A reassessment of Antarctic plateau reactive nitrogen based on ANTCI 2003 airborne and ground based measurements

The first airborne measurements of nitric oxide (NO) on the Antarctic plateau have demonstrated that the previously reported elevated levels of this species extend well beyond the immediate vicinity of South Pole. Although the current database is still relatively weak and critical laboratory experiments are still needed, the findings here suggest that the chemical uniqueness of the plateau may be substantially greater than first reported. For example, South Pole ground-based findings have provided new evidence showing that the dominant process driving the release of nitrogen from the snowpack during the spring/summer season (post-depositional loss) is photochemical in nature with evaporative processes playing a lesser role. There is also new evidence suggesting that nitrogen, in the form of nitrate, may undergo multiple recycling within a given photochemical season. Speculation here is that this may be a unique property of the plateau and much related to its having persistent cold temperatures even during summer. These conditions promote the efficient adsorption of molecules like HNO3 (and very likely HO2NO2) onto snow-pack surface ice where we have hypothesized enhanced photochemical processing can occur, leading to the efficient release of NOx to the atmosphere. In addition, to these process-oriented tentative conclusions, the findings from the airborne studies, in conjunction with modeling exercises suggest a new paradigm for the plateau atmosphere. The near-surface atmosphere over this massive region can be viewed as serving as much more than a temporary reservoir or holding tank for imported chemical species. It defines an immense atmospheric chemical reactor which is capable of modifying the chemical characteristics of select atmospheric constituents. This reactor has most likely been in place over geological time, and may have led to the chemical modulation of some trace species now found in ice cores. Reactive nitrogen has played a critical role in both establishing and in maintaining this reactor. © 2007 Elsevier Ltd. All rights reserved

New distinguished classes of spectral spaces: a survey

In the present survey paper, we present several new classes of Hochster's spectral spaces "occurring in nature", actually in multiplicative ideal theory, and not linked to or realized in an explicit way by prime spectra of rings. The general setting is the space of the semistar operations (of finite type), endowed with a Zariski-like topology, which turns out to be a natural topological extension of the space of the overrings of an integral domain, endowed with a topology introduced by Zariski. One of the key tool is a recent characterization of spectral spaces, based on the ultrafilter topology, given in a paper by C. Finocchiaro in Comm. Algebra 2014. Several applications are also discussed

Comparative Study of Inference Methods for Bayesian Nonnegative Matrix Factorisation

In this paper, we study the trade-offs of different inference approaches for Bayesian matrix factorisation methods, which are commonly used for predicting missing values, and for finding patterns in the data. In particular, we consider Bayesian nonnegative variants of matrix factorisation and tri-factorisation, and compare non-probabilistic inference, Gibbs sampling, variational Bayesian inference, and a maximum-a-posteriori approach. The variational approach is new for the Bayesian nonnegative models. We compare their convergence, and robustness to noise and sparsity of the data, on both synthetic and real-world datasets. Furthermore, we extend the models with the Bayesian automatic relevance determination prior, allowing the models to perform automatic model selection, and demonstrate its efficiency

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Degenerate Rotating Black Holes, Chiral CFTs and Fermi Surfaces I - Analytic Results for Quasinormal Modes

In this work we discuss charged rotating black holes in $AdS_5 \times S^5$ that degenerate to extremal black holes with zero entropy. These black holes have scaling properties between charge and angular momentum similar to those of Fermi surface operators in a subsector of $\mathcal{N}=4$ SYM. We add a massless uncharged scalar to the five dimensional supergravity theory, such that it still forms a consistent truncation of the type IIB ten dimensional supergravity and analyze its quasinormal modes. Separating the equation of motion to a radial and angular part, we proceed to solve the radial equation using the asymptotic matching expansion method applied to a Heun equation with two nearby singularities. We use the continued fraction method for the angular Heun equation and obtain numerical results for the quasinormal modes. In the case of the supersymmetric black hole we present some analytic results for the decay rates of the scalar perturbations. The spectrum of quasinormal modes obtained is similar to that of a chiral 1+1 CFT, which is consistent with the conjectured field-theoretic dual. In addition, some of the modes can be found analytically.Comment: 41 pages, 1 figure, LaTeX; v2: typos corrected, references adde

The effectiveness and safety of TNF-alpha blockers in the treatment of early psoriatic arthritis: an Italian multicentre longitudinal observational pilot study

The objective of this study is to assess the effectiveness and safety of TNF-α blockers in a group of early psoriatic arthritis (PsA) patients with an unsatisfactory response to previous conventional treatment consecutively enrolled in five Italian centres. A 24-week open-label trial was carried out in consecutive early PsA patients classified according to the CASPAR criteria, with unsatisfactory response to previous treatments and with a DAS28 threshold as ≥3.2, seen at the outpatient clinics of each centre. Exclusion criteria were previous usage of TNF-α blockers and a disease duration >12 months. The choice of any of the three TNF-α blockers was decided by the expert’s opinion, without any restriction. Effectiveness was considered as an improvement of DAS28 at 12 and 24 weeks of treatment. Secondary endpoints were an improvement of TJC, SWJ, HAQ score and PASI score. Changes from baseline to the 12- and 24-week follow-up assessments were analysed using the Wilcoxon paired sign rank test. Twenty-nine patients (14 males, 15 females, median age 37 years, range 20–65 years) were enrolled. A statistical improvement of the DAS28 was observed at 12 and 24 weeks from baseline (p < 0.001). Secondary endpoints also confirmed the effectiveness of the TNF-α blockers in the treatment of early PsA. No severe adverse events were observed during the treatment period, and no patient withdrew from the medications. This study suggests that the TNF-α blockers can be effective in the management of early PsA. Further controlled studies will provide more data on this challenging topic

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Targeting the rheumatoid arthritis synovial fibroblast via cyclin dependent kinase inhibition: An early phase trial

Introduction: Targeted biologic therapies demonstrate similar efficacies in rheumatoid arthritis despite distinct mechanisms of action. They also exhibit a ceiling effect, with 10% to 20% of patients achieving remission in clinical trials. None of these therapies target synovial fibroblasts, which drive and maintain synovitis. Seliciclib (R-roscovitine) is an orally available cyclin-dependent kinase inhibitor that suppresses fibroblast proliferation, and is efficacious in preclinical arthritis models. We aim to determine the toxicity and preliminary efficacy of seliciclib in combination with biologic therapies, to inform its potential as an adjunctive therapy in rheumatoid arthritis. Methods and analysis: TRAFIC is a non-commercial, multi-center, rolling phase Ib/IIa trial investigating the safety, tolerability, and efficacy of seliciclib in patients with moderate to severe rheumatoid arthritis receiving biologic therapies. All participants receive seliciclib with no control arm. The primary objective of part 1 (phase Ib) is to determine the maximum tolerated dose and safety of seliciclib over 4 weeks of dosing. Part 1 uses a restricted 1-stage Bayesian continual reassessment method based on a target dose-limiting toxicity probability of 35%. Part 2 (phase IIa) assesses the potential efficacy of seliciclib, and is designed as a single arm, single stage early phase trial based on a Fleming-A’Hern design using the maximum tolerated dose recommended from part 1. The primary response outcome after 12 weeks of therapy is a composite of clinical, histological and magnetic resonance imaging scores. Secondary outcomes include adverse events, pharmacodynamic and pharmacokinetic parameters, autoantibodies, and fatigue. Ethics and dissemination: The study has been reviewed and approved by the North East - Tyne & Wear South Research Ethics Committee (reference 14/NE/1075) and the Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom. Results will be disseminated through publication in relevant peer-reviewed journals and presentation at national and international conferences. Trials Registration: ISRCTN, ISRCTN36667085. Registered on September 26, 2014; http://www.isrctn.com/ISRCTN36667085 Current protocol version: Protocol version 11.0 (March 21, 2019