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https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#1
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28406394/a-randomised-controlled-trial-to-compare-the-safety-effectiveness-and-cost-effectiveness-of-doxycycline-200%C3%A2-mg-day-with-that-of-oral-prednisolone-0-5%C3%A2-mg-kg-day-for-initial-treatment-of-bullous-pemphigoid-the-bullous-pemphigoid-steroids-and-tetracyclines-blister
#2
Joanne R Chalmers, Fenella Wojnarowska, Gudula Kirtschig, James Mason, Margaret Childs, Diane Whitham, Karen Harman, Anna Chapman, Shernaz Walton, Enno Schmidt, Thomas R Godec, Andrew J Nunn, Hywel C Williams
BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly. OBJECTIVES: To evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone...
March 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28404649/the-microbiome-in-respiratory-medicine-current-challenges-and-future-perspectives
#3
REVIEW
Rosa Faner, Oriol Sibila, Alvar Agustí, Eric Bernasconi, James D Chalmers, Gary B Huffnagle, Chaysavanh Manichanh, Philip L Molyneaux, Roger Paredes, Vicente Pérez Brocal, Julia Ponomarenko, Sanjay Sethi, Jordi Dorca, Eduard Monsó
The healthy lung has previously been considered to be a sterile organ because standard microbiological culture techniques consistently yield negative results. However, culture-independent techniques report that large numbers of microorganisms coexist in the lung. There are many unknown aspects in the field, but available reports show that the lower respiratory tract microbiota: 1) is similar in healthy subjects to the oropharyngeal microbiota and dominated by members of the Firmicutes, Bacteroidetes and Proteobacteria phyla; 2) shows changes in smokers and well-defined differences in chronic respiratory diseases, although the temporal and spatial kinetics of these changes are only partially known; and 3) shows relatively abundant non-cultivable bacteria in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and bronchiectasis, with specific patterns for each disease...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28393141/using-cluster-analysis-of-cytokines-to-identify-patterns-of-inflammation-in-hospitalized-patients-with-community-acquired-pneumonia-a-pilot-study
#4
Timothy L Wiemken, Robert R Kelley, Rafael Fernandez-Botran, William A Mattingly, Forest W Arnold, Stephen P Furmanek, Marcos I Restrepo, James D Chalmers, Paula Peyrani, Rodrigo Cavallazzi, Jose Bordon, Stefano Aliberti, Julio A Ramirez
INTRODUCTION: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies...
2017: Univ Louisville J Respir Infect
https://www.readbyqxmd.com/read/28338705/cohort-profile-scottish-diabetes-research-network-type-1-bioresource-study-sdrnt1bio
#5
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, Helen M Colhoun
No abstract text is available yet for this article.
September 26, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28306354/bronchiectasis-phenotyping-a-complex-disease
#6
James D Chalmers
Bronchiectasis is a long-neglected disease currently experiencing a surge in interest. It is a highly complex condition with numerous aetiologies, co-morbidities and a heterogeneous disease presentation and clinical course. The past few years have seen major advances in our understanding of the disease, primarily through large real-life cohort studies. The main outcomes of interest in bronchiectasis are symptoms, exacerbations, treatment response, disease progression and death. We are now more able to identify clearly the radiological, clinical, microbiological and inflammatory contributors to these outcomes...
March 15, 2017: COPD
https://www.readbyqxmd.com/read/28306353/management-of-chronic-airway-diseases-what-can-we-learn-from-real-life-data
#7
James D Chalmers
No abstract text is available yet for this article.
March 15, 2017: COPD
https://www.readbyqxmd.com/read/28289927/nmr-assignments-of-sparsely-labeled-proteins-using-a-genetic-algorithm
#8
Qi Gao, Gordon R Chalmers, Kelley W Moremen, James H Prestegard
Sparse isotopic labeling of proteins for NMR studies using single types of amino acid ((15)N or (13)C enriched) has several advantages. Resolution is enhanced by reducing numbers of resonances for large proteins, and isotopic labeling becomes economically feasible for glycoproteins that must be expressed in mammalian cells. However, without access to the traditional triple resonance strategies that require uniform isotopic labeling, NMR assignment of crosspeaks in heteronuclear single quantum coherence (HSQC) spectra is challenging...
March 13, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28279484/doxycycline-versus-prednisolone-as-an-initial-treatment-strategy-for-bullous-pemphigoid-a-pragmatic-non-inferiority-randomised-controlled-trial
#9
Hywel C Williams, Fenella Wojnarowska, Gudula Kirtschig, James Mason, Thomas R Godec, Enno Schmidt, Joanne R Chalmers, Margaret Childs, Shernaz Walton, Karen Harman, Anna Chapman, Diane Whitham, Andrew J Nunn
BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3)...
March 6, 2017: Lancet
https://www.readbyqxmd.com/read/28270656/raising-awareness-of-bronchiectasis-in-primary-care-overview-of-diagnosis-and-management-strategies-in-adults
#10
James D Chalmers, Sanjay Sethi
Bronchiectasis is a chronic lung disease characterised by recurrent infection, inflammation, persistent cough and sputum production. The disease is increasing in prevalence, requiring a greater awareness of the disease across primary and secondary care. Mild and moderate cases of bronchiectasis in adults can often be managed by primary care clinicians. Initial assessments and long-term treatment plans that include both pharmacological and non-pharmacological treatments, however, should be undertaken in collaboration with a secondary care team that includes physiotherapists and specialists in respiratory medicine...
December 2017: NPJ Primary Care Respiratory Medicine
https://www.readbyqxmd.com/read/28244617/year-in-review-2016-respiratory-infections-acute-respiratory-distress-syndrome-pleural-diseases-lung-cancer-and-interventional-pulmonology
#11
REVIEW
Marcos I Restrepo, James D Chalmers, Yuanlin Song, Christopher Mallow, Justin Hewlett, Fabien Maldonado, Lonny Yarmus
No abstract text is available yet for this article.
April 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28212153/new-therapies-for-the-prevention-and-treatment-of-exacerbations-of-bronchiectasis
#12
Hani Abo-Leyah, James D Chalmers
PURPOSE OF REVIEW: Exacerbations of bronchiectasis have a major impact on quality of life, healthcare costs, and long-term risk of complications. Preventing exacerbations is one of the major goals of treatment. Bronchiectasis is increasingly recognized and the impact of bronchiectasis exacerbations on daily clinical practice is also increasing. RECENT FINDINGS: Preventing bronchiectasis exacerbations are dependent on appropriate risk assessment, identifying the patients at highest risk to rationally target preventive therapies...
May 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28210295/global-impact-of-bronchiectasis-and-cystic-fibrosis
#13
REVIEW
Margarida Redondo, Holly Keyt, Raja Dhar, James D Chalmers
EDUCATIONAL AIMS: To recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis.To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems. Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature...
September 2016: Breathe
https://www.readbyqxmd.com/read/28110337/investigating-the-etiology-of-bronchiectasis-you-do-not-find-what-you-do-not-look-for
#14
Francesco Amati, Elisa Franceschi, Andrea Gramegna, James D Chalmers, Stefano Aliberti
No abstract text is available yet for this article.
2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28093268/bronchiectasis-rheumatoid-overlap-syndrome-bros-is-an-independent-risk-factor-for-mortality-in-patients-with-bronchiectasis-a-multicentre-cohort-study
#15
Anthony De Soyza, Melissa J McDonnell, Pieter C Goeminne, Stefano Aliberti, Sara Lonni, John Davison, Lieven J Dupont, Thomas C Fardon, Robert M Rutherford, Adam T Hill, James D Chalmers
INTRODUCTION: We studied if Bronchiectasis (BR) and Rheumatoid arthritis (RA) when manifesting as an overlap syndrome (BROS) was associated with worse outcomes than other BR aetiologies applying the Bronchiectasis Severity Index (BSI). METHODS: We interrogated the Bronchiectasis Severity Index (BSI) databases of 1716 patients across 6 centres: Edinburgh, UK (608 patients), Dundee, UK (N=286), Leuven, Belgium (N=253), Monza, Italy (N=201), Galway Ireland (N=242) and Newcastle, UK (N=126)...
January 13, 2017: Chest
https://www.readbyqxmd.com/read/28069292/microbial-dysbiosis-in-bronchiectasis-and-cystic-fibrosis
#16
Alison J Dicker, James D Chalmers
No abstract text is available yet for this article.
January 6, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/27960211/the-modern-diagnostic-approach-to-community-acquired-pneumonia-in-adults
#17
James D Chalmers
Respiratory tract infections, the majority of which are community acquired, are among the leading causes of death worldwide and a leading indication for hospital admission. The burden of disease demonstrates a "U"-shaped distribution, primarily affecting young children as the immune system matures, and older adults as the process of immunosenescence and accumulation of comorbidities leads to increased susceptibility to infection. Diagnosis of community-acquired pneumonia (CAP) is traditionally based on demonstration of a new infiltrate on a chest radiograph in a patient presenting with an acute respiratory illness or sepsis...
December 2016: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27960203/community-acquired-pneumonia-a-global-perspective
#18
Charles Feldman, James D Chalmers
No abstract text is available yet for this article.
December 2016: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27911604/neutrophil-elastase-activity-is-associated-with-exacerbations-and-lung-function-decline-in-bronchiectasis
#19
James D Chalmers, Kelly L Moffitt, Guillermo Suarez-Cuartin, Oriol Sibila, Simon Finch, Elizabeth Furrie, Alison Dicker, Karolina Wrobel, J Stuart Elborn, Brian Walker, S Lorraine Martin, Sara E Marshall, Jeffrey T-J Huang, Thomas C Fardon
RATIONALE: Sputum neutrophil elastase and serum desmosine, a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis. METHODS: This was a single-centre prospective cohort study using the TAYBRIDGE registry in Dundee, UK. 433 patients with HRCT-confirmed bronchiectasis provided blood samples for desmosine measurement and 381 provided sputum for baseline elastase activity measurements using an activity based immunosassay and fluorometric substrate assay...
December 2, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27898680/a-core-outcome-set-for-the-benefits-and-adverse-events-of-bariatric-and-metabolic-surgery-the-bariact-project
#20
Karen D Coulman, James Hopkins, Sara T Brookes, Katy Chalmers, Barry Main, Amanda Owen-Smith, Robert C Andrews, James Byrne, Jenny L Donovan, Graziella Mazza, Barnaby C Reeves, Chris A Rogers, Janice L Thompson, Richard Welbourn, Sarah Wordsworth, Jane M Blazeby
BACKGROUND: Bariatric and metabolic surgery is used as a treatment for patients with severe and complex obesity. However, there is a need to improve outcome selection and reporting in bariatric surgery trials. A Core Outcome Set (COS), an agreed minimum set of outcomes reported in all studies of a specific condition, may achieve this. Here, we present the development of a COS for BARIAtric and metabolic surgery Clinical Trials-the BARIACT Study. METHODS AND FINDINGS: Outcomes identified from systematic reviews and patient interviews informed a questionnaire survey...
November 2016: PLoS Medicine
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