A model-based opinion dynamics approach to tackle vaccine hesitancy.

Uncovering the mechanisms underlying the diffusion of vaccine hesitancy is crucial in fighting epidemic spreading. Toward this ambitious goal, we treat vaccine hesitancy as an opinion, whose diffusion in a social group can be shaped over time by the influence of personal beliefs, social pressure, and other exogenous actions, such as pro-vaccine campaigns. We propose a simple mathematical model that, calibrated on survey data, can predict the modification of the pre-existing individual willingness to be vaccinated and estimate the fraction of a population that is expected to adhere to an immunization program. This work paves the way for enabling tools from network control towards the simulation of different intervention plans and the design of more effective targeted pro-vaccine campaigns. Compared to traditional mass media alternatives, these model-based campaigns can exploit the structural properties of social networks to provide a potentially pivotal advantage in epidemic mitigation.

Long-term clinical and serological follow-up of paediatric patients infected by SARS-CoV-2.

Studies concerning Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in paediatrics are limited to children mainly selected from hospitals, where patients with complications and co-morbidities are managed. We aimed to describe the course of the Coronavirus Disease 2019 (COVID-19) in a population of children enrolled by place of residence, from diagnosis to recovery, with a long-term clinical and serological follow-up. We identified patients aged <14 years old living in the Turin Health District 3 who had SARS-CoV-2 detected in at least one nasopharyngeal swab from 1st March to 1st June 2020. Epidemiological and clinical features of SARS-CoV-2 infection were collected by way of a telephone inquiry. Enrolled patients were tested for SARS-CoV-2 serology in order to provide evidence of seroconversion and persistence of specific antibodies some time after the infection. A total of 46 patients with SARS-CoV-2 infection/COVID-19 were identified. The main pattern of viral transmission was intra-family. Eleven children were totally asymptomatic. If symptoms appeared, the disease had a mild course. A single case of COVID-19-related respiratory insufficiency was registered. Among children who underwent serological evaluation, 84% had seroconversion. No significant differences in antibody development were found according to the age and the burden of the disease. Children tested farther from the primary infection had lower antibody index titre values than the others. In conclusion, COVID-19 has a good prognosis in paediatric age. Children are able to develop a valid immune response, although their index titres seem to decrease a long time after the disease.

Gastrointestinal involvement in paediatric COVID-19 - from pathogenesis to clinical management: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the first pandemic of the 21st century. As found in adults, signs and symptoms related to the disease mainly involve the respiratory tract in the paediatric population. However, a considerable number of children present with gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. The purpose of this review is an accurate description, from pathogenesis to clinical presentation, diagnosis and treatment, of COVID-19 effects on the gastrointestinal system at a paediatric age. SARS-CoV-2 can be identified in stool specimens of affected children by real-time polymerase chain reaction techniques. Positivity can last for several weeks after the end of the symptomatic phase. Gastrointestinal signs and symptoms are generally self-limited, can correlate with blood tests and imaging alterations, and may require supportive treatment such as hydration. However, they can precede severe disease manifestations such as the COVID-19-related multisystem inflammatory syndrome. Children belonging to risk categories such as those affected by celiac disease, inflammatory bowel disease, and hepatic disease seem to not have a more severe course than the others, even if they are undergoing immunosuppressant treatment. Medical follow-ups of patients with chronic diseases need to be revised during the pandemic period in order to postpone unnecessary tests, mainly endoscopic ones.

Pediatric admissions to emergency departments of North-Western Italy during COVID-19 pandemic: A retrospective observational study.

BACKGROUND: COVID-19 pandemic caused huge decrease of pediatric admissions to Emergency Department (ED), arising concerns about possible delays in diagnosis and treatment of severe disorders. METHODS: Impact of COVID-19 on Pediatric Emergency Room (ICOPER) was a retrospective multicentre observational study including 23 Italian EDs.All the children <18 years admitted, between March 9th and May 3rd 2020 stratified by age, priority code, cause of admission and outcome have been included and compared to those admitted in the same period of 2019.Our objectives were to assess the characteristics of pediatric admissions to EDs since COVID-19 outbreak until the end of lockdown, and to describe the features of critical children. FINDINGS: 16,426 children were admitted in 2020, compared to 55,643 in 2019 (-70·48%). Higher reduction was reported in hospitals without Pediatric Intensive Care Unit (PICU) (-73·38%) than in those with PICU (-64·08%) (P<0·0001). Admissions with low priority decreased more than critical ones (-82·77% vs. 44·17% respectively; P<0·0001). Reduction of discharged patients was observed both in hospitals with (-66·50%) and without PICU (-74·65%) (P<0·0001). No difference in the duration of symptoms before admission was reported between 2019 and 2020, with the majority of children accessing within 24 h (55·08% vs. 57·28% respectively; P = 0·2344). INTERPRETATION: Admissions with low priority decreased significantly more than those with high priority; we suppose that the fear of being infected in hospital maybe overcame the concerns of caregivers. Compared to 2019, no significant referral delay by caregivers was reported. Our data suggest the need of adaptation of EDs and primary care services to different needs of children during COVID-9 pandemic.

The inherent uncertainty of temporal networks is a true challenge for control.

Recently, it has been suggested that network temporality can be exploited to substantially reduce the energy required to control complex networks. This somewhat counterintuitive finding was explained through an evocative example of the advantage of temporal networks: when navigating a sailboat, we raise the sails when the wind helps us while lowering them when it works against us. Unfortunately, controlling complex networks inherits a further analogy with navigating a sailboat: having to face the inherent uncertainty of future winds. We rarely, if ever, have deterministic knowledge of the evolution of the network we want to control. Here, our challenge is to exploit the potential advantages of temporality when only a probabilistic description of the future is available. We prove that, in this more realistic setting, exploiting temporality is no more a panacea for network control, but rather an asset of a wider toolbox made available by the scientific community. One that can indeed turn out useful, provided that the temporality of the network structure matches the intrinsic time scales of the nodes we want to control.

Salivary glands involvement: a new indicator of juvenile idiopathic oligoarticular arthritis (preliminary results).

OBJECTIVE: Early diagnosis is critical to reduce long-term disability in patients with JIA by ensuring prompt treatment. The aim of this cross-sectional study was to evaluate the salivary gland function in JIA, addressing specifically oligoarticular (JIA1) and polyarticular (JIA2) subtypes, compared with healthy controls. This may contribute to the identification of salivary risk indicators of the disease that may help diagnosis at an early stage or even before the onset of other clinical evidence. METHODS: Twenty-eight patients with JIA1, 28 patients with JIA2, according to the ILAR criteria, and 28 healthy controls (C) were included in the study. Exclusion criteria were any concurrent medical condition. Data on medication, dietary and oral hygiene habits were collected using a questionnaire. All patients underwent oral examination and saliva measurement. RESULTS: While stimulated salivary flow rate (SFR) was significantly lower in JIA1 compared with JIA2 and C (P < 0.001), both salivary buffer capacity and pH were similar in the two JIA groups but statistically different from C (P = 0.002 and P = 0.010, respectively). Children with very low SFR (<3.5 ml) exhibited a 16-fold higher likelihood of being affected by JIA1 rather than JIA2 (P = 0.003), while no association was observed between low flow rate and JIA subtype (P = 0.744). CONCLUSION: These preliminary data suggest impairment of salivary gland function as a risk indicator for JIA1 with no association with dietary habits and drug intake.

Steering opinion dynamics via containment control.

In this paper, we model the problem of influencing the opinions of groups of individuals as a containment control problem, as in many practical scenarios, the control goal is not full consensus among all the individual opinions, but rather their containment in a certain range, determined by a set of leaders. As in classical bounded confidence models, we consider individuals affected by the confirmation bias, thus tending to influence and to be influenced only if their opinions are sufficiently close. However, here we assume that the confidence level, modeled as a proximity threshold, is not constant and uniform across the individuals, as it depends on their opinions. Specifically, in an extremist society, the most radical agents (i.e., those with the most extreme opinions) have a higher appeal and are capable of influencing nodes with very diverse opinions. The opposite happens in a moderate society, where the more connected (i.e., influential) nodes are those with an average opinion. In three artificial societies, characterized by different levels of extremism, we test through extensive simulations the effectiveness of three alternative containment strategies, where leaders have to select the set of followers they try to directly influence. We found that, when the network size is small, a stochastic time-varying pinning strategy that does not rely on information on the network topology proves to be more effective than static strategies where this information is leveraged, while the opposite happens for large networks where the relevance of the topological information is prevalent.

The evolving cobweb of relations among partially rational investors.

To overcome the limitations of neoclassical economics, researchers have leveraged tools of statistical physics to build novel theories. The idea was to elucidate the macroscopic features of financial markets from the interaction of its microscopic constituents, the investors. In this framework, the model of the financial agents has been kept separate from that of their interaction. Here, instead, we explore the possibility of letting the interaction topology emerge from the model of the agents' behavior. Then, we investigate how the emerging cobweb of relationship affects the overall market dynamics. To this aim, we leverage tools from complex systems analysis and nonlinear dynamics, and model the network of mutual influence as the output of a dynamical system describing the edge evolution. In this work, the driver of the link evolution is the relative reputation between possibly coupled agents. The reputation is built differently depending on the extent of rationality of the investors. The continuous edge activation or deactivation induces the emergence of leaders and of peculiar network structures, typical of real influence networks. The subsequent impact on the market dynamics is investigated through extensive numerical simulations in selected scenarios populated by partially rational investors.

Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial.

BACKGROUND: Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy. METHODS: We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m2; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70. FINDINGS: Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event. INTERPRETATION: Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis. FUNDING: Italian Agency of Drug Evaluation.

Structural permeability of complex networks to control signals.

Many biological, social and technological systems can be described as complex networks. The goal of affecting their behaviour has motivated recent work focusing on the relationship between the network structure and its propensity to be controlled. While this work has provided insight into several relevant problems, a comprehensive approach to address partial and complete controllability of networks is still lacking. Here, we bridge this gap by developing a framework to maximize the diffusion of the control signals through a network, while taking into account physical and economic constraints that inevitably arise in applications. This approach allows us to introduce the network permeability, a unified metric of the propensity of a network to be controllable. The analysis of the permeability of several synthetic and real networks enables us to extract some structural features that deepen our quantitative understanding of the ease with which specific controllability requirements can be met.

A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus.

OBJECTIVE: To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE). METHODS: Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied. RESULTS: There was a significant reduction in parent-adjusted height z score with time in females and males (p<0.0001), with a significant gender difference (p<0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p<0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age <12 years had a median parent-adjusted height z score of -0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than -0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose >426 mg/kg (OR: 3.6). CONCLUSIONS: The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with >400 mg/kg cumulative dose of corticosteroids.

Synchronization of complex networks through local adaptive coupling.

Two local adaptive strategies for the synchronization of complex networks are discussed in this paper. One, termed as vertex-based, uses local adaptive coupling gains at each node in the network. The other, named edge-based, associates to each edge in the network an adaptive coupling gain, determined solely on the basis of local information. The global asymptotic stability of the synchronous evolution is proven for both strategies using appropriate Lyapunov-based techniques. The effectiveness of the adaptive methodologies presented in the paper is shown via two representative examples: adaptive consensus and the adaptive synchronization of a network on N coupled Chua's circuits.

Controllability of complex networks via pinning.

We study the problem of controlling a general complex network toward an assigned synchronous evolution by means of a pinning control strategy. We define the pinning controllability of the network in terms of the spectral properties of an extended network topology. The roles of the control and coupling gains, as well as of the number of pinned nodes, are also discussed.

Bone mass and metabolism in thalassemic children and adolescents treated with different iron-chelating drugs.

We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients underwent treatment with desferrioxamine for the whole study period, while 12 patients stopped desferrioxamine and were then treated with deferiprone (L1). Lumbar and femoral BMD and bone metabolism markers were examined at baseline and after 1 and 3 years of follow up. All patients were prepubertal at baseline and they all became pubertal over the 3 years of follow up. At baseline, the mean lumbar Z score value was -2.048 SD +/- 0.75; the Z score was less than -2 SD in 13 children, within -1 and -2 SD in 6, and within 0 and -1 SD in only 3 subjects. A significant BMD increase (P < 0.0001) was observed at both the lumbar (+8.466%/year) and the femoral level (average of +3.46%/year at neck and +5.83%/year at the intertrochanteric region) after 3 years, without any significant difference being shown between patients treated with desferrioxamine and those treated with L1. The mean Z score SD values increased to -1.957 +/- 0.975 at 1 year (not significantly different from baseline) and to -1.864 +/- 1.221 at 3 year follow up (P < 0.05 vs baseline); an increase in bone turnover was also observed. These findings show that low BMD, a hallmark of beta-thalassemia, improves significantly when puberty begins; this increase involves different skeletal sites, regardless of pharmacological treatment with different iron-chelating drugs.