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This Job Ad shown on this page is the property of Express Newspaper and is copyrighted by them. Dr Duncan Sproul is a programme leader and CRUK Career Development Fellow at the MRC Human Genetics Unit and MRC Institute of Genetics and Molecular Medicine.A  Duncan studied Genetics at the University of Edinburgh before being awarded an MRC pre-doctoral fellowship to undertake a PhD on the regulation of gene clusters with Prof Wendy Bickmore at the MRC Human Genetics Unit. DNA does not exist in isolation in our cells but is packaged with proteins and marked by chemical modifications. I particularly focus on understanding the repressive epigenetic mark DNA methylation and its role in breast cancer.A  My laboratory takes interdisciplinary approach combining computational and laboratory biology.
The MRC Human Genetics Unit is a partner in the MRC Institute of Genetics and Molecular Medicine at The University of Edinburgh.
NB: We use cookies to help personalise your web experience and comply with Irish healthcare law. This site contains information, news and advice for healthcare professionals.You have informed us that you are not a healthcare professional and therefore we are unable to provide you with access to this site. The Medical Council and the Irish Network of Medical Educators (INMED) have announced the inaugural winners of annual grants aimed at building medical educational research capacity in Ireland. The Medical Council-INMED Research in Medical Education (RIME) award winners will undertake research projects that seek to answer questions of national and international importance, while contributing to the knowledge-base for Irish medical education and training. It is envisaged that their findings will enhance the quality of doctors’ education, training and lifelong learning for the benefit of patients. Prof Freddie Wood, President of the Medical Council, which will this month host its Annual Symposium for Medical Educators focusing on supporting doctors with the transition from medical student to practising doctor, believes this research will go on to influence medical education and training policy at every level. INMED Chair Prof Peter Cantillon said the new educational research funding initiative was critical to support the development of educational research capacity in undergraduate and postgraduate schools. Gabriel Ortiz serves as the American Academy of Physician Assistants (AAPA) liaison to the American Academy of Allergy, Asthma and Immunology (AAAAI) and as the AAAAI liaison to the AAPA.
Summary Information for Inhaled Corticosteroid and Long-Acting β2-Adrenergic Agonist Combination Product Use in Patients in the United States Who Have Asthma or Chronic Obstructive Pulmonary Disease. Applying the 2009 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines for the Pharmacological Management of Chronic Obstructive Pulmonary Disease in Clinical Practice.
The Importance of Accurate Obstructive Respiratory Disease Diagnoses: A Comparison of Asthma and Chronic Obstructive Pulmonary Disease.
Tools for Diagnosis and Assessment of Asthma and Chronic Obstructive Pulmonary Disease in Clinical Practice. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow obstruction that is usually progressive. Bronchodilator reversibility commonly is assessed based only on improvements in forced expiratory volume in 1 second (FEV1); however, lung-volume based measures of pulmonary function (ie, forced vital capacity [FVC]) may be especially important in patients with severe disease. Various factors may influence bronchodilator reversibility, including the specific criteria used to define reversibility and the drug and method used for testing. Bronchodilator reversibility results are not predictive of a patient’s long-term response to maintenance bronchodilator treatment.
Regardless of initial bronchodilator reversibility status, patients with COPD should be treated based on current guidelines.
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by persistent airflow limitation that is usually progressive [1]. In the past, bronchodilator reversibility was used diagnostically to differentiate between COPD and asthma because patients with COPD were thought to have little or no reversibility of airflow obstruction, and patients with asthma were viewed as having fully reversible airflow obstruction [2]. Standards have not been established for defining or testing bronchodilator reversibility [3], leading to challenges in interpreting results of reversibility testing. Several criteria for defining bronchodilator reversibility exist (Table 1) [4-8], and a patient’s bronchodilator reversibility status can vary depending on which criteria are used [9-12].
Despite the challenges in interpreting results of bronchodilator reversibility testing, recent studies have shown that patients with COPD demonstrate substantial bronchodilator response across different criteria and treatments [9, 10].


Bronchodilator reversibility tests cannot predict whether a patient will respond to long-term maintenance therapy. Furthermore, patients who do not demonstrate initial bronchodilator reversibility can still show benefits in health-related quality of life (HRQOL) with long-term treatment [18].
In patients with COPD, bronchodilators are central to preventing or managing symptoms and can be given as needed or as maintenance medication [1]. Reprinted with permission from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. I walk slower than people of the same age on the level because of breathlessness, or I have to stop for breath when walking on my own pace on the level.
COPD is a preventable and treatable disease characterized by chronic airflow limitation that is not fully reversible. Anthonisen NR, Lindgren PG, Tashkin DP, Kanner RE, Scanlon PD, Connett JE, for the Lung Health Study Research Group. Calverley PMA, Burge PS, Spencer S, Anderson JA, Jones PW, for the ISOLDE Study Investigators. This job Ad have various particular skill set categories including IT, accounting, engineering, medical, clerical, government, technical, teaching, administrative jobs and for different cities of Pakistan including Islamabad, Rawalpindi, Lahore, Karachi, Faislabad, Peshawar, Jhang and various more. During his postdoctoral training at the Edinburgh Breakthrough Breast Cancer Research Unit with Dr Andrew Sims, Duncan applied emerging epigenomic technologies to understand the role of epigenetic dysfunction in breast carcinogenesis. These modifications, known as epigenetic marks, signpost the DNA and are believed to help cells switch their genes on and off.
We apply machine-learning techniques to define molecular epigenomic signatures in patient cohorts and dissect the mechanisms underpinning these signatures using genome-editing techniques in experimental models.
He has served previously as the AAPA liaison to the National Asthma Education and Prevention Program.
He can no longer climb stairs without gasping for air, and he does not have the energy to play with his grandson. Airflow obstruction in COPD is caused by a chronic inflammatory response to noxious particles (eg, cigarette smoke) that induces parenchymal tissue destruction and causes structural narrowing of the small airways, diminishing the ability of the airways to remain open during exhalation [1]. Additionally, it was long believed that reversibility to short-acting bronchodilators can predict a patient’s response to long-term bronchodilator therapy [3].
Several factors may influence the results of bronchodilator reversibility testing, including the pulmonary function criteria used to define reversibility, the drug used for reversibility testing, and the inherent variability in an individual patient’s reversibility status over time.
In patients with greater COPD severity, those who do not exhibit reversibility based on FEV1 criteria can still demonstrate substantial improvements in FVC [3, 9-11], highlighting the importance of measuring lung volume in those patients.
Percentage of patients exhibiting reversibility based on different thresholds for FEV1 improvements in the UPLIFT study at baseline [3, 9].
Recent studies have demonstrated that the lack of an initial bronchodilator response to short- or long-acting medications does not preclude bronchodilator response to long-term maintenance therapy [16, 17].
Results from a post hoc analysis of the UPLIFT study (N=5783) showed that both reversible and nonreversible patients (based on ATS or ACCP definitions) experienced significant (P1 and FVC) and HRQOL and reductions in COPD exacerbations with long-term tiotropium therapy versus placebo [18].
In patients with severe and very severe COPD and frequent exacerbations that are not adequately controlled with long-acting bronchodilators, the addition of an inhaled corticosteroid is recommended [1].
Although several factors may influence bronchodilator reversibility status, including the definition of reversibility used, method and drug utilized for reversibility testing, and inherent within-patient variability in reversibility status over time, many patients with COPD, even those with more severe disease, can demonstrate a substantial response to bronchodilator therapy.
Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease.
Response of lung volumes to inhaled salbutamol in a large population of patients with severe hyperinflation. Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses.
Acute bronchodilator responsiveness and health outcomes in COPD patients in the UPLIFT trial. He joined the MRC Human Genetics Unit in 2013 as a research fellow and was awarded a Career Development Fellowship from CRUK in 2016.


For example, epigenetics ensures that the genes that make haemoglobin are switched on in blood cells but not brain cells.
While we principally work on DNA methylation in breast cancer, we also collaborate with other groups to understand the role of epigenetics in human disease much more widely. The presence of persistent airflow limitation [1] and the magnitude of bronchodilator reversibility [2] are assessed using spirometry.
However, recent evidence has shown that these beliefs are inaccurate, and current COPD guidelines state that the degree of bronchodilator reversibility is not recommended for differential diagnosis with asthma and should not be used to predict long-term response to maintenance bronchodilator treatment [1]. Findings from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) study of patients with moderate to very severe COPD also showed that the percentage of patients demonstrating reversibility varied depending on the specific threshold used for defining a clinically significant improvement in FEV1 (Figure 1) [3, 9]. Results from a study in 921 patients with COPD showed significant (P1 from baseline to the end of the study (day 344) with tiotropium compared with placebo, irrespective of FEV1 reversibility (ATS criteria) to tiotropium on day 1 [16]. Therefore, patients with COPD should be treated based on current guidelines, regardless of whether they have demonstrated initial bronchodilator reversibility. The goals of treatment are to reduce symptoms, including improving exercise tolerance and health status, and to reduce risk, including preventing disease progression and exacerbations and reducing mortality [1].
Additionally, recent findings show that results of bronchodilator reversibility testing are not able to differentiate between COPD and asthma and do not predict response to long-term maintenance bronchodilator therapy. My work seeks to understand the mechanisms responsible for placing epigenetic marks on a particular gene and how they might go wrong in diseases such as cancer. Thus, findings from bronchodilator reversibility testing should be interpreted with caution and in the context of other clinical assessments [2]. In the context of these pulmonary function measures, his clinician compares his pre- and postbronchodilator FEV1 values to assess the magnitude of bronchodilator reversibility to albuterol. In that analysis, a substantial percentage of patients with very severe COPD also exhibited bronchodilator reversibility within 60 minutes after formoterol-containing treatment based on ATS criteria for FEV1 improvements (39%-46%), which increased to 63%-73% when using ATS criteria for FVC improvements [10]. He notes that he often has to stop walking and rest from shortness of breath and checks the box for an mMRC score of 2. Instead, they should be interpreted in the context of the patient’s clinical history and other clinical assessments. Finally, a patient’s FEV1 response to the same bronchodilator can vary from day to day [14], and considerable within-patient variability exists in bronchodilator reversibility status over time [15].
Contrary to historical belief, findings from these studies show that many patients with COPD do, in fact, exhibit bronchodilator reversibility, indicating that reversibility testing is not a suitable measure to distinguish COPD from asthma [3]. Findings from these studies suggest that patients with COPD who demonstrate poor initial bronchodilator reversibility can benefit from long-term bronchodilator maintenance therapy. The mMRC is a measure of breathlessness that predicts mortality risk and relates to health status (Table 2), and the CAT is an 8-item questionnaire that assesses health status impairment [1].
Regardless of whether a patient exhibits initial bronchodilator reversibility, bronchodilators do play a central role in the pharmacologic management of COPD, and the optimal treatment should be selected based on current COPD management guidelines. All of these factors lead to challenges in interpreting results of bronchodilator reversibility testing in clinical practice.
This approach classifies patients into 1 of 4 different patient categories based on whether the patient has low or high risk and fewer or more symptoms (Figure 2) [1].
According to the GOLD guidelines, his clinician prescribes treatment with a long-acting anticholinergic to be taken once daily and a short-acting bronchodilator to be taken as needed. Based on the 4 patient categories, the pharmacological recommendations for treating COPD are presented in Table 3 [1].
Much confusion exists surrounding the concept of reversibility and the role of reversibility testing in clinical practice.



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