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Smoking and Airway Inflammation in Patients With Mild Asthma

George W. Chalmers, Kirsten J. MacLeod, Lorna Thomson, Stuart A. Little, Charles McSharry, Neil C. Thomson
2001 Chest  
Study objectives: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. Design: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. Setting: Asthma research unit in a university hospital. Patients or participants: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving
more » ... inhaled or oral steroids at the time of the study. Interventions: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. Measurements and results: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV 1 percent predicted) was negatively related to both sputum IL-8 (r ‫؍‬ ؊ 0.52) and sputum neutrophil proportion (r ‫؍‬ ؊ 0.38), and sputum IL-8 correlated positively with smoking pack-years (r ‫؍‬ 0.57) and percent neutrophil count (r ‫؍‬ 0.51). Conclusions: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics. (CHEST 2001; 120:1917-1922 Abbreviations: DTT ϭ dithiothreitol; ECP ϭ eosinophilic cationic protein; IL ϭ interleukin; IQR ϭ interquartile range; PC 20 ϭ provocative concentration of methacholine causing a 20% fall in FEV 1
doi:10.1378/chest.120.6.1917 pmid:11742922 fatcat:55p45ogudnalplyo4bj6svl2lm

CONOISE: Agent-Based Formation of Virtual Organisations [chapter]

Timothy J. Norman, Alun Preece, Stuart Chalmers, Nicholas R. Jennings, Michael Luck, Viet D. Dang, Thuc D. Nguyen, Vikas Deora, Jianhua Shao, W. Alex Gray, Nick J. Fiddian
2004 Research and Development in Intelligent Systems XX  
If R specifies no quality expectation on q i , then Q(q i ) = k j=1 w j × QR j (q i ).  ...  If R specifies a quality expectation E(q i ) = α ∈ [0, 1] on q i : (the quality expectation on q i is α), then Q(q i ) = m j=1 w j × QR j (q i ) Here, QR j (q i ) is a rating whose corresponding expectation  ... 
doi:10.1007/978-0-85729-412-8_26 dblp:conf/sgai/NormanPCJLDNDSG03 fatcat:ilqnxdph2vgzfhdamvh5jnxjjy

The effect of changes to GOLD severity stage on long term morbidity and mortality in COPD

Robert W. V. Flynn, Thomas M. MacDonald, James D. Chalmers, Stuart Schembri
2018 Respiratory Research  
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV 1 ). This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated. We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients. Methods: This was a
more » ... ge study using patients registered with a Scottish regional COPD network 2000-2015. Annual spirometry & symptoms were recorded and linked to healthcare records to identify exacerbations, hospitalisations and mortality. Spirometry, modified Medical Research Council (mMRC) dyspnoea scale and acute exacerbations over the previous year were used to assign GOLD severity at each visit. A time-dependent Cox model was used to model time to death. Secondary outcomes were respiratory specific mortality and hospitalisations. Effect sizes are expressed as Hazard Ratios HR (95%CI). Results: Four thousand, eight hundred and eighty-five patients (mean age 67.3 years; 51.3% female) with 21,348 visits were included. During a median 6.6 years follow-up there were 1530 deaths. For the secondary outcomes there were 712 respiratory deaths and 1629 first hospitalisations. Across 16,463 visit-pairs, improvement in COPD severity was seen in 2308 (14%), no change in 11,010 (66.9%) and worsening in 3145 (19.1). Compared to patients staying in GOLD stage A, those worsening had a stepwise increased mortality and hospitalisations. Conclusions: Improving COPD severity classification was associated with reduced mortality and worsening COPD severity was associated with increased mortality and hospitalisations. Change in GOLD group has potential as monitoring tool and outcome measure in clinical trials.
doi:10.1186/s12931-018-0960-3 fatcat:4izrlkrtdvbe7dfesemww6u5xi

Multi-Omics Studies Demonstrate Toxoplasma gondii-Induced Metabolic Reprogramming of Murine Dendritic Cells

Kerrie E. Hargrave, Stuart Woods, Owain Millington, Susan Chalmers, Gareth D. Westrop, Craig W. Roberts
2019 Frontiers in Cellular and Infection Microbiology  
Hargrave*, Stuart Woods, Owain Millington, Susan Chalmers, Gareth D. Westrop and Craig W.  ... 
doi:10.3389/fcimb.2019.00309 pmid:31572687 pmcid:PMC6749083 fatcat:sfb7l34mtzalpja5ysoipqhmqy

Comparing post-combustion CO2capture operation at retrofitted coal-fired power plants in the Texas and Great Britain electric grids

Stuart M Cohen, Hannah L Chalmers, Michael E Webber, Carey W King
2011 Environmental Research Letters  
This work analyses the carbon dioxide (CO 2 ) capture system operation within the Electric Reliability Council of Texas (ERCOT) and Great Britain (GB) electric grids using a previously developed first-order hourly electricity dispatch and pricing model. The grids are compared in their 2006 configuration with the addition of coal-based CO 2 capture retrofits and emissions penalties from 0 to 100 US dollars per metric ton of CO 2 (USD/tCO 2 ). CO 2 capture flexibility is investigated by comparing
more » ... inflexible CO 2 capture systems to flexible ones that can choose between full-and zero-load CO 2 capture depending on which operating mode has lower costs or higher profits. Comparing these two grids is interesting because they have similar installed capacity and peak demand, and both are isolated electricity systems with competitive wholesale electricity markets. However, differences in capacity mix, demand patterns, and fuel markets produce diverging behaviours of CO 2 capture at coal-fired power plants. Coal-fired facilities are primarily base load in ERCOT for a large range of CO 2 prices but are comparably later in the dispatch order in GB and consequently often supply intermediate load. As a result, the ability to capture CO 2 is more important for ensuring dispatch of coal-fired facilities in GB than in ERCOT when CO 2 prices are high. In GB, higher overall coal prices mean that CO 2 prices must be slightly higher than in ERCOT before the emissions savings of CO 2 capture offset capture energy costs. However, once CO 2 capture is economical, operating CO 2 capture on half the coal fleet in each grid achieves greater emissions reductions in GB because the total coal-based capacity is 6 GW greater than in ERCOT. The market characteristics studied suggest greater opportunity for flexible CO 2 capture to improve operating profits in ERCOT, but profit improvements can be offset by a flexibility cost penalty.
doi:10.1088/1748-9326/6/2/024001 fatcat:xfvswpiklzac3fsujg7bcwb5ny

Cohort Profile: Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO)

Tahira Akbar, Stuart McGurnaghan, Colin N.A. Palmer, Shona J. Livingstone, John Petrie, John Chalmers, Robert S. Lindsay, John A. McKnight, Donald W.M. Pearson, Alan W. Patrick, James Walker, Helen C. Looker (+1 others)
2016 International Journal of Epidemiology  
doi:10.1093/ije/dyw152 pmid:28338705 pmcid:PMC5582633 fatcat:n5hywcesd5fg3fmbzmid6mzfku

Agent-based virtual organisations for the Grid

Jigar Patel, Gareth Shercliff, Patrick J. Stockreisser, Jianhua Shao, W. Alex Gray, Nick J. Fiddian, Simon Thompson, W. T. Luke Teacy, Nicholas R. Jennings, Michael Luck, Stuart Chalmers, Nir Oren (+3 others)
2005 Proceedings of the fourth international joint conference on Autonomous agents and multiagent systems - AAMAS '05  
The ability to create reliable, scalable virtual organisations (VOs) on demand in a dynamic, open and competitive environment is one of the challenges that underlie Grid computing. In response, in the CONOISE-G project, we are developing an infrastructure to support robust and resilient virtual organisation formation and operation. Specifically, CONOISE-G provides mechanisms to assure effective operation of agent-based VOs in the face of disruptive and potentially malicious entities in dynamic,
more » ... open and competitive environments. In this paper, we describe the CONOISE-G system, outline its use in VO formation and perturbation, and review current work on dealing with unreliable information sources.
doi:10.1145/1082473.1082668 dblp:conf/atal/PatelTJLCONPGSSSGFT05 fatcat:2oejkifsanfa7e7efm2nmfhprm

Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Anita Jeyam, Helen Colhoun, Stuart McGurnaghan, Luke Blackbourn, Timothy J McDonald, Colin N A Palmer, John A McKnight, Mark W J Strachan, Alan W Patrick, John Chalmers, Robert S Lindsay, John R Petrie (+5 others)
2020 Diabetes Care  
To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower
more » ... (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.
doi:10.2337/dc20-0567 pmid:33303639 fatcat:badr7xjy3bcejd2l52jye6ob3q

Agent-based virtual organisations for the Grid

Jigar Patel, W.T. Luke Teacy, Nicholas R. Jennings, Michael Luck, Stuart Chalmers, Nir Oren, Timothy J. Norman, Alun Preece, Peter M. D. Gray, Gareth Shercliff, Patrick J. Stockreisser, Jianhua Shao (+7 others)
2005 Multiagent and Grid Systems  
The ability to create reliable, scalable virtual organisations (VOs) on demand in a dynamic, open and competitive environment is one of the challenges that underlie Grid computing. In response, in the CONOISE-G project, we are developing an infrastructure to support robust and resilient virtual organisation formation and operation. Specifically, CONOISE-G provides mechanisms to assure effective operation of agent-based VOs in the face of disruptive and potentially malicious entities in dynamic,
more » ... open and competitive environments. In this paper, we describe the CONOISE-G system, outline its use in VO formation and perturbation, and review current work on dealing with unreliable information sources.
doi:10.3233/mgs-2005-1402 fatcat:6czliujrzjgv5kbgfwbapvxa5u

Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes

Paul M. McKeigue, Athina Spiliopoulou, Stuart McGurnaghan, Marco Colombo, Luke Blackbourn, Timothy J. McDonald, Suna Onengut-Gomuscu, Stephen S. Rich, Colin N. A. Palmer, John A. McKnight, Mark W. J. Strachan, Alan W. Patrick (+7 others)
2019 BMC Medicine  
The objective of this cross-sectional study was to explore the relationship of detectable C-peptide secretion in type 1 diabetes to clinical features and to the genetic architecture of diabetes.
doi:10.1186/s12916-019-1392-8 pmid:31438962 pmcid:PMC6706940 fatcat:ncfbxv643rbrpfmcnn3loshvdq

British Thoracic Society Guideline for bronchiectasis in adults

Adam T Hill, Anita L Sullivan, James D Chalmers, Anthony De Soyza, J Stuart Elborn, R Andres Floto, Lizzie Grillo, Kevin Gruffydd-Jones, Alex Harvey, Charles S Haworth, Edwin Hiscocks, John R Hurst (+11 others)
2018 Thorax  
The Deteriorating Patient • Significant and prolonged deterioration of symptoms • Unexpected increased frequency or severity of exacerbations • Frequent hospital admissions • Early relapse after treatment of an exacerbation • Rapid decline in lung function
doi:10.1136/thoraxjnl-2018-212463 pmid:30545985 fatcat:iyqvo5ewtrb65memgdwor365j4

British Thoracic Society guideline for bronchiectasis in adults

Adam T Hill, Anita L Sullivan, James D Chalmers, Anthony De Soyza, J Stuart Elborn, R Andres Floto, Lizzie Grillo, Kevin Gruffydd-Jones, Alex Harvey, Charles S Haworth, Edwin Hiscocks, John R Hurst (+11 others)
2018 BMJ Open Respiratory Research  
The full British Thoracic Society Guideline for Bronchiectasis in Adults is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline.
doi:10.1136/bmjresp-2018-000348 pmid:30687502 pmcid:PMC6326298 fatcat:kbspz5anvnevxjbumarvckfoaq

N-Glycan Profile and Kidney Disease in Type 1 Diabetes

Mairead L. Bermingham, Marco Colombo, Stuart J. McGurnaghan, Luke A.K. Blackbourn, Frano Vučković, Maja Pučić Baković, Irena Trbojević-Akmačić, Gordan Lauc, Felix Agakov, Anna S. Agakova, Caroline Hayward, Lucija Klarić (+13 others)
2017 Diabetes Care  
OBJECTIVE Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes. RESEARCH DESIGN AND METHODS Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective
more » ... records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA 1c , albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG. RESULTS Higher HbA 1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 3 10 24 ). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 3 10 24 ). CONCLUSIONS
doi:10.2337/dc17-1042 pmid:29146600 fatcat:gkqrpmbwdfbfndak5s44a2tydi

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Benjamin A. Chalmers, Hui Xing, Sevan Houston, Charlotte Clark, Sussan Ghassabian, Andy Kuo, Benjamin Cao, Andrea Reitsma, Cody-Ellen P. Murray, Jeanette E. Stok, Glen M. Boyle, Carly J. Pierce (+14 others)
2016 Angewandte Chemie  
Chalmers, H. Xing, S. D. Houston, Dr. E. Figure 2 . 2 Figure 2.  ... 
doi:10.1002/ange.201510675 fatcat:mugfamrdxvam5chgiprqydjmva

Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere

Benjamin A. Chalmers, Hui Xing, Sevan Houston, Charlotte Clark, Sussan Ghassabian, Andy Kuo, Benjamin Cao, Andrea Reitsma, Cody-Ellen P. Murray, Jeanette E. Stok, Glen M. Boyle, Carly J. Pierce (+14 others)
2016 Angewandte Chemie International Edition  
Chalmers, H. Xing, S. D. Houston, Dr. E. Figure 2 . 2 Figure 2.  ... 
doi:10.1002/anie.201510675 pmid:26846616 fatcat:npsgmzlyobhdraoze6pe5c2rmm
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