Contrarian Majority Rule Model with External Oscillating Propaganda and Individual Inertias.

We study the Galam majority rule dynamics with contrarian behavior and an oscillating external propaganda in a population of agents that can adopt one of two possible opinions. In an iteration step, a random agent interacts with three other random agents and takes the majority opinion among the agents with probability p(t) (majority behavior) or the opposite opinion with probability 1-p(t) (contrarian behavior). The probability of following the majority rule p(t) varies with the temperature T and is coupled to a time-dependent oscillating field that mimics a mass media propaganda, in a way that agents are more likely to adopt the majority opinion when it is aligned with the sign of the field. We investigate the dynamics of this model on a complete graph and find various regimes as T is varied. A transition temperature Tc separates a bimodal oscillatory regime for TTc in which m oscillates around zero. These regimes are characterized by the distribution of residence times that exhibit a unique peak for a resonance temperature T*, where the response of the system is maximum. An insight into these results is given by a mean-field approach, which also shows that T* and Tc are closely related.

Random multi-player games.

The study of evolutionary games with pairwise local interactions has been of interest to many different disciplines. Also, local interactions with multiple opponents had been considered, although always for a fixed amount of players. In many situations, however, interactions between different numbers of players in each round could take place, and this case cannot be reduced to pairwise interactions. In this work, we formalize and generalize the definition of evolutionary stable strategy (ESS) to be able to include a scenario in which the game is played by two players with probability p and by three players with the complementary probability 1-p. We show the existence of equilibria in pure and mixed strategies depending on the probability p, on a concrete example of the duel-truel game. We find a range of p values for which the game has a mixed equilibrium and the proportion of players in each strategy depends on the particular value of p. We prove that each of these mixed equilibrium points is ESS. A more realistic way to study this dynamics with high-order interactions is to look at how it evolves in complex networks. We introduce and study an agent-based model on a network with a fixed number of nodes, which evolves as the replicator equation predicts. By studying the dynamics of this model on random networks, we find that the phase transitions between the pure and mixed equilibria depend on probability p and also on the mean degree of the network. We derive mean-field and pair approximation equations that give results in good agreement with simulations on different networks.

Modeling and Analysis of Social Phenomena: Challenges and Possible Research Directions.

This opening editorial aims to interest researchers and encourage novel research in the closely related fields of sociophysics and computational social science. We briefly discuss challenges and possible research directions in the study of social phenomena, with a particular focus on opinion dynamics. The aim of this Special Issue is to allow physicists, mathematicians, engineers and social scientists to show their current research interests in social dynamics, as well as to collect recent advances and new techniques in the analysis of social systems.

Contrarian Voter Model under the Influence of an Oscillating Propaganda: Consensus, Bimodal Behavior and Stochastic Resonance.

We study the contrarian voter model for opinion formation in a society under the influence of an external oscillating propaganda and stochastic noise. Each agent of the population can hold one of two possible opinions on a given issue­against or in favor­and interacts with its neighbors following either an imitation dynamics (voter behavior) or an anti-alignment dynamics (contrarian behavior): each agent adopts the opinion of a random neighbor with a time-dependent probability p(t), or takes the opposite opinion with probability 1−p(t). The imitation probability p(t) is controlled by the social temperature T, and varies in time according to a periodic field that mimics the influence of an external propaganda, so that a voter is more prone to adopt an opinion aligned with the field. We simulate the model in complete graph and in lattices, and find that the system exhibits a rich variety of behaviors as T is varied: opinion consensus for T=0, a bimodal behavior for TTc, and full disorder for T≫1. The transition temperature Tc vanishes with the population size N as Tc≃2/lnN in complete graph. In addition, the distribution of residence times tr in the bimodal phase decays approximately as tr−3/2. Within the oscillatory regime, we find a stochastic resonance-like phenomenon at a given temperature T*. Furthermore, mean-field analytical results show that the opinion oscillations reach a maximum amplitude at an intermediate temperature, and that exhibit a lag with respect to the field that decreases with T.

A model for the competition between political mono-polarization and bi-polarization.

We investigate the phenomena of political bi-polarization in a population of interacting agents by means of a generalized version of the model introduced by Vazquez et al. [Phys. Rev. E 101, 012101 (2020)] for the dynamics of voting intention. Each agent has a propensity p in [0,1] to vote for one of two political candidates. In an iteration step, two randomly chosen agents i and j with respective propensities pi and pj interact, and then pi either increases by an amount h>0 with a probability that is a nonlinear function of pi and pj or decreases by h with the complementary probability. We assume that each agent can interact with any other agent (all-to-all interactions). We study the behavior of the system under variations of a parameter q≥0 that measures the nonlinearity of the propensity update rule. We focus on the stability properties of the two distinct stationary states: mono-polarization in which all agents share the same extreme propensity (0 or 1), and bi-polarization where the population is divided into two groups with opposite and extreme propensities. We find that the bi-polarized state is stable for qqc, where qc(h) is a transition value that decreases as h decreases. We develop a rate equation approach whose stability analysis reveals that qc vanishes when h becomes infinitesimally small. This result is supported by the analysis of a transport equation derived in the continuum h→0 limit. We also show by Monte Carlo simulations that the mean time τ to reach mono-polarization in a system of size N scales as τ∼Nα at qc , where α is a nonuniversal exponent that depends on h.

Ballistic-Diffusive Model for Heat Transport in Superlattices and the Minimum Effective Heat Conductivity.

There has been much interest in semiconductor superlattices because of their low thermal conductivities. This makes them especially suitable for applications in a variety of devices for the thermoelectric generation of energy, heat control at the nanometric length scale, etc. Recent experiments have confirmed that the effective thermal conductivity of superlattices at room temperature have a minimum for very short periods (in the order of nanometers) as some kinetic calculations had anticipated previously. This work will show advances on a thermodynamic theory of heat transport in nanometric 1D multilayer systems by considering the separation of ballistic and diffusive heat fluxes, which are both described by Guyer-Krumhansl constitutive equations. The dispersion relations, as derived from the ballistic and diffusive heat transport equations, are used to derive an effective heat conductivity of the superlattice and to explain the minimum of the effective thermal conductivity.

Diagnostic Performance Evaluation of a Computer-Assisted Imaging Analysis System for Ultrasound Risk Stratification of Thyroid Nodules.

OBJECTIVE. Ultrasound-based stratification of the malignancy risk of thyroid nodules has potential variability. The purpose of this study is to evaluate the diagnostic effectiveness of the first commercially available system for computer-aided diagnosis (CADx) imaging analysis. MATERIALS AND METHODS. Ultrasound images of 300 thyroid nodules (135 of which were malignant) acquired before surgical treatment were retrospectively reviewed by a thyroid expert, and his classification of each image was then compared with the classification rendered by an image analysis program (AmCAD-UT, AmCAD Biomed). The American Thyroid Association (ATA) classification system, the European Thyroid Imaging Reporting and Data System (EU-TIRADS), and the classification system jointly proposed by American and Italian associations of clinical endocrinologists (the American Association of Clinical Endocrinologists [AACE], the American College of Endocrinology [ACE], and Associazione Medici Endocrinologi [AME]) were used for risk stratification. RESULTS. The diagnostic performance of the thyroid expert when the ATA system was used was as follows: sensitivity, 87.0%; specificity, 91.2%; positive predictive value, 90.5%; and negative predictive value, 90.9%. Compared with the expert, the CADx program, when used with the three classification systems, had a similar sensitivity but a lower specificity and positive predictive value. Regarding the negative predictive value, the results of the expert did not differ from those of the CADx program when it applied the ATA classification system (90.9% vs 86.3%; p = 0.07). The ROC AUC value was 0.88 for the expert clinician and 0.72 for the CADx program when the ATA classification system was used. CONCLUSION. The CADx ultrasound image analysis program described in the present study is useful for risk stratification of thyroid nodules, but it does not perform better than a sonography expert.

Controlling and Optimizing Entropy Production in Transient Heat Transfer in Graded Materials.

This paper presents a numerical analysis of the transient heat transfer problem arising when a functionally graded material is subjected to a fixed temperature difference. Varying the gradation of the system, the thermal performance of the material is assessed both in time-dependent and steady-state conditions by means of temperature profiles and entropy production. One of the main contributions of this paper is the analysis of the system in the transient, from which it is found that the entropy production has a non-monotonic behaviour since maximum and minimum values of this physical quantity could be identified by varying the grading profile of the material. The latter allows to propose an optimization criterion for functionally graded materials which consists of the identification of spatial regions where temperature gradients are large and find thermal conductivity profiles that attenuate those gradients, thus reducing the thermal stresses present inside the material.

Diabetic retinopathy is associated with the presence and burden of subclinical carotid atherosclerosis in type 1 diabetes.

BACKGROUND: Cardiovascular (CV) disease due to atherosclerosis is a major cause of morbidity and mortality in adult patients with diabetes, either type 1 or type 2 diabetes. The aim of the study was to assess the association of the frequency and the burden of subclinical carotid atherosclerotic disease in patients with type 1 diabetes according to the presence and severity of diabetic retinopathy (DR). METHODS: A cross-sectional study was conducted in 340 patients with type 1 diabetes (41.5% with DR), and in 304 non-diabetic individuals. All participants were free from previous CV disease and chronic kidney disease (CKD). B-mode carotid ultrasound imaging was performed in all the study subjects. Patients with type 1 diabetes underwent a full eye examination, and DR patients were divided into two groups: mild disease and advanced disease. RESULTS: In the group of patients with type 1 diabetes, the percentage of patients with carotid plaques was higher in those with DR compared with those without DR (44.7% vs. 24.1%, p < 0.001). Patients with DR also presented a higher incidence of ≥ 2 carotid plaques (25.5% vs. 11.1%, p < 0.001). Apart from other traditional cardiovascular risk factors, the presence of advanced stages of DR was independently associated with the presence (p = 0.044) and the burden (≥ 2 carotid plaques; p = 0.009) of subclinical carotid atherosclerosis. CONCLUSIONS: In patients with type 1 diabetes without previous CV disease or established CKD, the presence of advanced stages of DR is associated with a higher atherosclerotic burden in the carotid arteries. The presence of DR identifies patients at risk for carotid atherosclerotic disease.

Preclinical carotid atherosclerosis in patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes and classical type 1 diabetes.

BACKGROUND: LADA is probably the most prevalent form of autoimmune diabetes. Nevertheless, there are few data about cardiovascular disease in this group of patients. The aim of this study was to investigate the frequency of carotid atherosclerotic plaques in patients with LADA as compared with patients with classic type 1 diabetes and type 2 diabetes. METHODS: Patients with LADA were matched for age and gender in different proportions to patients with type 2 diabetes, and classic type 1 diabetes. None of the patients had clinical cardiovascular disease. All subjects underwent B-mode carotid ultrasound to detect atheroma plaques. Demographics were obtained from all subjects. RESULTS: We included 71 patients with LADA, 191 patients with type 2 diabetes and 116 patients with type 1 diabetes. Carotid atherosclerosis was more frequent in patients with LADA compared with type 2 diabetes (73.2% vs. 56.9%, P = 0.0018) and classic type 1 diabetes (57.1%, P = 0.026); these changes occurred despite healthier macrovascular risk profiles in the former. Age (P < 0.001), smoking (P = 0.003) and hypertension (P = 0.019) were independently associated with carotid atherosclerosis. Multiple plaques were also more frequent in patients with LADA as compared with classic type 1 diabetes and type 2 diabetes (45.1% and 33.6% vs. 27.2%, respectively, P = 0.022). The frequency of carotid plaques increased with increasing diabetes duration in LADA patients compared with type 2 diabetes (85.7% vs. 58.8%, inverse OR 5.72 [1.5-21.8]; P = 0.009). CONCLUSIONS: LADA patients do not present with less carotid atherosclerosis than patients with type 1 and type 2 diabetes. Their macrovascular risk occurs despite a healthier macrovascular risk profile than those patients with type 2 diabetes.

Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort.

BACKGROUND: In our randomised, controlled, phase 3 trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy. METHODS: We did this multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer. Participants were randomly assigned (1:1), by computer program with a minimisation technique, to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab (concurrently with neoadjuvant chemotherapy and continued after surgery). A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone. Our primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered at www.controlled-trials.com, ISRCTN86043495. FINDINGS: Between June 20, 2002, and Dec 12, 2005, we enrolled 235 patients with HER2-positive disease, of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab. 99 additional patients with HER2-negative disease were included in the parallel cohort. After a median follow-up of 5.4 years (IQR 3.1-6.8) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease. 5 year event-free survival was 58% (95% CI 48-66) in patients in the trastuzumab group and 43% (34-52) in those in the chemotherapy group; the unadjusted hazard ratio (HR) for event-free survival between the two randomised HER2-positive treatment groups was 0.64 (95% CI 0.44-0.93; two-sided log-rank p=0.016). Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab. Of the 68 patients with a pathological complete response (45 with trastuzumab and 23 with chemotherapy alone), the HR for event-free survival between those with and without trastuzumab was 0.29 (95% CI 0.11-0.78). During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related (grade 2 lymphostasis and grade 2 lymphoedema, each in one patient in the trastuzumab group, and grade 2 thrombosis and grade 2 deep vein thrombosis, each in one patient in the chemotherapy-alone group). INTERPRETATION: These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer, and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease.

Ordering dynamics of nonlinear voter models.

We study the ordering dynamics of nonlinear voter models with multiple states, also providing a discussion of the two-state model. The rate with which an individual adopts an opinion scales as the qth power of the number of the individual's neighbors in that state. For q>1 the dynamics favor the opinion held by the most agents. The ordering to consensus is driven by deterministic drift, and noise plays only a minor role. For q<1 the dynamics favors minority opinions, and for multistate models the ordering proceeds through a noise-driven succession of metastable states. Unlike linear multistate systems, the nonlinear model cannot be reduced to an effective two-state model. We find that the average density of active interfaces in the model with multiple opinion states does not show a single exponential decay in time for q<1, again at variance with the linear model. This highlights the special character of the conventional (linear) voter model, in which deterministic drift is absent. As part of our analysis, we develop a pair approximation for the multistate model on graphs, valid for any positive real value of q, improving on previous approximations for nonlinear two-state voter models.

Dual mTOR1/2 Inhibitor Sapanisertib (FTH-003/TAK-228) in Combination With Weekly Paclitaxel in Patients With Previously Treated Metastatic Urothelial Carcinoma: A Phase II Open-Label Study.

BACKGROUND: The PI3K/AKT/mTOR pathway is frequently altered at genomic level in metastatic urothelial carcinoma (mUC). Since mTOR is the last protein in the PI3K signaling cascade, it may have the largest impact on the pathway and has been a focus of targeted therapies. Sapanisertib (FTH-003/TAK-228) is an oral highly selective mTOR1 and mTOR2 inhibitor. NFE2L2 mutations have been described as predictive biomarkers of response in patients with advanced squamous cell lung cancer treated with sapanisertib. PATIENTS AND METHODS: This was an open-label, investigator-initiated phase II study evaluating safety and efficacy of sapanisertib plus paclitaxel in patients with mUC who had progressed to prior platinum therapy, and the correlation with NFE2L2 mutations in responders. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Patients were treated with weekly paclitaxel at dose of 80 mg/m2 on days 1, 8, and 15 in combination with sapanisertib 4 mg administered orally 3 days per week on days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle. NFE2L2 mutations were analyzed by Sanger sequencing in responders. RESULTS: 22 patients were enrolled from May 2018 to April 2020; the trial was halted early due to slow accrual and the COVID-19 pandemic. ORR was 18.2% (n = 4). Disease control rate was 50% (7 SD and 4 PR). Median PFS was 3.4 months (95% CI: 1.8-6.1) and median OS was 6.1 months (95% CI: 1.8-13.4). Adverse events (AE) of grade 3-4 were seen in 86% of patients, but no patients discontinued treatment due to AEs. NFE2L2 mutations were not found in responders. CONCLUSIONS: Although the primary endpoint was no met, sapanisertib and paclitaxel combination demonstrated clinical activity in a heavily pretreated population of mUC. This trial generates insight for future combination of sapaniserib with immunotherapy and/or antibody drug conjugates.

Corrigendum: NK cell subsets changes in partial remission and early stages of pediatric type 1 diabetes.

[This corrects the article DOI: 10.3389/fimmu.2020.611522.].

Corrigendum: Candidate biomarkers for the prediction and monitoring of partial remission in pediatric type 1 diabetes.

[This corrects the article DOI: 10.3389/fimmu.2022.825426.].

Personalized medicine in acromegaly: The ACROFAST study.

Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated. METHODS AND SUBJECTS: prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control. RESULTS: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01). CONCLUSION: Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly.

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) . Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively. Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01). Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.

ENDOCRINE OBESITY: Pituitary dysfunction in obesity.

Obesity, the growing pandemic of the 21st century, is associated with multiple organ dysfunction, either by a direct increase in fatty organ content or by indirect modifications related to general metabolic changes driven by a specific increase in biologic products. The pituitary gland is not protected against such a situation. Different hypothalamic-pituitary axes experience functional modifications initially oriented to an adaptive situation that, with years of obesity, turn to maladaptive dynamics that contribute to perpetuating obesity and specific symptoms of their hormonal nature. This paper reviews the recent knowledge on obesity-related pituitary dysfunction and its pathogenic mechanisms and discusses potential therapeutic actions aimed at contributing to ameliorating the complex treatment of severe cases of obesity.

Spatial effects in parasite-induced marine diseases of immobile hosts.

Emerging marine infectious diseases pose a substantial threat to marine ecosystems and the conservation of their biodiversity. Compartmental models of epidemic transmission in marine sessile organisms, available only recently, are based on non-spatial descriptions in which space is homogenized and parasite mobility is not explicitly accounted for. However, in realistic scenarios epidemic transmission is conditioned by the spatial distribution of hosts and the parasites' mobility patterns, calling for an explicit description of space. In this work, we develop a spatially explicit individual-based model to study disease transmission by waterborne parasites in sessile marine populations. We investigate the impact of spatial disease transmission through extensive numerical simulations and theoretical analysis. Specifically, the effects of parasite mobility into the epidemic threshold and the temporal progression of the epidemic are assessed. We show that larger values of pathogen mobility imply more severe epidemics, as the number of infections increases, and shorter timescales to extinction. An analytical expression for the basic reproduction number of the spatial model, R ~ 0 , is derived as a function of the non-spatial counterpart, R 0, which characterizes a transition between a disease-free and a propagation phase, in which the disease propagates over a large fraction of the system.

Optimal control for a SIR epidemic model with limited quarantine.

Social distance, quarantines and total lock-downs are non-pharmaceutical interventions that policymakers have used to mitigate the spread of the COVID-19 virus. However, these measures could be harmful to societies in terms of social and economic costs, and they can be maintained only for a short period of time. Here we investigate the optimal strategies that minimize the impact of an epidemic, by studying the conditions for an optimal control of a Susceptible-Infected-Recovered model with a limitation on the total duration of the quarantine. The control is done by means of the reproduction number [Formula: see text], i.e., the number of secondary infections produced by a primary infection, which can be arbitrarily varied in time over a quarantine period T to account for external interventions. We also assume that the most strict quarantine (lower bound of [Formula: see text]) cannot last for a period longer than a value [Formula: see text]. The aim is to minimize the cumulative number of ever-infected individuals (recovered) and the socioeconomic cost of interventions in the long term, by finding the optimal way to vary [Formula: see text]. We show that the optimal solution is a single bang-bang, i.e., the strict quarantine is turned on only once, and is turned off after the maximum allowed time [Formula: see text]. Besides, we calculate the optimal time to begin and end the strict quarantine, which depends on T, [Formula: see text] and the initial conditions. We provide rigorous proofs of these results and check that are in perfect agreement with numerical computations.