Chaotic, memory and cooling rate effects in spin glasses: Is the Edwards-Anderson model a good spin glass?

We investigate chaotic, memory and cooling rate effects in the three dimensional Edwards-Anderson model by doing thermoremanent (TRM) and AC susceptibility numerical experiments and making a detailed comparison with laboratory experiments on spin glasses. In contrast to the experiments, the Edwards-Anderson model does not show any trace of re-initialization processes in temperature change experiments (TRM or AC). A detailed comparison with AC relaxation experiments in the presence of DC magnetic field or coupling distribution perturbations reveals that the absence of chaotic effects in the Edwards-Anderson model is a consequence of the presence of strong cooling rate effects. We discuss possible solutions to this discrepancy, in particular the smallness of the time scales reached in numerical experiments, but we also question the validity of the Edwards-Anderson model to reproduce the experimental results.Comment: 17 pages, 10 figures. The original version of the paper has been split in two parts. The second part is now available as cond-mat/010224

Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children

Aim: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. Methods: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. Results: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. Conclusion: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking

Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia

The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages

Real-time non-equilibrium dynamics of quantum glassy systems

We develop a systematic analytic approach to aging effects in quantum disordered systems in contact with an environment. Within the closed-time path-integral formalism we include dissipation by coupling the system to a set of independent harmonic oscillators that mimic a quantum thermal bath. After integrating over the bath variables and averaging over disorder we obtain an effective action that determines the real-time dynamics of the system. The classical limit yields the Martin-Siggia-Rose generating functional associated to a colored noise. We apply this general formalism to a prototype model related to the $p$ spin-glass. We show that the model has a dynamic phase transition separating the paramagnetic from the spin-glass phase and that quantum fluctuations depress the transition temperature until a quantum critical point is reached. We show that the dynamics in the paramagnetic phase is stationary but presents an interesting crossover from a region controlled by the classical critical point to another one controlled by the quantum critical point. The most characteristic property of the dynamics in a glassy phase, namely aging, survives the quantum fluctuations. In the sub-critical region the quantum fluctuation-dissipation theorem is modified in a way that is consistent with the notion of effective temperatures introduced for the classical case. We discuss these results in connection with recent experiments in dipolar quantum spin-glasses and the relevance of the effective temperatures with respect to the understanding of the low temperature dynamics.Comment: 56 pages, Revtex, 17 figures include

Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: Effect of catalase overexpression

AbstractThe mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids

Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia

Importance: Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. Objective: To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. Design, Setting, and Participants: This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Main Outcomes and Measures: Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of disease duration and variation. Results: Of 232 patients with FTD, 115 (49.6%) had a C9orf72 expansion (median [interquartile range (IQR)] age at evaluation, 64.3 [57.5-69.7] years; 72 men [62.6%]; 115 White patients [100%]), 78 (33.6%) had a GRN variant (median [IQR] age, 63.4 [58.3-68.8] years; 40 women [51.3%]; 77 White patients [98.7%]), and 39 (16.8%) had a MAPT variant (median [IQR] age, 56.3 [49.9-62.4] years; 25 men [64.1%]; 37 White patients [94.9%]). All core behavioral symptoms, including disinhibition, apathy, loss of empathy, perseverative behavior, and hyperorality, were highly expressed in all gene variant carriers (>50% patients), with apathy being one of the most common and severe symptoms throughout the disease course (51.7%-100% of patients). Patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms, particularly disinhibition (79.3%-100% of patients) and compulsive behavior (64.3%-100% of patients), compared with C9orf72 carriers (51.7%-95.8% of patients with disinhibition and 34.5%-75.0% with compulsive behavior) and GRN carriers (38.2%-100% with disinhibition and 20.6%-100% with compulsive behavior). Alongside behavioral symptoms, neuropsychiatric symptoms were very frequently reported in patients with genetic FTD: anxiety and depression were most common in GRN carriers (23.8%-100% of patients) and MAPT carriers (26.1%-77.8% of patients); hallucinations, particularly auditory and visual, were most common in C9orf72 carriers (10.3%-54.5% of patients). Most behavioral and neuropsychiatric symptoms increased in the early-intermediate phases and plateaued in the late stages of disease, except for depression, which steadily declined in C9orf72 carriers, and depression and anxiety, which surged only in the late stages in GRN carriers. Conclusions and Relevance: This cohort study suggests that behavioral and neuropsychiatric disturbances differ between the common FTD gene variants and have different trajectories throughout the course of disease. These findings have crucial implications for counseling patients and caregivers and for the design of disease-modifying treatment trials in genetic FTD.

Quantitative MRI Harmonization to Maximize Clinical Impact: The RIN–Neuroimaging Network

Neuroimaging studies often lack reproducibility, one of the cardinal features of the scientific method. Multisite collaboration initiatives increase sample size and limit methodological flexibility, therefore providing the foundation for increased statistical power and generalizable results. However, multisite collaborative initiatives are inherently limited by hardware, software, and pulse and sequence design heterogeneities of both clinical and preclinical MRI scanners and the lack of benchmark for acquisition protocols, data analysis, and data sharing. We present the overarching vision that yielded to the constitution of RIN-Neuroimaging Network, a national consortium dedicated to identifying disease and subject-specific in-vivo neuroimaging biomarkers of diverse neurological and neuropsychiatric conditions. This ambitious goal needs efforts toward increasing the diagnostic and prognostic power of advanced MRI data. To this aim, 23 Italian Scientific Institutes of Hospitalization and Care (IRCCS), with technological and clinical specialization in the neurological and neuroimaging field, have gathered together. Each IRCCS is equipped with high- or ultra-high field MRI scanners (i.e., ≥3T) for clinical or preclinical research or has established expertise in MRI data analysis and infrastructure. The actions of this Network were defined across several work packages (WP). A clinical work package (WP1) defined the guidelines for a minimum standard clinical qualitative MRI assessment for the main neurological diseases. Two neuroimaging technical work packages (WP2 and WP3, for clinical and preclinical scanners) established Standard Operative Procedures for quality controls on phantoms as well as advanced harmonized quantitative MRI protocols for studying the brain of healthy human participants and wild type mice. Under FAIR principles, a web-based e-infrastructure to store and share data across sites was also implemented (WP4). Finally, the RIN translated all these efforts into a large-scale multimodal data collection in patients and animal models with dementia (i.e., case study). The RIN-Neuroimaging Network can maximize the impact of public investments in research and clinical practice acquiring data across institutes and pathologies with high-quality and highly-consistent acquisition protocols, optimizing the analysis pipeline and data sharing procedures