Traversed Graph Representation for Sparse Encoding of Macro-Reentrant Tachycardia

© Springer International Publishing Switzerland 2016.Macro-reentrant atrial and ventricular tachycardias originate from additional circuits in which the activation of the cardiac chambers follows a high-frequency rotating pattern. The macro-reentrant circuit can be interrupted by targeted radiofrequency energy delivery with a linear lesion transecting the pathway. The choice of the optimal ablation site is determined by the operator’s experience, thus limiting the procedure success, increasing its duration and also unnecessarily extending the ablated tissue area in the case of incorrect ablation target estimation. In this paper, an algorithm for automatic intraoperative detection of the tachycardia reentry path is proposed by modelling the propagation as a graph traverse problem. Moreover, the optimal ablation point where the path should be transected is computed. Finally, the proposed method is applied to sparse electroanatomical data to demonstrate its use when undersampled mapping occurs. Thirteen electroanatomical maps of right ventricle and right and left atrium tachycardias from patients treated for congenital heart disease were analysed retrospectively in this study, with prediction accuracy tested against the recorded ablation sites and arrhythmia termination points

Haploid Induction in Triticale × Wheat and Wheat × Rye Derivatives Following Imperata cylindrica-Mediated Chromosome Elimination Approach

The present research endeavor was undertaken to depict the response of different generations viz., F1, F2, BC1F1, BC1F2, BC1F3, BC1F4 and BC1F5 of triticale × wheat and wheat × rye hybrids towards the different parameters of haploid induction. The experimental material included the different generations obtained utilizing five genotypes of triticale (DT-123, DT-126, TL-2900, TL-2908 and TL-9335), four genotypes of Himalayan rye (Karoki rye, shanoor rye, tino rye and triloki rye) with various elite bread wheat genotypes as parents in wide hybridization programme. The triticale × wheat and wheat × rye recombinants were further subjected to Imperata cylindrica-mediated chromosome elimination approach of doubled haploidy breeding. The variability in the haploid induction parameters was observed to be under genetic control for embryo formation and regeneration, while pseudoseed formation was only affected by auxin treatment. Among the different generations, the backcross generations viz., BC1F1 and BC1F2 were found to exhibit significant positive response towards haploid induction parameters in both triticale × wheat and wheat × rye hybridization. Knowledge of effective generation for haploid induction in triticale × wheat and wheat × rye hybridization not only saved the time and energy but also enhanced the efficiency of haploid induction

Recombinant Human-C1 inhibitor is effective and safe for repeat hereditary angioedema attacks

BackgroundHereditary angioedema (HAE) caused by a deficiency in functional C1 esterase inhibitor (C1INH) is characterized by recurrent episodes of cutaneous and/or mucosal/submucosal tissue swelling affecting multiple anatomic locations. Previous studies demonstrated efficacy of recombinant human C1INH (rhC1INH) for acute HAE attacks.ObjectiveThis study evaluated the efficacy and safety of rhC1INH (50 IU/kg) for the treatment of multiple HAE attacks in an open-label extension study.MethodsTime to onset of symptom relief and time to minimal symptoms were assessed using a Treatment Effect Questionnaire (TEQ), a visual analog scale, and a 6-point ordinal scale Investigator Score.ResultsForty-four patients received rhC1INH, and a single dose was administered for 215 of 224 (96%) attacks. Median time to beginning of symptom relief based on TEQ for the first 5 attacks was 75.0 (95% CI, 69-89) minutes, ranging from 62.5 (95% CI, 48-90) to 134.0 (95% CI, 32-119) minutes. Median time to minimal symptoms using TEQ for the first 3 attacks was 303.0 (95% CI, 211-367) minutes. rhC1INH was well tolerated. There were no discontinuations due to adverse events. No thrombotic or anaphylactic events were reported, and repeat rhC1INH treatments were not associated with neutralizing anti-C1INH antibodies.ConclusionsA single 50-IU/kg dose rhC1INH was effective for improving symptoms of an HAE attack with sustained efficacy for treatment of subsequent attacks. rhC1INH had a positive safety profile throughout the study. This study supports repeated use of rhC1INH over time in patients with HAE attacks

Interim analysis:Open-label extension study of leniolisib for patients with APDS

Background: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS; or p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency) is an inborn error of immunity caused by PI3Kδ hyperactivity. Resultant immune deficiency and dysregulation lead to recurrent sinopulmonary infections, herpes viremia, autoimmunity, and lymphoproliferation. Objective: Leniolisib, a selective PI3Kδ inhibitor, demonstrated favorable impact on immune cell subsets and lymphoproliferation over placebo in patients with APDS over 12 weeks. Here, we report results from an interim analysis of an ongoing open-label, single-arm extension study. Methods: Patients with APDS aged 12 years or older who completed NCT02435173 or had previous exposure to PI3Kδ inhibitors were eligible. The primary end point was safety, assessed via investigator-reported adverse events (AEs) and clinical/laboratory evaluations. Secondary and exploratory end points included health-related quality of life, inflammatory markers, frequency of infections, and lymphoproliferation. Results: Between September 2016 and August 2021, 37 patients (median age, 20 years; 42.3% female) were enrolled. Of these 37 patients, 26, 9, and 2 patients had previously received leniolisib, placebo, or other PI3Kδ inhibitors, respectively. At the data cutoff date (December 13, 2021), median leniolisib exposure was 102 weeks. Overall, 32 patients (87%) experienced an AE. Most AEs were grades 1 to 3; none were grade 4. One patient with severe baseline comorbidities experienced a grade 5 AE, determined as unrelated to leniolisib treatment. While on leniolisib, patients had reduced annualized infection rates (P =.004), and reductions in immunoglobulin replacement therapy occurred in 10 of 27 patients. Other observations include reduced lymphadenopathy and splenomegaly, improved cytopenias, and normalized lymphocyte subsets. Conclusions: Leniolisib was well tolerated and maintained durable outcomes with up to 5 years of exposure in 37 patients with APDS. ClinicalTrials.gov identifier: NCT02859727.</p

Exploring non-linear associations between atmospheric new-particle formation and ambient variables: a mutual information approach

Atmospheric new-particle formation (NPF) is a very non-linear process that includes atmospheric chemistry of precursors and clustering physics as well as subsequent growth before NPF can be observed. Thanks to ongoing efforts, now there exists a tremendous amount of atmospheric data, obtained through continuous measurements directly from the atmosphere. This fact makes the analysis by human brains difficult but, on the other hand, enables the usage of modern data science techniques. Here, we calculate and explore the mutual information (MI) between observed NPF events (measured at Hyytiälä, Finland) and a wide variety of simultaneously monitored ambient variables: trace gas and aerosol particle concentrations, meteorology, radiation and a few derived quantities. The purpose of the investigations is to identify key factors contributing to the NPF. The applied mutual information method finds that the formation events are strongly linked to sulfuric acid concentration and water content, ultraviolet radiation, condensation sink (CS) and temperature. Previously, these quantities have been well-established to be important players in the phenomenon via dedicated field, laboratory and theoretical research. The novelty of this work is to demonstrate that the same results are now obtained by a data analysis method which operates without supervision and without the need of understanding the physics deeply. This suggests that the method is suitable to be implemented widely in the atmospheric field to discover other interesting phenomena and their relevant variables.</p

Endogenous laminin is required for human airway smooth muscle cell maturation

BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes