Event-chain Monte Carlo simulations of the liquid to solid transition of two-dimensional decagonal colloidal quasicrystals.

In event-chain Monte Carlo simulations, we model colloidal particles in two dimensions that interact according to an isotropic short-ranged pair potential which supports the two typical length scales present in decagonal quasicrystals. We investigate the assembled structures as we vary the density and temperature. Our special interest is related to the transition from quasicrystal to liquid. In contrast to the KTHNY melting theory for quasicrystals which predicts an intermediate pentahedratic phase, we find a one-step first-order melting transition. However, we discover that the slow relaxation of phasonic flips, i.e. rearrangements of the particles due to additional degrees of freedom in quasicrystals, changes the positional correlation functions, to the extent that structures with long-range orientational correlations, but exponentially decaying positional correlations, are observed.

Dislocation-free growth of quasicrystals from two seeds due to additional phasonic degrees of freedom.

We explore the growth of two-dimensional quasicrystals, i.e., aperiodic structures that possess long-range order, from two seeds at various distances and with different orientations by using dynamical phase-field crystal calculations. We compare the results to the growth of periodic crystals from two seeds. There, a domain border consisting of dislocations is observed in case of large distances between the seed and large angles between their orientation. Furthermore, a domain border is found if the seeds are placed at a distance that does not fit to the periodic lattice. In the case of the growth of quasicrystals, we only observe domain borders for large distances and different orientations. Note that all distances do inherently not match to a perfect domain wall-free quasicrystalline structure. Nevertheless, we find dislocation-free growth for all seeds at a small enough distance and for all seeds that approximately have the same orientation. In periodic structures, the stress that occurs due to incommensurate distances between the seeds results in phononic strain fields or, in the case of too large stresses, in dislocations. In contrast, in quasicrystals an additional phasonic strain field can occur and suppress dislocations. Phasons are additional degrees of freedom that are unique to quasicrystals. As a consequence, the additional phasonic strain field helps to distribute the stress and facilitates the growth of dislocation-free quasicrystals from multiple seeds. In contrast, in the periodic case the growth from multiple seeds most likely leads to a structure with multiple domains. Our work lays the theoretical foundations for growing perfect quasicrystals from different seeds and is therefore relevant for many applications.

Detection of phonon and phason modes in intrinsic colloidal quasicrystals by reconstructing their structure in hyperspace.

Phasons are additional degrees of freedom which occur in quasicrystals alongside the phonons known from conventional periodic crystals. The rearrangements of particles that are associated with a phason mode are hard to interpret in physical space. We reconstruct the quasicrystal structure by an embedding into extended higher-dimensional space, where phasons correspond to displacements perpendicular to the physical space. In dislocation-free decagonal colloidal quasicrystals annealed with Brownian dynamics simulations, we identify thermal phonon and phason modes. Finite phononic strain is pinned by phasonic excitations even after cooling down to zero temperature. For the phasonic displacements underlying the flip pattern, the reconstruction method gives an approximation within the limits of a multi-mode harmonic ansatz, and points to fundamental limitations of a harmonic picture for phasonic excitations in intrinsic colloidal quasicrystals.

CEA response is associated with tumor response and survival in patients with KRAS exon 2 wild-type and extended RAS wild-type metastatic colorectal cancer receiving first-line FOLFIRI plus cetuximab or bevacizumab (FIRE-3 trial).

BACKGROUND: To examine the relation of carcinoembryonic antigen (CEA) response with tumor response and survival in patients with (K)RAS wild-type metastatic colorectal cancer receiving first-line chemotherapy in the FIRE-3 trial comparing FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab. PATIENTS AND METHODS: CEA response assessed as the percentage of CEA decrease from baseline to nadir was evaluated for its association with tumor response and survival. Receiver operating characteristic analysis revealed an optimal cut-off value of 75% using the maximum of sensitivity and specificity for CEA response to discriminate CEA responders from non-responders. In addition, the time to CEA nadir was calculated. RESULTS: Of 592 patients in the intent-to-treat population, 472 were eligible for analysis of CEA (cetuximab arm: 230 and bevacizumab arm: 242). Maximal relative CEA decrease (%) significantly (P = 0.003) differed between the cetuximab arm (median 83.0%; IQR 40.9%-94.7%) and the bevacizumab arm (median 72.3%; IQR 26.3%-91.0%). In a longitudinal analysis, the CEA decrease occurred faster in the cetuximab arm and was greater than in the bevacizumab arm at all evaluated time points until 56 weeks after treatment start. CEA nadir occurred after 3.3 months (cetuximab arm) and 3.5 months (bevacizumab arm), (P = 0.49). In the cetuximab arm, CEA responders showed a significantly longer progression-free survival [11.8 versus 7.4 months; hazard ratio (HR) 1.53; 95% Cl, 1.15-2.04; P = 0.004] and longer overall survival (36.6 versus 21.3 months; HR 1.73; 95% Cl, 1.24-2.43; P = 0.001) than CEA non-responders. Analysis of extended RAS wild-type patients revealed similar results. CONCLUSION: In the FIRE-3 trial, CEA decrease was significantly faster and greater in the cetuximab arm than in the bevacizumab arm and correlated with the prolonged survival observed in patients receiving FOLFIRI plus cetuximab. CLINICAL TRIALS NUMBER: NCT00433927 (ClinicalTrials.gov); AIO KRK0306 FIRE-3.