Post-Newtonian evolution of massive black hole triplets in galactic nuclei - IV. Implications for LISA

Coalescing massive black hole binaries (MBHBs) of 10(4-7) M-circle dot, forming in the aftermath of galaxy mergers, are primary targets of the space mission LISA, the Laser Interferometer Space Antenna. An assessment of LISA detection prospects requires an estimate of the abundance and properties of MBHBs that form and evolve during the assembly of cosmic structures. To this aim, we employ a semi-analytic model to follow the co-evolution of MBHBs within their host galaxies. We identify three major evolutionary channels driving the binaries to coalescence: two standard paths along which the binary evolution is driven by interactions with the stellar and/or gaseous environment, and a novel channel where MBHB coalescence occurs during the interaction with a third black hole. For each channel, we follow the orbital evolution ofMBHBs with physically motivated models that include a self-consistent treatment of the orbital eccentricity. We find that LISA will detect between approximate to 25 and approximate to 75 events per year depending on the seed model. We show that triple-induced coalescences can range from a few detected events up to similar to 30 per cent of the total detected mergers. Moreover, even if the standard gas/stars-driven evolutionary channels should fail and MBHBs were to stall, triple interactions would still occur as a result of the hierarchical nature of galaxy formation, resulting in about approximate to 10 to approximate to 20 LISA detections per year. Remarkably, triple interactions among the black holes can produce coalescing binaries with large eccentricities (greater than or similar to 0.9) upon entrance into the LISA band. This eccentricity will remain significant (similar to 0.1) also at merger, requiring suitable templates for parameter estimation. Keyword

Post-Newtonian evolution of massive black hole triplets in galactic nuclei - I. Numerical implementation and tests

Massive black hole binaries (MBHBs) are thought to be the main source of gravitational waves (GWs) in the low-frequency domain surveyed by ongoing and forthcoming Pulsar Timing Array campaigns and future space-borne missions, such as eLISA. However, many low-redshift MBHBs in realistic astrophysical environments may not reach separations small enough to allow significant GW emission, but rather stall on (sub) pc-scale orbits. This 'last-parsec problem' can be eased by the appearance of a third massive black hole (MBH) - the 'intruder' - whose action can force, under certain conditions, the inner MBHB on a very eccentric orbit, hence allowing intense GW emission eventually leading to coalescence. A detailed assessment of the process, ultimately driven by the induced Kozai-Lidov oscillations of the MBHB orbit, requires a general relativistic treatment and the inclusion of external factors, such as the Newtonian precession of the intruder orbit in the galactic potential and its hardening by scattering off background stars. In order to tackle this problem, we developed a three-body post-Newtonian (PN) code framed in a realistic galactic potential, including both non-dissipative 1PN and 2PN terms, and dissipative terms such as 2.5PN effects, orbital hardening of the outer binary, and the effect of the dynamical friction on the early stages of the intruder dynamics. In this first paper of a series devoted at studying the dynamics of MBH triplets from a cosmological perspective, we describe, test and validate our code

Development of a screening tool to assess dehydration in hospitalized older population: a diagnostic, observational study

INTRODUCTION: dehydration is a frequent condition in older people and is associated with an increased risk of negative health outcomes. In order to adopt strategies to prevent complications, an early recognition of this status is of primary importance. For this reason, a comprehensive assessment tool to monitor hydration status in older people could be useful.AIM: to develop a screening tool to detect dehydration in older people in hospital settings.METHODS: this is a diagnostic, observational study. The new tool is a modified version of the Geriatric Dehydration Screening Tool (GDST), integrated with seven questions and two clinical signs based on updated literature. We tested the new tool with people aged 65 or over. We used as reference standard serum osmolarity. Cronbach's alpha was used to measure the tool's reliability and subscales. We calculated the Area Under ROC Curve (AUC) to choose the cut-off that gave the best balance between sensibility and specificity.RESULTS: 127 patients participated in the study. The reliability of the new GDST was acceptable (Cronbach's alpha 0.63). The diagnostic accuracy, measured with AUC analysis, was 0.83 ± 0.04, p<0.0001 95% CI 0.72-0.87. The best cut-off value was 6 and showed a sensibility of 78%, specificity of 70%. Tongue dryness proved to be the most significant clinical sign associated with poor hydration status (AUC 0.78; p<0.0001, 95% CI 0.69-0.86).CONCLUSION: The new GDST presented an acceptable reliability and diagnostic accuracy that increased with the assessment of some items, such as tongue dryness. This is the first screening tool that presents a promising cut-off value.KEYWORDS: dehydration, aged, screening, inpatients, sensibility, specificity.Sviluppo di uno strumento di screening per valutare la disidratazione nella popolazione anziana ospedalizzata: uno studio diagnostico, osservazionaleRIASSUNTOINTRODUZIONE: La disidratazione è una condizione comune nella persona anziana ed è associata a numerosi rischi per la salute e ad esiti negativi. È importante il precoce riconoscimento di questa condizione, al fine di adottare strategie per prevenirne le complicanze. Per questa ragione è necessario sviluppare strumenti validati per valutare il rischio di disidratazione nelle persone anzianeOBIETTIVO: sviluppare uno strumento di screening per individuare la disidratazione nelle persone anziane ospedalizzate.METODO: il disegno di studio adottato è di tipo diagnostico, osservazionale. Lo strumento creato è basato sul "Geriatric Dehydration Screening Tool" (GDST), che è stato modificato aggiungendo sette domande e due segni clinici, basati sulla letteratura recente. Lo strumento è stato testato in persone con un'etí  maggiore o uguale a 65 anni ospedalizzate. Come reference standard è stata usata l'osmolarití  sierica. È stato calcolato l'alfa di Cronbach per testare l'affidabilití  della consistenza interna dello strumento e delle sue sotto scale. È stata calcolata l'area sotto la curva di ROC (AUC) per individuare il cut-off che dava il miglior bilanciamento tra sensibilití  e specificití .RISULTATI: 127 pazienti hanno partecipato allo studio. L'affidabilití  dello strumento è risultata discreta (Alfa di Cronbach=0.63). L'accuratezza diagnostica, misurata con l'AUC era 0.83±0.04, p<0.0001, 95% IC 0.72-0.87. Il cut-off migliore è risultato essere il valore 6, con una sensibilití  del 78% e specificití  70%. La secchezza della lingua è risultato essere il segno clinico più associato con uno stato di disidratazione (AUC 0.78, p<0.0001 95%CI 0.69-0.86).CONCLUSIONI: il nuovo GDST ha dimostrato un'accettabile affidabilití  e accuratezza diagnostica che aumenta con la valutazione di alcuni items, come la secchezza della lingua. Questo è il primo strumento che presenta un valore di cut-off promettente.PAROLE CHIAVE: disidratazione, anziano, screening, pazienti ospedalizzati, sensibilití , specificití 

Zinc-finger-based transcriptional repression of rhodopsin in a model of dominant retinitis pigmentosa

Despite the recent success of gene-based complementation approaches for genetic recessive traits, the development of therapeutic strategies for gain-of-function mutations poses great challenges. General therapeutic principles to correct these genetic defects mostly rely on post-transcriptional gene regulation (RNA silencing). Engineered zinc-finger (ZF) protein-based repression of transcription may represent a novel approach for treating gain-of-function mutations, although proof-of-concept of this use is still lacking. Here, we generated a series of transcriptional repressors to silence human rhodopsin (hRHO), the gene most abundantly expressed in retinal photoreceptors. The strategy was designed to suppress both the mutated and the wild-type hRHO allele in a mutational-independent fashion, to overcome mutational heterogeneity of autosomal dominant retinitis pigmentosa due to hRHO mutations. Here we demonstrate that ZF proteins promote a robust transcriptional repression of hRHO in a transgenic mouse model of autosomal dominant retinitis pigmentosa. Furthermore, we show that specifically decreasing the mutated human RHO transcript in conjunction with unaltered expression of the endogenous murine Rho gene results in amelioration of disease progression, as demonstrated by significant improvements in retinal morphology and function. This zinc-finger-based mutation-independent approach paves the way towards a ‘repression–replacement’ strategy, which is expected to facilitate widespread applications in the development of novel therapeutics for a variety of disorders that are due to gain-of-function mutations

Post-Newtonian evolution of massive black hole triplets in galactic nuclei II. Survey of the parameter space

Massive black hole binaries (MBHBs) are expected to form at the centre of merging galaxies during the hierarchical assembly of the cosmic structure, and are expected to be the loudest sources of gravitational waves (GWs) in the low frequency domain. However, because of the dearth of energy exchanges with background stars and gas, many of these MBHBs may stall at separations too large for GW emission to drive them to coalescence in less than a Hubble time. Triple MBH systems are then bound to form after a further galaxy merger, triggering a complex and rich dynamics that can eventually lead to MBH coalescence. Here we report on the results of a large set of numerical simulations, where MBH triplets are set in spherical stellar potentials and MBH dynamics is followed through 2.5 post-Newtonian order in the equations of motion. From our full suite of simulated systems we find that a fraction 4320 1230% of the MBH binaries that would otherwise stall are led to coalesce within a Hubble time. The corresponding coalescence timescale peaks around 300 Myr, while the eccentricity close to the plunge, albeit small, is non-negligible ( 720.1). We construct and discuss marginalised probability distributions of the main parameters involved and, in a companion paper of the series, we will use the results presented here to forecast the contribution of MBH triplets to the GW signal in the nHz regime probed by Pulsar Timing Array experiments

Post-Newtonian evolution of massive black hole triplets in galactic nuclei - III. A robust lower limit to the nHz stochastic background of gravitational waves

Inspiraling massive black hole binaries (MBHBs) forming in the aftermath of galaxy mergers are expected to be the loudest gravitational-wave (GW) sources relevant for pulsar-timing arrays (PTAs) at nHz frequencies. The incoherent overlap of signals from a cosmic population of MBHBs gives rise to a stochastic GW background (GWB) with characteristic strain around h c ~ 10 -15 at a reference frequency of 1 yr -1 , although uncertainties around this value are large. Current PTAs are piercing into theGWamplitude range predicted by MBHB-population models, but no detection has been reported so far. To assess the future success prospects of PTA experiments, it is therefore important to estimate the minimum GWB level consistent with our current understanding of the formation and evolution of galaxies and massive black holes (MBHs). To this purpose, we couple a semi-analytic model of galaxy evolution and an extensive study of the statistical outcome of triple MBH interactions. We show that even in the most pessimistic scenario where all MBHBs stall before entering the GW-dominated regime, triple interactions resulting from subsequent galaxy mergers inevitably drive a considerable fraction of the MBHB population to coalescence. At frequencies relevant for PTA, the resulting GWB is only a factor of 2-3 suppressed compared to a fiducial model where binaries are allowed to merge over Gyr time-scales. Coupled with current estimates of the expected GWB amplitude range, our findings suggest that the minimum GWB from cosmic MBHBs is unlikely to be lower than h c ~ 10 -16 (at f = 1 yr -1 ), well within the expected sensitivity of projected PTAs based on future observations with FAST, MeerKAT, and SKA. \ua9 2018 The Author(s)

Psychological impact of Covid-19 pandemic on oncological patients: a survey in Northern Italy

The psychological impact of the Covid 19 pandemic on cancer patients, a population at higher risk of fatal consequences if infected, has been only rarely evaluated. This study was conducted at the Departments of Oncology of four hospitals located in the Verona area in Italy to investigate the psychological consequences of the pandemic on cancer patients under active anticancer treatments. A 13-item ad hoc questionnaire to evaluate the psychological status of patients before and during the pandemic was administered to 474 consecutive subjects in the time frame between April 27th and June 7th 2020. Among the 13 questions, 7 were considered appropriate to elaborate an Emotional Vulnerability Index (EVI) that allows to separate the population in two groups (low versus high emotional vulnerability) according to observed median values. During the emergency period, the feeling of high vulnerability was found in 246 patients (53%) and was significantly associated with the following clinical variables: female gender, being under chemotherapy treatment, age 64 65 years. Compared to the pre-pandemic phase, the feeling of vulnerability was increased in 41 patients (9%), remained stably high in 196 (42%) and, surprisingly, was reduced in 10 patients (2%). Overall, in a population characterized by an high level of emotional vulnerability the pandemic had a marginal impact and only a small proportion of patients reported an increase of their emotional vulnerability

Nanoscale transient polarization gratings

We present the generation of transient polarization gratings at the nanoscale, achieved using a tailored accelerator configuration of the FERMI free electron laser. We demonstrate the capabilities of such a transient polarization grating by comparing its induced dynamics with the ones triggered by a more conventional intensity grating on a thin film ferrimagnetic alloy. While the signal of the intensity grating is dominated by the thermoelastic response of the system, such a contribution is suppressed in the case of the polarization grating. This exposes helicity-dependent magnetization dynamics that have so-far remained hidden under the large thermally driven response. We anticipate nanoscale transient polarization gratings to become useful for the study of any physical, chemical and biological systems possessing chiral symmetry

About gravitational-wave generation by a three-body system

We highlight some subtleties that affect naive implementations of quadrupolar and octupolar gravitational waveforms from numerically-integrated trajectories of three-body systems. Some of those subtleties arise from the requirement that the source be contained in its "coordinate near zone" when applying the standard PN formulae for gravitational-wave emission, and from the need to use the non-linear Einstein equations to correctly derive the quadrupole emission formula. We show that some of these subtleties were occasionally overlooked in the literature, with consequences for published results. We also provide prescriptions that lead to correct and robust predictions for the waveforms computed from numerically-integrated orbits

Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis

The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system