Extraction of decision rules via imprecise probabilities

"This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of General Systems on 2017, available online: https://www.tandfonline.com/doi/full/10.1080/03081079.2017.1312359"Data analysis techniques can be applied to discover important relations among features. This is the main objective of the Information Root Node Variation (IRNV) technique, a new method to extract knowledge from data via decision trees. The decision trees used by the original method were built using classic split criteria. The performance of new split criteria based on imprecise probabilities and uncertainty measures, called credal split criteria, differs significantly from the performance obtained using the classic criteria. This paper extends the IRNV method using two credal split criteria: one based on a mathematical parametric model, and other one based on a non-parametric model. The performance of the method is analyzed using a case study of traffic accident data to identify patterns related to the severity of an accident. We found that a larger number of rules is generated, significantly supplementing the information obtained using the classic split criteria.This work has been supported by the Spanish "Ministerio de Economia y Competitividad" [Project number TEC2015-69496-R] and FEDER funds.Abellán, J.; López-Maldonado, G.; Garach, L.; Castellano, JG. (2017). Extraction of decision rules via imprecise probabilities. International Journal of General Systems. 46(4):313-331. https://doi.org/10.1080/03081079.2017.1312359S313331464Abellan, J., & Bosse, E. (2018). Drawbacks of Uncertainty Measures Based on the Pignistic Transformation. IEEE Transactions on Systems, Man, and Cybernetics: Systems, 48(3), 382-388. doi:10.1109/tsmc.2016.2597267Abellán, J., & Klir, G. J. (2005). Additivity of uncertainty measures on credal sets. 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Personalized monitoring of electrical remodelling during atrial fibrillation progression via remote transmissions from implantable devices

Aims: Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes. Methods and results: Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/-resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45). Conclusion: The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology

In vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig models

AIMS: Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. METHODS AND RESULTS: First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63-138) cm/s vs. 51 (41-64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217-254) ms vs. 192 (182-233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min-1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. CONCLUSIONS: In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.The CNIC is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC is a Severo Ochoa Center of Excellence (SEV-2015-0505). This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458), the Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission (ERA-CVD Joint Call [JTC2016/APCIN-ISCIII-2016], grant#AC16/00021). The study was also partially supported by the Fundacio´n Interhospitalaria para la Investigacio´n Cardiovascular (FIC) and the Heart Rhythm section of the Spanish Society of Cardiology. The work at the University of Connecticut was supported by grant EB001963 from the National Institutes of Health.S

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S

Lesion Index Titration Using Contact-Force Technology Enables Safe and Effective Radiofrequency Lesion Creation at the Root of the Aorta and Pulmonary Artery

BACKGROUND: Ablation of some myocardial substrates requires catheter-based radiofrequency delivery at the root of a great artery. We studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. METHODS: Thirty-six pigs underwent in-vivo catheter-based ablation under continuous contact-force and lesion index (power, contact-force, and time) monitoring during 60-s radiofrequency delivery with an open-irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 W (n=9), 50 W (n=10), or 60 W (n=9) radiofrequency energy, and acute (n=22) and chronic (n=6) arterial wall damage was quantified by multiphoton microscopy in ex vivo samples. Adjacent myocardial lesions were quantified in parallel samples. The remaining 8 pigs were used to validate safety and efficacy parameters. RESULTS: Acute collagen and elastin alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in lesions without steam pop. The main parameters associated with steam pops were median peak temperature >42°C and impedance falls >23 ohms. Unlike other parameters, lesion index values of 9.1 units (interquartile range, 8.7-9.8) were associated with the presence of adjacent myocardial lesions in both univariate ( P=0.03) and multivariate analyses ( P=0.049; odds ratio, 1.99; 95% CI, 1.02-3.98). In the validation group, lesion index values using 40 W over a range of contact-forces correlated with the size of radiofrequency lesions (R2=0.57; P=0.03), with no angiographic or histopathologic signs of coronary artery damage. CONCLUSIONS: Lesion index values obtained during 40 W radiofrequency applications reliably monitor safe and effective lesion creation at the root of the great arteries.This study was supported by the Fundación Interhospitalaria para la Investigación Cardiovascular (FIC) and the Heart Rhythm Section of the Spanish Society of Cardiology. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC is a Severo Ochoa Center of Excellence (SEV-2015- 0505). This study was supported by grants from Fondo Europeo de Desarrollo Regional (CB16/11/00458) and the Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R).S

The influence of the ectomycorrhizal fungus Rhizopogon subareolatus on growth and nutrient element localisation in two varieties of Douglas fir (Pseudotsuga menziesii var. menziesii and var. glauca) in response to manganese stress

Acidification of forest ecosystems leads to increased plant availability of the micronutrient manganese (Mn), which is toxic when taken up in excess. To investigate whether ectomycorrhizas protect against excessive Mn by improving plant growth and nutrition or by retention of excess Mn in the hyphal mantle, seedlings of two populations of Douglas fir (Pseudotsuga menziesii), two varieties, one being menziesii (DFM) and the other being glauca (DFG), were inoculated with the ectomycorrhizal fungus Rhizopogon subareolatus in sand cultures. Five months after inoculation, half of the inoculated and non-inoculated seedlings were exposed to excess Mn in the nutrient solution for further 5 months. At the end of this period, plant productivity, nutrient concentrations, Mn uptake and subcellular compartmentalisation were evaluated. Non-inoculated, non-stressed DFM plants produced about 2.5 times more biomass than similarly treated DFG. Excess Mn in the nutrient solution led to high accumulation of Mn in needles and roots but only to marginal loss in biomass. Colonisation with R. subareolatus slightly suppressed DFM growth but strongly reduced that of DFG (−50%) despite positive effects of mycorrhizas on plant phosphorus nutrition. Growth reductions of inoculated Douglas fir seedlings were unexpected since the degree of mycorrhization was not high, i.e. ca. 30% in DFM and 8% in DFG. Accumulation of high Mn was not prevented in inoculated seedlings. The hyphal mantle of mycorrhizal root tips accumulated divalent cations such as Ca, but not Mn, thus not providing a barrier against excessive Mn uptake into the plants associated with R. subareolatus

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

<p>Abstract</p> <p>Background</p> <p>Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia.</p> <p>Methods</p> <p>Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2.</p> <p>Results</p> <p>Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia.</p> <p>Conclusion</p> <p>Our results suggest that spermatozoa from asthenozoospermic patients present a reduced responsiveness to progesterone.</p

Observations of 4U 1626-67 with the Imaging X-ray Polarimetry Explorer

We present measurements of the polarization of X-rays in the 2-8 keV band from the pulsar in the ultracompact low mass X-ray binary 4U1626-67 using data from the Imaging X-ray Polarimetry Explorer (IXPE). The 7.66 s pulsations were clearly detected throughout the IXPE observations as well as in the NICER soft X-ray observations, which we use as the basis for our timing analysis and to constrain the spectral shape over 0.4-10 keV energy band. Chandra HETGS high-resolution X-ray spectra were also obtained near the times of the IXPE observations for firm spectral modeling. We find an upper limit on the pulse-averaged linear polarization of <4% (at 95% confidence). Similarly, there was no significant detection of polarized flux in pulse phase intervals when subdividing the bandpass by energy. However, spectropolarimetric modeling over the full bandpass in pulse phase intervals provide a marginal detection of polarization of the power-law spectral component at the 4.8 +/- 2.3% level (90% confidence). We discuss the implications concerning the accretion geometry onto the pulsar, favoring two-component models of the pulsed emission.Comment: 19 pages, 7 figures, 7 tables; accepted for publication in the Astrophysical Journa