Description: Aims Experiences with novel oral anticoagulants (NOACs) early after atrial fibrillation (AF) catheter ablation are limited and show controversial results. We aimed to assess the longer-term safety, efficacy, and acceptance of NOACs in a large real-world cohort of patients presenting for AF catheter ablation. Methods and results From July 2010 until June 2012, 259 patients undergoing AF catheter ablation were prospectively included. Novel oral anticoagulants were given for at least 3 months post-ablation. Clinical outcome (stroke, thromboembolic events, major bleeding), adverse effects, and drug adherence were assessed at discharge and follow-up. On admission patients were presented with a variety of anticoagulants including 54 patients (21%) already on NOACs prior ablation. After ablation 38% of patients received dabigatran 110 mg, 56% 150 mg, and 6% received rivaroxaban 20 mg. There were four periprocedural thromboembolic and major bleeding complications (1.5%), all in patients without NOACs prior ablation (two on warfarin and two on heparin). During long-term follow-up [311 (199; 418) days] no stroke, systemic embolism, or major haemorrhage could be observed. Uneventful electrical cardioversions and reablation procedures were performed in 27 and 12 patients on dabigatran, respectively. Novel oral anticoagulants were prematurely stopped or switched to another anticoagulant due to side effects or at the preference of the treating general practitioner in 9 and 10 patients, respectively. Conclusion In this prospective observational study, anticoagulation with NOACs following AF catheter ablation was safe and effective at long-term follow-up. Fast onset of action makes NOACs especially attractive in patients without effective anticoagulation on admission and in patients following periprocedural complications.

Description: This study describes the physiological response of two co-occurring tree species ( Eucalyptus marginata and Corymbia ­calophylla ) to seasonal drought at low- and high-quality restored bauxite mine sites in south-western Australia. Seasonal changes in photosynthesis ( A ), stomatal conductance ( g s ), leaf water potential (), leaf osmotic potential (), leaf relative water content (RWC) and pressure–volume analysis were captured over an 18-month field study to (i) determine the nature and severity of physiological stress in relation to site quality and (ii) identify any physiological differences between the two species. Root system restriction at the low-quality site reduced maximum rates of gas exchange ( g s and A ) and increased water stress ­(midday and daily RWC) in both species during drought. Both species showed high stomatal sensitivity ­during drought; however, E. marginata demonstrated a higher dehydration tolerance where and RWC fell to –3.2 MPa and 73% compared with –2.4 MPa and 80% for C. calophylla. Corymbia calophylla showed lower g s and higher and RWC during drought, indicating higher drought tolerance. Pressure–volume curves showed that cell-wall elasticity of E. marginata leaves increased in response to drought, while C. calophylla leaves showed lower osmotic potential at zero turgor in summer than in winter, indicating osmotic adjustment. Both species are clearly able to tolerate seasonal drought at hostile sites; however, by C. ­calophylla closing stomata earlier in the drought cycle, maintaining a higher water status during drought and having the additional mechanism of osmotic adjustment, it may have a greater capacity to survive extended periods of drought.

Description: Background We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. Patients and methods A ‘completion-time window’ variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed relative to chemotherapy cycle dates, defined as ‘before’, ‘on’ and ‘after’. HRQoL mean scores were calculated using a linear mixed model. Results Statistically significant differences ( P  〈 0.05) were observed on 6 and 5 scales for ‘on’ and ‘after’ comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the ‘before’ to ‘on’ and the ‘on’ to ‘after’ comparisons. For all three trials, including the ‘completion-time window’ variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. Conclusions We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies.

Description: Background: The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. Methods: The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. Results: Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue ( P 〈 .001), vomiting ( P = .01), nausea ( P 〈 .001), and constipation ( P = .01). Greater understanding of the association between symptom and/or functioning scales was developed by identifying physical, psychological, and gastrointestinal clusters. Additionally, minimally important differences in interpreting HRQOL changes for improvement and deterioration were found to vary across different patient populations and disease stages. Finally, HRQOL scores are statistically significantly affected by deviations from the intended time point at which the questionnaire is completed. Conclusions: The use of existing pooled data shows that it is possible to learn about general aspects of cancer HRQOL and methodology. Our work shows that setting up international pooled datasets holds great promise for understanding patients’ unmet psychosocial needs and calls for additional empirical investigation to improve clinical care and understand cancer through retrospective HRQOL analyses.

Description: Myoglobin is a respiratory protein that serves as a model system in a variety of biological fields. Its main function is to deliver and store O 2 in the heart and skeletal muscles, but myoglobin is also instrumental in homeostasis of nitric oxide (NO) and detoxification of reactive oxygen species (ROS). Almost every vertebrate harbors a single myoglobin gene; only some cyprinid fishes have two recently duplicated myoglobin genes. Here we show that the West African lungfish Protopterus annectens has at least seven distinct myoglobin genes ( PanMb1–7 ), which diverged early in the evolution of lungfish and showed an enhanced evolutionary rate. These myoglobins are lungfish specific, and no other globin gene was found amplified. The myoglobins are differentially expressed in various lungfish tissues, and the brain is the main site of myoglobin expression. The typical myoglobin-containing tissues, the skeletal muscle and the heart, have much lower myoglobin mRNA levels. Muscle and heart express distinct myoglobins ( PanMb1 and PanMb3 , respectively). In cell culture, lungfish myoglobins improved cellular survival under hypoxia albeit with different efficiencies and reduced the production of reactive oxygen species. Only Mb2 and Mb6 enhanced the energy status of the cells. The unexpected diversity of myoglobin hints to a functional diversification of this gene: some myoglobins may have adapted to the O 2 requirements of the specific tissue and help the lungfish to survive hypoxic periods; other myoglobins may have taken over the roles of neuroglobin and cytoglobin, which appear to be missing in the West African lungfish.