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Morpho-phonological patterns and semantic density influence the processing of spoken complex words and contribute to the dissociation between regularly and irregularly inflected forms. However, it is unclear whether all listeners rely on morpho-phonological and semantic cues to the same degree. The present paper examines whether a listener’s cognitive profile, indicated by processing efficiency, affects the processing strategy employed when listening to morphologically complex words. Two auditory judgement experiments demonstrate that slower responders rely more strongly on semantic processing than faster responders, but all listeners show morpho-phonological effects regardless of processing speed and form effects. This demonstrates that morpho-phonological processing is automatic for all listeners, but processing efficiency determines whether additional semantic cues are engaged. The results highlight the importance of integrating cognitive variability into current models of complex word processing.

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P, Junction plakoglobin (JUP) is a component of desmosomes and adherens junctions and reported to play divergent roles in tumorigenesis. JUP expression was analyzed in prostate cancer in a large‐enough patient cohort to reflect the molecular heterogeneity of the disease. Overall, high JUP expression was associated with adverse tumor features, while low JUP expression indicated poor prognosis in CHD1‐deleted patients.

We introduce frequency propagation, a learning algorithm for nonlinear physical networks. In a resistive electrical circuit with variable resistors, an activation current is applied at a set of input nodes at one frequency, and an error current is applied at a set of output nodes at another frequency. The voltage response of the circuit to these boundary currents is the superposition of an `activation signal' and an `error signal' whose coefficients can be read in different frequencies of the frequency domain. Each conductance is updated proportionally to the product of the two coefficients. The learning rule is local and proved to perform gradient descent on a loss function. We argue that frequency propagation is an instance of a multi-mechanism learning strategy for physical networks, be it resistive, elastic, or flow networks. Multi-mechanism learning strategies incorporate at least two physical quantities, potentially governed by independent physical mechanisms, to act as activation and error signals in the training process. Locally available information about these two signals is then used to update the trainable parameters to perform gradient descent. We demonstrate how earlier work implementing learning via chemical signaling in flow networks also falls under the rubric of multi-mechanism learning., 9 pages, 0 figures

The ASTRI Mini-Array (MA) is an INAF project to build and operate a facility to study astronomical sources emitting at very high-energy in the TeV spectral band. The ASTRI MA consists of a group of nine innovative Imaging Atmospheric Cherenkov telescopes. The telescopes will be installed at the Teide Astronomical Observatory of the Instituto de Astrofisica de Canarias (IAC) in Tenerife (Canary Islands, Spain) on the basis of a host agreement with INAF. Thanks to its expected overall performance, better than those of current Cherenkov telescopes' arrays for energies above \sim 5 TeV and up to 100 TeV and beyond, the ASTRI MA will represent an important instrument to perform deep observations of the Galactic and extra-Galactic sky at these energies., 19 pages, 22 figures

Organoids are in vitro cellular collectives from which brain-like, or gut-like, or kidney-like structures emerge. To make quantitative predictions regarding the morphology and rheology of a cellular collective in its initial stages of development, we construct and study a three-dimensional vertex model. In such a model, the cells are represented as deformable polyhedrons with cells sharing faces such that there are no gaps between them, otherwise known as confluent. In a bulk model with periodic boundary conditions, we find a rigidity transition as a function of the target cell shape index $s_0$ with a critical value $s_0^*=5.39\pm0.01$. For a confluent cellular collective with a finite boundary, and in the presence of lateral extensile and in-plane, radial extensile deformations, we find significant boundary-bulk patterning that is one-cell layer thick. More specifically, for lateral extensile deformations, the cells in the bulk are much less aligned with the direction of the lateral deformation than the cells at the boundary. For in-plane, radial deformations, the cells in the bulk exhibit much less reorientation perpendicular to the radial direction than the cells at the boundary. In other words, for both deformations, the bulk cells are insulated from the deformations, at least over time scales much slower than the timescale for cellular rearrangements. Our results provide an underlying mechanism for some observed cell shape patterning in organoids. Finally, we discuss the use of a cellular-based approach to designing organoids with new types of morphologies to study the intricate relationship between structure and function at the multi-cellular scale.

Full list of authors: Acharyya, A.; Adam, R.; Adams, C.; Agudo, I.; Aguirre-Santaella, A.; Alfaro, R.; Alfaro, J.; Alispach, C.; Aloisio, R.; Alves Batista, R.; Amati, L.; Ambrosi, G.; Angüner, E. O.; Antonelli, L. A.; Aramo, C.; Araudo, A.; Armstrong, T.; Arqueros, F.; Asano, K.; Ascasíbar, Y. Ashley, M.; Balazs, C.; Ballester, O.; Baquero Larriva, A.; Barbosa Martins, V.; Barkov, M.; Barres de Almeida, U.; Barrio, J. A.; Bastieri, D.; Becerra, J.; Beck, G.; Becker Tjus, J.; Benbow, W.; Benito, M.; Berge, D.; Bernardini, E.; Bernlöhr, K.; Berti, A.; Bertucci, B.; Beshley, V.; Biasuzzi, B.; Biland, A.; Bissaldi, E.; Biteau, J.; Blanch, O.; Blazek, J.; Bocchino, F.; Boisson, C.; Bonneau Arbeletche, L.; Bordas, P.; Bosnjak, Z.; Bottacini, E.; Bozhilov, V.; Bregeon, J.; Brill, A.; Bringmann, T.; Brown, A. M.; Brun, P.; Brun, F.; Bruno, P.; Bulgarelli, A.; Burton, M.; Burtovoi, A.; Buscemi, M.; Cameron, R.; Capasso, M.; Caproni, A.; Capuzzo-Dolcetta, R.; Caraveo, P.; Carosi, R.; Carosi, A.; Casanova, S.; Cascone, E.; Cassol, F.; Catalani, F.; Cauz, D.; Cerruti, M.; Chadwick, P.; Chaty, S.; Chen, A.; Chernyakova, M.; Chiaro, G.; Chiavassa, A.; Chikawa, M.; Chudoba, J.; Çolak, M.; Conforti, V.; Coniglione, R.; Conte, F.; Contreras, J. L.; Coronado-Blazquez, J.; Costa, A.; Costantini, H.; Cotter, G.; Cristofari, P.; D'Aimath, A.; D'Ammando, F.; Damone, L. A.; Daniel, M. K.; Dazzi, F.; De Angelis, A.; De Caprio, V.; de Cássia dos Anjos, R.; de Gouveia Dal Pino, E. M.; De Lotto, B.; De Martino, D.; de Oña Wilhelmi, E.; De Palma, F.; de Souza, V.; Delgado, C.; Delgado Giler, A. G.; della Volpe, D.; Depaoli, D.; Di Girolamo, T.; Di Pierro, F.; Di Venere, L.; Diebold, S.; Dmytriiev, A.; Domínguez, A.; Donini, A.; Doro, M.; Ebr, J.; Eckner, C.; Edwards, T. D. P.; Ekoume, T. R. N.; Elsässer, D.; Evoli, C.; Falceta-Goncalves, D.; Fedorova, E.; Fegan, S.; Feng, Q.; Ferrand, G.; Ferrara, G.; Fiandrini, E.; Fiasson, A.; Filipovic, M.; Fioretti, V.; Fiori, M.; Foffano, L.; Fontaine, G.; Fornieri, O.; Franco, F. J.; Fukami, S.; Fukui, Y.; Gaggero, D.; Galaz, G.; Gammaldi, V.; Garcia, E.; Garczarczyk, M.; Gascon, D.; Gent, A.; Ghalumyan, A.; Gianotti, F.; Giarrusso, M.; Giavitto, G.; Giglietto, N.; Giordano, F.; Giuliani, A.; Glicenstein, J.; Gnatyk, R.; Goldoni, P.; González, M. M.; Gourgouliatos, K.; Granot, J.; Grasso, D.; Green, J.; Grillo, A.; Gueta, O.; Gunji, S.; Halim, A.; Hassan, T.; Heller, M.; Hernández Cadena, S.; Hiroshima, N.; Hnatyk, B.; Hofmann, W.; Holder, J.; Horan, D.; Hörandel, J.; Horvath, P.; Hovatta, T.; Hrabovsky, M.; Hrupec, D.; Hughes, G.; Humensky, T. B.; Hütten, M.; Iarlori, M.; Inada, T.; Inoue, S.; Iocco, F.; Iori, M.; Jamrozy, M.; Janecek, P.; Jin, W.; Jouvin, L.; Jurysek, J.; Karukes, E.; Katarzyński, K.; Kazanas, D.; Kerszberg, D.; Kherlakian, M. C.; Kissmann, R.; Knödlseder, J.; Kobayashi, Y.; Kohri, K.; Komin, N.; Kubo, H.; Kushida, J.; Lamanna, G.; Lapington, J.; Laporte, P.; Leigui de Oliveira, M. A.; Lenain, J.; Leone, F.; Leto, G.; Lindfors, E.; Lohse, T.; Lombardi, S.; Longo, F.; Lopez, A.; López, M.; López-Coto, R.; Loporchio, S.; Luque-Escamilla, P. L.; Mach, E.; Maggio, C.; Maier, G.; Mallamaci, M.; Malta Nunes de Almeida, R.; Mandat, D.; Manganaro, M.; Mangano, S.; Manicò, G.; Marculewicz, M.; Mariotti, M.; Markoff, S.; Marquez, P.; Martí, J.; Martinez, O.; Martínez, M.; Martínez, G.; Martínez-Huerta, H.; Maurin, G.; Mazin, D.; Mbarubucyeye, J. D.; Medina Miranda, D.; Meyer, M.; Miceli, M.; Miener, T.; Minev, M.; Miranda, J. M.; Mirzoyan, R.; Mizuno, T.; Mode, B.; Moderski, R.; Mohrmann, L.; Molina, E.; Montaruli, T.; Moralejo, A.; Morcuende-Parrilla, D.; Morselli, A.; Mukherjee, R.; Mundell, C.; Nagai, A.; Nakamori, T.; Nemmen, R.; Niemiec, J.; Nieto, D.; Nikołajuk, M.; Ninci, D.; Noda, K.; Nosek, D.; Nozaki, S.; Ohira, Y.; Ohishi, M.; Ohtani, Y.; Oka, T.; Okumura, A.; Ong, R. A.; Orienti, M.; Orito, R.; Orlandini, M.; Orlando, S.; Orlando, E.; Ostrowski, M.; Oya, I.; Pagano, I.; Pagliaro, A.; Palatiello, M.; Pantaleo, F. R.; Paredes, J. M.; Pareschi, G.; Parmiggiani, N.; Patricelli, B.; Pavletić, L.; Pe'er, A.; Pecimotika, M.; Pérez-Romero, J.; Persic, M.; Petruk, O.; Pfrang, K.; Piano, G.; Piatteli, P.; Pietropaolo, E.; Pillera, R.; Pilszyk, B.; Pintore, F.; Pohl, M.; Poireau, V.; Prado, R. R.; Prandini, E.; Prast, J.; Principe, G.; Prokoph, H.; Prouza, M.; Przybilski, H.; Pühlhofer, G.; Pumo, M. L.; Queiroz, F.; Quirrenbach, A.; Rainò, S.; Rando, R.; Razzaque, S.; Recchia, S.; Reimer, O.; Reisenegger, A.; Renier, Y.; Rhode, W.; Ribeiro, D.; Ribó, M.; Richtler, T.; Rico, J.; Rieger, F.; Rinchiuso, L.; Rizi, V.; Rodriguez, J.; Rodriguez Fernandez, G.; Rodriguez Ramirez, J. C.; Rojas, G.; Romano, P.; Romeo, G.; Rosado, J.; Rowell, G.; Rudak, B.; Russo, F.; Sadeh, I.; Sæther Hatlen, E.; Safi-Harb, S.; Salesa Greus, F.; Salina, G.; Sanchez, D.; Sánchez-Conde, M.; Sangiorgi, P.; Sano, H.; Santander, M.; Santos, E. M.; Santos-Lima, R.; Sanuy, A.; Sarkar, S.; Saturni, F. G.; Sawangwit, U.; Schussler, F.; Schwanke, U.; Sciacca, E.; Scuderi, S.; Seglar-Arroyo, M.; Sergijenko, O.; Servillat, M.; Seweryn, K.; Shalchi, A.; Sharma, P.; Shellard, R. C.; Siejkowski, H.; Silk, J.; Siqueira, C.; Sliusar, V.; Słowikowska, A.; Sokolenko, A.; Sol, H.; Spencer, S.; Stamerra, A.; Stanič, S.; Starling, R.; Stolarczyk, T.; Straumann, U.; Strišković, J.; Suda, Y.; Suomijarvi, T.; Świerk, P.; Tavecchio, F.; Taylor, L.; Tejedor, L. A.; Teshima, M.; Testa, V.; Tibaldo, L.; Todero Peixoto, C. J.; Tokanai, F.; Tonev, D.; Tosti, G.; Tosti, L.; Tothill, N.; Truzzi, S.; Travnicek, P.; Vagelli, V.; Vallage, B.; Vallania, P.; van Eldik, C.; Vandenbroucke, J.; Varner, G. S.; Vassiliev, V.; Vázquez Acosta, M.; Vecchi, M.; Ventura, S.; Vercellone, S.; Vergani, S.; Verna, G.; Viana, A.; Vigorito, C. F.; Vink, J.; Vitale, V.; Vorobiov, S.; Vovk, I.; Vuillaume, T.; Wagner, S. J.; Walter, R.; Watson, J.; Weniger, C.; White, R.; White, M.; Wiemann, R.; Wierzcholska, A.; Will, M.; Williams, D. A.; Wischnewski, R.; Yanagita, S.; Yang, L.; Yoshikoshi, T.; Zacharias, M.; Zaharijas, G.; Zakaria, A. A.; Zampieri, L.; Zanin, R.; Zaric, D.; Zavrtanik, M.; Zavrtanik, D.; Zdziarski, A. A.; Zech, A.; Zechlin, H.; Zhdanov, V. I.; Živec, M.-- This is an open access article published by IOP Publishing Ltd on behalf of Sissa Medialab. Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI., We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies. © 2021 The Author(s)., We gratefully acknowledge financial support from the following agencies and organisations: State Committee of Science of Armenia, Armenia; The Australian Research Council, Astronomy Australia Ltd, The University of Adelaide, Australian National University, Monash University, The University of New South Wales, The University of Sydney, Western Sydney University, Australia; Federal Ministry of Education, Science and Research, and Innsbruck University, Austria; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Ministry of Science, Technology, Innovations and Communications (MCTIC), and Instituto Serrapilheira, Brasil; Ministry of Education and Science, National RI Roadmap Project DO1-153/28.08.2018, Bulgaria; The Natural Sciences and Engineering Research Council of Canada and the Canadian Space Agency, Canada; CONICYT-Chile grants CATA AFB 170002, ANID PIA/APOYO AFB 180002, ACT 1406, FONDECYT-Chile grants, 1161463, 1170171, 1190886, 1171421, 1170345, 1201582, Gemini-ANID 32180007, Chile; Croatian Science Foundation, Rudjer Boskovic Institute, University of Osijek, University of Rijeka, University of Split, Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture, University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia; Ministry of Education, Youth and Sports, MEYS LM2015046, LM2018105, LTT17006, EU/MEYS CZ.02.1.01/0.0/0.0/16_013/0001403, CZ.02.1.01/0.0/0.0/18_046/0016007 and CZ.02.1.01/0.0/0.0/16_019/0000754, Czech Republic; Academy of Finland (grant nr.317636, 320045, 317383 and 320085), Finland; Ministry of Higher Education and Research, CNRS-INSU and CNRS-IN2P3, CEA-Irfu, ANR, Regional Council Ile de France, Labex ENIGMASS, OSUG2020, P2IO and OCEVU, France; Max Planck Society, BMBF, DESY, Helmholtz Association, Germany; Department of Atomic Energy, Department of Science and Technology, India; Istituto Nazionale di Astrofisica (INAF), Istituto Nazionale di Fisica Nucleare (INFN), MIUR, Istituto Nazionale di Astrofisica (INAF-OABRERA) Grant Fondazione Cariplo/Regione Lombardia ID 2014-1980/RST_ERC, Italy; ICRR, University of Tokyo, JSPS, MEXT, Japan; Netherlands Research School for Astronomy (NOVA), Netherlands Organization for Scientific Research (NWO), Netherlands; University of Oslo, Norway; Ministry of Science and Higher Education, DIR/WK/2017/12, the National Centre for Research and Development and the National Science Centre, UMO-2016/22/M/ST9/00583, Poland; Slovenian Research Agency, grants P1-0031, P1-0385, I0-0033, J1-9146, J1-1700, N1-0111, and the Young Researcher program, Slovenia; South African Department of Science and Technology and National Research Foundation through the South African Gamma-Ray Astronomy Programme, South Africa; The Spanish Ministry of Science and Innovation and the Spanish Research State Agency (AEI) through grants AYA2016-79724-C4-1-P, AYA2016-80889-P, AYA2016-76012-C3-1-P, BES-2016-076342, ESP2017-87055-C2-1-P, FPA2017-82729-C6-1-R, FPA2017-82729-C6-2-R, FPA2017-82729-C6-3-R, FPA2017-82729-C6-4-R, FPA2017-82729-C6-5-R, FPA2017-82729-C6-6-R, PGC2018-095161-B-I00, PGC2018-095512-B-I00; the \Centro de Excelencia Severo Ochoa"program through grants no. SEV-2015-0548, SEV-2016-0597, SEV-2016-0588, SEV-2017-0709; the "Unidad de Excelencia Maria de Maeztu" program through grant no. MDM-2015-0509; the "Ramon y Cajal" programme through grants RYC-2013-14511, RyC-2013-14660, RYC-2017-22665; and the MultiDark Consolider Network FPA2017-90566-REDC. Atraccion de Talento contract no. 2016-T1/TIC-1542 granted by the Comunidad de Madrid; the "Postdoctoral Junior Leader Fellowship" programme from La Caixa Banking Foundation, grants no. LCF/BQ/LI18/11630014 and LCF/BQ/PI18/11630012; the "Programa Operativo" FEDER2014-2020, Consejeria de Economia y Conocimiento de la Junta de Andalucia (ref. 1257737), PAIDI 2020 (ref. P18-FR-1580), and Universidad de Jaen; the Spanish AEI EQC2018-005094-P FEDER 2014-2020; the European Union's "Horizon 2020" research and innovation programme under Marie Sklodowska-Curie grant agreement no. 665919; and the ESCAPE project with grant no. GA:824064, Spain; Swedish Research Council, Royal Physiographic Society of Lund, Royal Swedish Academy of Sciences, The Swedish National Infrastructure for Computing (SNIC) at Lunarc (Lund), Sweden; State Secretariat for Education, Research and Innovation (SERI) and Swiss National Science Foundation (SNSF), Switzerland; Durham University, Leverhulme Trust, Liverpool University, University of Leicester, University of Oxford, Royal Society, Science and Technology Facilities Council, U.K.; U.S. National Science Foundation, U.S. Department of Energy, Argonne National Laboratory, Barnard College, University of California, University of Chicago, Columbia University, Georgia Institute of Technology, Institute for Nuclear and Particle Astrophysics (INPAC-MRPI program), Iowa State University, the Smithsonian Institution, Washington University McDonnell Center for the Space Sciences, The University of Wisconsin and the Wisconsin Alumni Research Foundation, U.S.A. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements No 262053 and No 317446. This project is receiving funding from the European Union's Horizon 2020 research and innovation programs under agreement No 676134.

Purpose: The effect of the duration of an educational rotation presented at a palliative care unit on the palliative care knowledge gain and the increase of palliative care self-efficacy expectations are unclear. Methods: This national prospective multicenter pre–post survey conducted at twelve German University Comprehensive Cancer Centers prospectively enrolled physicians who were assigned to training rotations in specialized palliative care units for three, six, or twelve months. Palliative care knowledge [in %] and palliative care self-efficacy expectations [max. 57 points] were evaluated before and after the rotation with a validated questionnaire. Results: From March 2018 to October 2020, questionnaires of 43 physicians were analyzed. Physicians participated in a 3- (n = 3), 6- (n = 21), or 12-month (n = 19) palliative care rotation after a median of 8 (0–19) professional years. The training background of rotating physicians covered a diverse spectrum of specialties; most frequently represented were medical oncology (n = 15), and anesthesiology (n = 11). After the rotation, median palliative care knowledge increased from 81.1% to 86.5% (p

Employing the elemental sensitivity of x-ray absorption spectroscopy (XAS) and x-ray magnetic circular dichroism (XMCD), we study the valence and magnetic order in the heavy fermion superconductor CeCoIn$_5$. We probe spin population of the f-electrons in Ce and d-electrons in Co as a function of temperature (down to 0.1 K) and magnetic field (up to 6 T). From the XAS we find a pronounced contribution of Ce$^{4+}$ component at low temperature and a clear temperature dependence of the Ce valence below 5 K, suggesting enhanced valence fluctuations, an indication for the presence of a nearby quantum critical point (QCP). We observe no significant corresponding change with magnetic field. The XMCD displays a weak signal for Ce becoming clear only at 6 T. This splitting of the Kramers doublet ground state of Ce$^{3+}$ is significantly smaller than expected for independent but screened ions, indicating strong antiferromagnetic pair interactions. The unconventional character of superconductivity in CeCoIn$_5$ is evident in the extremely large specific heat step at the superconducting transition., Comment: 5 pages, 5 figures. Supplementary information (4 pages, 5 figures)

Isabel Blumenroth, Das Alexandrinische Schisma in Briefen und Ideenwelt des Arnulf von Lisieux und Johannes von Salisbury, Wien, K��ln (B��hlau) 2021, 847 S., 2 s/w. Abb. (Papsttum im mittelalterlichen Europa, 10), ISBN 978-3-412-52207-0, EUR 110,00., Francia-Recensio, 2021/4

Disordered spring networks can exhibit rigidity transitions, due to either the removal of materials in over-constrained networks or the application of strain in under-constrained ones. While an effective medium theory (EMT) exists for the former, there is none for the latter. We, therefore, formulate an EMT for random regular networks, under-constrained spring networks with purely geometrical disorder, to predict their stiffness via the distribution of tensions. We find a linear dependence of stiffness on strain in the rigid phase and a nontrivial dependence on both the mean and standard deviation of the tension distribution. While EMT does not yield highly accurate predictions of shear modulus due to spatial heterogeneities, the noninvasiveness of this EMT makes it an ideal starting point for experimentalists quantifying the mechanics of such networks., 10 pages, 8 figures

Measurements of surface ozone (O3), nitrogen oxides (NOx = NO + NO2), carbon monoxide (CO), and dew point were made at Qinghai Lake (QHL), China, a basin in the remote Tibetan Plateau area, in October 2010 and October 2011. The O3 mixing ratio was found to be high with average of 41 ± 9ppb in October 2010 and 57 ± 10ppb in October 2011. The observed diurnal pattern of O3 mixing ratio was characterized by a minimum between 07:00 and 10:00 local standard time (LST) increasing ~20ppb to a broad peak occurring between 13:00 and 18:00 LST. This diurnal pattern differs substantially from that observed at WMO's GAW Baseline Observatory located above the basin on Mount Waliguan, ~130km southeast of QHL. The elevated O3 mixing ratios observed in the afternoon are attributed to in situ photochemical production in the air trapped in the QHL basin by surrounding mountains. The low O3 mixing ratios observed in the morning are most likely due to surface removal in a shallow nocturnal boundary layer. The data indicate substantial impacts of pollution on air quality even in this remote area. The high O3 values observed in 2011 may cause observable damage to the vegetation, adding stress to an ecosystem ready under the threat of desertification.

Background: Safinamide modulates both dopaminergic and glutamatergic systems with positive effects on motor and non-motor symptoms of Parkinson's disease (PD). The drug utilization study SYNAPSES was designed to investigate the use of safinamide in routine clinical practice, as recommended by the European Medicines Agency. Objective: To describe the occurrence of adverse events in PD patients treated with safinamide in real-life conditions. Methods: The SYNAPSES trial is an observational, European, multicenter, retrospective-prospective cohort study. Patients were followed up to 12 months with analyses performed in the overall population and in patients aged >75 years, with relevant comorbidities and with psychiatric conditions. Results: Of the 1610 patients included, 82.4% were evaluable after 12 months with 25.1% of patients >75 years, 70.8% with relevant comorbidities and 42.4% with psychiatric conditions. During observation 45.8% patients experienced adverse events, 27.7% patients had adverse drug reactions and 9.2% patients had serious adverse events. The adverse events were those already described in the patients' information leaflet. The majority were mild or moderate and completely resolved and no differences were detected between the subgroup of patients. Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in >= 40% of patients, according to the criteria developed by Shulman et al. Conclusion: The SYNAPSES study confirms the good safety profile of safinamide even in special groups of patients. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.

Brain organoids recapitulate a number of brain properties, including neuronal diversity. However, do they recapitulate brain structure? Using a hydrodynamic description for cell nuclei as particles interacting initially via an effective, attractive force as mediated by the respective, surrounding cytoskeletons, we quantify structure development in brain organoids to determine what physical mechanism regulates the number of cortex-core structures. Regions of cell nuclei overdensity in the linear regime drive the initial seeding for cortex-core structures, which ultimately develop in the non-linear regime, as inferred by the emergent form of an effective interaction between cell nuclei and with the extracellular environment, as mediated by a dynamic cytoskeleton. Individual cortex-core structures then provide a basis upon which we build an extended version of the buckling without bending morphogenesis (BWBM) model, with its proliferating cortex and constraining core, to predict foliations/folds of the cortex in the presence of a nonlinearity due to cortical cells actively regulating strain. In doing so, we obtain asymmetric foliations/folds with respect to the trough (sulci) and the crest (gyri). In addition to laying new groundwork for the design of more familiar and less familiar brain structures, the hydrodynamic description for cell nuclei during the initial stages of brain organoid development provides an intriguing quantitative connection with large-scale structure formation in the universe., 13 pages, 9 figures. Comments are welcome

We determined bulk crystal nucleation rates in aqueous suspensions of charged spheres at low metastability. Experiments were performed in dependence on electrolyte concen-tration and for two different particle number densities. The time-dependent nucleation rate shows a pronounced initial peak, while post-solidification crystal size distributions are skewed towards larger crystallite sizes. At each concentration, the nucleation rate density initially drops exponentially with increasing salt concentration. The complete data set, however, shows an unexpected scaling of the nucleation rate densities with met-astability times the number density of particles. Parameterization of our results in terms of Classical Nucleation Theory reveals unusually low interfacial free energies of the nu-cleus surfaces and nucleation barriers well below the thermal energy. We tentatively attribute our observations to the presence of doublets introduced by the employed con-ditioning technique and acting as nucleation seeds., 37 pages preprint, 13 Figs. revised version for PRE

Dans cet article, nous rapportons de brefs extraits de 8 entrevues avec des clinicien·ne·s sensibilisé·e·s au genre, dans le but d’illustrer comment un intérêt pour ce domaine peut influencer la pratique quotidienne. Les personnes interrogées expliquent que le fait d’avoir un·e proche intéressé·e au genre les a rendues attentives à ce sujet. Dans leur pratique, elles disent avoir conscience de biais liés, d’une part, à l’acquisition des connaissances médicales ne tenant pas compte du genre et, d’autre part, à des stéréotypes de genre menant à une pratique médicale inégalitaire. Le genre a aussi un effet sur leurs carrières. Certaines personnes interrogées souhaiteraient bénéficier de plus de formation afin de diminuer les inégalités dues au genre.

Similarities and differences in the submicron atmospheric aerosol chemical composition are analyzed from a unique set of measurements performed at 21 sites across Europe for at least one year. These sites are located between 35 and 62°N and 10° W – 26°E, and represent various types of settings (remote, coastal, rural, industrial, urban). Measurements were all carried out on-line with a 30-min time resolution using mass spectroscopy based instruments known as Aerosol Chemical Speciation Monitors (ACSM) and Aerosol Mass Spectrometers (AMS) and following common measurement guidelines. Data regarding organics, sulfate, nitrate and ammonium concentrations, as well as the sum of them called non-refractory submicron aerosol mass concentration ([NR-PM1]) are discussed. NR-PM1 concentrations generally increase from remote to urban sites. They are mostly larger in the mid-latitude band than in southern and northern Europe. On average, organics account for the major part (36–64%) of NR-PM1 followed by sulfate (12–44%) and nitrate (6–35%). The annual mean chemical composition of NR-PM1 at rural (or regional background) sites and urban background sites are very similar. Considering rural and regional background sites only, nitrate contribution is higher and sulfate contribution is lower in mid-latitude Europe compared to northern and southern Europe. Large seasonal variations in concentrations (μg/m³) of one or more components of NR-PM1 can be observed at all sites, as well as in the chemical composition of NR-PM1 (%) at most sites. Significant diel cycles in the contribution to [NR-PM1] of organics, sulfate, and nitrate can be observed at a majority of sites both in winter and summer. Early morning minima in organics in concomitance with maxima in nitrate are common features at regional and urban background sites. Daily variations are much smaller at a number of coastal and rural sites. Looking at NR-PM1 chemical composition as a function of NR-PM1 mass concentration reveals that although organics account for the major fraction of NR-PM1 at all concentration levels at most sites, nitrate contribution generally increases with NR-PM1 mass concentration and predominates when NR-PM1 mass concentrations exceed 40 μg/m³ at half of the sites., This study was partially supported by the European Union's projects ACTRIS (EU FP7-262254) and ACTRIS-2 (EU Horizon 2020–654109). COST Action CA16109 COLOSSAL, Chemical On-Line cOmpoSition and Source Apportionment of fine aerosoL, is acknowledged. The ACSM observations at Birkenes was funded by the Norwegian Ministry of Climate and Environment Strategic Institute Program. IDAEA-CSIC (3 datasets: BCN, MSA, MSY) was partially supported by the Spanish Ministry of Economy and Competitiveness and FEDER funds under the PRISMA project (CGL 2012-39623-C02-1). The London measurements were supported by the UK National Research Council through the ClearfLo project and a PhD studentship (grant refs. NE/H008136/1 and NE/I528142/1) and the Department of Environment, Food and Rural Affairs (DEFRA). ECPL personel, namely Nikolaos Mihalopoulos, Aikaterini Bougiatioti and Iasonas Stavroulas acknowledge support by the project “Panhellenic infrastructure for atmospheric composition and climate change, PANACEA” (MIS 5021516) which is implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Programme” Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the European Union (European Regional Development Fund). IMT Lille Douai acknowledges financial support from the CaPPA (Chemical and Physical Properties of the Atmosphere) project funded by the French National Research Agency (ANR) through the PIA (Programme d'Investissement d'Avenir) under contract ANR-11-LABX-0005-01, and two CPER projects funded by the French Ministry of Higher Education and Research, the CNRS, the Regional Council “Hauts-de-France” and the European Regional Development Fund (ERDF): Climibio, and IRENI (additionally financed by the Communauté Urbaine de Dunkerque). S. Zhang thanks IMT Lille Douai and the Regional Council “Hauts-de-France” for her PhD grant. Prague co-authors would like to acknowledge a Czech MEYS's project under INTER-EXCELENCE INTERCOST program under grant agreement LTC18068 and from European Regional Development Fund-Project under the grant ACTRIS-CZ RI (CZ.02.1.01/0.0/0.0/16_013/0001315). EPA Ireland, Department of Communications, Climate Action and Environment (DCCAE) and the European Union's Seventh Framework Programme (FP7/2007–2013) project BACCHUS under grant agreement n_603445 are acknowledged for research support at Mace Head. The physical measurements were also funded by the German Ultrafine Aerosol Network GUAN, which was jointly established with help of the German Federal Environment Ministry (BMU) grants F&E 370343200 (German title: “Erfassung der Zahl feiner und ultrafeiner Partikel in der Auβenluft”), 2008–2010, and F&E 371143232 (German title: “Trendanalysen gesundheitsgefährdender Fein-und Ultrafeinstaubfraktionen unter Nutzung der im German Ultrafine Aerosol Network (GUAN) ermittelten Immissionsdaten durch Fortführung und Interpretation der Messreihen”) 2012–2014. We also acknowledge the WCCAP (World Calibration Center for Aerosol Physics) as part of the WMO-GAW program. The WCCAP is base-funded by the German Federal Environmental Agency (Umweltbundesamt), Germany. Support by the European Regional Development Funds (EFRE – Europe funds Saxony) is gratefully acknowledged. Atmospheric measurements performed in Corsica is part of the ChArMEx project supported by CNRS-INSU, ADEME, Météo-France and CEA in the framework of the multidisciplinary programme MISTRALS (Mediterranean Integrated Studies aT Regional And Local Scales; http://mistrals-home.org/, last access: June 10, 2020). Final data processing of these measurements has been supported by the EMME-CARE (Eastern Mediterranean and Middle East Climate and Atmosphere Research Center) which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 856612 and the Cyprus Government. The measurements in Switzerland were supported by the Federal Office for the Environment. We thank the International Foundation High Altitude Research Stations Jungfraujoch and Gornergrat (HFSJG) for the opportunity to perform experiments on the Jungfraujoch.

The interface separating a liquid from its vapor phase is diffuse: the composition varies continuously from one phase to the other over a finite length. Recent experiments on dynamic jamming fronts in two dimensions [Waitukaitis et al., Europhysics Letters 102, 44001 (2013)] identified a diffuse interface between jammed and unjammed discs. In both cases, the thickness of the interface diverges as a critical transition is approached. We investigate the generality of this behavior using a third system: a model of cyclically-sheared non-Brownian suspensions. As we sediment the particles towards a boundary, we observe a diffuse traveling front that marks the interface between irreversible and reversible phases. We argue that the front width is linked to a diverging correlation lengthscale in the bulk, which we probe by studying avalanches near criticality. Our results show how diffuse interfaces may arise generally when an incompressible phase is brought to a critical point., Comment: 6 pages, 3 figures, 1 table

Background: Religiously motivated Bahá'í fasting (BF) is a form of intermittent dry fasting celebrated by abstaining from food and drinks during daylight hours every year in March for 19 consecutive days.Aim: To test the safety and effects of BF on hydration, metabolism, and the circadian clock.Methods: Thirty-four healthy Bahá'í volunteers (15 women) participated in this prospective, exploratory cohort study. Laboratory examinations were carried out in four study visits: before fasting (V0), in the third week of fasting (V1) as well as 3 weeks (V3) and 3 months (V4) after fasting. Data collection included blood and urine samples, anthropometric measurements and bioelectrical impedance analysis. At V0 and V1, 24- and 12-hour urine and serum osmolality were measured. At V0-V2, alterations in the circadian clock phase were monitored in 16 participants. Our study was augmented by an additional survey with 144 healthy Bahá'í volunteers filling out questionnaires and with subgroups attending metabolic measurements (n = 11) and qualitative interviews (n = 13), the results of which will be published separately.Results: Exploratory data analysis revealed that serum osmolality (n = 34, p < 0.001) and 24-hour urine osmolality (n = 34, p = 0.003) decreased during daytime fasting but remained largely within the physiological range and returned to pre-fasting levels during night hours. BMI (body mass index), total body fat mass, and resting metabolic rate decreased during fasting (n = 34, p < 0.001), while body cell mass and body water appeared unchanged. The circadian phase estimated by transcript biomarkers of blood monocytes advanced by 1.1 h (n = 16, p < 0.005) during fasting and returned to pre-fasting values 3 weeks after fasting. Most observed changes were not detectable anymore 3 months after fasting.Conclusions: Results indicate that BF (Bahá'í fasting) is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.Trial Registration:https://www.clinicaltrials.gov/, identifier: NCT03443739. published

Konstrukcijski sustavi okvir-ziđe jedni su od najčešćih vrsta građevnih konstrukcija. Iako se ispunsko ziđe u kojem se ne nalaze otvori pri provjeri potresne otpornosti pouzdano predočava tlačnim štapovima, način uzimanja u obzir veličine, vrste i razmještaja otvora u ziđu nije u potpunosti razjašnjen. Nekolicina razvijenih proračunskih postupaka u kojima se razmatra ovaj problem su, ili proračunski vrlo zahtjevni, ili su nepouzdani, jer pokazuju prevelika odstupanja u rezultatima proračuna. Razvijeni proračunski postupak također se temelji postupku zamjenjujućih tlačnih štapova, ali se ziđe u kojem se nalaze otvori raščlanjuje na dovoljan broj dijelova kako bi se izdvojio otvor. Proračunski postupak odlikuje se mogućnošću izravnog uzimanja u obzir veličine, vrste i razmještaja otvora te utvrđivanja djelomičnog oštećenja ispunskog ziđa.

Hintergrund und Stand (inter)nationaler Forschung: Die sektorale Trennung gilt als Quelle von Informations- und Kommunikationsbrüchen sowie als signifikanter Kostentreiber im deutschen Gesundheitswesen [ref:1]. Im internationalen Vergleich weist Deutschland hohe Fallzahlen bei relativ[zum vollständigen Text gelangen Sie über die oben angegebene URL], 19. Deutscher Kongress für Versorgungsforschung (DKVF)

Groin hernia in women is an entity whose clinical manifestations can be quite subtle, and which therefore risks to go unnoticed. Imaging studies by ultrasound or dynamic CT/MRI is strongly recommended in case of a clinical doubt. Optimal treatment consists of laparoscopic surgery, even in oligosymptomatic patients, because the risk of incarceration, and subsequent morbidity and mortality is high especially in cases of femoral hernia, which are frequent and often overlooked in women. During pregnancy, the risk of developing a groin hernia is very low (around 0,1%) and a wait-and-see attitude is to be preferred as much as possible, except in the case of an acute complication (incarceration).

This paper considers the scope of initial teacher training (ITT) programmes at UK universities and the extent to which they prepare teachers to empower learners outside of mainstream, compulsory schooling. Education is widely considered as a human right and an essential tool for social mobility, with the power to ‘enrich human capabilities and change behaviour’ (Cohen 2011: 4–5); in this paper, we explore the limitations of that in reality, considering educational provision, opportunities for funding and attitudes towards adult education. The paper compares attitudes towards school education and prison education, examining the potential for greater cohesion and the importance of rehabilitation. We draw on evidence from the literature; our own experience as ITT students and, subsequently, secondary school teachers; and a collaborative trainee teacher and prison learner programme between the School of Education, University of East London, and the prison HMP Isis. The paper concludes by discussing the potential for future, more inclusive ITT programmes which consider the role of education outside of schools, the implications of this and recommendations for the future.

Torbjörn Åkerstedt,1,2 Mats Lekander,1,2 Gustav Nilsonne,1,2 Sandra Tamm,1,2 Paolo d’Onofrio,1,2 Göran Kecklund,1,2 Håkan Fischer,3 Johanna Schwarz,1,2 Predrag Petrovic,1 Kristoffer NT Månsson4– 6 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Stress Research Institute, Department of Psychology, Stockholm University, Stockholm, Sweden; 3Department of Psychology, Stockholm University, Stockholm, Sweden; 4Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 5Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; 6Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, GermanyCorrespondence: Torbjörn ÅkerstedtDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm 17177, SwedenEmail torbjorn.akerstedt@ki.seBackground: Subjectively experienced sleepiness is a problem in society, possibly linked with gray matter (GM) volume. Given a different sleep pattern, aging may affect such associations, possibly due to shrinking brain volume.Purpose: The purpose of the present study was to investigate the association between subjectively rated sleepiness and GM volume in thalamus, insula, hippocampus, and orbitofrontal cortex of young and older adults, after a normal night’s sleep.Methods: Eighty-four healthy individuals participated (46 aged 20– 30 years, and 38 aged 65– 75 years). Morphological brain data were collected in a 3T magnetic resonance imaging (MRI) scanner. Sleepiness was rated multiple times during the imaging sessions.Results: In older, relative to younger, adults, clusters within bilateral mid-anterior insular cortex and right thalamus were negatively associated with sleepiness. Adjustment for the immediately preceding total sleep time eliminated the significant associations.Conclusion: Self-rated momentary sleepiness in a monotonous situation appears to be negatively associated with GM volume in clusters within both thalamus and insula in older individuals, and total sleep time seems to play a role in this association. Possibly, this suggests that larger GM volume in these clusters may be protective against sleepiness in older individuals. This notion needs confirmation in further studies.Keywords: brain imaging, thalamus, insula, sleep, KSS

Diagramme

Cellularized tissue and polymer networks can both transition from floppy to rigid as a function of their control parameters, and, yet, the two systems often mechanically interact, which may affect their respective rigidities. To study this interaction, we consider a vertex model with interfacial tension (a spheroid) embedded in a spring network in two dimensions. We identify two regimes with different global spheroid shapes, governed by the pressure resulting from competition between interfacial tension and tension in the network. In the first regime, the tissue remains compact, while in the second, a cavitation-like instability leads to the emergence of gaps at the tissue-network interface. Intriguingly, compression of the tissue promotes fluidization, while tension promotes cellular alignment and rigidification, with the mechanisms driving rigidification differing on either side of the instability., Comment: Main text: 5 pages, 3 figures. Supplementary Material: 13 pages, 14 figures

The Research in Teacher Education publication is published twice a year by the School of Education and Communities, University of East London, Water Lane, London E15 4LZ. The periodical offers a forum for informed debate and discussion on all aspects of teacher education. The publication showcases work from the teacher education teams at the School of Education and Communities and the wider teacher education community in the UK. The definition of ‘research’, in its broadest sense includes any gathering of data, information and ‘facts’ designed to advance knowledge. While nurturing and publicising the creative talent within teacher education the periodical seeks to stimulate, provoke and extend discussion and debate with other professionals associated with this field. In addition to contributions from the team of teacher educators at the School, each edition of Research in Teacher Education will publish research findings, book reviews and/or opinion pieces from guest writers associated with the School of Education and Communities.

Hintergrund: Im Rahmen eines Konzeptwechsels einer Hochschulklinik für Psychiatrie und Psychotherapie soll die alterspsychiatrische Versorgung angepasst werden. Eine bisher bereichs- bzw. stationsbezogene Behandlung wird zukünftig durch eine bereichsübergreifende, spezialisierte Behandlung[zum vollständigen Text gelangen Sie über die oben angegebene URL], 18. Deutscher Kongress für Versorgungsforschung (DKVF)

Francia, Bd. 28 Nr. 1 (2001)

Many real world tasks exhibit rich structure that is repeated across different parts of the state space or in time. In this work we study the possibility of leveraging such repeated structure to speed up and regularize learning. We start from the KL regularized expected reward objective which introduces an additional component, a default policy. Instead of relying on a fixed default policy, we learn it from data. But crucially, we restrict the amount of information the default policy receives, forcing it to learn reusable behaviors that help the policy learn faster. We formalize this strategy and discuss connections to information bottleneck approaches and to the variational EM algorithm. We present empirical results in both discrete and continuous action domains and demonstrate that, for certain tasks, learning a default policy alongside the policy can significantly speed up and improve learning., Accepted as a conference paper at ICLR 2019

Surface tension governed by differential adhesion can drive fluid particle mixtures to sort into separate regions, i.e., demix. Does the same phenomenon occur in confluent biological tissues? We begin to answer this question for epithelial monolayers with a combination of theory via a vertex model and experiments on keratinocyte monolayers. Vertex models are distinct from particle models in that the interactions between the cells are shape-based, as opposed to distance-dependent. We investigate whether a disparity in cell shape or size alone is sufficient to drive demixing in bidisperse vertex model fluid mixtures. Surprisingly, we observe that both types of bidisperse systems robustly mix on large lengthscales. On the other hand, shape disparity generates slight demixing over a few cell diameters, a phenomenon we term micro-demixing. This result can be understood by examining the differential energy barriers for neighbor exchanges (T1 transitions). Experiments with mixtures of wild-type and E-cadherin-deficient keratinocytes on a substrate are consistent with the predicted phenomenon of micro-demixing, which biology may exploit to create subtle patterning. The robustness of mixing at large scales, however, suggests that despite some differences in cell shape and size, progenitor cells can readily mix throughout a developing tissue until acquiring means of recognizing cells of different types., Comment: 32 pages, 17 figures

IMPORTANCE Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). OBJECTIVE To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100mmHg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. INTERVENTIONS Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. MAIN OUTCOMES AND MEASURES The primary end pointwas a composite of all-cause mortality or rehospitalization for AHF at 180 days. RESULTS Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P =.59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). CONCLUSIONS AND RELEVANCE Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

IMPORTANCE Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). OBJECTIVE To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100mmHg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. INTERVENTIONS Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. MAIN OUTCOMES AND MEASURES The primary end pointwas a composite of all-cause mortality or rehospitalization for AHF at 180 days. RESULTS Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P =.59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). CONCLUSIONS AND RELEVANCE Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

We report on the neutrino mass measurement result from the first four-week science run of the Karlsruhe Tritium Neutrino experiment KATRIN in spring 2019. Beta-decay electrons from a high-purity gaseous molecular tritium source are energy analyzed by a high-resolution MAC-E filter. A fit of the integrated electron spectrum over a narrow interval around the kinematic end point at 18.57 keV gives an effective neutrino mass square value of (−1.0−1.1+0.9) eV2. From this, we derive an upper limit of 1.1 eV (90% confidence level) on the absolute mass scale of neutrinos. This value coincides with the KATRIN sensitivity. It improves upon previous mass limits from kinematic measurements by almost a factor of 2 and provides model-independent input to cosmological studies of structure formation.

© 2018 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Calories from any food have the potential to increase risk for obesity and cardiometabolic disease because all calories can directly contribute to positive energy balance and fat gain. However, various dietary components or patterns may promote obesity and cardiometabolic disease by additional mechanisms that are not mediated solely by caloric content. Researchers explored this topic at the 2017 CrossFit Foundation Academic Conference ‘Diet and Cardiometabolic Health – Beyond Calories’, and this paper summarizes the presentations and follow-up discussions. Regarding the health effects of dietary fat, sugar and non-nutritive sweeteners, it is concluded that food-specific saturated fatty acids and sugar-sweetened beverages promote cardiometabolic diseases by mechanisms that are additional to their contribution of calories to positive energy balance and that aspartame does not promote weight gain. The challenges involved in conducting and interpreting clinical nutritional research, which preclude more extensive conclusions, are detailed. Emerging research is presented exploring the possibility that responses to certain dietary components/patterns are influenced by the metabolic status, developmental period or genotype of the individual; by the responsiveness of brain regions associated with reward to food cues; or by the microbiome. More research regarding these potential ‘beyond calories’ mechanisms may lead to new strategies for attenuating the obesity crisis.

We introduce two new concepts, frictional rigidity percolation and minimal rigidity proliferation, to help identify the nature of the frictional jamming transition as well as significantly broaden the scope of rigidity percolation. For frictional rigidity percolation, we construct rigid clusters in two different lattice models using a $(3,3)$ pebble game, while taking into account contacts below and at the Coulomb threshold. The first lattice is a honeycomb lattice with next-nearest neighbors, the second, a hierarchical lattice. For both, we generally find a continuous rigidity transition. Our numerical results suggest that, for the honeycomb lattice, the exponents associated with the transition found with the frictional $(3,3)$ pebble game are distinct from those of a central-force $(2,3)$ pebble game. We propose that localized motifs, such as hinges, connecting rigid clusters that are allowed only with friction could give rise to this new frictional universality class. However, the closeness of the order parameter exponent between the two cases hints at potential superuniversality. To explore this possibility, we construct a bespoke cluster generating algorithm invoking generalized Henneberg moves, dubbed minimal rigidity proliferation. The minimally rigid clusters the algorithm generates appear to be in the same universality class as connectivity percolation, suggesting superuniversality between all three types of transitions. Finally, the hierarchical lattice is analytically tractable and we find that the exponents depend both on the type of force and on the fraction of contacts at the Coulomb threshold. These combined results allow us to compare two universality classes on the same lattice via rigid clusters for the first time to highlight unifying and distinguishing concepts within the set of all possible rigidity transitions in disordered systems., 18 pages, 16 figures

International audience

We define a class of quantum linear Galois algebras which include the universal enveloping algebra Uq(gln), the quantum Heisenberg Lie algebra and other quantum orthogonal Gelfand-Zetlin algebras of type A, the subalgebras of G-invariants of the quantum affine space, quantum torus for G = G(m, p, n), and of the quantum Weyl algebra for G = Sn. We show that all quantum linear Galois algebras satisfy the quantum Gelfand-Kirillov conjecture. Moreover, it is shown that the the subalgebras of invariants of the quantum affine space and of quantum torus for the reflection groups and of the quantum Weyl algebra for symmetric groups are, in fact, Galois orders over an adequate commutative subalgebras and free as right (left) modules over these subalgebras. In the rank 1 cases the results hold for an arbitrary finite group of automorphisms when the field is C.

Selective Mutism (SM) is an anxiety disorder often diagnosed in early childhood and characterized by persistent failure to speak in certain social situations but not others. Diagnosing SM and monitoring treatment response can be quite complex, due in part to changing definitions of and scarcity of research about the disorder. Subjective self-reports and parent/teacher interviews can complicate SM diagnosis and therapy, given that similar speech problems of etiologically heterogeneous origin can be attributed to SM. The present perspective discusses the potential for passive audio capture to help overcome psychiatry’s current lack of objective and quantifiable assessments in the context of SM. We present evidence from two pilot studies indicating the feasibility of using a digital wearable device to quantify child vocalization features affected by SM. We also highlight limitations in the design and implementation of this preliminary work that can help guide future efforts.

MPLW515l/K mutated Essential Thrombocythemia (ET) usually present with increased platelet counts around 1000 x 109/L as the only abnormal laboratory finding with normal values for hemoglobin and leukocytes and minor splenomegaly on palpation only in a few. Early stage MPL515 mutated ET show the presence of clustered small and giant megakaryocytes with pronounced deeply lobulated nuclei, which are not seen in JAK2V617F positive ET, prodromal PV, and classical PV. Indicating that MPL515 mutated ET has no clinical, laboratory and bone marrow features of prodromal PV. Clustering of large mature large to giant megakaryocytes with pronounced hyper lobulated nuclei in a normocellular bone marrow is the hallmark of JAK2-wild type MPL515 mutated thrombocythemia. Bone marrow histology in MPL515 mutant patients revealed isolated megakaryocytic proliferation in a normocellular bone marrow at diagnosis with a reduction of erythropoiesis. MPL515 Thrombocythemia do not have PV features at diagnosis, do not evolve into PV during follow-up, have normal LAP score, serum EPO and ferritin levels. In contrast to JAK2V617F positive ET, no spontaneous endogenous erythroid colonies (EEC) was found in any of evaluated MPLW515L cases. Spontaneous megakaryocyte growth in culture with an overall normal response to thrombopoietin (TPO) has been demonstrated in two MPL515 mutated cases.

Software and Cyberinfrastructure for Astronomy V : [Proceedings] - SPIE, 2018. - ISBN:9781510619678 ISBN:9781510619685(electronic) - doi:10.1117/12.2313437 Software and Cyberinfrastructure for Astronomy V, Austin, United States, 10 Jun 2018 - 13 Jun 2018; Proceedings of SPIE 10707, 107071R (2018). doi:10.1117/12.2309659, The Cherenkov Telescope Array (CTA) will be the next generation ground-based observatory for gamma-ray astronomy at very-high energies. CTA will consist of two large arrays with 118 Cherenkov telescopes in total, deployed in the northern and southern hemispheres. The Observation Execution System (OES) provides the means to execute observations and to handle the acquisition of scientific data in CTA. The Manager and Central Control (MCC) system is a core element in the OES system that implements the execution of observation requests received from the scheduler sub-system. This contribution provides a summary of the main MCC design features and of the plans for prototyping., Published by SPIE, Bellingham, Wash.

International audience

As business model (BM) innovation has become one of management’s top priorities, anecdotal evidence suggests that firms do not have one single BM but run multiple BMs in parallel. From an academic perspective, only few attempts have been made until today, to broaden the scope of research from one to many BMs within firm boundaries. To close this gap, we systematically review the emerging literature on “multiple” BMs, based on a theoretical framework that links the BM concept with general mechanisms of corporate portfolio management. Our results show that firms develop BM portfolios as a direct result of challenges in today’s technology-driven environment, such as disruptive industry BMs and the need to commercialize technologies with innovative BMs. More specifically, our findings challenge the general assumption that firms should (or can) be described based on a single BM. Segmentation, configuration and coordination of multiple BMs can complement a customer-centric perspective in the BM development and management process, not only for large organizations. We provide initial characteristics of these mechanisms and outline areas for future research.

The subthalamic nucleus (STN) plays a crucial role in the surgical treatment of Parkinson’s disease (PD). Studies investigating optimal protocols for STN visualization using state of the art magnetic resonance imaging (MRI) techniques have shown that susceptibility weighted images, which display the magnetic susceptibility distribution, yield better results than T1-weighted, T2-weighted, and T2*-weighted contrasts. However, these findings are based on young healthy individuals, and require validation in elderly individuals and persons suffering from PD. Using 7T MRI, the present study set out to investigate which MRI contrasts yielded the best results for STN visualization in 12 PD patients and age-matched healthy controls (HC). We found that STNs were more difficult to delineate in PD as reflected by a lower inter-rater agreement when compared to HCs. No STN size differences were observed between the groups. Analyses of quantitative susceptibility mapping (QSM) images showed a higher inter-rater agreement reflected by increased Dice-coefficients. The location of the center of mass of the STN was not affected by contrast. Overall, contrast-to-noise ratios (CNR) were higher in QSM than in T2*-weighted images. This can at least partially, explain the higher inter-rater agreement in QSM. The current results indicate that the calculation of QSM contrasts contributes to an improved visualization of the entire STN. We conclude that QSM contrast is the preferred choice for the visualization of the STN in persons with PD as well as in aging HC.

This paper explores the concept of business model management, defined as a generic process covering all phases of the business model lifecycle. In contrast to previous business model literature, which is mainly focused on the design of business models, we argue that the successful exploitation of the business model concept requires a dedicated management approach. Due to the lack of extant research in the domain, we build on multiple, exploratory case studies of large organizations, based on 20 expert interviews. This paper contributes to a better understanding of the current practices and needs in business model management and the multifaceted role of the business model concept in each of its phases. Moreover, we suggest roles of IT in the business model management process.

The physical properties of indoor particles were measured with an Scanning Mobility Particle Sizer (SMPS) system (14.6-850 nm), an Aerodynamic Particle Sizer (APS, 0.54-18 mu m) and an Hygroscopic Tandem Differential Mobility Analyzer (H-TDMA) in an apartment located in an urban background site in Prague (Czech Republic) from 15 August to 8 September, 2014. The total particle maximum number concentration was 9.38 x 10(4), 1.46 x 10(5), 2.89 x 10(4), 2.25 x 10(5) and 1.57 x 10(6) particles cm(-3) for particles released from vacuum cleaning, soap/W5 cleaning spray, smoking, incense burning and cooking (frying) activities, respectively. Particles emitted from cleaning activities showed unimodal number size distributions, with the majority of particles (> 98.2 %) in the ultrafine size range (Dp < 100 nm) and modes at a diameter of 19.8 nm for vacuum cleaning and 30.6 nm for soap/W5 cleaning. Smoking and incense burning predominantly generated particles in the accumulation mode with a count median diameter around 90-150 nm while cooking emissions showed a bimodal structure with a main mode at 47.8 nm. Particles from vacuum cleaning, incense burning, smoking and cooking emissions were found to be "nearly hydrophobic" with an average growth factor (G(f)) around 1.01-1.10, while particles emitted from desk cleaning using organic compounds were found to be "less-hygroscopic" (G(f) similar to 1.12-1.16). Based on an adjusted MPPD model with a consideration of the hygroscopic properties of particles, the total lung deposition fractions of these particles by number when they penetrate into the human lung were 0.73 +/- 0.02, 0.62 +/- 0.03, 0.37 +/- 0.03, 0.32 +/- 0.03 and 0.49 +/- 0.02 for vacuum cleaning, desk cleaning, smoking, incense burning and cooking, respectively.

Background Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab—a human IgG1 VEGFR-2 antagonist—or placebo in this patient population. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m2 plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Findings Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96–4·47] vs 2·76 months [2·60–2·96]; hazard ratio [HR] 0·757, 95% CI 0·607–0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8–30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4–18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1–2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. Interpretation To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Funding Eli Lilly and Company. © 2017 Elsevier Ltd

Angiogenesis, the fundamental process by which new blood vessels form from existing ones, depends on precise spatial and temporal gene expression within specific compartments of the endothelium. However, the molecular links between proangiogenic signals and downstream gene expression remain unclear. During sprouting angiogenesis, the specification of endothelial cells into the tip cells that lead new blood vessel sprouts is coordinated by vascular endothelial growth factor A (VEGFA) and Delta-like ligand 4 (Dll4)/Notch signaling and requires high levels of Notch ligand DLL4. Here, we identify MEF2 transcription factors as crucial regulators of sprouting angiogenesis directly downstream from VEGFA. Through the characterization of a Dll4 enhancer directing expression to endothelial cells at the angiogenic front, we found that MEF2 factors directly transcriptionally activate the expression of Dll4 and many other key genes up-regulated during sprouting angiogenesis in both physiological and tumor vascularization. Unlike ETS-mediated regulation, MEF2-binding motifs are not ubiquitous to all endothelial gene enhancers and promoters but are instead overrepresented around genes associated with sprouting angiogenesis. MEF2 target gene activation is directly linked to VEGFA-induced release of repressive histone deacetylases and concurrent recruitment of the histone acetyltransferase EP300 to MEF2 target gene regulatory elements, thus establishing MEF2 factors as the transcriptional effectors of VEGFA signaling during angiogenesis.