreased. Relevant inter-subject variability was apparent (scatter factor 1.08/1.05/1.11 for T2/pre-contrast T1/post-contrast T1). T2 and post-contrast T1 were influenced by heart rate (p < 0.0001, p = 0.0020), pre-contrast T1 by age (p < 0.0001). Inter- and intra-observer agreement of T2 (r = 0.95; r = 0.95) and T1 (r = 0.91; r = 0.93) were high. T2 maps: 97.7% of all segments were diagnostic and 2.3% were excluded (susceptibility artifact). T1 maps (pre-/post-contrast): 91.6%/93.9% were diagnostic, 8.4%/6.1% were excluded (predominantly susceptibility artifact 7.7%/3.2%). CONCLUSIONS: Myocardial T2 and T1 reference values for the specific CMR setting are provided. The diagnostic impact of the high inter-subject variability of T2 and T1 relaxation times requires further investigation

Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart

Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901. Differentiated PCs became more proangiogenic, more responsive to vasoactive agents, and insensitive to chemoattractants. RNA sequencing revealed transcripts marking the PD0325901-induced transition into proangiogenic, stationary VSMC-like cells, including the unique expression of 2 angiogenesis-related markers, aquaporin 1 (AQP1) and cellular retinoic acid–binding protein 2 (CRABP2), which were further verified at the protein level. This enabled us to trace PCs during in vivo studies. In mice, implantation of Matrigel plugs containing human PCs plus PD0325901 promoted the formation of αSMA(+) neovessels compared with PC only. Two-week oral administration of PD0325901 to mice increased the heart arteriolar density, total vascular area, arteriole coverage by PDGFRβ(+)AQP1(+)CRABP2(+) PCs, and myocardial perfusion. Short-duration PD0325901 treatment of mice after myocardial infarction enhanced the peri-infarct vascularization, reduced the scar, and improved systolic function. In conclusion, myocardial PCs have intrinsic plasticity that can be pharmacologically modulated to promote reparative vascularization of the ischemic heart

On the Development of a New Nonequilibrium Chemistry Model for Mars Entry

This paper represents a summary of results to date of an on-going effort at NASA Ames Research Center to develop a physics-based non-equilibrium model for hypersonic entry into the Martian atmosphere. Our approach is to first compute potential energy surfaces based on accurate solutions of the electronic Schroedinger equation and then use quasiclassical trajectory calculations to obtain reaction cross sections and rate coefficients based on these potentials. We have presented new rate coefficients for N2 dissociation and CO dissociation and exchange reactions. These results illustrate shortcomings with some of the rate coefficients in Parks original T-Tv model for Mars entries and with some of the 30-45 year old shock tube data. We observe that the shock tube experiments of CO + O dissociation did not adequately account for the exchange reaction that leads to formation of C + O2. This reaction is actually the primary channel for CO removal in the shock layer at temperatures below 10,000 K, because the reaction enthalpy for exchange is considerably lower than the comparable value for dissociation

Identification of the Beutler-Fano formula in eigenphase shifts and eigentime delays near a resonance

Eigenphase shifts and eigentime delays near a resonance for a system of one discrete state and two continua are shown to be functionals of the Beutler- Fano formulas using appropriate dimensionless energy units and line profile indices. Parameters responsible for the avoided crossing of eigenphase shifts and eigentime delays are identified. Similarly, parameters responsible for the eigentime delays due to a frame change are identified. With the help of new parameters, an analogy with the spin model is pursued for the S matrix and time delay matrix. The time delay matrix is shown to comprise three terms, one due to resonance, one due to a avoided crossing interaction, and one due to a frame change. It is found that the squared sum of time delays due to the avoided crossing interaction and frame change is unity.Comment: 17 pages, 3 figures, RevTe