Adaptive Optimal Designs for Dose-Finding Studies with Time-to-Event Outcomes

We consider optimal design problems for dose-finding studies with censored Weibull time-to-event outcomes. Locally D-optimal designs are investigated for a quadratic dose–response model for log-transformed data subject to right censoring. Two-stage adaptive D-optimal designs using maximum likelihood estimation (MLE) model updating are explored through simulation for a range of different dose–response scenarios and different amounts of censoring in the model. The adaptive optimal designs are found to be nearly as efficient as the locally D-optimal designs. A popular equal allocation design can be highly inefficient when the amount of censored data is high and when the Weibull model hazard is increasing. The issues of sample size planning/early stopping for an adaptive trial are investigated as well. The adaptive D-optimal design with early stopping can potentially reduce study size while achieving similar estimation precision as the fixed allocation design.     

Correction to: Closed‑suction drainage in thoracolumbar spinal surgery–clinical routine without evidence? a systematic review

European Spine Journal -     

The Formation of Cr-Al Spinel under a Reductive Atmosphere

In the present work, for the first time, the possibility of formation of CrAl₂O₄ was shown from the equimolar mixture of co-precipitated Al₂O₃ and Cr₂O₃ oxides under a reductive environment. The crystallographic properties of the formed compound were calculated using the DICVOL procedure. It was determined that it has a cubic crystal structure with space group Fd-3m and a unit cell parameter equal to 8.22(3) Å. The formed CrAl₂O₄ is not stable under ambient conditions and easily undergoes oxidation to α-Al₂O₃ and α-Cr₂O₃. The overall sequence of the phase transformations of co-precipitated oxides leading to the formation of spinel structure is proposed.     

Assessment of Technological Capabilities for Forming Al-C-B System Coatings on Steel Surfaces by Electrospark Alloying Method

In this paper, the possibility of applying the electrospark alloying (ESA) method to obtain boron-containing coatings characterised by increased hardness and wear resistance is considered. A new method for producing such coatings is proposed. The method consists in applying grease containing aluminium powder and amorphous boron to the surface to be treated and subsequently processing the obtained surface using the ESA method by a graphite electrode. The microstructural analysis of the Al-C-B coatings on steel C40 showed that the surface layer consists of several zones, the number and parameters of which are determined by the energy conditions of the ESA process. Durametric studies showed that with an increase in the discharge energy influence, the microhardness values of both the upper strengthened layer and the diffusion zone increased to W_p = 0.13 J, Hµ = 6487 MPa, and W_p = 4.9 J, Hµ = 12350 MPa, respectively. The results of X-ray diffraction analysis indicate that at the discharge energies of 0.13 and 0.55 J, the phase composition of the coating is represented by solid solutions of body-centred cubic lattice (BCC) and face-centred cubic lattice (FCC). The coatings obtained at W_p = 4.9 J were characterised by the presence of intermetallics Fe₄Al₁₃ and borocementite Fe₃ (CB) in addition to the solid solutions. The X-ray spectral analysis of the obtained coatings indicated that during the electrospark alloying process, the surface layers were saturated with aluminium, boron, and carbon. With increasing discharge energy, the diffusion zone increases; during the ESA process with the use of the discharge energy of 0.13 J for steel C40, the diffusion zone is 10–15 μm. When replacing a substrate made of steel C40 with the same one material but of steel C22, an increase in the thickness of the surface layer accompanied by a slight decrease in microhardness is observed as a result of processing with the use of the ESA method. There were simulated phase portraits of the Al-C-B coatings. It is shown that near the stationary points in the phase portraits, one can see either a slowing down of the evolution or a spiral twisting of the diffusion-process particle.     

Ligand binding and protein dynamics in neuroglobin

Neuroglobin (Ngb) is a recently discovered protein in vertebrate brain tissue that belongs to the globin family of proteins. It has been implicated in the neuronal response to hypoxia or ischemia, although its physiological role has been hitherto unknown. Ngb is hexacoordinate in the ferrous deoxy form under physiological conditions. To bind exogenous ligands like O(2) and CO, the His E7 endogenous ligand is displaced from the sixth coordination. By using infrared spectroscopy and nanosecond time-resolved visible spectroscopy, we have investigated the ligand-binding reaction over a wide temperature range (3-353 K). Multiple, intrinsically heterogeneous distal heme pocket conformations exist in NgbCO. Photolysis at cryogenic temperatures creates a five-coordinate deoxy species with very low geminate-rebinding barriers. The photodissociated CO is observed to migrate within the distal heme pocket even at 20 K. Flash photolysis near physiological temperature (275-353 K) exhibits four sequential kinetic features: (i) geminate rebinding (t < 1 micros); (ii) extremely fast bimolecular exogenous ligand binding (10 micros < t < 1 ms) with a nontrivial temperature dependence; (iii) endogenous ligand binding (100 micros < t < 10 ms), which can be studied by using flash photolysis on deoxy Ngb; and (iv) displacement of the endogenous by the exogenous ligand (10 ms < t < 10 ks). All four processes are markedly nonexponential, suggesting that Ngb fluctuates among different conformations on surprisingly long time scales.