The risk of inflammatory bowel disease in patients with axial spondyloarthritis treated with biologic agents : BSRBR-AS and meta-analysis

Funding: The BSRBR-AS is supported by the British Society for Rheumatology and they have received funds for the registry from Pfizer, AbbVie and UCB. These companies have no input in determining the topics for analysis or work involved in undertaking it but do receive an advance copy of the manuscript on which they may make comments. ACKNOWLEDGEMENTS: The original idea for the study was suggested by John Mansfield and discussed with Lesley Kay (both Newcastle upon Tyne Hospitals NHS Foundation Trust). All authors discussed and contributed to designing this study and the analysis plan, which was undertaken by RLB and (updated and) overseen by OR, LED and GJM. Results were reviewed by all authors. GJM, RLB, OR and LED all contributed to drafting the manuscript which was critically reviewed by all authors. RLB undertook this work while a visiting student based at the University of Aberdeen from Ludwig-Maximilians Universität (Munich).Peer reviewedPostprin

Corrigendum: Solar cycles or random processes? Evaluating solar variability in Holocene climate records

This is the final version of the article. Available from Springer Nature via the DOI in this record.The article to which this is the corrigendum is in ORE at http://hdl.handle.net/10871/21766A coding error in the Monte Carlo procedure for the determination of critical values in running correlation analysis (presented in Supplementary Data S8) has been brought to the attention of the authors.[...

Enhancing Symbolic Execution of Heap-based Programs with Separation Logic for Test Input Generation

Symbolic execution is a well established method for test input generation. Despite of having achieved tremendous success over numerical domains, existing symbolic execution techniques for heap-based programs are limited due to the lack of a succinct and precise description for symbolic values over unbounded heaps. In this work, we present a new symbolic execution method for heap-based programs based on separation logic. The essence of our proposal is context-sensitive lazy initialization, a novel approach for efficient test input generation. Our approach differs from existing approaches in two ways. Firstly, our approach is based on separation logic, which allows us to precisely capture preconditions of heap-based programs so that we avoid generating invalid test inputs. Secondly, we generate only fully initialized test inputs, which are more useful in practice compared to those partially initialized test inputs generated by the state-of-the-art tools. We have implemented our approach as a tool, called Java StarFinder, and evaluated it on a set of programs with complex heap inputs. The results show that our approach significantly reduces the number of invalid test inputs and improves the test coverage

Comparative analysis of inspection and diagnosis tools for ancient buildings

The survey and inspection of the state of conservation of buildings is understood as an active process of selecting information to support decision making in the rehabilitation of the built heritage. The development of new technologies applied to the integrated management of the built heritage resulted in digital tools able to support the technicians in on-site procedures. The purpose of this study was to analyse existing methods for the survey and inspection of the state of conservation of ancient buildings. It uses a qualitative methodology, focused on bibliographical survey and comparative analysis. Only methods with identical characteristics were considered: evaluation based on visual inspection of buildings with heritage value. This research shows that structuring information in computer systems is a solution to overcome the main problems pointed out in previous studies related to survey and inspection: expensive, time-consuming, inconsequential procedures and dispersed information. However, this is only valid if computer-based methods are adapted to the different geographic and chronological contexts. Future research may contribute to the development of a method that brings together this added value with a simple but objective way to diagnose the condition of ancient buildings with heritage value.The authors would like to acknowledge the support granted by the Portuguese Foundation for Science and Technology (FCT), in the scope of the Doctoral Program Eco-Construction and Rehabilitation (EcoCoRe), to the Ph.D. scholarship with the reference PD/BD/127853/2016 that was fundamental for the development of this study.info:eu-repo/semantics/publishedVersio

Adsorption mechanism of hexavalent chromium onto layered double hydroxides-based adsorbents: A systematic in-depth review

© 2019 Elsevier B.V. An attempt has been made in this review to provide some insights into the possible adsorption mechanisms of hexavalent chromium onto layered double hydroxides-based adsorbents by critically examining the past and present literature. Layered double hydroxides (LDH) nanomaterials are typical dual-electronic adsorbents because they exhibit positively charged external surfaces and abundant interlayer anions. A high positive zeta potential value indicates that LDH has a high affinity to Cr(VI) anions in solution through electrostatic attraction. The host interlayer anions (i.e., Cl−, NO3−, SO42−, and CO32−) provide a high anion exchange capacity (53–520 meq/100 g) which is expected to have an excellent exchangeable capacity to Cr(VI) oxyanions in water. Regarding the adsorption-coupled reduction mechanism, when Cr(VI) anions make contact with the electron-donor groups in the LDH, they are partly reduced to Cr(III) cations. The reduced Cr(III) cations are then adsorbed by LDH via numerous interactions, such as isomorphic substitution and complexation. Nonetheless, the adsorption-coupled reduction mechanism is greatly dependent on: (1) the nature of divalent and trivalent salts utilized in LDH preparation, and the types of interlayer anions (i.e., guest intercalated organic anions), and (3) the adsorption experiment conditions. The low Brunauer–Emmett–Teller specific surface area of LDH (1.80–179 m2/g) suggests that pore filling played an insignificant role in Cr(VI) adsorption. The Langmuir maximum adsorption capacity of LDH (Qomax) toward Cr(VI) was significantly affected by the natures of used inorganic salts and synthetic methods of LDH. The Qomax values range from 16.3 mg/g to 726 mg/g. Almost all adsorption processes of Cr(VI) by LDH-based adsorbent occur spontaneously (ΔG° 0) and increase the randomness (ΔS° >0) in the system. Thus, LDH has much potential as a promising material that can effectively remove anion pollutants, especially Cr(VI) anions in industrial wastewater

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

Antimicrobial resistance in humans, livestock and the wider environment

Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes