Frequency map analysis of a three-dimensional particle in the core model of a high intensity linac

We consider the dynamical properties of a particle-core model for a uniformly filled triaxial ellipsoid in a periodic lattice of a high intensity linac. The mismatched oscillation modes are analytically computed in the smooth approximation and are compared with the numerical results of a tracking program. The study of the phase space in the mismatched case is performed by the frequency map analysis. In particular, we can analyze the effect of the nonlinear resonances between the envelope modes and the single particle sincrobetatron frequencies. A chaoticity criterion based on the frequency map analysis allows one to compute the stability region around the beam core. An estimate of the transport and its enhancement due to mismatch is provided by tracking orbits at the border of the stability region

Frailness and resilience of gene networks predicted by detection of co-occurring mutations via a stochastic perturbative approach

In recent years complex networks have been identified as powerful mathematical frameworks for the adequate modeling of many applied problems in disparate research fields. Assuming a Master Equation (ME) modeling the exchange of information within the network, we set up a perturbative approach in order to investigate how node alterations impact on the network information flow. The main assumption of the perturbed ME (pME) model is that the simultaneous presence of multiple node alterations causes more or less intense network frailties depending on the specific features of the perturbation. In this perspective the collective behavior of a set of molecular alterations on a gene network is a particularly adapt scenario for a first application of the proposed method, since most diseases are neither related to a single mutation nor to an established set of molecular alterations. Therefore, after characterizing the method numerically, we applied as a proof of principle the pME approach to breast cancer (BC) somatic mutation data downloaded from Cancer Genome Atlas (TCGA) database. For each patient we measured the network frailness of over 90 significant subnetworks of the protein-protein interaction network, where each perturbation was defined by patient-specific somatic mutations. Interestingly the frailness measures depend on the position of the alterations on the gene network more than on their amount, unlike most traditional enrichment scores. In particular low-degree mutations play an important role in causing high frailness measures. The potential applicability of the proposed method is wide and suggests future development in the control theory context

Stochastic Properties of Colliding Hard Spheres in a Non-equilibrium Thermal Bath

We consider the problem of describing the dynamics of a test particle moving in a thermal bath using the stochastic differential equations. We briefly recall the stochastic approach to the Brownian based on the statistical properties of collision theory for a gas of elastic particles and the molecular chaos hypothesis. The mathematical formulation of the Brownian motion leads to the formulation of the Ornstein-Uhlenbeck equation that provides a stationary solution consistent with the Maxwell-Boltzmann distribution. According to the stochastic thermodynamics, we assume that the stochastic differential equations allow to describe the transient states of the test particle dynamics in a thermal bath and it extends their application to the study of the non-equilibrium statistical physics. Then we consider the problem of the dynamics of a test massive particle in a non homogeneous thermal bath where a gradient of temperature is present. We discuss as the existence of a local thermodynamics equilibrium is consistent with a Stratonovich interpretation of the stochastic differential equations with a multiplicative noise. The stochastic model applied to the test particle dynamics implies the existence of a long transient state during which the particle shows a net drift toward the cold region of the system. This effect recalls the thermophoresis phenomenon performed by large molecule in a solution in response to a macroscopic temperature gradient and it can be explained as an effect of the non-locality character of the collision interactions between the test particle and the thermal bath particles. To validate the stochastic model assumptions we analyze the simulation results of the 2-dimensional hard sphere gas obtained by using an event-based computer code, that solves exactly the sphere dynamics. The temperature gradient is simulated by the presence of two reflecting boundary conditions at different temperature. The simulations suggest that existence of a local thermodynamic equilibrium is justified and highlight the presence of a drift in the average dynamics of an ensemble of massive particles. The results of the paper could be relevant for the applications of stochastic dynamical systems to the non-equilibrium statistical physics that is a key issue for the Complex Systems Physics

Didactic and narrative persuasion: An experiment to promote colorectal cancer screening

We tested whether a didactic and a narrative video (i.e. educational content and personal stories versus irrelevant information) could boost colorectal cancer (CRC) screening intention directly and through cognitive predictors of CRC screening behavior. We also tested whether exposure to a story changed participants' affective forecasting, reducing the perception of negative emotions associated with CRC screening (disgust, embarrassment, and fear). The study was conducted online with a between-participants design and recruiting a convenience sample (N =375). We found that, compared with watching the control video, being exposed to the narrative video about CRC screening was indirectly associated with greater screening inten- tion via vicarious experience and positive attitudes, whereas watching the didactic video was positively associated with CRC screening intention only among participants who had received an invitation letter but did not get screened, and among those yet to receive an invitation to screen. In the latter group, screening intention was boosted through positive attitudes. Our findings do not confirm that stories change affective forecasting, but narration likely fosters messages acceptance through vicarious experience. We also found support for the effectiveness of physicians' rec- ommendations in promoting CRC screening, an intervention that might be effectively administered through a generalized, cost-effective video

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry.Patients and methods: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model.Results: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis.Conclusion: Although ETA demonstrated a high persistence in biologic-naive RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register.

Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX)

Human Mobility in a Continuum Approach

Human mobility is investigated using a continuum approach that allows to calculate the probability to observe a trip to anyarbitrary region, and the fluxes between any two regions. The considered description offers a general and unified framework, in which previously proposed mobility models like the gravity model, the intervening opportunities model, and the recently introduced radiation model are naturally resulting as special cases. A new form of radiation model is derived and its validity is investigated using observational data offered by commuting trips obtained from the United States census data set, and the mobility fluxesextracted from mobile phone data collected in a western European country. The new modeling paradigm offered by this description suggests that the complex topological features observed in large mobility and transportation networks may be the result of a simple stochastic process taking place on an inhomogeneous landscape.Comment: 13 pages, 3 figure

The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol

[EN] Introduction Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%¿12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults. Method The My Active and Healthy Aging (My-AHA) consortium has developed an information and communications technology¿based platform to support active and healthy aging through early detection of prefrailty and provision of individually tailored interventions, targeting multidomain risks for frailty across physical activity, cognitive activity, diet and nutrition, sleep, and psychosocial activities. Six hundred adults aged 60 years and older will be recruited to participate in a multinational, multisite 18-month randomized controlled trial to test the efficacy of the My-AHA platform to detect prefrailty and the efficacy of individually tailored interventions to prevent development of clinical frailty in this cohort. A total of 10 centers from Italy, Germany, Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and Australia will participate in the randomized controlled trial. Results Pilot testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been completed with a small group of older adults in Europe with the full randomized controlled trial scheduled to commence in 2018. Discussion The My-AHA study will expand the understanding of antecedent risk factors for clinical frailty so as to deliver targeted interventions to adults with prefrailty. Through the use of an information and communications technology platform that can connect with multiple devices within the older adult's own home, the My-AHA platform is designed to measure an individual's risk factors for frailty across multiple domains and then deliver personalized domain-specific interventions to the individual. The My-AHA platform is technology-agnostic, enabling the integration of new devices and sensor platforms as they emerge.This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 689582 and the Australian National Health and Medical Research Council (NHRMC) European Union grant scheme (1115818). M.J.S. reports personal fees from Eli Lilly (Australia) Pty Ltd and grants from Novotech Pty Ltd, outside the submitted work. All other authors report nothing to disclose.Summers, MJ.; Rainero, I.; Vercelli, AE.; Aumayr, GA.; De Rosario Martínez, H.; Mönter, M.; Kawashima, R. (2018). 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