Automatic diagnosis of strict left bundle branch block using a wavelet-based approach

Patients with left bundle branch block (LBBB) are known to have a good clinical response to cardiac resynchronization therapy. However, the high number of false positive diagnosis obtained with the conventional LBBB criteria limits the effectiveness of this therapy, which has yielded to the definition of new stricter criteria. They require prolonged QRS duration, a QS or rS pattern in the QRS complexes at leads V1 and V2 and the presence of mid-QRS notch/slurs in 2 leads within V1, V2, V5, V6, I and aVL. The aim of this work was to develop and assess a fully-automatic algorithm for strict LBBB diagnosis based on the wavelet transform. Twelve-lead, high-resolution, 10-second ECGs from 602 patients enrolled in the MADIT-CRT trial were available. Data were labelled for strict LBBB by 2 independent experts and divided into training (n = 300) and validation sets (n = 302) for assessing algorithm performance. After QRS detection, a wavelet-based delineator was used to detect individual QRS waves (Q, R, S), QRS onsets and ends, and to identify the morphological QRS pattern on each standard lead. Then, multilead QRS boundaries were defined in order to compute the global QRS duration. Finally, an automatic algorithm for notch/slur detection within the QRS complex was applied based on the same wavelet approach used for delineation. In the validation set, LBBB was diagnosed with a sensitivity and specificity of Se = 92.9% and Sp = 65.1% (Acc = 79.5%, PPV = 74% and NPV = 89.6%). The results confirmed that diagnosis of strict LBBB can be done based on a fully automatic extraction of temporal and morphological QRS features. However, it became evident that consensus in the definition of QRS duration as well as notch and slurs definitions is necessary in order to guarantee accurate and repeatable diagnosis of complete LBBB

mer, fac, and bidentate coordination of an alkyl-POP ligand in the chemistry of nonclassical osmium hydrides

Nonclassical and classical osmium polyhydrides containing the diphosphine 9,9-dimethyl-4,5-bis(diisopropylphosphino)xanthene (xant(PiPr2)2), coordinated in κ3-mer, κ3-fac, and κ2-P,P fashions, have been isolated during the cyclic formation of H2 by means of the sequential addition of H+ and H– or H– and H+ to the classical trihydride OsH3Cl{xant(PiPr2)2} (1). This complex adds H+ to form the compressed dihydride dihydrogen complex [OsCl(H···H)(η2-H2){xant(PiPr2)2}]+ (2). Under argon, cation 2 loses H2 and the resulting unsaturated fragment dimerizes to give [(Os(H···H){xant(PiPr2)2})2(μ-Cl)2]2+ (3). During the transformation the phosphine changes its coordination mode from mer to fac. The benzofuran counterpart of 1, OsH3Cl{dbf(PiPr2)2} (4; dbf(PiPr2)2 = 4,6-bis(diisopropylphosphino)dibenzofuran), also adds H+ to afford the benzofuran counterpart of 2, [OsCl(H···H)(η2-H2){xant(PiPr2)2}]+ (5), which in contrast to the latter is stable and does not dimerize. Acetonitrile breaks the chloride bridge of 3 to form the dihydrogen [OsCl(η2-H2)(CH3CN){xant(PiPr2)2}]+ (6), regenerating the mer coordination of the diphosphine. The hydride ion also breaks the chloride bridge of 3. The addition of KH to 3 leads to 1, closing a cycle for the formation of H2. Complex 1 reacts with a second hydride ion to give OsH4{xant(PiPr2)2} (7) as consequence of the displacement of the chloride. Similarly to the latter, the oxygen atom of the mer-coordinated diphosphine of 7 has a tendency to be displaced by the hydride ion. Thus, the addition of KH to 7 yields [OsH5{xant(PiPr2)2}]− (8), containing a κ2-P,P-diphosphine. Complex 8 is easily protonated to afford OsH6{xant(PiPr2)2} (9), which releases H2 to regenerate 7, closing a second cycle for the formation of molecular hydrogen.Financial support from the MINECO of Spain (Projects CTQ2014-52799-P and CTQ2014-51912-REDC), Gobierno de Aragon (E35), FEDER, and the European Social Fund is acknowledged.Peer reviewe

Monitoring blood potassium concentration in hemodialysis patients by quantifying T-wave morphology dynamics.

We investigated the ability of time-warping-based ECG-derived markers of T-wave morphology changes in time ([Formula: see text]) and amplitude ([Formula: see text]), as well as their non-linear components ([Formula: see text] and [Formula: see text]), and the heart rate corrected counterpart ([Formula: see text]), to monitor potassium concentration ([Formula: see text]) changes ([Formula: see text]) in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). We compared the performance of the proposed time-warping markers, together with other previously proposed [Formula: see text] markers, such as T-wave width ([Formula: see text]) and T-wave slope-to-amplitude ratio ([Formula: see text]), when computed from standard ECG leads as well as from principal component analysis (PCA)-based leads. 48-hour ECG recordings and a set of hourly-collected blood samples from 29 ESRD-HD patients were acquired. Values of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] were calculated by comparing the morphology of the mean warped T-waves (MWTWs) derived at each hour along the HD with that from a reference MWTW, measured at the end of the HD. From the same MWTWs [Formula: see text] and [Formula: see text] were also extracted. Similarly, [Formula: see text] was calculated as the difference between the [Formula: see text] values at each hour and the [Formula: see text] reference level at the end of the HD session. We found that [Formula: see text] and [Formula: see text] showed higher correlation coefficients with [Formula: see text] than [Formula: see text]-Spearman's ([Formula: see text]) and Pearson's (r)-and [Formula: see text]-Spearman's ([Formula: see text])-in both SL and PCA approaches being the intra-patient median [Formula: see text] and [Formula: see text] in SL and [Formula: see text] and [Formula: see text] in PCA respectively. Our findings would point at [Formula: see text] and [Formula: see text] as the most suitable surrogate of [Formula: see text], suggesting that they could be potentially useful for non-invasive monitoring of ESRD-HD patients in hospital, as well as in ambulatory settings. Therefore, the tracking of T-wave morphology variations by means of time-warping analysis could improve continuous and remote [Formula: see text] monitoring of ESRD-HD patients and flagging risk of [Formula: see text]-related cardiovascular events

T-Wave Morphology Changes as Surrogate for Blood Potassium Concentration in Hemodialysis Patients

End-stage renal disease (ESRD) patients undergoing hemodialysis (HD) are at high risk of arrhythmias and sudden cardiac death as a result of blood potassium concentration ([K+ ]) changes. The aim of this study is to investigate if dw, a time-warping-based electrocardiogram (ECG) biomarker of T-wave morphology changes, reflects [K+] evolution in HD patients, facilitating noninvasive [K+] monitoring and avoiding in-hospital blood tests analysis. 48-hour ECGs and a set of hourly-collected blood samples from 12 ESRD patients were acquired and analyzed. dw was calculated between a reference T-wave, measured at the end of the HD session, and the T-waves corresponding to each hour along the whole HD session, when [K+] was measured from blood samples. The values of dw correlated with the relative variations in [K+] with respect to the reference value (end of HD, ¿[K+ ]), with a median (interquartile) correlation coefficient of 0.90 (0.30), evidencing a strong relation between them. Our findings support the use of dw as a surrogate of ¿[K+], suggesting a potential use of dw for non-invasive hyperkalemia monitoring both in hospital and ambulatory settings

Modified magnetic anisotropy at LaCoO_(3)/La_(0.7)Sr_(0.3)MnO_(3) interfaces

Controlling magnetic anisotropy is an important objective towards engineering novel magnetic device concepts in oxide electronics. In thin film manganites, magnetic anisotropy is weak and it is primarily determined by the substrate, through induced structural distortions resulting from epitaxial mismatch strain. On the other hand, in cobaltites, with a stronger spin orbit interaction, magnetic anisotropy is typically much stronger. In this paper, we show that interfacing La0.7Sr0.3MnO3 (LSMO) with an ultrathin LaCoO3 (LCO) layer drastically modifies the magnetic anisotropy of the manganite, making it independent of the substrate and closer to the magnetic isotropy characterizing its rhombohedral structure. Ferromagnetic resonance measurements evidence a tendency of manganite magnetic moments to point out-of-plane suggesting non collinear magnetic interactions at the interface. These results may be of interest for the design of oxide interfaces with tailored magnetic structures for new oxide devices

Markov Influence Diagrams.

Markov influence diagrams (MIDs) are a new type of probabilistic graphical model that extends influence diagrams in the same way that Markov decision trees extend decision trees. They have been designed to build state-transition models, mainly in medicine, and perform cost-effectiveness analyses. Using a causal graph that may contain several variables per cycle, MIDs can model various patient characteristics without multiplying the number of states; in particular, they can represent the history of the patient without using tunnel states. OpenMarkov, an open-source tool, allows the decision analyst to build and evaluate MIDs-including cost-effectiveness analysis and several types of deterministic and probabilistic sensitivity analysis-with a graphical user interface, without writing any code. This way, MIDs can be used to easily build and evaluate complex models whose implementation as spreadsheets or decision trees would be cumbersome or unfeasible in practice. Furthermore, many problems that previously required discrete event simulation can be solved with MIDs; i.e., within the paradigm of state-transition models, in which many health economists feel more comfortable

Development of a framework for fire risk assessment using remote sensing and geographic information system technologies

Forest fires play a critical role in landscape transformation, vegetation succession, soil degradation and air quality. Improvements in fire risk estimation are vital to reduce the negative impacts of fire, either by lessen burn severity or intensity through fuel management, or by aiding the natural vegetation recovery using post-fire treatments. This paper presents the methods to generate the input variables and the risk integration developed within the Firemap project (funded under the Spanish Ministry of Science and Technology) to map wildland fire risk for several regions of Spain. After defining the conceptual scheme for fire risk assessment, the paper describes the methods used to generate the risk parameters, and presents proposals for their integration into synthetic risk indices. The generation of the input variables was based on an extensive use of geographic information system and remote sensing technologies, since the project was intended to provide a spatial and temporal assessment of risk conditions. All variables were mapped at 1 km2 spatial resolution, and were integrated into a web-mapping service system. This service was active in the summer of 2007 for semi-operational testing of end-users. The paper also presents the first validation results of the danger index, by comparing temporal trends of different danger components and fire occurrence in the different study regions.The Firemap project was funded by the Spanish Ministry of Science and Education (CGL2004-060490C04-01/CLI) through the Environment and Climate programPeer reviewe

Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases

CarbaPIRASOA team.[Background] Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB.[Methods] We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends.[Results] A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) −1.5%, P < 0.001] and a −8.170 (−16.064 to −0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC −3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC −0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae.[Conclusions] In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.This work was funded by the Spanish Infectious Diseases and Clinical Microbiology Society (SEIMC).Peer reviewe

Contribution of the Microbial Communities Detected on an Oil Painting on Canvas to Its Biodeterioration

In this study, we investigated the microbial community (bacteria and fungi) colonising an oil painting on canvas, which showed visible signs of biodeterioration. A combined strategy, comprising culture-dependent and -independent techniques, was selected. The results derived from the two techniques were disparate. Most of the isolated bacterial strains belonged to related species of the phylum Firmicutes, as Bacillus sp. and Paenisporosarcina sp., whereas the majority of the non-cultivable members of the bacterial community were shown to be related to species of the phylum Proteobacteria, as Stenotrophomonas sp. Fungal communities also showed discrepancies: the isolated fungal strains belonged to different genera of the order Eurotiales, as Penicillium and Eurotium, and the non-cultivable belonged to species of the order Pleosporales and Saccharomycetales. The cultivable microorganisms, which exhibited enzymatic activities related to the deterioration processes, were selected to evaluate their biodeteriorative potential on canvas paintings; namely Arthrobacter sp. as the representative bacterium and Penicillium sp. as the representative fungus. With this aim, a sample taken from the painting studied in this work was examined to determine the stratigraphic sequence of its cross-section. From this information, “mock paintings,” simulating the structure of the original painting, were prepared, inoculated with the selected bacterial and fungal strains, and subsequently examined by micro-Fourier Transform Infrared spectroscopy, in order to determine their potential susceptibility to microbial degradation. The FTIR-spectra revealed that neither Arthrobacter sp. nor Penicillium sp. alone, were able to induce chemical changes on the various materials used to prepare “mock paintings.” Only when inoculated together, could a synergistic effect on the FTIR-spectra be observed, in the form of a variation in band position on the spectrum.The FTIR analyses performed in this study were financed by the Junta de Andalucía (RNM-325 group). The molecular analyses performed in this study were financed by the Austrian Science Fund (FWF) project ‘Hertha-Firnberg T137’ and the Spanish Ministry of Science and Innovation (Project CTQ2008-06727-C03-03). G. Piñar also thanks the “Elise-Richter V194-B20” projects

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.We thank all members of the Brain Metastasis Group and A. Chalmers, E. Wagner, O. Fernández-Capetillo, R. Ciérvide and A. Hidalgo for critical discussion of the manuscript; the CNIO Core Facilities for their excellent assistance; and Fox Chase Cancer Center Transgenic Facility for generation of S100A9 mice. We thank EuCOMM repository for providing S100A9 targeted embryonic stem cells. We also thank J. Massagué (MSKCC) for some of the BrM cell lines and M. Bosenberg (Yale) for the YUMM1.1 cell line. Samples from patients included in this study that provided by the Girona Biomedical Research Institute (IDIBGI) (Biobanc IDIBGI, B.0000872) are integrated into the Spanish National Biobanks Network and in the Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by the Pla Director d’Oncologia de Catalunya. All patients consented to the storage of these samples in the biobank and for their use in research projects. This study was funded by MINECO (SAF2017-89643-R) (M.V.), Fundació La Marató de TV3 (201906-30-31-32) (J.B.-B., M.V. and A.C.), Fundación Ramón Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V. and E.C.-J.M.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Portuguese Foundation for Science and Technology (SFRH/bd/100089/2014) (C.M.), Boehringer-Ingelheim Fonds MD Fellowship (L.M.), La Caixa International PhD Program Fellowship-Marie Skłodowska-Curie (LCF/BQ/DI17/11620028) (P.G.-G.), La Caixa INPhINIT Fellowship (LCF/BQ/DI19/11730044) (A.P.-A.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A.-E.) and an AECC postdoctoral fellowship (POSTD19016PRIE) (N.P.). M.V. is an EMBO YIP member (4053). Additional support was provided by Gertrud and Erich Roggenbuck Stiftung (M.M.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award with the generous support of Walk the Walk (2019AugSF1310) (D.V.), Science Foundation Ireland (20/FFP-P/8597) (D.V.), Paradifference Foundation (C.F.-T.), “la Caixa” Foundation (ID 100010434) (A.I.), European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 847648 (CF/BQ/PI20/11760029) (A.I.), Champalimaud Centre for the Unknown (N.S.), Lisboa Regional Operational Programme (Lisboa 2020) (LISBOA01-0145-FEDER-022170) (N.S.), NCI (R01 CA227629; R01 CA218133) (S.I.G.), Fundació Roses Contra el Càncer (J.B.-B.), Ministerio de Universidades FPU Fellowship (FPU 18/00069) (P.T.), MICIN-Agencia Estatal de Investigación Fellowships (PRE2020-093032 and BES-2017-080415) (P.M. and E. Cintado, respectively), Ministerio de Ciencia, Innovación y Universidades-E050251 (PID2019-110292RB-I00) (J.L.T.), FCT (PTDC/MED-ONC/32222/2017) (C.C.F.), Fundação Millennium bcp (C.C.F.), private donations (C.C.F.) and the Foundation for Applied Cancer Research in Zurich (E.L.R. and M.W.)