Heart rate modulation in stable coronary artery disease without clinical heart failure: What we have already learned from SIGNIFY?

An elevated heart rate is a marker of cardiovascular risk in patients with stable coronary artery disease. Ivabradine selectively inhibits the “f” current in the sinus node and reduces heart rate without any modifications of blood pressure, myocardial contractility and arteriolar resistance. However the addition of ivabradine to standard therapy to reduce heart rate did not improve outcomes in the recent SIGNIFY trial. Moreover, a significant interaction between the effect of ivabradine among subgroups with and without angina was detected, with a worse outcome in patients in CCS class >II at baseline. The explanation for this surprising finding despite a significant reduction in angina and myocardial revascularization procedures is uncertain. A J-curve for heart rate was not demonstrated. We speculate a significant interference on adverse events (mainly atrial fibrillation and consequently acute coronary syndromes) and on the outcome of unfavorable interactions between ivabradine and diltiazem, verapamil and strong inhibitors of CYP3A4 (4.6% of the total population). Indeed, when these patients are excluded from subgroup analysis, the harmful effect of Ivabradine among patients with severe angina disappears. In conclusion, heart rate is a marker of risk but is not a risk factor and/or a target of therapy in patients with stable coronary artery disease and preserved ventricular systolic function. Standard doses of ivabradine are indicated for treatment of angina as an alternative or in addition to beta-blockers, but should not be administered in association with CYP3A4 inhibitors or heart rate-lowering calcium-channel blockers

Advancing the interfacing performances of chronically implantable neural probes in the era of CMOS neuroelectronics

Tissue penetrating microelectrode neural probes can record electrophysiological brain signals at resolutions down to single neurons, making them invaluable tools for neuroscience research and Brain-Computer-Interfaces (BCIs). The known gradual decrease of their electrical interfacing performances in chronic settings, however, remains a major challenge. A key factor leading to such decay is Foreign Body Reaction (FBR), which is the cascade of biological responses that occurs in the brain in the presence of a tissue damaging artificial device. Interestingly, the recent adoption of Complementary Metal Oxide Semiconductor (CMOS) technology to realize implantable neural probes capable of monitoring hundreds to thousands of neurons simultaneously, may open new opportunities to face the FBR challenge. Indeed, this shift from passive Micro Electro-Mechanical Systems (MEMS) to active CMOS neural probe technologies creates important, yet unexplored, opportunities to tune probe features such as the mechanical properties of the probe, its layout, size, and surface physicochemical properties, to minimize tissue damage and consequently FBR. Here, we will first review relevant literature on FBR to provide a better understanding of the processes and sources underlying this tissue response. Methods to assess FBR will be described, including conventional approaches based on the imaging of biomarkers, and more recent transcriptomics technologies. Then, we will consider emerging opportunities offered by the features of CMOS probes. Finally, we will describe a prototypical neural probe that may meet the needs for advancing clinical BCIs, and we propose axial insertion force as a potential metric to assess the influence of probe features on acute tissue damage and to control the implantation procedure to minimize iatrogenic injury and subsequent FBR

l efficacia del customer relationship management nei mercati dei servizi tecnologici il caso di una media impresa italiana

L'analisi dell'efficacia dei sistemi CRM e un tema ancora fortemente dibattuto ed oggetto di numerosi studi nelle discipline di management (Elmuti et al., 2009; Perna-Baraldi, 2014). In tal senso, risulta interessante verificare le ragioni per cui numerosi progetti CRM intrapresi da imprese – soprattutto quelle operanti in mercati business-to-business e focalizzate sulla fornitura di servizi tecnologici piu o meno complessi – non generino benefici attesi e, quindi, falliscano successivamente o addirittura durante la fase implementativa. Il principale obiettivo del presente lavoro e quello di comprendere i fattori e le dimensioni che impattano sul livello di efficacia del CRM. Gli autori sono interessati, in modo particolare, ad investigare il complesso rapporto tra efficacia del CRM ed aspettative che le imprese manifestano circa il raggiungimento di benefici tangibili durante le fasi di gestione del cliente. Metodologicamente gli autori fanno riferimento all'uso del caso di studio qualitativo come strategia di ricerca. Nello specifico viene proposto il caso del gruppo Loccioni, impresa operante nel settore della produzione e fornitura di macchine di collaudo e servizi integrati ad alto contenuto tecnologico. L'azienda si caratterizza per aver avviato un processo di implementazione di un software CRM che ha comportato sensibili effetti a livello organizzativo e strategico. Inoltre, interessante notare come l'uso del sistema abbia a sua volta generato effetti inaspettati, non sempre prevedibili e variabili rispetto le diverse tipologie di relazioni aziendali. Lo studio propone diversi tipi di contributi. Dal lato empirico, il caso evidenzia ed illustra le problematiche relative al miglioramento di processi gestionali legati alla implementazione ed uso del CRM in un settore abbastanza particolare come quello della fornitura di servizi altamente tecnologici. Dal punto di vista teorico, si vuole contribuire nel marketing b2b e dei servizi riguardo al tema della efficacia di azioni di marketing in contesti di mercato altamente complessi

The outburst decay of the low magnetic field magnetar SWIFT J1822.3−1606: phase-resolved analysis and evidence for a variable cyclotron feature

We study the timing and spectral properties of the low-magnetic field, transient magnetar SWIFT J1822.3−1606 as it approached quiescence. We coherently phase-connect the observations over a time-span of ∼500 d since the discovery of SWIFT J1822.3−1606 following the Swift-Burst Alert Telescope (BAT) trigger on 2011 July 14, and carried out a detailed pulse phase spectroscopy along the outburst decay. We follow the spectral evolution of different pulse phase intervals and find a phase and energy-variable spectral feature, which we interpret as proton cyclotron resonant scattering of soft photon from currents circulating in a strong (≳1014 G) small-scale component of the magnetic field near the neutron star surface, superimposed to the much weaker (∼3 × 1013 G) magnetic field. We discuss also the implications of the pulse-resolved spectral analysis for the emission regions on the surface of the cooling magnetar

The discovery, monitoring and environment of SGR J1935+2154

We report on the discovery of a new member of the magnetar class, SGR J1935+2154, and on its timing and spectral properties measured by an extensive observational campaign carried out between 2014 July and 2015 March with Chandra and XMM–Newton (11 pointings). We discovered the spin period of SGR J1935+2154 through the detection of coherent pulsations at a period of about 3.24 s. The magnetar is slowing down at a rate of P˙=1.43(1)×10−11 s s−1 and with a decreasing trend due to a negative P¨ of −3.5(7) × 10−19 s s−2. This implies a surface dipolar magnetic field strength of ∼2.2 × 1014 G, a characteristic age of about 3.6 kyr and a spin-down luminosity Lsd ∼1.7 × 1034 erg s−1. The source spectrum is well modelled by a blackbody with temperature of about 500 eV plus a power-law component with photon index of about 2. The source showed a moderate long-term variability, with a flux decay of about 25 per cent during the first four months since its discovery, and a re-brightening of the same amount during the second four months. The X-ray data were also used to study the source environment. In particular, we discovered a diffuse emission extending on spatial scales from about 1 arcsec up to at least 1 arcmin around SGR J1935+2154 both in Chandra and XMM–Newton data. This component is constant in flux (at least within uncertainties) and its spectrum is well modelled by a power-law spectrum steeper than that of the pulsar. Though a scattering halo origin seems to be more probable we cannot exclude that part, or all, of the diffuse emission is due to a pulsar wind nebula.NR is supported by an NWO Vidi Grant, and by grants AYA2012-39303 and SGR2014-1073. This work is partially supported by the European COST ActionMP1304 (NewCOMPSTAR)

Gazing at the ultraslow magnetar in RCW 103 with NuSTAR and Swift

We report on a new NuSTAR observation and on the ongoing Swift X-Ray Telescope monitoring campaign of the peculiar source 1E 161348–5055, located at the centre of the supernova remnant RCW 103, which is recovering from its last outburst in 2016 June. The X-ray spectrum at the epoch of the NuSTAR observation can be described by either two absorbed blackbodies (kTBB1 ∼ 0.5 keV, kTBB2 ∼ 1.2 keV) or an absorbed blackbody plus a power law (kTBB1∼ 0.6 keV, Γ ∼ 3.9). The observed flux was ∼9 × 10−12 erg s−1 cm−2, ∼3 times lower than what observed at the outburst onset, but about one order of magnitude higher than the historical quiescent level. A periodic modulation was detected at the known 6.67 h periodicity. The spectral decomposition and evolution along the outburst decay are consistent with 1E 161348–5055 being a magnetar, the slowest ever detected.The results reported in this paper are based on observations obtained with Swift and NuSTAR. Swift is a NASA mission with participation of the Italian Space Agency and the UK Space Agency. The NuSTAR mission is a project led by the Californian Institute of Technology. AB, PE, and NR are supported by an NWO Vidi Grant (PI: Rea). FCZ and NR are supported by grants AYA2015-71042-P and SGR2014-1073. We thank the PHAROS COST Action (CA16214) for partial support and the referee for the comments

The X-Ray Outburst of the Galactic Center Magnetar over Six Years of Chandra Observations

The magnetar SGR J1745−2900, discovered at a distance of parsecs from the Milky Way central black hole, Sagittarius A*, represents the closest pulsar to a supermassive black hole ever detected. Furthermore, its intriguing radio emission has been used to study the environment of the black hole, as well as to derive a precise position and proper motion for this object. The discovery of SGR J1745−2900 has led to interesting debates about the number, age, and nature of pulsars expected in the Galactic center region. In this work, we present extensive X-ray monitoring of the outburst of SGR J1745−2900 using the Chandra X-ray Observatory, the only instrument with the spatial resolution to distinguish the magnetar from the supermassive black hole (2"4 angular distance). It was monitored from its outburst onset in 2013 April until 2019 August, collecting more than 50 Chandra observations for a total of more than 2.3 Ms of data. Soon after the outburst onset, the magnetar emission settled onto a purely thermal emission state that cooled from a temperature of about 0.9–0.6 keV over 6 yr. The pulsar timing properties showed at least two changes in the period derivative, increasing by a factor of about 4 during the outburst decay. We find that the long-term properties of this outburst challenge current models for the magnetar outbursts.N.R., D.V., and A.B. are supported by the H2020 ERC Consolidator Grant “MAGNESIA” under grant agreement No. 817661 (PI: Rea). N.R., F.C.Z., D.V., A.B., and D.F.T. also acknowledge support from grants SGR2017-1383 and PGC2018-095512-BI00. F.C.Z. is supported by a Juan de la Cierva fellowship. A.P. acknowledges financial support from grants ASI/INAF I/037/12/0, ASI/INAF 2017-14-H.0 (PI: Belloni) and from INAF grant “Sostegno alla ricerca scientifica main streams dell’INAF,” Presidential Decree 43/2018 (PI: Belloni). D.H. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, the Fonds de recherche du Québec–Nature et Technologies (FRQNT) Nouveaux Chercheurs program, and the Canadian Institute for Advanced Research (CIFAR). G.L.I., S.M., and R.T. have been partially supported by PRIN-MIUR 2017. J.A.P. acknowledges support by the Generalitat Valenciana (PROMETEO/2019/071) and by Agencia Estatal de Investigación (PGC2018-095984-B-I00). G.P. is supported by the H2020 ERC Consolidator Grant “Hot Milk” under grant agreement No. 865637. L.S. acknowledges financial contributions from ASI-INAF agreements 2017-14-H.O and I/037/12/0 and from “iPeska” research grant (PI: Andrea Possenti) funded under the INAF call PRIN-SKA/CTA (resolution 70/2016). We acknowledge support from the PHAROS COST Action (CA16214)