Animal Inhalation Models to Investigate Modulation of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) comprise primarily two disease manifestations, ulcerative colitis (UC) and Crohn’s disease (CD), each with distinctive clinical and pathological features. Environmental and clinical factors strongly affect the development and clinical outcomes of IBDs. Among environmental factors, cigarette smoke (CS) is considered the most important risk factor for CD, while it attenuates the disease course of UC. Various animal models have been used to assess the impact of CS on intestinal pathophysiology. This chapter examines the suitability of animal inhalation/smoke exposure models for assessing the contrary effects of CS on UC and CD. It presents an updated literature review of IBD mouse models and a description of possible mechanisms relevant to relationships between IBD and smoking. In addition, it summarises various technical inhalation approaches, in the context of mouse disease models of IBD

A Highly Active Esterase from \u3cem\u3eLactobacillus helveticus\u3c/em\u3e Hydrolyzes Chlorogenic Acid in Sunflower Meal to Prevent Chlorogenic Acid Induced Greening in Sunflower Protein Isolates

Chlorogenic acid (CGA) is an ester between caffeic and quinic acid. It is found in many foods and reacts with free amino groups in proteins at alkaline pH, leading to the formation of an undesirable green pigment in sunflower seed-derived ingredients. This paper presents the biochemical characterization and application of a highly active chlorogenic acid esterase from Lactobacillus helveticus. The enzyme is one of the most active CGA esterases known to date with a Km of 0.090 mM and a kcat of 82.1 s−1. The CGA esterase is easily expressed recombinantly in E. coli in large yields and is stable over a wide range of pH and temperatures. We characterized CGA esterase’s kinetic properties in sunflower meal and demonstrated that the enzyme completely hydrolyzes CGA in the meal. Finally, we showed that CGA esterase treatment of sunflower seed meal enables the production of pale brown sunflower protein isolates using alkaline extraction. This work will allow for more widespread use of sunflower-derived products in applications where neutrally-colored food products are desired

Decoherence-Free Subspaces for Multiple-Qubit Errors: (II) Universal, Fault-Tolerant Quantum Computation

Decoherence-free subspaces (DFSs) shield quantum information from errors induced by the interaction with an uncontrollable environment. Here we study a model of correlated errors forming an Abelian subgroup (stabilizer) of the Pauli group (the group of tensor products of Pauli matrices). Unlike previous studies of DFSs, this type of errors does not involve any spatial symmetry assumptions on the system-environment interaction. We solve the problem of universal, fault-tolerant quantum computation on the associated class of DFSs.Comment: 22 pages, 4 figures. Sequel to quant-ph/990806

Decoherence-Free Subspaces for Multiple-Qubit Errors: (I) Characterization

Coherence in an open quantum system is degraded through its interaction with a bath. This decoherence can be avoided by restricting the dynamics of the system to special decoherence-free subspaces. These subspaces are usually constructed under the assumption of spatially symmetric system-bath coupling. Here we show that decoherence-free subspaces may appear without spatial symmetry. Instead, we consider a model of system-bath interactions in which to first order only multiple-qubit coupling to the bath is present, with single-qubit system-bath coupling absent. We derive necessary and sufficient conditions for the appearance of decoherence-free states in this model, and give a number of examples. In a sequel paper we show how to perform universal and fault tolerant quantum computation on the decoherence-free subspaces considered in this paper.Comment: 18 pages, no figures. Major changes. Section on universal fault tolerant computation removed. This section contained a crucial error. A new paper [quant-ph/0007013] presents the correct analysi

SO(10) Cosmic Strings and SU(3) Color Cheshire Charge

Certain cosmic strings that occur in GUT models such as $SO(10)$ can carry a magnetic flux which acts nontrivially on objects carrying $SU(3)_{color}$ quantum numbers. We show that such strings are non-Abelian Alice strings carrying nonlocalizable colored ``Cheshire" charge. We examine claims made in the literature that $SO(10)$ strings can have a long-range, topological Aharonov-Bohm interaction that turns quarks into leptons, and observe that such a process is impossible. We also discuss flux-flux scattering using a multi-sheeted formalism.Comment: 37 Pages, 8 Figures (available upon request) phyzzx, iassns-hep-93-6, itp-sb-93-6

Factors associated with completion of bowel cancer screening and the potential effects of simplifying the screening test algorithm

BACKGROUND: The primary colorectal cancer screening test in England is a guaiac faecal occult blood test (gFOBt). The NHS Bowel Cancer Screening Programme (BCSP) interprets tests on six samples on up to three test kits to determine a definitive positive or negative result. However, the test algorithm fails to achieve a definitive result for a significant number of participants because they do not comply with the programme requirements. This study identifies factors associated with failed compliance and modifications to the screening algorithm that will improve the clinical effectiveness of the screening programme. METHODS: The BCSP Southern Hub data for screening episodes started in 2006–2012 were analysed for participants aged 60–69 years. The variables included age, sex, level of deprivation, gFOBt results and clinical outcome. RESULTS: The data set included 1 409 335 screening episodes; 95.08% of participants had a definitively normal result on kit 1 (no positive spots). Among participants asked to complete a second or third gFOBt, 5.10% and 4.65%, respectively, failed to return a valid kit. Among participants referred for follow up, 13.80% did not comply. Older age was associated with compliance at repeat testing, but non-compliance at follow up. Increasing levels of deprivation were associated with non-compliance at repeat testing and follow up. Modelling a reduction in the threshold for immediate referral led to a small increase in completion of the screening pathway. CONCLUSIONS: Reducing the number of positive spots required on the first gFOBt kit for referral for follow-up and targeted measures to improve compliance with follow-up may improve completion of the screening pathway

Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London