Impact of Radiotherapy, Chemotherapy and Surgery in Multimodal Treatment of Locally Advanced Esophageal Cancer

Objectives: It was the aim of this study to assess our institutional experience with definitive chemoradiation (CRT) versus induction chemotherapy followed by CRT with or without surgery (C-CRT/S) in esophageal cancer. Methods: We retrospectively analyzed 129 institutional patients with locally advanced esophageal cancer who had been treated by either CRT in analogy to the RTOG 8501 trial (n = 78) or C-CRT/S (n = 51). Results: The median, 2-and 5-year overall survival (OS) of the entire collective was 17.6 months, 42 and 24%, respectively, without a significant difference between the CRT and C-CRT/S groups. In C-CRT/S patients, surgery statistically improved the locoregional control (LRC) rates (2-year LRC 73.6 vs. 21.2%; p = 0.003); however, this was translated only into a trend towards improved OS (p = 0.084). The impact of escalated radiation doses (>= 60.0 vs. <60.0 Gy) on LRC was detectable only in T1-3 N0-1 M0 patients of the CRT group (2-year LRC 77.8 vs. 42.3%; p = 0.036). Conclusion: Definitive CRT and a trimodality approach including surgery (C-CRT/S) had a comparable outcome in this unselected patient collective. Surgery and higher radiation doses improve LRC rates in subgroups of patients, respectively, but without effect on OS. Copyright (C) 2012 S. Karger AG, Base

A Universal Model of Global Civil Unrest

Civil unrest is a powerful form of collective human dynamics, which has led to major transitions of societies in modern history. The study of collective human dynamics, including collective aggression, has been the focus of much discussion in the context of modeling and identification of universal patterns of behavior. In contrast, the possibility that civil unrest activities, across countries and over long time periods, are governed by universal mechanisms has not been explored. Here, we analyze records of civil unrest of 170 countries during the period 1919-2008. We demonstrate that the distributions of the number of unrest events per year are robustly reproduced by a nonlinear, spatially extended dynamical model, which reflects the spread of civil disorder between geographic regions connected through social and communication networks. The results also expose the similarity between global social instability and the dynamics of natural hazards and epidemics.Comment: 8 pages, 3 figure

Pathomechanisms of ulnar ligament lesions of the wrist in a cadaveric distal radius fracture model

Background and purpose: Mechanisms of injury to ulnar sided ligaments, stabilizing the distal radioulnar joint and the ulna to the carpus, associated with dorsally displaced distal radius fractures are poorly described. We investigated the injury patterns in a human cadaver fracture model. Methods: Fresh frozen human cadaver arms were used. A dorsal open wedge osteotomy was made in the distal radius. In 8 specimens pressure was applied to the palm with the wrist in dorsiflexion and ulnar sided stabilizing structures subsequently severed. Dorsal angulation was measured on digitized radiographs. In 8 more specimens the triangular fibrocartilage complex was forced into rupture by axially loading the forearm with the wrist in dorsiflexion. The ulnar side was dissected and injuries were recorded. Results: Intact ulnar soft tissues limited the dorsal angulation of the distal radius fragment to a median of 32o (16-34o). A combination of bending and shearing of the distal radius fragment was needed to create TFCC injuries. Both palmar and dorsal injuries were observed simultaneously in 6/8 specimens. Interpretation: A TFCC injury can be expected when dorsal angulation of a distal radius fracture exceeds 32o. The extensor carpi ulnaris subsheath may be a functionally integral part of the TFCC. Both dorsal and palmar structures can tear simultaneously. These findings may have implications for reconstruction of ulnar sided soft tissue injuries

Bipolar supercurrent in graphene

Graphene -a recently discovered one-atom-thick layer of graphite- constitutes a new model system in condensed matter physics, because it is the first material in which charge carriers behave as massless chiral relativistic particles. The anomalous quantization of the Hall conductance, which is now understood theoretically, is one of the experimental signatures of the peculiar transport properties of relativistic electrons in graphene. Other unusual phenomena, like the finite conductivity of order 4e^2/h at the charge neutrality (or Dirac) point, have come as a surprise and remain to be explained. Here, we study the Josephson effect in graphene. Our experiments rely on mesoscopic superconducting junctions consisting of a graphene layer contacted by two closely spaced superconducting electrodes, where the charge density can be controlled by means of a gate electrode. We observe a supercurrent that, depending on the gate voltage, is carried by either electrons in the conduction band or by holes in the valence band. More importantly, we find that not only the normal state conductance of graphene is finite, but also a finite supercurrent can flow at zero charge density. Our observations shed light on the special role of time reversal symmetry in graphene and constitute the first demonstration of phase coherent electronic transport at the Dirac point.Comment: Under review, 12 pages, 4 Figs., suppl. info (v2 identical, resolved file problems

KamLAND Sensitivity to Neutrinos from Pre-Supernova Stars

In the late stages of nuclear burning for massive stars (M>8~M_{\sun}), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25~M_{\sun} at a distance less than 690~pc with 3$\sigma$ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.Comment: 19 pages, 6 figures, 1 tabl

The Logic of Fashion Cycles

Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

Variability Measures of Positive Random Variables

During the stationary part of neuronal spiking response, the stimulus can be encoded in the firing rate, but also in the statistical structure of the interspike intervals. We propose and discuss two information-based measures of statistical dispersion of the interspike interval distribution, the entropy-based dispersion and Fisher information-based dispersion. The measures are compared with the frequently used concept of standard deviation. It is shown, that standard deviation is not well suited to quantify some aspects of dispersion that are often expected intuitively, such as the degree of randomness. The proposed dispersion measures are not entirely independent, although each describes the interspike intervals from a different point of view. The new methods are applied to common models of neuronal firing and to both simulated and experimental data