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- Dittrich, Christian, et al.
(författare)
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ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016
- 2016
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 1:5
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Tidskriftsartikel (refereegranskat)abstract
- The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ ASCO Global Curriculum (GC) thanks to contribution of 64 ESMOappointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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- Reynolds, Harmony R., et al.
(författare)
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Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia Secondary Analysis of the ISCHEMIA Randomized Clinical Trial
- 2020
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:7, s. 773-786
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Tidskriftsartikel (refereegranskat)abstract
- Key PointsQuestion When considering patients who have obstructive coronary artery disease and ischemia on stress testing, are there sex differences in severity of coronary artery disease, ischemia, and/or symptoms?Findings In this secondary analysis of the ISCHEMIA randomized clinical trial of 5179 patients, women had more frequent angina, less extensive coronary artery disease, and less severe ischemia than men. On multivariate analysis, female sex was independently associated with greater angina frequency.Meaning There may be inherent sex differences in the complex relationships between angina, ischemia, and atherosclerosis that may have implications for testing and treatment of patients with suspected coronary artery disease.AbstractImportance While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.Objective To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.Design, Setting, and Participants This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.Interventions CCTA and angina assessment.Main Outcomes and Measures Sex differences in stress test, CCTA findings, and symptom severity.Results Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Conclusions and Relevance Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.
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- Bairy, Sneha, et al.
(författare)
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Automation aided optimization of cloning, expression and purification of enzymes of the bacterial sialic acid catabolic and sialylation pathways enzymes for structural studies.
- 2018
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Ingår i: Microbial biotechnology. - : Wiley. - 1751-7915. ; 11:2, s. 420-428
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Tidskriftsartikel (refereegranskat)abstract
- The process of obtaining a well-expressing, soluble and correctly folded constructs can be made easier and quicker by automating the optimization of cloning, expression and purification. While there are many semiautomated pipelines available for cloning, expression and purification, there is hardly any pipeline that involves complete automation. Here, we achieve complete automation of all the steps involved in cloning and invivo expression screening. This is demonstrated using 18 genes involved in sialic acid catabolism and the surface sialylation pathway. Our main objective was to clone these genes into a His-tagged Gateway vector, followed by their small-scale expression optimization invivo. The constructs that showed best soluble expression were then selected for purification studies and scaled up for crystallization studies. Our technique allowed us to quickly find conditions for producing significant quantities of soluble proteins in Escherichia coli, their large-scale purification and successful crystallization of a number of these proteins. The method can be implemented in other cases where one needs to screen a large number of constructs, clones and expression vectors for successful recombinant production of functional proteins.
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- Gopalan, D, et al.
(författare)
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Biatrial Volumetric Assessment by Non-ECG-Gated CT Pulmonary Angiography Correlated with Transthoracic Echocardiography in Patients with Normal Diastology
- 2022
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Ingår i: Tomography (Ann Arbor, Mich.). - : MDPI AG. - 2379-139X. ; 8:6, s. 2761-2771
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Tidskriftsartikel (refereegranskat)abstract
- Atrial size is a predictor of cardiovascular mortality. Non-ECG-gated computed tomography pulmonary angiography (CTPA) is a common test for cardiopulmonary evaluation but normative values for biatrial volumes are lacking. We derived normal CT biatrial volumes using manual and semiautomated segmentation with contemporaneous transthoracic echocardiography (TTE) to confirm normal diastology. Thirty-five consecutive cases in sinus rhythm with no history of cardio-vascular, renal, or pulmonary disease and normal diastolic function were selected. Planimetric CTPA measurements were compared to TTE volumes measured using area length method. TTE and CTPA derived normal LAVi and RAVi were 27 + 5 and 20 + 6 mL/m2, and 30 + 8 and 29 + 9 mL/m2, respectively. Bland–Altman analysis revealed an underestimation of biatrial volumes by TTE. TTE-CT mean biases for LAV and RAV were −5.7 + 12.0 mL and −16.2 + 14.8 mL, respectively. The CT intraclass correlation coefficients (ICC 95% CI) for LA and RA volumes were 0.99 (0.96–1.00) and 0.96 (0.76–0.99), respectively. There was excellent correlation (p < 0.001) between the semiautomated and manual measurements for LA (r 0.99, 95% CI 0.98–0.99) and RA (r 0.99, 95% CI 0.99–1.00). Atrial volumetric assessment on CTPA is easy and reproducible and can provide additional metric in cardiopulmonary assessment.
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- Mao, Guanzhong, et al.
(författare)
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Cleavage of Model Substrates by Arabidopsis thaliana PRORP1 Reveals New Insights into Its Substrate Requirements
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Two broad classes of RNase P trim the 5' leader of precursor tRNAs (pre-tRNAs): ribonucleoprotein (RNP)- and proteinaceous (PRORP)-variants. These two RNase P types, which use different scaffolds for catalysis, reflect independent evolutionary paths. While the catalytic RNA-based RNP form is present in all three domains of life, the PRORP family is restricted to eukaryotes. To obtain insights on substrate recognition by PRORPs, we examined the 5' processing ability of recombinant Arabidopsis thaliana PRORP1 (AtPRORP1) using a panel of pre-tRNA(Ser) variants and model hairpin-loop derivatives (pATSer type) that consist of the acceptor-T-stem stack and the T-/D-loop. Our data indicate the importance of the identity of N-1 (the residue immediately 5' to the cleavage site) and the N-1: N+73 base pair for cleavage rate and site selection of pre-tRNA(Ser) and pATSer. The nucleobase preferences that we observed mirror the frequency of occurrence in the complete suite of organellar pre-tRNAs in eight algae/plants that we analyzed. The importance of the T-/D-loop in pre-tRNA(Ser) for tight binding to AtPRORP1 is indicated by the 200-fold weaker binding of pATSer compared to pre-tRNA(Ser), while the essentiality of the T-loop for cleavage is reflected by the near-complete loss of activity when a GAAA-tetraloop replaced the T-loop in pATSer. Substituting the 2'-OH at N-1 with 2'-H also resulted in no detectable cleavage, hinting at the possible role of this 2'-OH in coordinating Mg2+ ions critical for catalysis. Collectively, our results indicate similarities but also key differences in substrate recognition by the bacterial RNase P RNP and AtPRORP1: while both forms exploit the acceptor-T-stem stack and the elbow region in the pre-tRNA, the RNP form appears to require more recognition determinants for cleavage-site selection.
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