Emergence of spike correlations in periodically forced excitable systems

In sensory neurons the presence of noise can facilitate the detection of weak information-carrying signals, which are encoded and transmitted via correlated sequences of spikes. Here we investigate relative temporal order in spike sequences induced by a subthreshold periodic input, in the presence of white Gaussian noise. To simulate the spikes, we use the FitzHugh-Nagumo model, and to investigate the output sequence of inter-spike intervals (ISIs), we use the symbolic method of ordinal analysis. We find different types of relative temporal order, in the form of preferred ordinal patterns which depend on both, the strength of the noise and the period of the input signal. We also demonstrate a resonance-like behavior, as certain periods and noise levels enhance temporal ordering in the ISI sequence, maximizing the probability of the preferred patterns. Our findings could be relevant for understanding the mechanisms underlying temporal coding, by which single sensory neurons represent in spike sequences the information about weak periodic stimuli

Analysis of noise-induced temporal correlations in neuronal spike sequences

This is a copy of the author 's final draft version of an article published in the journal European physical journal. Special topics. The final publication is available at Springer via http://dx.doi.org/10.1140/epjst/e2016-60024-6We investigate temporal correlations in sequences of noise-induced neuronal spikes, using a symbolic method of time-series analysis. We focus on the sequence of time-intervals between consecutive spikes (inter-spike-intervals, ISIs). The analysis method, known as ordinal analysis, transforms the ISI sequence into a sequence of ordinal patterns (OPs), which are defined in terms of the relative ordering of consecutive ISIs. The ISI sequences are obtained from extensive simulations of two neuron models (FitzHugh-Nagumo, FHN, and integrate-and-fire, IF), with correlated noise. We find that, as the noise strength increases, temporal order gradually emerges, revealed by the existence of more frequent ordinal patterns in the ISI sequence. While in the FHN model the most frequent OP depends on the noise strength, in the IF model it is independent of the noise strength. In both models, the correlation time of the noise affects the OP probabilities but does not modify the most probable pattern.Peer ReviewedPostprint (author's final draft

The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody-drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma

Majorana-like Zero Modes in Kekule Distorted Sonic Lattices

[EN] Topological phases have recently been realized in bosonic systems. The associated boundary modes between regions of distinct topology have been used to demonstrate robust waveguiding, protected from defects by the topology of the surrounding bulk. A related type of topologically protected state that is not propagating but is bound to a defect has not been demonstrated to date in a bosonic setting. Here we demonstrate numerically and experimentally that an acoustic mode can be topologically bound to a vortex fabricated in a two-dimensional, Kekul¿e-distorted triangular acoustic lattice. Such lattice realizes an acoustic analog of the Jackiw-Rossi mechanism that topologically binds a bound state in a p-wave superconductor vortex. The acoustic bound state is thus a bosonic analog of a Majorana bound state, where the two valleys replace particle and hole components. We numerically show that it is topologically protected against arbitrary symmetry-preserving local perturbations, and remains pinned to the Dirac frequency of the unperturbed lattice regardless of parameter variations. We demonstrate our prediction experimentally by 3D printing the vortex pattern in a plastic matrix and measuring the spectrum of the acoustic response of the device. Despite viscothermal losses, the measured topological resonance remains robust, with its frequency closely matching our simulations.J. C. acknowledges support from the European Research Council (ERC) through the Starting Grant No. 714577 PHONOMETA and from the MINECO through a Ramon y Cajal grant (No. RYC-2015-17156). J. S.-D. acknowledges support from the Ministerio de Economia y Competitividad of the Spanish Government and the European Union "Fondo Europeo de Desarrollo Regional (FEDER)" through Project No. TEC2014-53088-C3-1-R. P. S.-J. acknowledges support from MINECO/FEDER under Grant No. FIS2015-65706-P. D. T. acknowledges financial support through the Ramon y Cajal fellowship under Grant No. RYC-2016-21188 and to the Ministry of Science, Innovation and Universities through Project No. RTI2018-093921-A-C42.Gao, P.; Torrent Martí, D.; Cervera Moreno, FS.; San-Jose, P.; Sánchez-Dehesa Moreno-Cid, J.; Christensen, J. (2019). Majorana-like Zero Modes in Kekule Distorted Sonic Lattices. Physical Review Letters. 123(19):196601-1-196601-4. https://doi.org/10.1103/PhysRevLett.123.196601S196601-1196601-412319Hasan, M. Z., & Kane, C. L. (2010). Colloquium: Topological insulators. Reviews of Modern Physics, 82(4), 3045-3067. doi:10.1103/revmodphys.82.3045Elliott, S. R., & Franz, M. (2015). Colloquium: Majorana fermions in nuclear, particle, and solid-state physics. Reviews of Modern Physics, 87(1), 137-163. doi:10.1103/revmodphys.87.137Acín, A., Bloch, I., Buhrman, H., Calarco, T., Eichler, C., Eisert, J., … Wilhelm, F. K. (2018). The quantum technologies roadmap: a European community view. New Journal of Physics, 20(8), 080201. doi:10.1088/1367-2630/aad1eaAlicea, J. (2012). New directions in the pursuit of Majorana fermions in solid state systems. Reports on Progress in Physics, 75(7), 076501. doi:10.1088/0034-4885/75/7/076501Nayak, C., Simon, S. H., Stern, A., Freedman, M., & Das Sarma, S. (2008). Non-Abelian anyons and topological quantum computation. Reviews of Modern Physics, 80(3), 1083-1159. doi:10.1103/revmodphys.80.1083Kushwaha, M. S., Halevi, P., Dobrzynski, L., & Djafari-Rouhani, B. (1993). Acoustic band structure of periodic elastic composites. Physical Review Letters, 71(13), 2022-2025. doi:10.1103/physrevlett.71.2022Martínez-Sala, R., Sancho, J., Sánchez, J. V., Gómez, V., Llinares, J., & Meseguer, F. (1995). Sound attenuation by sculpture. Nature, 378(6554), 241-241. doi:10.1038/378241a0Yang, Z., Gao, F., Shi, X., Lin, X., Gao, Z., Chong, Y., & Zhang, B. (2015). Topological Acoustics. Physical Review Letters, 114(11). doi:10.1103/physrevlett.114.114301He, C., Ni, X., Ge, H., Sun, X.-C., Chen, Y.-B., Lu, M.-H., … Chen, Y.-F. (2016). Acoustic topological insulator and robust one-way sound transport. Nature Physics, 12(12), 1124-1129. doi:10.1038/nphys3867Lu, J., Qiu, C., Ye, L., Fan, X., Ke, M., Zhang, F., & Liu, Z. (2016). Observation of topological valley transport of sound in sonic crystals. Nature Physics, 13(4), 369-374. doi:10.1038/nphys3999Deng, Y., Ge, H., Tian, Y., Lu, M., & Jing, Y. (2017). Observation of zone folding induced acoustic topological insulators and the role of spin-mixing defects. Physical Review B, 96(18). doi:10.1103/physrevb.96.184305Wang, M., Ye, L., Christensen, J., & Liu, Z. (2018). Valley Physics in Non-Hermitian Artificial Acoustic Boron Nitride. Physical Review Letters, 120(24). doi:10.1103/physrevlett.120.246601Zhang, Z., Tian, Y., Cheng, Y., Wei, Q., Liu, X., & Christensen, J. (2018). Topological Acoustic Delay Line. Physical Review Applied, 9(3). doi:10.1103/physrevapplied.9.034032Zhang, X., Xiao, M., Cheng, Y., Lu, M.-H., & Christensen, J. (2018). Topological sound. Communications Physics, 1(1). doi:10.1038/s42005-018-0094-4Jackiw, R., & Rossi, P. (1981). Zero modes of the vortex-fermion system. Nuclear Physics B, 190(4), 681-691. doi:10.1016/0550-3213(81)90044-4Shore, J. D., Huang, M., Dorsey, A. T., & Sethna, J. P. (1989). Density of states in a vortex core and the zero-bias tunneling peak. Physical Review Letters, 62(26), 3089-3092. doi:10.1103/physrevlett.62.3089Gygi, F., & Schluter, M. (1990). Electronic tunneling into an isolated vortex in a clean type-II superconductor. Physical Review B, 41(1), 822-825. doi:10.1103/physrevb.41.822Torrent, D., & Sánchez-Dehesa, J. (2012). Acoustic Analogue of Graphene: Observation of Dirac Cones in Acoustic Surface Waves. Physical Review Letters, 108(17). doi:10.1103/physrevlett.108.174301Kekuié, A. (1866). Untersuchungen über aromatische Verbindungen Ueber die Constitution der aromatischen Verbindungen. I. Ueber die Constitution der aromatischen Verbindungen. Annalen der Chemie und Pharmacie, 137(2), 129-196. doi:10.1002/jlac.18661370202Read, N., & Green, D. (2000). Paired states of fermions in two dimensions with breaking of parity and time-reversal symmetries and the fractional quantum Hall effect. Physical Review B, 61(15), 10267-10297. doi:10.1103/physrevb.61.10267Fu, L., & Kane, C. L. (2008). Superconducting Proximity Effect and Majorana Fermions at the Surface of a Topological Insulator. Physical Review Letters, 100(9). doi:10.1103/physrevlett.100.096407Nishida, Y., Santos, L., & Chamon, C. (2010). Topological superconductors as nonrelativistic limits of Jackiw-Rossi and Jackiw-Rebbi models. Physical Review B, 82(14). doi:10.1103/physrevb.82.144513Hou, C.-Y., Chamon, C., & Mudry, C. (2007). Electron Fractionalization in Two-Dimensional Graphenelike Structures. Physical Review Letters, 98(18). doi:10.1103/physrevlett.98.186809Caroli, C., De Gennes, P. G., & Matricon, J. (1964). Bound Fermion states on a vortex line in a type II superconductor. Physics Letters, 9(4), 307-309. doi:10.1016/0031-9163(64)90375-

Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder

doi:10.1186/1745-0179-3

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

Visceral leishmaniasis with cardiac involvement in a dog: a case report

A dog presented with cutaneous nodules, enlarged lymph nodes and oedema in limbs, face and abdomen. The diagnosis of visceral leishmaniasis was established by identification of Leishmania amastigotes within macrophages from skin and popliteal lymph node biopsies. At necropsy, lesions were found in different organs, but it was particularly striking to observe large areas of pallor in the myocardium. Histological examination revealed an intense chronic inflammatory reaction in many organs, and numerous macrophages were found to contain amastigote forms of Leishmania. The inflammatory reaction was especially severe in the heart, where large areas of the myocardium appeared infiltrated with huge numbers of mononuclear immune cells, causing cardiac muscle atrophy and degeneration. Despite the severe inflammation, the number of parasitized macrophages was low in the myocardium, as revealed by immunohistochemical staining of Leishmania amastigotes. Because cardiac involvement is not usually described in this condition, this dog represents a very rare case of canine visceral leishmaniasis with affection of the myocardium