Antioxidant Therapy Does Not Reduce Pain in Patients with Chronic Pancreatitis: The ANTICIPATE Study

Background & Aims: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. Methods: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed up for 6 months while receiving either Antox version 1.2 (Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/d). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative analyses of clinic and diary pain scores, scores on quality-of-life tests (the EORTC-QLQ-C30, QLQ-PAN28, EuroQOL EQ-5D, and EQ visual analog score), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively protocol-defined. Results: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (−0.36; 95% confidence interval, −1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group, 2.93 for the antioxidant group, a difference of 0.11; 95% confidence interval, 1.05–0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group. Conclusi1ons: In patients with painful chronic pancreatitis of predominantly alcoholic origin, antioxidant therapy did not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants. Trial registration: ISRCTN-21047731

Superconductor-Insulator Transition in a Capacitively Coupled Dissipative Environment

We present results on disordered amorphous films which are expected to undergo a field-tuned Superconductor-Insulator Transition.The addition of a parallel ground plane in proximity to the film changes the character of the transition.Although the screening effects expected from "dirty-boson" theories are not evident,there is evidence that the ground plane couples a certain type of dissipation into the system,causing a dissipation-induced phase transition.The dissipation due to the phase transition couples similarly into quantum phase transition systems such as superconductor-insulator transitions and Josephson junction arrays.Comment: 4 pages, 4 figure

The Ising-Kondo lattice with transverse field: an f-moment Hamiltonian for URu2Si2?

We study the phase diagram of the Ising-Kondo lattice with transverse magnetic field as a possible model for the weak-moment heavy-fermion compound URu2Si2, in terms of two low-lying f singlets in which the uranium moment is coupled by on-site exchange to the conduction electron spins. In the mean-field approximation for an extended range of parameters, we show that the conduction electron magnetization responds logarithmically to f-moment formation, that the ordered moment in the antiferromagnetic state is anomalously small, and that the Neel temperature is of the order observed. The model gives a qualitatively correct temperature-dependence, but not magnitude, of the specific heat. The majority of the specific heat jump at the Neel temperature arises from the formation of a spin gap in the conduction electron spectrum. We also discuss the single-impurity version of the model and speculate on ways to increase the specific heat coefficient. In the limits of small bandwidth and of small Ising-Kondo coupling, we find that the model corresponds to anisotropic Heisenberg and Hubbard models respectively.Comment: 20 pages RevTeX including 5 figures (1 in LaTeX, 4 in uuencoded EPS), Received by Phys. Rev. B 19 April 199

Comparison of the Oxidation State of Fe in Comet 81P/Wild 2 and Chondritic-Porous Interplanetary Dust Particles

The fragile structure of chondritic-porous interplanetary dust particles (CP- IDPs) and their minimal parent-body alteration have led researchers to believe these particles originate in comets rather than asteroids where aqueous and thermal alteration have occurred. The solar elemental abundances and atmospheric entry speed of CP-IDPs also suggest a cometary origin. With the return of the Stardust samples from Jupiter-family comet 81P/Wild 2, this hypothesis can be tested. We have measured the Fe oxidation state of 15 CP-IDPs and 194 Stardust fragments using a synchrotron-based x-ray microprobe. We analyzed ~300 nanograms of Wild 2 material - three orders of magnitude more material than other analyses comparing Wild 2 and CP-IDPs. The Fe oxidation state of these two samples of material are >2{\sigma} different: the CP-IDPs are more oxidized than the Wild 2 grains. We conclude that comet Wild 2 contains material that formed at a lower oxygen fugacity than the parent body, or parent bodies, of CP-IDPs. If all Jupiter-family comets are similar, they do not appear to be consistent with the origin of CP-IDPs. However, comets that formed from a different mix of nebular material and are more oxidized than Wild 2 could be the source of CP-IDPs.Comment: Earth and Planetary Science Letters, in pres

Magnetic Coherence in Cuprate Superconductors

Recent inelastic neutron scattering (INS) experiments on La$_{2-x}$Sr$_x$CuO$_4$ observed a {\it magnetic coherence effect}, i.e., strong frequency and momentum dependent changes of the spin susceptibility, $\chi''$, in the superconducting phase. We show that this effect is a direct consequence of changes in the damping of incommensurate antiferromagnetic spin fluctuations due to the appearance of a d-wave gap in the fermionic spectrum. Our theoretical results provide a quantitative explanation for the weak momentum dependence of the observed spin-gap. Moreover, we predict {\bf (a)} a Fermi surface in La$_{2-x}$Sr$_x$CuO$_4$ which is closed around $(\pi,\pi)$ up to optimal doping, and {\bf (b)} similar changes in $\chi''$ for all cuprates with an incommensurate magnetic response.Comment: 5 pages, 4 figures, Fig.3 is in colo

Speleothems Reveal 500,000-year History of Siberian Permafrost

Soils in permafrost regions contain twice as much carbon as the atmosphere, and permafrost has an important influence on the natural and built environment at high northern latitudes. The response of permafrost to warming climate is uncertain and occurs on time scales longer than those assessed by direct observation. We dated periods of speleothem growth in a north-south transect of caves in Siberia to reconstruct the history of permafrost in past climate states. Speleothem growth is restricted to full interglacial conditions in all studied caves. In the northernmost cave (at 60°N), no growth has occurred since Marine Isotopic Stage (MIS) 11. Growth at that time indicates that global climates only slightly warmer than today are sufficient to thaw extensive regions of permafrost

Penultimate Deglacial Sea-Level Timing from Uranium/Thorium Dating of Tahitian Corals

The timing of sea-level change provides important constraints on the mechanisms driving Earth's climate between glacial and interglacial states. Fossil corals constrain the timing of past sea level by their suitability for dating and their growth position close to sea level. The coral-derived age for the last deglaciation is consistent with climate change forced by Northern Hemisphere summer insolation (NHI), but the timing of the penultimate deglaciation is more controversial. We found, by means of uranium/thorium dating of fossil corals, that sea level during the penultimate deglaciation had risen to similar to 85 meters below the present sea level by 137,000 years ago, and that it fluctuated on a millennial time scale during deglaciation. This indicates that the penultimate deglaciation occurred earlier with respect to NHI than the last deglacial, beginning when NHI was at a minimum

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens.

Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings. Indeed, present therapies that lack this molecular understanding have not been universally effective. Here, we describe methods that we commonly employ in the laboratory to determine how the nature of the interaction between TCRs and pHLA governs T-cell functionality. These methods include the generation of soluble TCRs and pHLA and the use of these reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-cell staining with pHLA multimers. Using these approaches and guided by structural analysis, it is possible to modify the interaction between TCRs and pHLA and to then test how these modifications impact T-cell antigen recognition. These findings have already helped to clarify the mechanism of T-cell recognition of a number of cancer antigens and could direct the development of altered peptides and modified TCRs for new cancer therapies