Outcomes of First-Line Chemotherapy in Patients with Advanced or Metastatic Leiomyosarcoma of Uterine and Non-Uterine Origin

Although leiomyosarcomas (LMSs) form the largest subgroup of soft tissue sarcomas (STSs), the efficacy of chemotherapy in this group is largely unclear, partly because older studies are contaminated with gastrointestinal stromal tumors (GISTs). In this retrospective study we investigated the outcome of first line chemotherapy in 65 patients with unresectable or metastatic LMS. The overall response rate (ORR) was 18%; and the median progression-free (PFS) and overall survival (OS) were 3.8 and 9.7 months respectively. No statistically significant differences in outcomes for uterine and non-uterine LMS were found. In non-uterine LMS, however, the PFS and OS seemed to be longer for females than for males, potentially negatively affecting outcomes in this group. If our observations are confirmed in other series, they would suggest that studies performed in STS patients should not only stratify for histological subtype but also for uterine versus non-uterine LMS and for gender

Loops versus lines and the compression stiffening of cells

Both animal and plant tissue exhibit a nonlinear rheological phenomenon known as compression stiffening, or an increase in moduli with increasing uniaxial compressive strain. Does such a phenomenon exist in single cells, which are the building blocks of tissues? One expects an individual cell to compression soften since the semiflexible biopolymer-based cytoskeletal network maintains the mechanical integrity of the cell and in vitro semiflexible biopolymer networks typically compression soften. To the contrary, we find that mouse embryonic fibroblasts (mEFs) compression stiffen under uniaxial compression via atomic force microscopy (AFM) studies. To understand this finding, we uncover several potential mechanisms for compression stiffening. First, we study a single semiflexible polymer loop modeling the actomyosin cortex enclosing a viscous medium modeled as an incompressible fluid. Second, we study a two-dimensional semiflexible polymer/fiber network interspersed with area-conserving loops, which are a proxy for vesicles and fluid-based organelles. Third, we study two-dimensional fiber networks with angular-constraining crosslinks, i.e. semiflexible loops on the mesh scale. In the latter two cases, the loops act as geometric constraints on the fiber network to help stiffen it via increased angular interactions. We find that the single semiflexible polymer loop model agrees well with our AFM experiments until approximately 35% compressive strain. We also find for the fiber network with area-conserving loops model that the stress-strain curves are sensitive to the packing fraction and size distribution of the area-conserving loops, thereby creating a mechanical fingerprint across different cell types. Finally, we make comparisons between this model and experiments on fibrin networks interlaced with beads as well as discuss the tissue-scale implications of cellular compression stiffening.Comment: 19 pages, 17 figure

Excitations of a Bose-Einstein condensate in a one-dimensional optical lattice

We investigate the low-lying excitations of a stack of weakly-coupled two-dimensional Bose-Einstein condensates that is formed by a one-dimensional optical lattice. In particular, we calculate the dispersion relations of the monopole and quadrupole modes, both for the ground state as well as for the case in which the system contains a vortex along the direction of the lasers creating the optical lattice. Our variational approach enables us to determine analytically the dispersion relations for an arbitrary number of atoms in every two-dimensional condensate and for an arbitrary momentum. We also discuss the feasibility of experimentally observing our results.Comment: 16 pages, 5 figures, minor changes,accepted for publication in Phys. Rev.

Insulator-Superfluid transition of spin-1 bosons in an optical lattice in magnetic field

We study the insulator-superfluid transition of spin-1 bosons in an optical lattice in a uniform magnetic field. Based on a mean-field approximation we obtained a zero-temperature phase diagram. We found that depending on the particle number the transition for bosons with antiferromagnetic interaction may occur into different superfluid phases with spins aligned along or opposite to the field direction. This is qualitatively different from the field-free transition for which the mean-field theory predicts a unique (polar) superfluid state for any particle number.Comment: 10 pages, 2 eps figure

On the Role of Penning Ionization in Photoassociation Spectroscopy

We study the role of Penning ionization on the photoassociation spectra of He(^3S)-He(^3S). The experimental setup is discussed and experimental results for different intensities of the probe laser are shown. For modelling the experimental results we consider coupled-channel calculations of the crossing of the ground state with the excited state at the Condon point. The coupled-channel calculations are first applied to model systems, where we consider two coupled channels without ionization, two coupled channels with ionization, and three coupled channels, for which only one of the excited states is ionizing. Finally, coupled-channel calculations are applied to photoassociation of He(^3S)-He(^3S) and good agreement is obtained between the model and the experimental results.Comment: 14 pages, 18 figures, submitted to the special issue on Cold Molecules of J. Phys.

Quantum phase transitions of light

Recently, condensed matter and atomic experiments have reached a length-scale and temperature regime where new quantum collective phenomena emerge. Finding such physics in systems of photons, however, is problematic, as photons typically do not interact with each other and can be created or destroyed at will. Here, we introduce a physical system of photons that exhibits strongly correlated dynamics on a meso-scale. By adding photons to a two-dimensional array of coupled optical cavities each containing a single two-level atom in the photon-blockade regime, we form dressed states, or polaritons, that are both long-lived and strongly interacting. Our zero temperature results predict that this photonic system will undergo a characteristic Mott insulator (excitations localised on each site) to superfluid (excitations delocalised across the lattice) quantum phase transition. Each cavity's impressive photon out-coupling potential may lead to actual devices based on these quantum many-body effects, as well as observable, tunable quantum simulators. We explicitly show that such phenomena may be observable in micro-machined diamond containing nitrogen-vacancy colour centres and superconducting microwave strip-line resonators.Comment: 11 pages, 5 figures (2 in colour

Second-line treatment for acute graft-versus-host disease with mesenchymal stromal cells. a decision model

Objective: No standard second-line treatment exists for acute graft-versus-host disease steroid-refractory (SR-aGvHD), and long-term outcomes remain poor. Mesenchymal stromal cells (MSCs) have been evaluated as treatment, but no disease model (DM) exists that integrates and extrapolates currently available evidence. The aim of this study was to develop such a DM to describe the natural history of SR-aGvHD and to predict long-term outcomes. Method: The DM was developed in collaboration with experts in haematology-oncology. Subsequently, a model simulation was run. Input parameters for transition and survival estimates were informed by published data of clinical trials on MSC treatment for SR-aGvHD. Parametric distributions were used to estimate long-term survival rates after MSCs. Results: The newly developed DM is a cohort model that consists of eight health states. For the model simulation, we obtained data on 327 patients from 14 published phase II trials. Due to limited evidence, DM structure was simplified and several assumptions had to be made. Median overall survival was 3.2 years for complete response and 0.5 years for no complete response. Conclusion: The DM provides a comprehensive overview on the second-line treatment pathway for aGvHD and enables long-term predictions that can be used to perform a cost-effectiveness analysis comparing any treatment for SR-aGvHD

Transmittivity of a Bose-Einstein condensate on a lattice: interference from period doubling and the effect of disorder

We evaluate the particle current flowing in steady state through a Bose-Einstein condensate subject to a constant force in a quasi-onedimensional lattice and to attractive interactions from fermionic atoms that are localized in various configurations inside the lattice wells. The system is treated within a Bose-Hubbard tight binding model by an out-of-equilibrium Green's function approach. A new band gap opens up when the lattice period is doubled by locating the fermions in alternate wells and yields an interference pattern in the transmittivity on varying the intensity of the driving force. The positions of the transmittivity minima are determined by matching the period of Bloch oscillations and the time for tunnelling across the band gap. Massive disorder in the distribution of the fermions will wash out the interference pattern, but the same period doubling of the lattice can be experimentally realized in a four-beam set-up. We report illustrative numerical results for a mixture of 87Rb and 40K atoms in an optical lattice created by laser beams with a wavelength of 763 nm.Comment: 13 pages, 5 figure

Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model:a feasibility study for clinical diagnosis of prosthetic joint infections

Purpose Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints. Methods Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses. Results We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW. Conclusion The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection

Phase Diagram of Bosonic Atoms in Two-Color Superlattices

We investigate the zero temperature phase diagram of a gas of bosonic atoms in one- and two-color standing-wave lattices in the framework of the Bose-Hubbard model. We first introduce some relevant physical quantities; superfluid fraction, condensate fraction, quasimomentum distribution, and matter-wave interference pattern. We then discuss the relationships between them on the formal level and show that the superfluid fraction, which is the relevant order parameter for the superfluid to Mott-insulator transition, cannot be probed directly via the matter wave interference patterns. The formal considerations are supported by exact numerical solutions of the Bose-Hubbard model for uniform one-dimensional systems. We then map out the phase diagram of bosons in non-uniform lattices. The emphasis is on optical two-color superlattices which exhibit a sinusoidal modulation of the well depth and can be easily realized experimentally. From the study of the superfluid fraction, the energy gap, and other quantities we identify new zero-temperature phases, including a localized and a quasi Bose-glass phase, and discuss prospects for their experimental observation.Comment: 18 pages, 17 figures, using REVTEX