Evaluation of the ADVIA (R) Centaur (TM) TSH-3 assay

An analytical evaluation of the thyroid stimulating hormone (TSH-3) assay on the Sayer ADVIA(R) Centaur(TM) immunoassay system was performed. General analytical requirements (linearity, resistance to typical interferences, absence of a carry-over effect) were fulfilled and reproducibility was satisfactory. Inter-assay coefficient of variation (CV) of a human serum pool with a concentration of 0.014 mU/l was 22.3%; at concentrations between 0.26 and 83 mU/l CV was below 6%. Method comparison study demonstrated close agreement of TSH results compared to those obtained with the Roche Elecsys(R) 2010 TSH assay (ADVIA Centaur = 1.08 x Elecsys - 0.18 mU/l; r = 0.987; n = 324). Handling and practicability of the ADVIA Centaur system proved to be convenient with a very high sample throughput. We conclude that the ADVIA Centaur TSH-3 assay meets requirements for clinical use

Particle Production near an AdS Crunch

We numerically study the dual field theory evolution of five-dimensional asymptotically anti-de Sitter solutions of supergravity that develop cosmological singularities. The dual theory is an unstable deformation of the N = 4 gauge theory on R $\times$ S3, and the big crunch singularity in the bulk occurs when a boundary scalar field runs to infinity. Consistent quantum evolution requires one imposes boundary conditions at infinity. Modeling these by a steep regularization of the scalar potential, we find that when an initially nearly homogeneous wavepacket rolls down the potential, most of the potential energy of the initial configuration is converted into gradient energy during the first oscillation of the field. This indicates there is no transition from a big crunch to a big bang in the bulk for dual boundary conditions of this kind.Comment: 20 pages, 6 figure

Geometric construction of D-branes in WZW models

The geometric description of D-branes in WZW models is pushed forward. Our starting point is a gluing condition\, $J_{+}=FJ_-$ that matches the model's chiral currents at the worldsheet boundary through a linear map $F$ acting on the WZW Lie algebra. The equivalence of boundary and gluing conditions of this type is studied in detail. The analysis involves a thorough discussion of Frobenius integrability, shows that $F$ must be an isometry, and applies to both metrically degenerate and nondegenerate D-branes. The isometry $F$ need not be a Lie algebra automorphism nor constantly defined over the brane. This approach, when applied to isometries of the form $F=R$ with $R$ a constant Lie algebra automorphism, validates metrically degenerate $R$-twined conjugacy classes as D-branes. It also shows that no D-branes exist in semisimple WZW models for constant\, $F=-R$.Comment: 23 pages, discussion of limitations of the gluing condition approach adde

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss

This is the final version of the article. Available from American Society for Clinical Investigation via the DOI in this record.The current frontline symptomatic treatment for Alzheimer’s disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR–selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD.ABT, AC, and PMS received funding from a Wellcome Trust Collaborative Award (201529/Z/16/Z). ABT, SJB, AJB, and TMH were funded through a Medical Research Council programme leader grant provided by the MRC Toxicology Unit. CCF, LMB, AJM, and HES were funded by the Eli Lilly Company. JMB received funding through a Lilly Research Award Program (LRAP) grant (Eli Lilly). RP received funding from the Marie Curie grant “Extrabrain” (European Commission). AC is a senior principal research fellow and PMS a principal research fellow of the National Health and Medical Research Council of Australia. Tissue samples were from Randy Woltjer at the Oregon Alzheimer’s Disease Center. The Oregon Alzheimer’s Disease Center is supported by NIH grant P30AG008017

Determinant representations of scalar products for the open XXZ chain with non-diagonal boundary terms

With the help of the F-basis provided by the Drinfeld twist or factorizing F-matrix for the open XXZ spin chain with non-diagonal boundary terms, we obtain the determinant representations of the scalar products of Bethe states of the model.Comment: Latex file, 28 pages, based on the talk given by W. -L. Yang at Statphys 24, Cairns, Australia, 19-23 July, 201

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

T-folds, doubled geometry, and the SU(2) WZW model

The SU(2) WZW model at large level N can be interpreted semiclassically as string theory on S^3 with N units of Neveu-Schwarz H-flux. While globally geometric, the model nevertheless exhibits an interesting doubled geometry possessing features in common with nongeometric string theory compactifications, for example, nonzero Q-flux. Therefore, it can serve as a fertile testing ground through which to improve our understanding of more exotic compactifications, in a context in which we have a firm understanding of the background from standard techniques. Three frameworks have been used to systematize the study of nongeometric backgrounds: the T-fold construction, Hitchin's generalized geometry, and fully doubled geometry. All of these double the standard description in some way, in order to geometrize the combined metric and Neveu Schwarz B-field data. We present the T-fold and fully doubled descriptions of WZW models, first for SU(2) and then for general group. Applying the formalism of Hull and Reid-Edwards, we indeed recover the physical metric and H-flux of the WZW model from the doubled description. As additional checks, we reproduce the abelian T-duality group and known semiclassical spectrum of D-branes.Comment: 69 pages; uses amslatex; v4 minor revision

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit