The use of prevalence as a measure of lice burden: a case study of Lepeophtheirus salmonis on Scottish Atlantic salmon, Salmo salar L., farms

This study investigates the benefits of using prevalence as a summary measure of sea lice infestation on farmed Atlantic salmon, Salmo salar L. Aspects such as sampling effort, the relationship between abundance and prevalence arising from the negative binomial distribution, and how this relationship can be used to indicate the degree of aggregation of lice on a site at a given time point are discussed. As a case study, data were drawn from over 50 commercial Atlantic salmon farms on the west coast of Scotland between 2002 and 2006. Descriptive statistics and formal analysis using a linear modelling technique identified significant variations in sea lice prevalence across year class, region and season. Supporting evidence of a functional relationship between prevalence and abundance of sea lice is provided, which is explained through the negative binomial distribution

Detecting a stochastic background of gravitational radiation: Signal processing strategies and sensitivities

We analyze the signal processing required for the optimal detection of a stochastic background of gravitational radiation using laser interferometric detectors. Starting with basic assumptions about the statistical properties of a stochastic gravity-wave background, we derive expressions for the optimal filter function and signal-to-noise ratio for the cross-correlation of the outputs of two gravity-wave detectors. Sensitivity levels required for detection are then calculated. Issues related to: (i) calculating the signal-to-noise ratio for arbitrarily large stochastic backgrounds, (ii) performing the data analysis in the presence of nonstationary detector noise, (iii) combining data from multiple detector pairs to increase the sensitivity of a stochastic background search, (iv) correlating the outputs of 4 or more detectors, and (v) allowing for the possibility of correlated noise in the outputs of two detectors are discussed. We briefly describe a computer simulation which mimics the generation and detection of a simulated stochastic gravity-wave signal in the presence of simulated detector noise. Numerous graphs and tables of numerical data for the five major interferometers (LIGO-WA, LIGO-LA, VIRGO, GEO-600, and TAMA-300) are also given. The treatment given in this paper should be accessible to both theorists involved in data analysis and experimentalists involved in detector design and data acquisition.Comment: 81 pages, 30 postscript figures, REVTE

The management of iron deficiency in inflammatory bowel disease

__Background__ Iron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). __Aim__ To develop an online tool to support treatment choice at the patient-specific level. __Methods__ Using the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds and three plenary discussion meetings. __Results__ The panel reached agreement on 71% of treatment indications. 'No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. __Conclusions__ The RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/

Simulated Optimisation of Disordered Structures with negative Poisson’s ratios

Copyright © 2009 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Mechanics of Materials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mechanics of Materials, Vol. 41 Issue 8 (2009). DOI: 10.1016/j.mechmat.2009.04.008Two-dimensional regular theoretical units that give a negative Poisson’s ratio (NPR) are well documented and well understood. Predicted mechanical properties resulting from these models are reasonably accurate in two dimensions but fall down when used for heterogeneous real-world materials. Manufacturing processes are seldom perfect and some measure of heterogeneity is therefore required to account for the deviations from the regular unit cells in this real-life situation. Analysis of heterogeneous materials in three dimensions is a formidable problem; we must first understand heterogeneity in two dimensions. This paper approaches the problem of finding a link between heterogeneous networks and its material properties from a new angle. Existing optimisation tools are used to create random two-dimensional topologies that display NPR, and the disorder in the structure and its relationship with NPR is investigated

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Systemic Inflammation in Preclinical Ulcerative Colitis

Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins. Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored. Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1ß, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-¿B, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis. Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors. © 2021 The Author

Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16–50 years

BACKGROUND: Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. AIM: This large retrospective study aimed to determine the most effective use of FC in patients aged 16–50 presenting with GI symptoms. METHODS: FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. RESULTS: 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 μg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 μg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. CONCLUSIONS: Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The study protocol including the statistical analysis plan is available at https://www.clarityibd.org/. Individual participant de-identified data that underlie the results reported in this article will be available immediately after publication for a period of 5 years. Due to the sensitive nature of the data, this will be made available to investigators whose proposed use of the data has been approved by an independent review committee. Analyses will be restricted to the aims in the approved proposal. Proposals should be directed to [email protected]. To gain access data requestors will need to sign a data access agreement. Data from the Virus Watch study is currently being archived on the Office of National Statistics Secure Research Service and will be available shortly. Source data are provided with this paper in the Source Data file. Source data are provided with this paper.Code availability: Statistical analyses were undertaken in R 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria. Code has been made available at: https://github.com/exeteribd/clarityibd-public.Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients

Study of B^{+-} -> K^{+-}(K_S K pi)^0 Decay and Determination of eta_c and eta_c(2S) Parameters

We report the results of a study of $B^{\pm}\to K^{\pm}\eta_c$ and $B^{\pm}\to K^{\pm}\eta_c(2S)$ decays followed by $\eta_c$ and $\eta_c(2S)$ decays to $(K_SK\pi)^0$. The results are obtained from a data sample containing 535 million $B\bar{B}$-meson pairs collected by the Belle experiment at the KEKB $e^+e^-$ collider. We measure the products of the branching fractions ${\mathcal B}(B^{\pm}\to K^{\pm}\eta_c){\mathcal B}(\eta_c\to K_S K^{\pm}\pi^{\mp})=(26.7\pm 1.4(stat)^{+2.9}_{-2.6}(syst)\pm 4.9(model))\times 10^{-6}$ and ${\mathcal B}(B^{\pm}\to K^{\pm}\eta_c(2S)){\mathcal B}(\eta_c(2S)\to K_S K^{\pm}\pi^{\mp})=(3.4^{+2.2}_{-1.5}(stat+model)^{+0.5}_{-0.4} syst))\times 10^{-6}$. Interference with the non-resonant component leads to significant model uncertainty in the measurement of these product branching fractions. Our analysis accounts for this interference and allows the model uncertainty to be reduced. We also obtain the following charmonia masses and widths: $M(\eta_c)=(2985.4\pm 1.5(stat)^{+0.5}_{-2.0}(syst))$ MeV/$c^2$, $\Gamma(\eta_c)=(35.1\pm 3.1(stat)^{+1.0}_{-1.6}(syst))$ MeV/$c^2$, $M(\eta_c(2S))=(3636.1^{+3.9}_{-4.2}(stat+model)^{+0.7}_{-2.0}(syst))$ MeV/$c^2$, $\Gamma(\eta_c(2S))=(6.6^{+8.4}_{-5.1}(stat+model)^{+2.6}_{-0.9}(syst))$ MeV/$c^2$.Comment: 23 pages, 10 figures, submitted to PL