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This work describes and compares two phaselocked- loop (PLL) algorithms aimed at tracking a biased sinusoidal signal with unknown frequency, amplitude and phase, with inherent robustness to dc-offset. The proposed methods endow Quadrature PLLs, renowned for their excellent tracking performance, with frequency-adaptation capability, while providing robust global stability certificates. The large-gain global stability, proven by Lyapunov-like arguments borrowed from adaptive control theory, represents a major benefit compared to conventional PLLs, whose convergence instead can be proven only locally by small-signal analysis or small-gain assumptions. In this connection, the proposed algorithms represent the first frequency-adaptive and DC-bias rejecting PLL-type architectures with Lyapunov-certified global stability. When used for signal tracking, the proposed methods are shown to outperform the adaptive observer, especially in noisy conditions. Moreover, they provide more accurate frequency estimates than existent frequency-adaptive PLLs, showing enhanced robustness in facing both phase-noise and measurement perturbations.

To evaluate the decline of antibodies induced by SARS-CoV-2 infection, the individuals resident in 5 municipalities of the Autonomous Province of Trento, Northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) in May 2020, were tested four months later.Anti-SARS-CoV-2 NC antibodies were detected using the Abbott SARS-CoV-2 IgG assay. Samples that gave a negative result were re-tested using the Liaison SARS-CoV-2 IgG assay to assess anti-spike (S) S1/S2 antibodies. The fifty-percent tissue culture infective dose (TCID50) neutralizing assay was performed on a subgroup of formerly positive sera. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA).Overall, 480 out of 1159 participants became seronegative for anti-NC IgG antibodies. Age above 70 years and cough were associated with persistent anti-NC IgG levels. Most anti-NC IgG negative sera were positive for anti-S IgG (77.9%). The neutralization assay showed high concordance with anti-S antibodies positivity.In conclusion, a decline of anti-NC IgG values was recorded four months after the first evaluation. A high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.

ObjectiveTo determine whether systematic screening for adverse effects of antiepileptic drugs (AEDs) reduces toxicity burden and improves health-related quality of life in patients with epilepsy.MethodsConsecutive patients with uncontrolled seizures aged ≥16 years and a high Adverse Event Profile (AEP) score were randomized to 2 groups and followed up for 18 months at 11 referral centers. AEP scores were made available to treating physicians at all visits in the intervention group, but not in the control group. Co–primary endpoints were changes in AEP scores and Quality of Life Inventory for Epilepsy-31 (QOLIE–31) scores.ResultsOf 809 enrolled patients able to complete the AEP questionnaire, 222 had AEP scores ≥45 and were randomized to the intervention (n = 111) or control group (n = 111). A total of 206 patients completed the 18-month follow-up. Compared with baseline, AEP scores decreased on average by 7.2% at 6 months, 12.1% at 12 months, and 13.8% at 18 months in the intervention group (p < 0.0001), and by 7.7% at 6 months, 9.2% at 12 months, and 12.0% at 18 months in controls (p < 0.0001). QOLIE-31 scores also improved from baseline to final visit, with a mean 20.7% increase in the intervention group and a mean 24.9% increase in the control group (p < 0.0001). However, there were no statistically significant differences in outcomes between groups for the 2 co–primary variables.ConclusionsContrary to findings from a previous study, systematic screening for adverse effects of AEDs using AEP scores did not lead to a reduced burden of toxicity over usual physician treatment.Italian Medicines Agency (AIFA) identifierFARM52K2WM_003.Clinicaltrials.gov identifierNCT03939507 (registered retrospectively in 2019; the study was conducted during the 2006–2009 period and registration of clinical trials was not a widely established practice when this study was initiated).Classification of evidenceThis study provides Class II evidence that the additional collection of formal questionnaires regarding adverse effects of AEDs does not reduce toxicity burden over usual physician treatment.

Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedule was associated with a marked reduction in pertussis cases in the vaccinated cohort. However, due to the frequency of local and systemic adverse events after immunization with wPV, work on a less reactive vaccine was undertaken based on isolated B. pertussis components that induced protective immune responses with fewer local and systemic reactions. These component vaccines were termed acellular vaccines and contained one or more pertussis antigens, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), and fimbrial proteins 2 (FIM2) and 3 (FIM3). Preparations containing up to five components were developed, and several efficacy trials clearly demonstrated that the aPVs were able to confer comparable short-term protection than the most effective wPVs with fewer local and systemic reactions. There has been a resurgence of pertussis observed in recent years. This paper reports the results of a Consensus Conference organized by the World Association for Infectious Disease and Immunological Disorders (WAidid) on June 22, 2018, in Perugia, Italy, with the goal of evaluating the most important reasons for the pertussis resurgence and the role of different aPVs in this resurgence.

This study was planned to collect evidences of familial pertussis transmission to infants younger than 6 months of age. Understanding the dynamics of transmission of pertussis in families is essential to plan effective prevention strategies that could be integrated in pertussis control.The seroprevalence of IgG antibodies to pertussis toxin (PT-IgG) and prolonged cough symptoms were evaluated in parents of 55 infants aged6 months hospitalized for confirmed pertussis. Parents of 33 infants with lower respiratory tract infection (LRTI) and parents of 57 healthy infants admitted as outpatients for hip ultrasound examination (HE) were enrolled as controls.Parents of pertussis cases had PT-IgG levels significantly higher as compared to LRTI and HE parents. More than 40 % were compatible as transmitters of pertussis to their babies, since they had a level of PT-IgG ≥ 100 IU/ml, which is considered diagnostic for a recent pertussis episode. Based on serology, the percentage of pertussis cases that had at least one parent as source of infection was 49.1 %. When cough symptoms were taken into account, the percentage of parents putative transmitters of the infection to their infants increased to 56.4 %.Parents are scarcely aware of the household transmission of pertussis to their newborns. Our study highlights the need to advise parents about the likelihood of transmission to the newborn and to be particularly aware of coughing symptoms in the household. Since infection can be asymptomatic, a serological survey of family members should also be considered.

BACKGROUND Pertussis infection can be severe in unvaccinated infants. A case-control study was conducted to investigate the potential role of breastfeeding in protecting young, unvaccinated infants from pertussis. METHODS Hospitalized infants