Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke

BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin

Self-organised criticality in base-pair breathing in DNA with a defect

We analyse base-pair breathing in a DNA sequence of 12 base-pairs with a defective base at its centre. We use both all-atom molecular dynamics (MD) simulations and a system of stochastic differential equations (SDE). In both cases, Fourier analysis of the trajectories reveals self-organised critical behaviour in the breathing of base-pairs. The Fourier Transforms (FT) of the interbase distances show power-law behaviour with gradients close to -1. The scale-invariant behaviour we have found provides evidence for the view that base-pair breathing corresponds to the nucleation stage of large-scale DNA opening (or 'melting') and that this process is a (second-order) phase transition. Although the random forces in our SDE system were introduced as white noise, FTs of the displacements exhibit pink noise, as do the displacements in the AMBER/MD simulations.Comment: 18 pages, 8 figure

Exact sampling of self-avoiding paths via discrete Schramm-Loewner evolution

We present an algorithm, based on the iteration of conformal maps, that produces independent samples of self-avoiding paths in the plane. It is a discrete process approximating radial Schramm-Loewner evolution growing to infinity. We focus on the problem of reproducing the parametrization corresponding to that of lattice models, namely self-avoiding walks on the lattice, and we propose a strategy that gives rise to discrete paths where consecutive points lie an approximately constant distance apart from each other. This new method allows us to tackle two non-trivial features of self-avoiding walks that critically depend on the parametrization: the asphericity of a portion of chain and the correction-to-scaling exponent.Comment: 18 pages, 4 figures. Some sections rewritten (including title and abstract), numerical results added, references added. Accepted for publication in J. Stat. Phy

Correlation effects in ionic crystals: I. The cohesive energy of MgO

High-level quantum-chemical calculations, using the coupled-cluster approach and extended one-particle basis sets, have been performed for (Mg2+)n (O2-)m clusters embedded in a Madelung potential. The results of these calculations are used for setting up an incremental expansion for the correlation energy of bulk MgO. This way, 96% of the experimental cohesive energy of the MgO crystal is recovered. It is shown that only 60% of the correlation contribution to the cohesive energy is of intra-ionic origin, the remaining part being caused by van der Waals-like inter-ionic excitations.Comment: LaTeX, 20 pages, no figure

Consistent histories, the quantum Zeno effect, and time of arrival

We present a decomposition of the general quantum mechanical evolution operator, that corresponds to the path decomposition expansion, and interpret its constituents in terms of the quantum Zeno effect (QZE). This decomposition is applied to a finite dimensional example and to the case of a free particle in the real line, where the possibility of boundary conditions more general than those hitherto considered in the literature is shown. We reinterpret the assignment of consistent probabilities to different regions of spacetime in terms of the QZE. The comparison of the approach of consistent histories to the problem of time of arrival with the solution provided by the probability distribution of Kijowski shows the strength of the latter point of view

Polariton Analysis of a Four-Level Atom Strongly Coupled to a Cavity Mode

We present a complete analytical solution for a single four-level atom strongly coupled to a cavity field mode and driven by external coherent laser fields. The four-level atomic system consists of a three-level subsystem in an EIT configuration, plus an additional atomic level; this system has been predicted to exhibit a photon blockade effect. The solution is presented in terms of polaritons. An effective Hamiltonian obtained by this procedure is analyzed from the viewpoint of an effective two-level system, and the dynamic Stark splitting of dressed states is discussed. The fluorescence spectrum of light exiting the cavity mode is analyzed and relevant transitions identified.Comment: 12 pages, 9 figure

Time-of-arrival distributions from position-momentum and energy-time joint measurements

The position-momentum quasi-distribution obtained from an Arthurs and Kelly joint measurement model is used to obtain indirectly an ``operational'' time-of-arrival (TOA) distribution following a quantization procedure proposed by Kocha\'nski and W\'odkiewicz [Phys. Rev. A 60, 2689 (1999)]. This TOA distribution is not time covariant. The procedure is generalized by using other phase-space quasi-distributions, and sufficient conditions are provided for time covariance that limit the possible phase-space quasi-distributions essentially to the Wigner function, which, however, provides a non-positive TOA quasi-distribution. These problems are remedied with a different quantization procedure which, on the other hand, does not guarantee normalization. Finally an Arthurs and Kelly measurement model for TOA and energy (valid also for arbitrary conjugate variables when one of the variables is bounded from below) is worked out. The marginal TOA distribution so obtained, a distorted version of Kijowski's distribution, is time covariant, positive, and normalized

Quantum state merging and negative information

We consider a quantum state shared between many distant locations, and define a quantum information processing primitive, state merging, that optimally merges the state into one location. As announced in [Horodecki, Oppenheim, Winter, Nature 436, 673 (2005)], the optimal entanglement cost of this task is the conditional entropy if classical communication is free. Since this quantity can be negative, and the state merging rate measures partial quantum information, we find that quantum information can be negative. The classical communication rate also has a minimum rate: a certain quantum mutual information. State merging enabled one to solve a number of open problems: distributed quantum data compression, quantum coding with side information at the decoder and sender, multi-party entanglement of assistance, and the capacity of the quantum multiple access channel. It also provides an operational proof of strong subadditivity. Here, we give precise definitions and prove these results rigorously.Comment: 23 pages, 3 figure

Endoscopic resection of advanced ampullary adenomas: a single-center 14-year retrospective cohort study

Background: Endoscopic ampullectomy has been recognized as a safe and reliable means to resect selective tumors of the ampulla of Vater and is associated with lower morbidity and mortality rates compared to surgical resection. Success rates range from 42 to 92%, with recurrences reported in up to 33%. Studies on endoscopic resection of advanced lesions such as those with intraductal extension of adenoma (IEA) and lateral spreading adenomas (LSA) are limited. We aimed to evaluate the technical success, complications, and recurrence of endoscopic resection of ampullary adenomas, including advanced lesions. Methods: All patients referred to the Erasmus Medical Center for endoscopic resection of an ampullary lesion were retrospectively identified between 2002 and 2016. Endoscopic success was defined as complete excision of the adenoma, irrespective of the number of attempts, in the absence of recurrence. Results: We included 87 patients with a median age of 65 years. Of these, 56 patients (64%) had an adenoma confined to the ampulla (ACA), 20 patients (23%) had an LSA, and 11 patients (13%) were treated for an IEA. The median lesion sizes were 24.6 mm, 41.4 mm, and 16.3 mm, respectively (P < 0.001). Complications occurred in 22 patients (25.3%), of which hemorrhage was most prevalent (12.6%), followed by perforation (8.1%). Complications were equally divided (P = 0.874). The median follow-up duration was 21.1 months (12–45.9) for ACA, 14.7 months (4.2–34.5) for LSA, and 5.8 months (3.7–22.0) for IEA (P = 0.051). Endoscopic resection was curative in 87.5% of patients with an ACA, 85% in patients with an LSA, and in only one patient with an IEA (P < 0.001). Recurrence occurred in 10 patients (11.5%) (P = 0.733). Conclusion: Endoscopic ampullectomy is safe and highly successful in selected patients with an adenoma with or without lateral spreading. Outcomes of endoscopic treatment adenomas with an intraductal extension are less favorable and in these cases surgery should be considered

The microscopic spin-phonon coupling constants in CuGeO_3

Using RPA results, mean field theory, and refined data for the polarization vectors we determine the coupling constants of the four Peierls-active phonon modes to the spin chains of CuGeO_3. We then derive the values of the coupling of the spin system to the linear ionic displacements, the bond lengths and the angles between bonds. Our values are consistent with microscopic theories and various experimental results. We discuss the applicability of static approaches to the spin-phonon coupling. The c-axis anomaly of the thermal expansion is explained. We give the values of the coupling constants in an effective one-dimensional Hamiltonian.Comment: 11 pages, two figures, 13 tables, PRB 59 (in press