Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum

Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches

The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies

Pancreatic cancer is a devastating disease with very poor prognosis. Currently, surgery followed by adjuvant chemotherapy represents the only curative option which, unfortunately, is only available for a small group of patients. The majority of pancreatic cancer cases are diagnosed at advanced or metastatic stage when surgical resection is not possible and treatment options are limited. Thus, novel and more effective therapeutic strategies are urgently needed. Molecular profiling together with targeted therapies against key hallmarks of pancreatic cancer appear as a promising approach that could overcome the limitations of conventional chemo- and radio-therapy. In this review, we focus on the latest personalised and multimodal targeted therapies currently undergoing phase II or III clinical trials. We discuss the most promising findings of agents targeting surface receptors, angiogenesis, DNA damage and cell cycle arrest, key signalling pathways, immunotherapies, and the tumour microenvironment

Observations and simulations of recurrent novae: U Sco and V394 CrA

Observations and analysis of the Aug. 1987 outburst of the recurrent nova V394 CrA are presented. This nova is extremely fast and its outburst characteristics closely resemble those of the recurrent nova U Sco. Hydrodynamic simulations of the outbursts of recurrent novae were performed. Results as applied to the outbursts of V394 CrA and U Sco are summarized

Global-String and Vortex Superfluids in a Supersymmetric Scenario

The main goal of this work is to investigate the possibility of finding the supersymmetric version of the U(1)-global string model which behaves as a vortex-superfluid. To describe the superfluid phase, we introduce a Lorentz-symmetry breaking background that, in an approach based on supersymmetry, leads to a discussion on the relation between the violation of Lorentz symmetry and explicit soft supersymmetry breakings. We also study the relation between the string configuration and the vortex-superfluid phase. In the framework we settle down in terms of superspace and superfields, we actually establish a duality between the vortex degrees of freedom and the component fields of the Kalb-Ramond superfield. We make also considerations about the fermionic excitations that may appear in connection with the vortex formation.Comment: 9 pages. This version presented the relation between Lorentz symmetry violation by the background and the appearance of terms that explicitly break SUS

Observations of classical novae in outburst

The IUE obtained ultraviolet data on novae in outburst. The characteristics of every one of the outbursts are different. Optical and infrared data on many of the same novae were also obtained. Three members of the carbon-oxygen class of novae are presented

Fragility of the Free-Energy Landscape of a Directed Polymer in Random Media

We examine the sensitiveness of the free-energy landscape of a directed polymer in random media with respect to various kinds of infinitesimally weak perturbation including the intriguing case of temperature-chaos. To this end, we combine the replica Bethe ansatz approach outlined in cond-mat/0112384, the mapping to a modified Sinai model and numerically exact calculations by the transfer-matrix method. Our results imply that for all the perturbations under study there is a slow crossover from a weakly perturbed regime where rare events take place to a strongly perturbed regime at larger length scales beyond the so called overlap length where typical events take place leading to chaos, i.e. a complete reshuffling of the free-energy landscape. Within the replica space, the evidence for chaos is found in the factorization of the replicated partition function induced by infinitesimal perturbations. This is the reflex of explicit replica symmetry breaking.Comment: 29 pages, Revtex4, ps figure

Numerical study of the strongly screened vortex glass model in an external field

The vortex glass model for a disordered high-T_c superconductor in an external magnetic field is studied in the strong screening limit. With exact ground state (i.e. T=0) calculations we show that 1) the ground state of the vortex configuration varies drastically with infinitesimal variations of the strength of the external field, 2) the minimum energy of global excitation loops of length scale L do not depend on the strength of the external field, however 3) the excitation loops themself depend sensibly on the field. From 2) we infer the absence of a true superconducting state at any finite temperature independent of the external field.Comment: 6 pages RevTeX, 5 eps-figures include

Concentration Kinetics of Serum MMP-9 and TIMP-1 after Blunt Multiple Injuries in the Early Posttraumatic Period

Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs). Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16) were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P < 0.05) whereas TIMP-1 levels significantly increased in all patients (P < 0.05). MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS ≤ 33) and survivors, initially after trauma

Numerical Study of Order in a Gauge Glass Model

The XY model with quenched random phase shifts is studied by a T=0 finite size defect energy scaling method in 2d and 3d. The defect energy is defined by a change in the boundary conditions from those compatible with the true ground state configuration for a given realization of disorder. A numerical technique, which is exact in principle, is used to evaluate this energy and to estimate the stiffness exponent $\theta$. This method gives $\theta = -0.36\pm0.013$ in 2d and $\theta = +0.31\pm 0.015$ in 3d, which are considerably larger than previous estimates, strongly suggesting that the lower critical dimension is less than three. Some arguments in favor of these new estimates are given.Comment: 4 pages, 2 figures, revtex. Submitted to Phys. Rev. Let

'Theory for the enhanced induced magnetization in coupled magnetic trilayers in the presence of spin fluctuations'

Motivated by recent experiments, the effect of the interlayer exchange interaction $J_{inter}$ on the magnetic properties of coupled Co/Cu/Ni trilayers is studied theoretically. Here the Ni film has a lower Curie temperature $T_{C,\rm Ni}$ than the Co film in case of decoupled layers. We show that by taking into account magnetic fluctuations the interlayer coupling induces a strong magnetization for T\gtsim T_{C,\rm Ni} in the Ni film. For an increasing $J_{inter}$ the resonance-like peak of the longitudinal Ni susceptibility is shifted to larger temperatures, whereas its maximum value decreases strongly. A decreasing Ni film thickness enhances the induced Ni magnetization for T\gtsim T_{C,\rm Ni}. The measurements cannot be explained properly by a mean field estimate, which yields a ten times smaller effect. Thus, the observed magnetic properties indicate the strong effect of 2D magnetic fluctuations in these layered magnetic systems. The calculations are performed with the help of a Heisenberg Hamiltonian and a Green's function approach.Comment: 4 pages, 3 figure