The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based ...therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC.
Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis.
Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% 95% confidence interval (CI) 17.2–34.4 for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2–30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89–9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62–9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74–1.36). The response rates were 49.1% (95% CI 39.7–58.6) and 45.9% (95% CI 36.4–55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%).
No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity.
NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.
When fractionation of meat lipids is not required, procedures such as saponification can be used to extract total fatty acids, reducing reliance on toxic organic compounds. However, saponification of ...muscle fatty acids is laborious, and requires extended heating times, and a second methylation step to convert the extracted fatty acids to fatty acid methyl esters prior to gas chromatography. Therefore the development of a more rapid direct methylation procedure would be of merit. The use of freeze-dried material for analysis is common and allows for greater homogenisation of the sample. The present study investigated the potential of using freeze-dried muscle samples and a direct bimethylation to analyse total fatty acids of meat (beef, chicken and lamb) in comparison with a saponification procedure followed by bimethylation. Both methods compared favourably for all major fatty acids measured. There was a minor difference in relation to the C18:1 trans 10 isomer with a greater (P<0.05) recovery with saponification. However, numerically the difference was small and likely as a result of approaching the limits of isomer identification by single column gas chromatography. Differences (P<0.001) between species were found for all fatty acids measured with no interaction effects. The described technique offers a simplified, quick and reliable alternative to saponification to analyse total fatty acids from muscle samples.
Park JK, Nam SH, Kwon HC, Mohamed AAH, Lee JK, Kim GC. Feasibility of nonthermal atmospheric pressure plasma for intracoronal bleaching. International Endodontic Journal, 44, 170–175, 2011.
Aim To ...investigate the effect of nonthermal atmospheric pressure plasma on intracoronal tooth bleaching in blood stained human teeth.
Methodology Forty extracted single‐root and blood stained human teeth were used. The teeth were randomly divided into two groups (n = 20): group 1 received 30% HP activated by nonthermal atmospheric pressure plasma in the pulp chamber for 30 min, whilst group 2 received 30% HP alone in the pulp chamber for 30 min. The overall colour changes (ΔE) were assessed using the Commission Internationale de L’Eclairage (CIE) Lab Colour System. The data were analysed using Student’s t‐test to determine the significant differences.
Results The temperature of all teeth was maintained at approximately 37 °C during plasma bleaching. The plasma treatment with 30% HP resulted in significantly higher bleaching efficacy compared to 30% HP alone in discoloured teeth (P < 0.05). The average ΔE values of group 1 and group 2 were 9.24 (0.37) and 4.47 (1.62), respectively, at 30 min.
Conclusions The application of nonthermal atmospheric pressure plasma to intracoronal bleaching could be a novel and efficient therapy in the bleaching of haemorrhagically stained teeth.
Purpose: The protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly ...used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date. Methods: We examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes. Results: We compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression. Conclusion: This study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems. Keywords: protein Corona, atopic dermatitis, mesoporous silica, colloidal silica, claudin-1, immunotoxicity
We report the results of a search for the B → Y ( 4260 ) K , Y ( 4260 ) → J / ψπ+π- decays. This study is based on a data sample corresponding to an integrated luminosity of 711 fb-1 , collected at ...the Υ ( 4S ) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We investigate the J / ψπ+π- invariant mass distribution in the range 4.0 to 4.6 GeV/c2 using both B+ → J / ψπ+π-K+ and B0 → J / ψπ+π-KS0 decays. We find excesses of events above the background levels, with significances of 2.1 and 0.9 standard deviations for charged and neutral B → Y ( 4260 ) K decays, respectively, taking into account the systematic uncertainties. These correspond to upper limits on the product of branching fractions, B ( B+ → Y ( 4260 ) K+ ) × B ( Y ( 4260 ) → J / ψπ+π- ) <1.4×10-5 and B ( B0 → Y ( 4260 ) K0 ) × B ( Y ( 4260 ) → J / ψπ+π- ) <1.7×10-5 at the 90% confidence level.
In four patients with rotational vertebral artery syndrome (RVAS), the initial nystagmus was mostly downbeat, with the horizontal and torsional components beating toward the compressed vertebral ...artery side (n = 3) or directed away (n = 1). Three patients showed spontaneous reversal of the nystagmus and two exhibited no or markedly diminished responses on immediate retrial of head rotation (habituation). The patterns of nystagmus suggest that RVAS may result from differing mechanisms.
Abstract
Nonlinear 3D MHD simulations and validations reveal that the hybrid particle-MHD transport is a key process for driving the pump-out in the presence of Resonant Magnetic Perturbations (RMPs) ...in the KSTAR tokamak. Particle transport and the resulting density pump-out by RMPs are shown to be composed of not only the classical flow convection near magnetic islands due to polarization but also the neoclassical ion diffusion across perturbed magnetic surfaces. The latter is known as the Neoclassical Toroidal Viscosity (NTV) and is integrated into nonlinear MHD simulations here for the first time, revealing that the two-stage pump-outs observed in KSTAR experiments are reproduced only with such integrated nonlinear MHD and transport evolution. Near-resonant responses, which have received less attention than the resonant response, play distinct roles in the pump-out along with the island formation. In addition, this modeling is used to investigate the pump-outs in double-null-like plasmas and numerically capture the effect of the double-null shape on the pump-outs, which may explain the difficulty of Edge Localized Mode (ELM) suppression access in double-like plasmas. This reveals new aspects of the impact toroidal geometry and mode coupling have on 3D physics and reveals the importance of near-resonant components in suppressing ELMs.
Magnesium alloy sheets have been extending their field of applications to automotive and electronic industries taking advantage of their excellent light weight property. In addition to well-known ...lower formability, magnesium alloys have unique mechanical properties which have not been thoroughly studied: high in-plane anisotropy/asymmetry of yield stress and hardening response. The reason of the unusual mechanical behavior of magnesium alloys has been understood by the limited symmetry crystal structure of HCP metals and thus by deformation twinning. In this paper, the phenomenological continuum plasticity models considering the unusual plastic behavior of magnesium alloy sheet were developed for a finite element analysis. A hardening law based on two-surface model was further extended to consider the general stress–strain response of metal sheets including Bauschinger effect, transient behavior and the unusual asymmetry. Three deformation modes observed during the continuous in-plane tension/compression tests were mathematically formulated with simplified relations between the state of deformation and their histories. In terms of the anisotropy and asymmetry of the initial yield stress, the Drucker–Prager’s pressure dependent yield surface was modified to include the anisotropy of magnesium alloy. The numerical formulations and characterization procedures were also presented and finally the correlation of simulation with measurements was performed to validate the proposed theory.
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding ...proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.
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