Neutron scattering search for static magnetism in oxygen ordered YBa2Cu3O6.5

We present elastic and inelastic neutron scattering results on highly oxygen ordered YBa2Cu3O6.5 ortho-II. We find no evidence for the presence of ordered magnetic moments to a sensitivity of 0.003 Bohr magnetons, an order of magnitude smaller than has been suggested in theories of orbital or d-density-wave (DDW) currents. The absence of sharp elastic peaks, shows that the d-density-wave phase is not present, at least for the superconductor with the doping of 6.5 and the ordered ortho-II structure. We cannot exclude the possibility that a broad peak may exist with extremely short-range DDW correlations. For less ordered or more doped crystals it is possible that disorder may lead to static magnetism. We have also searched for the large normal state spin gap that is predicted to exist in an ordered DDW phase. Instead of a gap we find that the Q-correlated spin susceptibility persists to the lowest energies studied, 6 meV. Our results are compatible with the coexistence of superconductivity with orbital currents, but only if they are dynamic, and exclude a sharp phase transition to an ordered d-density-wave phase.Comment: 6 pages 4 figures RevTex Submitted to Phys Rev B January 23, 200

Antihydrogen formation dynamics in a multipolar neutral anti-atom trap

Antihydrogen production in a neutral atom trap formed by an octupole-based magnetic field minimum is demonstrated using field-ionization of weakly bound anti-atoms. Using our unique annihilation imaging detector, we correlate antihydrogen detection by imaging and by field-ionization for the first time. We further establish how field-ionization causes radial redistribution of the antiprotons during antihydrogen formation and use this effect for the first simultaneous measurements of strongly and weakly bound antihydrogen atoms. Distinguishing between these provides critical information needed in the process of optimizing for trappable antihydrogen. These observations are of crucial importance to the ultimate goal of performing CPT tests involving antihydrogen, which likely depends upon trapping the anti-atom

Cornerstones of Sampling of Operator Theory

This paper reviews some results on the identifiability of classes of operators whose Kohn-Nirenberg symbols are band-limited (called band-limited operators), which we refer to as sampling of operators. We trace the motivation and history of the subject back to the original work of the third-named author in the late 1950s and early 1960s, and to the innovations in spread-spectrum communications that preceded that work. We give a brief overview of the NOMAC (Noise Modulation and Correlation) and Rake receivers, which were early implementations of spread-spectrum multi-path wireless communication systems. We examine in detail the original proof of the third-named author characterizing identifiability of channels in terms of the maximum time and Doppler spread of the channel, and do the same for the subsequent generalization of that work by Bello. The mathematical limitations inherent in the proofs of Bello and the third author are removed by using mathematical tools unavailable at the time. We survey more recent advances in sampling of operators and discuss the implications of the use of periodically-weighted delta-trains as identifiers for operator classes that satisfy Bello's criterion for identifiability, leading to new insights into the theory of finite-dimensional Gabor systems. We present novel results on operator sampling in higher dimensions, and review implications and generalizations of the results to stochastic operators, MIMO systems, and operators with unknown spreading domains

Search For Trapped Antihydrogen

We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 10^7 antiprotons with 1.3 10^9 positrons to produce 6 10^5 antihydrogen atoms, we have identified six antiproton annihilation events that are consistent with the release of trapped antihydrogen. The cosmic ray background, estimated to contribute 0.14 counts, is incompatible with this observation at a significance of 5.6 sigma. Extensive simulations predict that an alternative source of annihilations, the escape of mirror-trapped antiprotons, is highly unlikely, though this possibility has not yet been ruled out experimentally.Comment: 12 pages, 7 figure

QED3 theory of underdoped high temperature superconductors

Low-energy theory of d-wave quasiparticles coupled to fluctuating vortex loops that describes the loss of phase coherence in a two dimensional d-wave superconductor at T=0 is derived. The theory has the form of 2+1 dimensional quantum electrodynamics (QED3), and is proposed as an effective description of the T=0 superconductor-insulator transition in underdoped cuprates. The coupling constant ("charge") in this theory is proportional to the dual order parameter of the XY model, which is assumed to be describing the quantum fluctuations of the phase of the superconducting order parameter. The principal result is that the destruction of phase coherence in d-wave superconductors typically, and immediately, leads to antiferromagnetism. The transition can be understood in terms of the spontaneous breaking of an approximate "chiral" SU(2) symmetry, which may be discerned at low enough energies in the standard d-wave superconductor. The mechanism of the symmetry breaking is analogous to the dynamical mass generation in the QED3, with the "mass" here being proportional to staggered magnetization. Other insulating phases that break chiral symmetry include the translationally invariant "d+ip" and "d+is" insulators, and various one dimensional charge-density and spin-density waves. The theory offers an explanation for the rounded d-wave-like dispersion seen in ARPES experiments on Ca2CuO2Cl2 (F. Ronning et. al., Science 282, 2067 (1998)).Comment: Revtex, 20 pages, 5 figures; this is a much extended follow-up to the Phys. Rev. Lett. vol.88, 047006 (2002) (cond-mat/0110188); improved presentation, many additional explanations, comments, and references added, sec. IV rewritten. Final version, to appear in Phys. Rev.

Error sources and data limitations for the prediction ofsurface gravity: a case study using benchmarks

Gravity-based heights require gravity values at levelled benchmarks (BMs), whichsometimes have to be predicted from surrounding observations. We use EGM2008 andthe Australian National Gravity Database (ANGD) as examples of model and terrestrialobserved data respectively to predict gravity at Australian national levelling network(ANLN) BMs. The aim is to quantify errors that may propagate into the predicted BMgravity values and then into gravimetric height corrections (HCs). Our results indicatethat an approximate ±1 arc-minute horizontal position error of the BMs causesmaximum errors in EGM2008 BM gravity of ~ 22 mGal (~55 mm in the HC at ~2200 melevation) and ~18 mGal for ANGD BM gravity because the values are not computed atthe true location of the BM. We use RTM (residual terrain modelling) techniques toshow that ~50% of EGM2008 BM gravity error in a moderately mountainous regioncan be accounted for by signal omission. Non-representative sampling of ANGDgravity in this region may cause errors of up to 50 mGals (~120 mm for the Helmertorthometric correction at ~2200 m elevation). For modelled gravity at BMs to beviable, levelling networks need horizontal BM positions accurate to a few metres, whileRTM techniques can be used to reduce signal omission error. Unrepresentative gravitysampling in mountains can be remedied by denser and more representative re-surveys,and/or gravity can be forward modelled into regions of sparser gravity

Management of acute hypercortisolism

An occasional patient with Cushing's syndrome may require urgent management primarily because the chronic ravages of hypercortisolism have caused the patient to be in a precarious metabolic condition. The side effects of prolonged excess corticosteroids increase the risk of operations in such patients and must be considered in overall management. Among the many effects of hypercortisolism to be considered are hypertension, diabetes, ocular hypertension, myopathies, dermatologic changes including skin infection, pancreatitis, osteoporosis, pathological fractures, peptic ulcers, renal calculi, coagulopathies, hypokalemia, poor wound healing, and increased susceptibility to infection. The most effective way to avert these complications is by earlier diagnosis and definitive treatment of Cushing's syndrome. The present report includes a review of the etiology and diagnosis of Cushing's syndrome and the management of problems associated with hypercortisolism . Il est possible qu'un malade atteint de maladie de Cushing ait besoin d'être traité sans attente en raisons de troubles métaboliques sévères dus aux effets nocifs de l'hypercortisolisme chronique qui augmentent les risques opératoires et doivent être pris en considération avant tout traitement. Il en est ainsi de l'hypertension, du diabète, de l'hypertension intra-oculaire, des lésions dermiques comprenant l'infection cutanée, la pancréatite, l'ostéoporose, les fractures pathologiques, l'ulcère peptique, les calculs rénaux, les coagulopathies, l'hypokaliémie, la lenteur du processus de cicatrisation et l'augmentation de la suceptibilité à l'infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41309/1/268_2005_Article_BF01655367.pd

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease