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james chalmers

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https://www.readbyqxmd.com/read/29109530/a-clinical-scale-bioartificial-liver-developed-for-gmp-improved-clinical-parameters-of-liver-function-in-porcine-liver-failure
#1
Clare Selden, James Bundy, Eloy Erro, Eva Puschmann, Malcolm Miller, Delawir Kahn, Humphrey Hodgson, Barry Fuller, Jordi Gonzalez-Molina, Aurelie Le Lay, Stephanie Gibbons, Sherri Chalmers, Sunil Modi, Amy Thomas, Peter Kilbride, Agnes Isaacs, Richard Ginsburg, Helen Ilsley, David Thomson, Galya Chinnery, Ncedile Mankahla, Lizel Loo, C Wendy Spearman
Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29101284/genetic-mannose-binding-lectin-deficiency-is-associated-with-airway-microbiota-diversity-and-reduced-exacerbation-frequency-in-copd
#2
Alison J Dicker, Megan L Crichton, Andrew J Cassidy, Gill Brady, Adrian Hapca, Roger Tavendale, Gisli G Einarsson, Elizabeth Furrie, J Stuart Elborn, Stuart Schembri, Sara E Marshall, Colin N A Palmer, James D Chalmers
BACKGROUND: In cystic fibrosis and bronchiectasis, genetic mannose binding lectin (MBL) deficiency is associated with increased exacerbations and earlier mortality; associations in COPD are less clear. Preclinical data suggest MBL interferes with phagocytosis of Haemophilus influenzae, a key COPD pathogen. We investigated whether MBL deficiency impacted on clinical outcomes or microbiota composition in COPD. METHODS: Patients with COPD (n=1796) underwent MBL genotyping; linkage to health records identified exacerbations, lung function decline and mortality...
November 3, 2017: Thorax
https://www.readbyqxmd.com/read/29043150/community-acquired-pneumonia-in-the-united-kingdom-a-call-to-action
#3
EDITORIAL
James Chalmers, James Campling, Gillian Ellsbury, Peter M Hawkey, Harish Madhava, Mary Slack
Pneumococcal disease has a high burden in adults in the United Kingdom (UK); however, the total burden is underestimated, principally because most cases of community-acquired pneumonia (CAP) are non-invasive. Research into pneumonia receives poor funding relative to its disease burden (global mortality, disability-adjusted life years, and years lived with disability), ranking just 20 out of 25 for investment in infectious diseases in the UK. The current accuracy of data for establishing incidence rates is questionable, and it is a reflection of the paucity of research that much of the background information available derives from nearly 30 years ago...
2017: Pneumonia
https://www.readbyqxmd.com/read/28931673/10%C3%A2-years-since-torch-shining-a-new-light-on-the-risks-of-inhaled-corticosteroids-in-copd
#4
EDITORIAL
James D Chalmers, Holly R Keir
No abstract text is available yet for this article.
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28928219/o2-sensing-associated-glycosylation-exposes-the-f-box-combining-site-of-the-dictyostelium-skp1-subunit-in-e3-ubiquitin-ligases
#5
M Osman Sheikh, David Thieker, Gordon Chalmers, Christopher M Schafer, Mayumi Ishihara, Parastoo Azadi, Robert J Woods, John N Glushka, Brad Bendiak, James H Prestegard, Christopher M West
Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box binding domain. Prolyl hydroxylation of Skp1 contributes to O2-dependent Dictyostelium development, but full glycosylation at that position is required for optimal O2 sensing...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#6
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28894480/patient-participation-in-ers-guidelines-and-research-projects-the-embarc-experience
#7
REVIEW
James D Chalmers, Alan Timothy, Eva Polverino, Marta Almagro, Thomas Ruddy, Pippa Powell, Jeanette Boyd
The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration dedicated to improving research and clinical care for people with bronchiectasis. EMBARC has created a European Bronchiectasis Registry, funded by the ERS and by the European Union (EU) Innovative Medicines Initiative Programme. From the outset, EMBARC had the ambition to be a patient-focussed project. In contrast to many respiratory diseases, however, there are no specific patient charities or European patient organisations for patients with bronchiectasis and no existing infrastructure for patient engagement...
September 2017: Breathe
https://www.readbyqxmd.com/read/28894479/the-european-multicentre-bronchiectasis-audit-and-research-collaboration-embarc-experiences-from-a-successful-ers-clinical-research-collaboration
#8
REVIEW
James D Chalmers, Megan Crichton, Pieter C Goeminne, Michael R Loebinger, Charles Haworth, Marta Almagro, Montse Vendrell, Anthony De Soyza, Raja Dhar, Lucy Morgan, Francesco Blasi, Stefano Aliberti, Jeanette Boyd, Eva Polverino
In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers...
September 2017: Breathe
https://www.readbyqxmd.com/read/28890433/evaluation-of-severity-score-guided-approaches-to-macrolide-use-in-community-acquired-pneumonia
#9
Aran Singanayagam, Stefano Aliberti, Catia Cillóniz, Antoni Torres, Francesco Blasi, James D Chalmers
International guidelines including those in the UK, Japan, Australia and South Africa recommend the avoidance of macrolides in patients with low-severity community-acquired pneumonia (CAP). We hypothesised that severity scores are poor predictors of atypical pneumonia and response to macrolide therapy, and thus, inadequate tools for guiding antibiotic prescriptions.Secondary analysis of four independent prospective CAP datasets was conducted. The predictive values of the CURB-65 and pneumonia severity index (PSI) for clinically important groups of causative pathogens were evaluated...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28889110/european-respiratory-society-guidelines-for-the-management-of-adult-bronchiectasis
#10
Eva Polverino, Pieter C Goeminne, Melissa J McDonnell, Stefano Aliberti, Sara E Marshall, Michael R Loebinger, Marlene Murris, Rafael Cantón, Antoni Torres, Katerina Dimakou, Anthony De Soyza, Adam T Hill, Charles S Haworth, Montserrat Vendrell, Felix C Ringshausen, Dragan Subotic, Robert Wilson, Jordi Vilaró, Bjorn Stallberg, Tobias Welte, Gernot Rohde, Francesco Blasi, Stuart Elborn, Marta Almagro, Alan Timothy, Thomas Ruddy, Thomy Tonia, David Rigau, James D Chalmers
Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28854829/profile-of-the-proaxsis-active-neutrophil-elastase-immunoassay-for-precision-medicine-in-chronic-respiratory-disease
#11
Holly R Keir, Christopher J Fong, Alison J Dicker, James D Chalmers
Neutrophil elastase (NE) is a 29kDa serine protease released from the azurophilic granules of neutrophils. It may be directly involved in the pathogenesis and disease progression in cystic fibrosis, bronchiectasis and COPD through the degradation of airway elastin and by impairing host defence. Areas covered: Measurement of NE activity has emerged as a promising biomarker strategy in inflammatory lung disease. The authors review studies where NE activity has been linked with clinical outcomes such as lung function decline, exacerbation frequency or other cross-sectional and longitudinal markers of disease severity...
September 7, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28854070/first-in-human-phase-i-study-of-the-tamoxifen-metabolite-z-endoxifen-in-women-with-endocrine-refractory-metastatic-breast-cancer
#12
Matthew P Goetz, Vera J Suman, Joel M Reid, Don W Northfelt, Michael A Mahr, Andrew T Ralya, Mary Kuffel, Sarah A Buhrow, Stephanie L Safgren, Renee M McGovern, John Black, Travis Dockter, Tufia Haddad, Charles Erlichman, Alex A Adjei, Dan Visscher, Zachary R Chalmers, Garrett Frampton, Benjamin R Kipp, Minetta C Liu, John R Hawse, James H Doroshow, Jerry M Collins, Howard Streicher, Matthew M Ames, James N Ingle
Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed a phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity. Eligibility included endocrine-refractory, estrogen receptor-positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by a 3+3 design and expansion at 40, 80, and 100 mg per day...
October 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28749387/a-new-free-cost-e-service-supporting-clinicians-to-manage-their-difficult-to-treat-tuberculosis-cases-the-european-respiratory-society-world-health-organization-tuberculosis-consilium
#13
EDITORIAL
Lia D'Ambrosio, Marina Tadolini, Rosella Centis, James D Chalmers, Giovanni Battista Migliori
No abstract text is available yet for this article.
March 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28738058/establishing-a-library-of-resources-to-help-people-understand-key-concepts-in-assessing-treatment-claims-the-critical-thinking-and-appraisal-resource-library-carl
#14
John C Castle, Iain Chalmers, Patricia Atkinson, Douglas Badenoch, Andrew D Oxman, Astrid Austvoll-Dahlgren, Lena Nordheim, L Kendall Krause, Lisa M Schwartz, Steven Woloshin, Amanda Burls, Paola Mosconi, Tammy Hoffmann, Leila Cusack, Loai Albarqouni, Paul Glasziou
BACKGROUND: People are frequently confronted with untrustworthy claims about the effects of treatments. Uncritical acceptance of these claims can lead to poor, and sometimes dangerous, treatment decisions, and wasted time and money. Resources to help people learn to think critically about treatment claims are scarce, and they are widely scattered. Furthermore, very few learning-resources have been assessed to see if they improve knowledge and behavior. OBJECTIVES: Our objectives were to develop the Critical thinking and Appraisal Resource Library (CARL)...
2017: PloS One
https://www.readbyqxmd.com/read/28736342/tfos-dews-ii-diagnostic-methodology-report
#15
REVIEW
James S Wolffsohn, Reiko Arita, Robin Chalmers, Ali Djalilian, Murat Dogru, Kathy Dumbleton, Preeya Gupta, Paul Karpecki, Sihem Lazreg, Heiko Pult, Benjamin D Sullivan, Alan Tomlinson, Louis Tong, Edoardo Villani, Kyung Chul Yoon, Lyndon Jones, Jennifer Craig
The role of the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II Diagnostic Methodology Subcommittee was 1) to identify tests used to diagnose and monitor dry eye disease (DED), 2) to identify those most appropriate to fulfil the definition of DED and its sub-classifications, 3) to propose the most appropriate order and technique to conduct these tests in a clinical setting, and 4) to provide a differential diagnosis for DED and distinguish conditions where it is a comorbidity. Symptom screening with the DEQ-5 or OSDI confirms that a patient might have DED and triggers the diagnostic tests of (ideally non-invasive) breakup time, osmolarity and ocular surface staining with fluorescein and lissamine green (observing the cornea, conjunctiva and eyelid margin)...
May 4, 2017: Ocular Surface
https://www.readbyqxmd.com/read/28702304/oral-versus-intravenous-clarithromycin-in-moderate-to-severe-community-acquired-pneumonia-an-observational-study
#16
Nikolas Rae, Aran Singanayagam, Stuart Schembri, James D Chalmers
OBJECTIVES: British Thoracic Society guidelines recommend clarithromycin in addition to beta-lactam antibiotics for patients with community-acquired pneumonia and CURB-65 score 2-5. Intravenous therapy is commonly used but there are few data on whether oral therapy is equally effective. METHODS: This observational study used propensity matching to compare two groups of patients with moderate to severe community-acquired pneumonia (CURB-65 score 2-5) treated with oral (n = 226) or intravenous (n = 226) clarithromycin on admission...
2017: Pneumonia
https://www.readbyqxmd.com/read/28663549/determinants-of-initial-inhaled-corticosteroid-use-in-patients-with-gold-a-b-copd-a-retrospective-study-of-uk-general-practice
#17
James D Chalmers, Abigail Tebboth, Alicia Gayle, Andrew Ternouth, Nick Ramscar
Initial use of inhaled corticosteroid therapy is common in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) A or B chronic obstructive pulmonary disease, contrary to GOLD guidelines. We investigated UK prescribing of inhaled corticosteroid therapy in these patients, to identify predictors of inhaled corticosteroid use in newly diagnosed chronic obstructive pulmonary disease patients. A cohort of newly diagnosed GOLD A/B chronic obstructive pulmonary disease patients was identified from the UK Clinical Practice Research Datalink (June 2005-June 2015)...
June 29, 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28657170/the-past-decade-in-bench-research-into-pulmonary-infectious-diseases-what-do-clinicians-need-to-know
#18
REVIEW
Simon Finch, Holly R Keir, Alison J Dicker, James D Chalmers
Respiratory infections are primarily treated with antibiotics, drugs that are mostly inexpensive and have been widely available since the 1940s and 1950s. Nevertheless, despite antibiotics, the burden of disease in pneumonia, bronchiectasis, cystic fibrosis, COPD and rare respiratory infections remains exceptionally high. There is an urgent need for translational studies to develop new treatments or new biomarkers to improve outcomes in these conditions. The 'translational gaps' between bench science and clinical practice are particularly challenging in respiratory infections...
June 28, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28653216/nmr-characterization-of-htpg-the-e-coli-hsp90-using-sparse-labeling-with-13-c-methyl-alanine
#19
Kari Pederson, Gordon R Chalmers, Qi Gao, Daniel Elnatan, Theresa A Ramelot, Li-Chung Ma, Gaetano T Montelione, Michael A Kennedy, David A Agard, James H Prestegard
A strategy for acquiring structural information from sparsely isotopically labeled large proteins is illustrated with an application to the E. coli heat-shock protein, HtpG (high temperature protein G), a 145 kDa dimer. It uses (13)C-alanine methyl labeling in a perdeuterated background to take advantage of the sensitivity and resolution of Methyl-TROSY spectra, as well as the backbone-centered structural information from (1)H-(13)C residual dipolar couplings (RDCs) of alanine methyl groups. In all, 40 of the 47 expected crosspeaks were resolved and 36 gave RDC data...
July 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28614669/severe-pneumococcal-pneumonia-causes-acute-cardiac-toxicity-and-subsequent-cardiac-remodeling
#20
Luis F Reyes, Marcos I Restrepo, Cecilia A Hinojosa, Nilam J Soni, Antonio Anzueto, Bettina L Babu, Norberto Gonzalez-Juarbe, Alejandro H Rodriguez, Alejandro Jimenez, James D Chalmers, Stefano Aliberti, Oriol Sibila, Vicki T Winter, Jacqueline J Coalson, Luis D Giavedoni, Charles S Dela Cruz, Grant W Waterer, Martin Witzenrath, Norbert Suttorp, Peter H Dube, Carlos J Orihuela
RATIONALE: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. OBJECTIVES: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model...
September 1, 2017: American Journal of Respiratory and Critical Care Medicine
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