A model of working memory for encoding multiple items and ordered sequences exploiting the theta-gamma code

Recent experimental evidence suggests that oscillatory activity plays a pivotal role in the maintenance of information in working memory, both in rodents and humans. In particular, cross-frequency coupling between theta and gamma oscillations has been suggested as a core mechanism for multi-item memory. The aim of this work is to present an original neural network model, based on oscillating neural masses, to investigate mechanisms at the basis of working memory in different conditions. We show that this model, with different synapse values, can be used to address different problems, such as the reconstruction of an item from partial information, the maintenance of multiple items simultaneously in memory, without any sequential order, and the reconstruction of an ordered sequence starting from an initial cue. The model consists of four interconnected layers; synapses are trained using Hebbian and anti-Hebbian mechanisms, in order to synchronize features in the same items, and desynchronize features in different items. Simulations show that the trained network is able to desynchronize up to nine items without a fixed order using the gamma rhythm. Moreover, the network can replicate a sequence of items using a gamma rhythm nested inside a theta rhythm. The reduction in some parameters, mainly concerning the strength of GABAergic synapses, induce memory alterations which mimic neurological deficits. Finally, the network, isolated from the external environment ("imagination phase") and stimulated with high uniform noise, can randomly recover sequences previously learned, and link them together by exploiting the similarity among items

Effect of Citrus bergamia juice on human neuroblastoma cells in vitro and in metastatic xenograft models

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dfpk : An R-package for Bayesian dose-finding designs using Pharmacokinetics (PK) for phase I clinical trials

Background and objective Dose-finding, aiming at finding the maximum tolerated dose, and pharmacokinetics studies are the first in human studies in the development process of a new pharmacological treatment. In the literature, to date only few attempts have been made to combine pharmacokinetics and dose-finding and to our knowledge no software implementation is generally available. In previous papers, we proposed several Bayesian adaptive pharmacokinetics-based dose-finding designs in small populations. The objective of this work is to implement these dose-finding methods in an R package, called dfpk. Methods All methods were developed in a sequential Bayesian setting and Bayesian parameter estimation is carried out using the rstan package. All available pharmacokinetics and toxicity data are used to suggest the dose of the next cohort with a constraint regarding the probability of toxicity. Stopping rules are also considered for each method. The ggplot2 package is used to create summary plots of toxicities or concentration curves. Results For all implemented methods, dfpk provides a function (nextDose) to estimate the probability of efficacy and to suggest the dose to give to the next cohort, and a function to run trial simulations to design a trial (nsim). The sim.data function generates at each dose the toxicity value related to a pharmacokinetic measure of exposure, the AUC, with an underlying pharmacokinetic one compartmental model with linear absorption. It is included as an example since similar data-frames can be generated directly by the user and passed to nsim. Conclusion The developed user-friendly R package dfpk, available on the CRAN repository, supports the design of innovative dose-finding studies using PK information

Intracranial pressure dynamics in patients with acute brain damage

The time pattern of intracranial pressure (ICP) during pressure-volume index (PVI) tests was analyzed in 20 patients with severe acute brain damage by means of a simple mathematical model. In most cases, a satisfactory fitting between model response and patient data was achieved by adjusting only four parameters: the cerebrospinal fluid (CSF) outflow resistance, the intracranial elastance coefficient, and the gain and time constant of cerebral autoregulation. The correlation between the parameter estimates was also analyzed to elucidate the main mechanisms responsible for ICP changes in each patient. Starting from information on the estimated parameter values and their correlation, the patients were classified into two main classes: those with weak autoregulation (8 of 20 patients) and those with strong autoregulation (12 of 20 patients). In the first group of patients, ICP mainly reflects CSF circulation and passive cerebral blood volume changes. In the second group, ICP exhibits paradoxical responses attributable to active changes in cerebral blood volume. Moreover, in two patients of the second group, the time constant of autoregulation is significantly increased (>40 s). The correlation between the parameter estimates was significantly different in the two groups of patients, suggesting the existence of different mechanisms responsible for ICP changes. Moreover, analysis of the correlation between the parameter estimates might give information on the directions of parameter changes that have a greater impact on ICP

The effect of feedback on the emission properties of the Warm-Hot Intergalactic Medium

At present, 30-40 per cent of the baryons in the local Universe is still undetected. According to theoretical predictions, this gas should reside in filaments filling the large-scale structure (LSS) in the form of a Warm-Hot Intergalactic Medium (WHIM), at temperatures of 10^5 - 10^7 K, thus emitting in the soft X-ray energies via free-free interaction and line emission from heavy elements. In this work we characterize the properties of the X-ray emission of the WHIM, and the LSS in general, focusing on the influence of different physical mechanisms, namely galactic winds (GWs), black-hole feedback and star-formation, and providing estimates of possible observational constraints. To this purpose we use a set of cosmological hydrodynamical simulations that include a self-consistent treatment of star-formation and chemical enrichment of the intergalactic medium, that allows us to follow the evolution of different metal species. We construct a set of simulated light-cones to make predictions of the emission in the 0.3-10 keV energy range. We obtain that GWs increase by a factor of 2 the emission of both galaxy clusters and WHIM. The amount of oxygen at average temperature and, consequently, the amount of expected bright Ovii and Oviii lines is increased by a factor of 3 due to GWs and by 20 per cent when assuming a top-heavy IMF. We compare our results with current observational constraints and find that the emission from faint groups and WHIM should account from half to all of the unresolved X-ray background in the 1-2 keV band.Comment: 15 pages, 8 figures, 4 tables. Accepted for publication in the MNRAS. Minor changes after referee repor

Motor imagery training speeds up gait recovery and decreases the risk of falls in patients submitted to total knee arthroplasty

With Motor imagery (MI), movements are mentally rehearsed without overt actions; this procedure has been adopted in motor rehabilitation, primarily in brain-damaged patients. Here we rather tested the clinical potentials of MI in purely orthopaedic patients who, by definition, should maximally benefit of mental exercises because of their intact brain. To this end we studied the recovery of gait after total knee arthroplasty and evaluated whether MI combined with physiotherapy could speed up the recovery of gait and even limit the occurrence of future falls. We studied 48 patients at the beginning and by the end of the post-surgery residential rehabilitation program: half of them completed a specific MI training supported by computerized visual stimulation (experimental group); the other half performed a non-motoric cognitive training (control group). All patients also had standard physiotherapy. By the end of the rehabilitation, the experimental group showed a better recovery of gait and active knee flexion-extension movements, and less pain. The number of falls or near falls after surgery was significantly lower in the experimental group. These results show that MI can improve gait abilities and limit future falls in orthopaedic patients, without collateral risks and with limited costs

Xmm-Newton Observations of the Diffuse X-ray Background

We analyzed two XMM-Newton observations in the direction of the high density, high latitude, neutral hydrogen cloud MBM20 and of a nearby low density region that we called the Eridanus hole. The cloud MBM20 is at a distance evaluated between 100 and 200 pc from the Sun and its density is sufficiently high to shield about 75% of the foreground emission in the 3/4 keV energy band.The combination of the two observations makes possible an evaluation of the OVII and OVIII emission both for the foreground component due to the Local Bubble,and the background one, due primary to the galactic halo.The two observations are in good agreement with each other and with ROSAT observations of the same part of the sky and the OVII and OVIII fluxes are OVII=3.89+/-0.56 photons cm^-2 s^-1 sr^-1, OVIII=0.68+/-0.24 photons cm^-2 s^-1 sr^-1 for MBM20 and OVII=7.26+/-0.34 photons cm^-2 s^-1 sr^-1,OVIII=1.63+/-0.17 photons cm^-2 s^-1 sr^-1 for the Eridanus hole. The spectra are in agreement with a simple three component model, one unabsorbed and one absorbed plasma component, and a power law, without evidence for any strong contamination from ion exchange in the solar system. Assuming that the two plasma components are in thermal equilibrium we obtain a temperature of 0.096 keV for the foreground component and 0.197 keV for the background one. Assuming the foreground component is due solely to Local Bubble emission we obtain a lower and upper limit for the plasma density of 0.0079 cm^-3 and 0.0095 cm^-3 and limits of 16,200 cm^-3 K and 19,500 cm^-3 K for the plasma pressure, in good agreement with theoretical predictions. Similarly, assuming that the absorbed plasma component is due to Galactic halo emission, we obtain a plasma density ranging from 0.0009 cm^-3 to 0.0016 cm^-3, and a pressure ranging from 3.0*10^3 to 6.7*10^3 cm^-3 K.Comment: 31 pages, 5 figures, Accepted for publication in Ap