Accurate cell segmentation in microscopy images using membrane patterns

Motivation: Identifying cells in an image (cell segmentation) is essential for quantitative single-cell biology via optical microscopy. Although a plethora of segmentation methods exists, accurate segmentation is challenging and usually requires problem-specific tailoring of algorithms. In addition, most current segmentation algorithms rely on a few basic approaches that use the gradient field of the image to detect cell boundaries. However, many microscopy protocols can generate images with characteristic intensity profiles at the cell membrane. This has not yet been algorithmically exploited to establish more general segmentation methods. Results: We present an automatic cell segmentation method that decodes the information across the cell membrane and guarantees optimal detection of the cell boundaries on a per-cell basis. Graph cuts account for the information of the cell boundaries through directional cross-correlations, and they automatically incorporate spatial constraints. The method accurately segments images of various cell types grown in dense cultures that are acquired with different microscopy techniques. In quantitative benchmarks and comparisons with established methods on synthetic and real images, we demonstrate significantly improved segmentation performance despite cell-shape irregularity, cell-to-cell variability and image noise. As a proof of concept, we monitor the internalization of green fluorescent protein-tagged plasma membrane transporters in single yeast cells. Availability and implementation: Matlab code and examples are available at http://www.csb.ethz.ch/tools/cellSegmPackage.zip. Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Plasmonic nanomeshes: Their ambivalent role as transparent electrodes in organic solar cells

In this contribution, the optical losses and gains attributed to periodic nanohole array electrodes in polymer solar cells are systematically studied. For this, thin gold nanomeshes with hexagonally ordered holes and periodicities (P) ranging from 202 nm to 2560 nm are prepared by colloidal lithography. In combination with two different active layer materials (P3HT:PC 61 BM and PTB7:PC 71 BM), the optical properties are correlated with the power conversion efficiency (PCE) of the solar cells. A cavity mode is identified at the absorption edge of the active layer material. The resonance wavelength of this cavity mode is hardly defined by the nanomesh periodicity but rather by the absorption of the photoactive layer. This constitutes a fundamental dilemma when using nanomeshes as ITO replacement. The highest plasmonic enhancement requires small periodicities. This is accompanied by an overall low transmittance and high parasitic absorption losses. Consequently, larger periodicities with a less efficient cavity mode, yet lower absorptive losses were found to yield the highest PCE. Nevertheless, ITO-free solar cells reaching ∼77% PCE compared to ITO reference devices are fabricated. Concomitantly, the benefits and drawbacks of this transparent nanomesh electrode are identified, which is of high relevance for future ITO replacement strategies

Exercise-based cardiac rehabilitation for adults with atrial fibrillation

BACKGROUND:Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria. OBJECTIVES:To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS:We searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and three clinical trial registers on 14 July 2016. We also checked the bibliographies of relevant systematic reviews identified by the searches. We imposed no language restrictions. SELECTION CRITERIA:We included randomised controlled trials (RCT) that investigated exercise-based interventions compared with any type of no-exercise control. We included trials that included adults aged 18 years or older with atrial fibrillation, or post-treatment for atrial fibrillation. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data. We assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. We performed meta-analyses using fixed-effect and random-effects models; we used standardised mean differences where different scales were used for the same outcome. We assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the 'Summary of findings' table. MAIN RESULTS:We included six RCTs with a total of 421 patients with various types of atrial fibrillation. All trials were conducted between 2006 and 2016, and had short follow-up (eight weeks to six months). Risks of bias ranged from high risk to low risk.The exercise-based programmes in four trials consisted of both aerobic exercise and resistance training, in one trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training.For mortality, very low-quality evidence from six trials suggested no clear difference in deaths between the exercise and no-exercise groups (relative risk (RR) 1.00, 95% confidence interval (CI) 0.06 to 15.78; participants = 421; I² = 0%; deaths = 2). Very low-quality evidence from five trials suggested no clear difference between groups for serious adverse events (RR 1.01, 95% CI 0.98 to 1.05; participants = 381; I² = 0%; events = 8). Low-quality evidence from two trials suggested no clear difference in health-related quality of life for the Short Form-36 (SF-36) physical component summary measure (mean difference (MD) 1.96, 95% CI -2.50 to 6.42; participants = 224; I² = 69%), or the SF-36 mental component summary measure (MD 1.99, 95% CI -0.48 to 4.46; participants = 224; I² = 0%). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by six minute walking test, or ergospirometry testing measuring VO2 peak. We found moderate-quality evidence from two studies that exercise-based rehabilitation increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95% CI 1.37 to 6.15; participants = 208; I² = 0%); and very low-quality evidence from four studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the six-minute walking test (MD 75.76, 95% CI 14.00 to 137.53; participants = 272; I² = 85%). When we combined the different assessment tools for exercise capacity, we found very low-quality evidence from six trials that exercise-based rehabilitation increased exercise capacity more than no exercise (standardised mean difference (SMD) 0.86, 95% CI 0.46 to 1.26; participants = 359; I² = 65%). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low. AUTHORS' CONCLUSIONS:Due to few randomised patients and outcomes, we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events. The evidence showed no clinically relevant effect on health-related quality of life. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, we could not be certain of the magnitude of the effect. Future high-quality randomised trials are needed to assess the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes

The effect of integrated cardiac rehabilitation versus treatment as usual for atrial fibrillation patients treated with ablation:the randomised CopenHeartRFA trial protocol

INTRODUCTION: Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components. AIM: To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation. METHODS AND ANALYSIS DESIGN: The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO(2) peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group. ETHICS AND DISSEMINATION: The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01523145

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution