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© The Author(s) 2020.With Liquid-Cell Transmission Electron Microscopy (LCTEM) we can observe the kinetic processes taking place in nanoscale materials that are in a solvated environment. However, the beam-driven solvent radiolysis, which results from the microscope's high-energy electron beam, can dramatically influence the dynamics of the system. Recent research suggests that radical-induced redox chemistry can be used to investigate the various redox-driven dynamics for a wide range of functional nanomaterials. In view of this, the interplay between the formation of various highly reactive radiolysis species and the nanomaterials under investigation needs to be quantified in order to formulate new strategies for nanomaterials research. We have developed a comprehensive radiolysis model by using the electron-dose rate, the temperature of the solvent, the H2 and O2 gas saturation concentrations and the pH values as the key variables. These improved kinetic models make it possible to simulate the material's specific radical-induced redox reactions. As in the case of the Au model system, the kinetic models are presented using Temperature/Dose-rate Redox potential (TDR) diagrams, which indicate the equilibrium [Au0]/[Au+] concentration ratios that are directly related to the temperature-/dose-rate-dependent precipitation or dissolution regions of the Au nanoparticles. Our radiolysis and radical-induced redox models were successfully verified using previously reported data from low-dose experiments with γ radiation and experimentally via TDR-dependent LCTEM. Staurosporine The presented study represents a holistic approach to the radical-induced redox chemistry in LCTEM, including the complex kinetics of the radiolysis species and their influence on the redox chemistry of the materials under investigation, which are represented here by Au nanoparticles. This journal is © The Royal Society of Chemistry 2019.[This corrects the article DOI 10.1039/C5SC01828E.]. This journal is © The Royal Society of Chemistry 2019.Despite its apparent simplicity, water displays unique behavior across the phase diagram which is strictly related to the ability of the water molecules to form dense, yet dynamic, hydrogen-bond networks that continually fluctuate in time and space. The competition between different local hydrogen-bonding environments has been hypothesized as a possible origin of the anomalous properties of liquid water. Through a systematic application of the many-body expansion of the total energy, we demonstrate that the local structure of liquid water at room temperature is determined by a delicate balance between two-body and three-body energies, which is further modulated by higher-order many-body effects. Besides providing fundamental insights into the structure of liquid water, this analysis also emphasizes that a correct representation of two-body and three-body energies requires sub-chemical accuracy that is nowadays only achieved by many-body models rigorously derived from the many-body expansion of the total energy, which thus hold great promise for shedding light on the molecular origin of the anomalous behavior of liquid water. This journal is © The Royal Society of Chemistry 2019.Extraintestinal manifestations of gastrointestinal disease can form an important aspect of the diagnosis, monitoring and management in these diseases. Ocular manifestations in particular are often disregarded and can, albeit rarely, present as an emergency. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Parenteral nutrition transformed the prognosis for infants and children with intestinal failure. Soon after its introduction into clinical care 50 years ago, parenteral nutrition was also rapidly adopted for use in the preterm infant, where immaturity of gastrointestinal motor function precluded enteral feeding. Preterm infants subsequently became the single largest group of patients to be fed in this way. Although the development of scientific knowledge and the lessons of clinical experience have reduced the risk of complications, some of the problems and difficulties associated with this form of nutritional support remain challenging. These include central venous catheter-related sepsis, thrombosis, liver disease, bone disease and metabolic disturbance. In an initiative to promote best practice, guidelines on parenteral nutrition were first published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and collaborating organisations in 2005. These were constructed following a thorough review of the scientific literature, allowing a series of evidence-based recommendations to be made. The exercise was repeated just over 10 years later and updated guidelines published in 2018. This review summarises key elements from the new guideline, with a focus on what has changed since 2005. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which accounts for a substantial proportion of a gastroenterologist's time in the outpatient clinic. However, there is variability in approaches to diagnosis and investigation between physicians, dependent on expertise. Many patients express disappointment over the lack of a patient-centred approach. Consequently, there have been calls for the care of patients with IBS to be standardised, a process which aims to promote high-quality and high-value care. Making an early diagnosis, based on a clinical assessment of symptoms, while limiting use of investigations, are key tenets of this process. Exhaustive investigation to exclude all organic pathology is unnecessary, and may be counterproductive. Routine blood tests in suspected IBS have low yield, but are an acceptable part of routine practice. All patients should have coeliac serology tested, regardless of their predominant stool form. Patients with diarrhoea should have a faecal calprotectin measured, and should proceed to colonoscopy to exclude inflammatory bowel disease (IBD) if this is positive. Beyond this, the need for investigations should be made on a case-by-case basis, contingent on the reporting of known risk factors for organic pathology. Colonoscopy should be considered in any patient with alarm features for colorectal cancer, and in those whose clinical features are suggestive of microscopic colitis. A 23-seleno-25-homotaurocholic acid (SeHCAT) scan should be considered in patients with IBS-D, a third of whom may actually have bile acid diarrhoea. There is no role for routine hydrogen breath tests for lactose malabsorption or small intestinal bacterial overgrowth. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Alcoholic hepatitis (AH) is an acute deterioration in liver function seen in the context of prolonged excessive alcohol consumption and is characterised by the rapid onset of jaundice. The diagnosis of AH has been controversial for many years it is now accepted that there are clear clinical criteria which can be used to diagnose AH without the need for a liver biopsy. Corticosteroids remain the only treatment proven to be effective in reducing short-term mortality in severe AH; abstinence from alcohol is the most important factor in determining long-term survival. It is recommended a trial of corticosteroid therapy is considered only in those patients with high baseline 'static' scores (Glasgow Alcoholic Hepatitis score and model for end-stage liver disease). Response to corticosteroid therapy should be assessed using a 'dynamic' score such as the Lille score at day 7, with corticosteroids continuing only in patients with a favourable score. Infection and acute kidney injury are associated with poorer outcomes in AH. Early screening for and treatment of infection is recommended with antibiotic therapy overlapping with any subsequent corticosteroid treatment. A biomarker which predicts benefit from corticosteroids at baseline would avoid a trial of therapy to determine response. More efficacious therapeutic options for AH patients are required with N-acetylcysteine, granulocyte colony stimulating factor, faecal microbiota transplantation and routine antibiotics showing promise, but adequate controlled trials are needed to confirm efficacy. Liver transplant has an emerging role for some patients with severe AH not responding to corticosteroids and is likely to become more acceptable with improved methods of patient selection. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with an increased risk of colorectal cancer (CRC). This has led to the implementation of surveillance programmes to minimise this risk. Overall, these proactive programmes in association with better medical therapies have reduced the incidence of CRC in this population. Specific populations remain at increased risk, such as younger age at diagnosis, primary sclerosing cholangitis, colonic strictures and pseudopolyps. The majority of gastrointestinal international societies favour chromoendoscopy with targeted biopsies or random biopsies. The aim of this review is to present the current literature on dysplasia surveillance, the methodology and endoscopic technology available to assess dysplasia in UC. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Objective To establish the relationship between trough vedolizumab levels and outcomes during maintenance therapy. Design Cross-sectional service evaluation was performed on patients with inflammatory bowel disease (IBD) receiving maintenance vedolizumab therapy (minimum of 12 weeks following induction). Prior to infusion, data on clinical activity (Harvey-Bradshaw Index or partial Mayo score), trough C-reactive protein (CRP)/vedolizumab levels and faecal calprotectin were collected. Endoscopic data (±8 weeks from vedolizumab level testing) were obtained by review of medical records. Vedolizumab levels were processed using the Immundiagnostik monitor ELISA. Setting The Edinburgh IBD Unit, Western General Hospital (tertiary IBD referral centre). Patients Seventy-three patients (30 ulcerative colitis and 43 Crohn's disease) were identified who fulfilled inclusion criteria and had vedolizumab levels matched with clinical activity scores, CRP and faecal calprotectin. Of these, 40 patients also had matched endoscos. Published by BMJ.Objective To understand the effectiveness of ustekinumab in treating Crohn's disease (CD) in a UK real-world setting. Design Retrospective cohort study using prospectively maintained clinical records. Setting Single UK inflammatory bowel disease centre. Patients Adult patients with an established diagnosis of CD prescribed ustekinumab outside of clinical trials at University Hospital Southampton (UHS). Interventions Ustekinumab, a monoclonal antibody to the shared p40 subunit of interleukin (IL) 12 and IL-23 as part of routine clinical care. Main outcome measures Effectiveness as measured by an improvement in physician's global assessment, drug persistence and improvement in biomarkers (C-reactive protein (CRP), albumin and calprotectin). Results 84 patients were included, 72 had a postinduction review and 49 had 1-year data. At postinduction clinical review, clinical response occurred in 53% of patients and clinical remission occurred in 8%. For patients on ustekinumab at 1 year, clinical response occurred in 71% and remission in 14%.

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