64 research outputs found
PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study
BACKGROUND: This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference
trastuzumab (HerceptinÂź) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line
treatment for HER2-positive metastatic breast cancer.
METHODS: Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014
plus paclitaxel (PF-05280014 group; n = 352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n = 355). PF-05280014 or
trastuzumab-EU was administered weekly (first dose 4 mg/kg, subsequent doses 2 mg/kg), with the option to change to a 3-weekly
regimen (6 mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression.
Paclitaxel (starting dose 80 mg/m2
) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal
benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and
confirmed by Week 33, based on blinded central radiology review.
RESULTS: The risk ratio for ORR was 0.940 (95% CI: 0.842â1.049). The 95% CI fell within the pre-specified equivalence margin of
0.80â1.25. ORR was 62.5% (95% CI: 57.2â67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3â71.4%) in the trastuzumab-EU
group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences
between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU
group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety
outcomes and immunogenicity were similar between the treatment groups.
CONCLUSION: When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel
demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT0198967
Double-exchange model study of multiferroic MnO perovskites
In this proceeding, recent theoretical investigations by the authors on the
multiferroic MnO perovskites are briefly reviewed at first. Using the
double-exchange model, the realistic spiral spin order in undoped manganites
such as TbMnO and DyMnO is well reproduced by incorporating a weak
next-nearest neighbor superexchange ( of nearest neighbor
superexchange) and moderate Jahn-Teller distortion. The phase transitions from
the A-type antiferromagnet (as in LaMnO), to the spiral phase (as in
TbMnO), and finally to the E-type antiferromagnet (as in HoMnO), with
decreasing size of the ions, were also explained. Moreover, new results of
phase diagram of the three-dimensional lattice are also included. The
ferromagnetic tendency recently discovered in the LaMnO and TbMnO thin
films is explained by considering the substrate stress. Finally, the
relationship between our double-exchange model and a previously used
-- model is further discussed from the perspective of spin wave
excitations.Comment: 6 pages, 3 figures; Proceeding of the Workshop on Magnetoelectric
Interaction Phenomena in Crystals (MEIPIC-6); To be appeared in European
Physical Journal
Optimal Resting-Growth Strategies of Microbial Populations in Fluctuating Environments
Bacteria spend most of their lifetime in non-growing states which allow them to survive extended periods of stress and starvation. When environments improve, they must quickly resume growth to maximize their share of limited nutrients. Cells with higher stress resistance often survive longer stress durations at the cost of needing more time to resume growth, a strong disadvantage in competitive environments. Here we analyze the basis of optimal strategies that microorganisms can use to cope with this tradeoff. We explicitly show that the prototypical inverse relation between stress resistance and growth rate can explain much of the different types of behavior observed in stressed microbial populations. Using analytical mathematical methods, we determine the environmental parameters that decide whether cells should remain vegetative upon stress exposure, downregulate their metabolism to an intermediate optimum level, or become dormant. We find that cell-cell variability, or intercellular noise, is consistently beneficial in the presence of extreme environmental fluctuations, and that it provides an efficient population-level mechanism for adaption in a deteriorating environment. Our results reveal key novel aspects of responsive phenotype switching and its role as an adaptive strategy in changing environments
Neuer Kopf, alte Ideen? : "Normalisierung" des Front National unter Marine Le Pen
In this article, it is investigated
whether vibrational entropy
(VE) is an important contribution to the free energy of globular proteins
at ambient conditions. VE represents the major configurational-entropy
contribution of these proteins. By definition, it is an average of
the configurational entropies of the protein within single minima
of the energy landscape, weighted by their occupation probabilities.
Its large part originates from thermal motion of flexible torsion
angles giving rise to the finite peak widths observed in torsion angle
distributions. While VE may affect the equilibrium properties of proteins,
it is usually neglected in numerical calculations as its consideration
is difficult. Moreover, it is sometimes believed that all well-packed
conformations of a globular protein have similar VE anyway. Here, we measure explicitly the VE for six different conformations from simulation data of a test protein. Estimates
are obtained using the quasi-harmonic approximation for three coordinate
sets, Cartesian, bond-angle-torsion (BAT), and a new set termed rotamer-degeneracy
lifted BAT coordinates by us. The new set gives improved estimates
as it overcomes a known shortcoming of the quasi-harmonic approximation
caused by multiply populated rotamer states, and it may serve for
VE estimation of macromolecules in a very general context. The obtained
VE values depend considerably on the type of coordinates used. However,
for all coordinate sets we find large entropy differences between
the conformations, of the order of the overall stability of the protein.
This result may have important implications on the choice of free
energy expressions used in software for protein structure prediction,
protein design, and NMR refinement
Evidence for widespread hydrated minerals on asteroid (101955) Bennu
Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7â”m and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4â”m) Bennuâs spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth
The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements
The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennuâs surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennuâs surface has been most recently migrating towards its equator (given Bennuâs increasing spin rate), we infer that Bennuâs surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennuâs top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennuâs top-shape morphology and its link to the formation of binary asteroids
Sunitinib in metastatic renal cell carcinoma: An ethnic Asian subpopulation analysis for safety and efficacy
Aims: We evaluated and compared the safety and efficacy of sunitinib in Asian and non-Asian patients with metastatic renal cell carcinoma enrolled in a previously reported global expanded access program. Methods: Previously treated and treatment-naive patients received open-label sunitinib at a starting dose of 50 mg/day for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles. Safety was assessed regularly, tumor measurements were performed per local practice, and survival data collected where possible. Results: Data were available for 212 Asian patients from Asian sites (Asian-A), 113 Asian patients from non-Asian sites (Asian-O) and 4046 non-Asian patients. The most common grade 3/4 treatment-related adverse events were neutropenia, thrombocytopenia, hand-foot syndrome, diarrhea, asthenia and fatigue. The incidence of many adverse events was greater in Asian-A than in Asian-O or non-Asian patients. Sunitinib efficacy was comparable between Asian and non-Asian patients, with an objective response rate of 18% versus 14%; median progression-free survival of 8.7 versus 10.9 months; and overall survival of 18.9 versus 18.4 months, respectively. Conclusions: Sunitinib demonstrated tolerable safety and similar efficacy in Asian and non-Asian patients. Geographic differences in the reported frequency of specific adverse events were noted across Asian patients
Effects of SWCNTs on mechanical and thermal performance of epoxy at elevated temperatures
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