Personalized modeling of Alzheimer's disease progression estimates neurodegeneration severity from EEG recordings.

INTRODUCTION: Early identification of Alzheimer's disease (AD) is necessary for a timely onset of therapeutic care. However, cortical structural alterations associated with AD are difficult to discern. METHODS: We developed a cortical model of AD-related neurodegeneration accounting for slowing of local dynamics and global connectivity degradation. In a monocentric study we collected electroencephalography (EEG) recordings at rest from participants in healthy (HC, n = 17), subjective cognitive decline (SCD, n = 58), and mild cognitive impairment (MCI, n = 44) conditions. For each patient, we estimated neurodegeneration model parameters based on individual EEG recordings. RESULTS: Our model outperformed standard EEG analysis not only in discriminating between HC and MCI conditions (F1 score 0.95 vs 0.75) but also in identifying SCD patients with biological hallmarks of AD in the cerebrospinal fluid (recall 0.87 vs 0.50). DISCUSSION: Personalized models could (1) support classification of MCI, (2) assess the presence of AD pathology, and (3) estimate the risk of cognitive decline progression, based only on economical and non-invasive EEG recordings. Highlights: Personalized cortical model estimating structural alterations from EEG recordings.Discrimination of Mild Cognitive Impairment (MCI) and Healthy (HC) subjects (95%)Prediction of biological markers of Alzheimer's in Subjective Decline (SCD) Subjects (87%)Transition correctly predicted for 3/3 subjects that converted from SCD to MCI after 1y.

Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band.

Motor symptoms of Parkinson's Disease (PD) are associated with dopamine deficits and pathological oscillation of basal ganglia (BG) neurons in the ß range ([12-30] Hz). However, how dopamine depletion affects the oscillation dynamics of BG nuclei is still unclear. With a spiking neurons model, we here capture the features of BG nuclei interactions leading to oscillations in dopamine-depleted condition. We highlight that both the loop between subthalamic nucleus (STN) and Globus Pallidus pars externa (GPe) and the loop between striatal fast spiking and medium spiny neurons and GPe display resonances in the ß range, and synchronize to a common ß frequency through interaction. Crucially, the synchronization depends on dopamine depletion: the two loops are largely independent for high levels of dopamine, but progressively synchronize as dopamine is depleted due to the increased strength of the striatal loop. The model is validated against recent experimental reports on the role of cortical inputs, STN and GPe activity in the generation of ß oscillations. Our results highlight the role of the interplay between the GPe-STN and the GPe-striatum loop in generating sustained ß oscillations in PD subjects, and explain how this interplay depends on the level of dopamine. This paves the way to the design of therapies specifically addressing the onset of pathological ß oscillations.

On the determination of the optimal parameters in the CAM model.

In the field of complex systems, it is often possible to arrive at some simple stochastic or chaotic Low Order Models (LOMs) exploiting the time scale separation between leading modes of interest and fast fluctuations. These LOMs, although approximate, might provide interesting qualitative insights regarding some important aspects like the average time between two extreme events. Recently, the simplest example of a LOM with multiplicative noise, namely, a linear system with a linearly state dependent noise [also called correlated additive and multiplicative (CAM) model], has been considered as archetypal for numerous phenomena that present markedly non-Gaussian statistics. We show in this paper that the determination of the parameters of a CAM model from the (few) available data is far from trivial and that the actual most likely parameters might differ substantially from the ones determined directly from a (necessarily limited) short sequence of observations. We illustrate how this problem can be tackled, at least to the extent possible, using an approach that is based on Bayes' theorem. We shall focus on a CAM modeling the El Niño Southern Oscillation but the methodology can be extended to any phenomenon that can be described by a simplified LOM similar to the one examined here and where the available sequence of data is relatively short. We conclude that indeed a Bayesian approach can fix the problem.

Estimate of the average timing for strong El Niño events using the recharge oscillator model with a multiplicative perturbation.

El Niño Southern Oscillation (ENSO) is the leading mode of tropical Pacific variability at interannual timescales. Through atmospheric teleconnections, ENSO exerts large influences worldwide, so that improved understanding of this phenomenon can be of critical societal relevance. Extreme ENSO events, in particular, have been associated with devastating weather events in many parts of the world, so that the ability to assess their frequency and probability of occurrence is extremely important. In this study, we describe the ENSO phenomenon in terms of the Recharge Oscillator Model perturbed by multiplicative deterministic chaotic forcing, and use methodologies from the field of Statistical Mechanics to determine the average time between El Niño events of given strengths. This is achieved by describing the system in terms of its probability density function, which is governed by a Fokker Planck equation, and then using the Mean First Passage Time technique for the determination of the mean time between extreme events. The ability to obtain analytical solutions to the problem allows a clear identification of the most relevant model parameters for controlling the frequency of extreme events. The key parameter is the strength of the multiplicative component of the stochastic perturbation, but the decorrelation timescale of the stochastic forcing is also very influential. Results obtained with this approach suggest an average waiting time between extreme events of only some tens of years.

Encephalitozoon cuniculi in rabbits: Serological screening and histopathological findings.

Serological prevalence of E. cuniculi infection was assessed in 183 rabbits from central Italy. In seropositive deceased rabbits, histopathological lesions were also evaluated. Sera from 118 rabbits from 6 intensive farms, 10 rabbits from 6 family farms, 16 rabbits from a zoo, 30 rabbits from 5 research laboratories and 9 pet rabbits from 9 different owners, were tested by an enzyme-linked immunosorbent assay. Data were statistically analysed. Tissue samples from brain and kidney of 10 deceased rabbits were formalin-fixed and subsequently analysed by histopathology and immunohistochemistry. Anti-E. cuniculi antibodies were found in 129/183 (70.5%) analysed sera. At statistical analysis, E. cuniculi seropositivity was significantly higher (p<0.05) in industrial and zoo rabbits. At histology, different degrees of pathological lesions were found in serological positive (9) deceased animals. In three rabbits deceased after showing neurological signs, the severity of the lesions was interpreted as a likely cause for their death.

Intestinal and lung parasites in owned dogs and cats from central Italy.

Prevalence and risk factors of intestinal and lung parasites were investigated in 239 owned dogs and 81 owned cats from central Italy. In 36 dogs and 20 cats found infected by nematodes, pre and post-treatment faecal egg count (FEC) was also evaluated. About 31% of dogs and about 35% of cats resulted positive for at least one intestinal or lung parasitic species. Helminthic, intestinal and zoonotic infections resulted prevalent in examined animals. Examined dogs resulted infected by Toxocara canis (13.0%), Toxascaris leonina (1.7%), Trichuris vulpis (3.3%), Ancylostoma caninum (2.0%), Uncinaria stenocephala (1.25%), Strongyloides stercoralis (0.8%), Angiostrongylus vasorum (0.4%), Dipylidium caninum (1.25%), Taeniidae eggs (0.4%), Giardia duodenalis (3.8%), and Cystoisospora (Isospora) spp. (7.5%). Examined cats were infected by Toxocara cati (22.2%), Capillaria aerophila (1.2%), Ancylostoma tubaeformae (1.2%), U. stenocephala (3.7%), Aelurostrongylus abstrusus (1.2%), Mesocestoides sp. (1.2%), D. caninum (1.2%), G. duodenalis (1.2%) and Cystoisospora spp. (4.5%). The presence of clinical signs and the young age (less than 6 months) were identified as risk factors by univariate and multivariate statistical analysis. In 63.9% treated dogs and in 80.0% treated cats, percentages of post-treatment FEC reduction higher than 90% were found. Results obtained in this study are discussed.

The Italian veterinary medicine admission test: analysis of student intake in the years 2007, 2008, and 2009, and of the test's relationship with students' academic careers.

The present paper analyzes the admission test administered to candidates to the veterinary medicine program in Italy for the academic years 2007-2008, 2008-2009, and 2009-2010 nationwide as well as the University of Pisa student intake from 2001-2002 through 2009-2010, comparing the relationship between the admission test and students' academic careers at Pisa. This paper finds that the Italian system of a locally enforced fixed intake number does not select the best possible candidates for admission because (1) there are significant variations in the candidates' preparation among the different locations where the test is held, (2) the subjects tested are not equally selective in identifying the best candidates, and (3) there is a very strong relationship between candidates' performance on the admission test and the subsequent academic career of the admitted candidates. In its findings, this study in part contradicts what is commonly believed by the Italian veterinary medicine community, and, as a result, it is extremely important that care is taken in the decision-making process-in the process, that is, of identifying a fixed intake number and of selecting the subjects to be tested on the admission test.

Gastrointestinal parasites in mammals of two Italian zoological gardens.

The prevalence of gastrointestinal parasites was investigated in mammals housed in two of the main Italian zoological gardens: the Zoo Safari of Fasano (province of Bindisi, Apulia, Italy) and the Giardino Zoologico of Pistoia (Tuscany, Italy). In November 2007, fecal samples were collected at the Zoo Safari of Fasano (n = 96) and at the Giardino Zoologico of Pistoia (n = 60), from primates, carnivores, perissodactyls, artiodactyls and proboscideans. In most of the cases, the same animal species or genera were considered in both the zoos. One or more intestinal parasites were detected in 61.5% of the examined samples. However, very different percentages of protozoa- and helminth-positive samples were obtained in the animals from the two zoos, with an overall gastrointestinal parasitic infection of 77.1% in the Zoo Safari of Fasano and 36.7% in the Giardino Zoologico of Pistoia. Overall, 10% (Cryptosporidium sp.) and 43.3% (Toxocara cati, Strongyloides stercoralis, Toxascaris leonina, and hookworms) of carnivores, 66.7% (Cryptosporidium spp.) and 100% (Trichuris spp. and Strongyloides fülleborni) of primates, 25.0% (Eimeria spp., Cryptosporidium spp.), and 57.1% (Trichuris sp., Toxocara [Neoascaris] vitulorum, gastrointestinal strongyles, and Paramphistomidae) of artiodactyls were infected with protozoa and helminthes parasites, respectively. Only gastrointestinal strongyles were diagnosed in 16.7% of proboscideans and in 50.0% of perissodactyls examined. The results of this study suggest that zoonotic protozoans and gastrointestinal helminths are common in zoo mammals and that these animals may serve as a potential reservoir and transmit these parasites to humans. The different animal management in the two zoos indicates that the regular monitoring of parasitic diseases and the use of selective treatments can represent effective measures for the control of several gastrointestinal infections in zoological gardens.

Many-body interband tunneling as a witness of complex dynamics in the Bose-Hubbard model.

A perturbative model is studied for the tunneling of many-particle states from the ground band to the first excited energy band, mimicking Landau-Zener decay for ultracold, spinless atoms in quasi-one-dimensional optical lattices subjected to a tunable tilting force. The distributions of the computed tunneling rates provide an independent and experimentally accessible signature of the regular-chaotic transition in the strongly correlated many-body dynamics of the ground band.

Resonant nonlinear quantum transport for a periodically kicked bose condensate.

Our realistic numerical results show that the fundamental and higher-order quantum resonances of the delta-kicked rotor are observable in state-of-the-art experiments with a Bose condensate in a shallow harmonic trap, kicked by a spatially periodic optical lattice. For stronger confinement, interaction-induced destruction of the resonant motion of the kicked harmonic oscillator is predicted.