The neuroimmunology of chronic pain: from rodents to humans

Chronic pain, encompassing conditions, such as low back pain, arthritis, persistent post-surgical pain, fibromyalgia, and neuropathic pain disorders, is highly prevalent but remains poorly treated. The vast majority of therapeutics are directed solely at neurons, despite the fact that signaling between immune cells, glia, and neurons is now recognized as indispensable for the initiation and maintenance of chronic pain. This review highlights recent advances in understanding fundamental neuroimmune signaling mechanisms and novel therapeutic targets in rodent models of chronic pain. We further discuss new technological developments to study, diagnose, and quantify neuroimmune contributions to chronic pain in patient populations.Peter M. Grace, Vivianne L. Tawfik, Camilla I. Svensson, Michael D. Burton, Marco L. Loggia and Mark R. Hutchinso

Percolation model for structural phase transitions in Li1−x_{1-x}Hx_xIO3_3 mixed crystals

A percolation model is proposed to explain the structural phase transitions found in Li$_{1-x}$H$_x$IO$_3$ mixed crystals as a function of the concentration parameter $x$. The percolation thresholds are obtained from Monte Carlo simulations on the specific lattices occupied by lithium atoms and hydrogen bonds. The theoretical results strongly suggest that percolating lithium vacancies and hydrogen bonds are indeed responsible for the solid solution observed in the experimental range $0.22 < x < 0.36$.Comment: 4 pages, 2 figure

Particle density fluctuations

Event-by-event fluctuations in the multiplicities of charged particles and photons at SPS energies are discussed. Fluctuations are studied by controlling the centrality of the reaction and rapidity acceptance of the detectors. Results are also presented on the event-by-event study of correlations between the multiplicity of charged particles and photons to search for DCC-like signals.Comment: Talk presented at Quark Matter 2002, Nantes, Franc

Search for DCC in 158A GeV Pb+Pb Collisions

A detailed analysis of the phase space distributions of charged particles and photons have been carried out using two independent methods. The results indicate the presence of nonstatistical fluctuations in localized regions of phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199

Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry

Two-particle correlations have been measured for identified negative pions from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all dimensions have been obtained. A multi-dimensional study of the radii as a function of kT is presented, including a full correction for the resolution effects of the apparatus. The cross term Rout-long of the standard fit in the Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a boost invariant expansion. The shapes of the correlation functions in Qinv and Qspace have been analyzed in detail. They are not Gaussian but better represented by exponentials. As a consequence, fitting Gaussians to these correlation functions may produce different radii depending on the acceptance of the experimental setup used for the measurement.Comment: 13 pages including 10 figure

Present Status and Future of DCC Analysis

Disoriented Chiral Condensates (DCC) have been predicted to form in high energy heavy ion collisions where the approximate chiral symmetry of QCD has been restored. This leads to large imbalances in the production of charged to neutral pions. Sophisticated analysis methods are being developed to disentangle DCC events out of the large background of events with conventionally produced particles. We present a short review of current analysis methods and future prospects.Comment: 12 pages, 5 figures. Invited talk presented at the 13th International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 97), Tsukuba, Japan, 1-5 Dec 199

Search for Disoriented Chiral Condensates in 158 AGeV Pb+Pb Collisions

The restoration of chiral symmetry and its subsequent breaking through a phase transition has been predicted to create regions of Disoriented Chiral Condensates (DCC). This phenomenon has been predicted to cause anomalous fluctuations in the relative production of charged and neutral pions in high-energy hadronic and nuclear collisions. The WA98 experiment has been used to measure charged and photon multiplicities in the central region of 158 AGeV Pb+Pb collisions at the CERN SPS. In a sample of 212646 events, no clear DCC signal can be distinguished. Using a simple DCC model, we have set a 90% C.L. upper limit on the maximum DCC production allowed by the data.Comment: 20 Pages, LaTeX, uses elsart.cls, 8 eps figures included, submitted to Physics Letters

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study

Introduction Congenital anomalies are the fifth leading cause of death in children <5 years of age globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally. Methods and analysis The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung''s disease). Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre. The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of postoperative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal

Directed Flow in 158 A GeV 208Pb^{208}Pb + 208Pb^{208}Pb Collisions

The directed flow of protons and positive pions have been studied in 158 A GeV Pb + Pb collisions. A directed flow analysis of the rapidity dependence of the average transverse momentum projected onto the reaction plane is presented for semi-central collisions with impact parameters of approximately 8 fm, where the flow effect is largest. The magnitude of the directed flow is found to be significantly smaller than observed at AGS energies and than RQMD model predictions.The directed flow of protons and positive pions have been studied in 158 A GeV Pb + Pb collisions. A directed flow analysis of the rapidity dependence of the average transverse momentum projected onto the reaction plane is presented for semi-central collisions with impact parameters of approximately 8 fm, where the flow effect is largest. The magnitude of the directed flow is found to be significantly smaller than observed at AGS energies and than RQMD model predictions

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies