Rational Fair Consensus in the GOSSIP Model

The \emph{rational fair consensus problem} can be informally defined as follows. Consider a network of $n$ (selfish) \emph{rational agents}, each of them initially supporting a \emph{color} chosen from a finite set $\Sigma$. The goal is to design a protocol that leads the network to a stable monochromatic configuration (i.e. a consensus) such that the probability that the winning color is $c$ is equal to the fraction of the agents that initially support $c$, for any $c \in \Sigma$. Furthermore, this fairness property must be guaranteed (with high probability) even in presence of any fixed \emph{coalition} of rational agents that may deviate from the protocol in order to increase the winning probability of their supported colors. A protocol having this property, in presence of coalitions of size at most $t$, is said to be a \emph{whp\,-$t$-strong equilibrium}. We investigate, for the first time, the rational fair consensus problem in the GOSSIP communication model where, at every round, every agent can actively contact at most one neighbor via a \emph{push$/$pull} operation. We provide a randomized GOSSIP protocol that, starting from any initial color configuration of the complete graph, achieves rational fair consensus within $O(\log n)$ rounds using messages of $O(\log^2n)$ size, w.h.p. More in details, we prove that our protocol is a whp\,-$t$-strong equilibrium for any $t = o(n/\log n)$ and, moreover, it tolerates worst-case permanent faults provided that the number of non-faulty agents is $\Omega(n)$. As far as we know, our protocol is the first solution which avoids any all-to-all communication, thus resulting in $o(n^2)$ message complexity.Comment: Accepted at IPDPS'1

Possible future monoclonal antibody (mAb)-based therapy against arbovirus infections

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminary in vitro and in vivo models of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy

Overall Lack of Regulated Secretion in a PC12 Variant Cell Clone

Abstract A stable clone of PC12 neuroendocrine cells, named 27, known from previous studies to exhibit a defect of regulated secretion (lack of regulated secretory proteins, of synaptophysin, of dense granules and of catecholamine uptake and release; Clementi, E., Racchetti, G., Zacchetti, D., Panzeri, M. C., and Meldolesi, J. (1992) Eur. J. Neurosci. 4, 944-953) was characterized in detail to clarify the nature of its phenotype and the mechanisms of its establishment. The neuroendocrine nature of the PC12-27 phenotype was documented by specific markers: synapsins, neurofilament subunit H, neuronal kinesin, and α-latrotoxin receptor. Moreover, various intracellular membrane systems of PC12-27, including the endoplasmic reticulum and the Golgi complex, appeared similar to control PC12 in both morphology and marker expression. In contrast, all the investigated markers located either in dense granules (dopamine-β-hydroxylase), in synaptic-like microvesicles (the acetylcholine transporter) or in both these regulated secretory organelles (VAMP2/synaptobrevin-2, synaptotagmin) were missing in PC12-27 cells, and the same was true also for the cytosolic and plasmalemma proteins involved in regulated exocytosis (Rab3, SNAP25, syntaxin). Pulse labeling and in vitro translation experiments revealed the defect to consist in a protein synthesis blockade that mRNA studies (reverse transcription-polymerase chain reaction, Northern blotting, and actinomycin D experiments) revealed to take place primarily at the transcriptional level. The secretion defect of PC12-27 cells was modified neither by various types of long term stimulation nor by nerve growth factor treatment. Moreover, when one of the missing regulated secretory proteins, chromogranin B, was expressed by cDNA transfection, it was secreted, however via the constitutive pathway. Our results demonstrate that PC12-27 cells are fully incompetent for both branches of regulated secretion, those of dense granules and synaptic-like microvesicles, possibly because of the impairment of a general expression control system that appears to operate independently of neuroendocrine cell differentiation

Consensus vs Broadcast, with and without Noise

International audienceConsensus and Broadcast are two fundamental problems in distributed computing, whose solutions have several applications. Intuitively, Consensus should be no harder than Broadcast , and this can be rigorously established in several models. Can Consensus be easier than Broadcast? In models that allow noiseless communication, we prove a reduction of (a suitable variant of) Broadcast to binary Consensus, that preserves the communication model and all complexity parameters such as randomness, number of rounds, communication per round, etc., while there is a loss in the success probability of the protocol. Using this reduction, we get, among other applications, the first logarithmic lower bound on the number of rounds needed to achieve Consensus in the uniform GOSSIP model on the complete graph. The lower bound is tight and, in this model, Consensus and Broadcast are equivalent. We then turn to distributed models with noisy communication channels that have been studied in the context of some bio-inspired systems. In such models, only one noisy bit is exchanged when a communication channel is established between two nodes, and so one cannot easily simulate a noiseless protocol by using error-correcting codes. An Ω(ε −2 n) lower bound on the number of rounds needed for Broadcast is proved by Boczkowski et al. [PLOS Comp. Bio. 2018] in one such model (noisy uniform PULL, where ε is a parameter that measures the amount of noise). We prove an O(ε −2 log n) upper bound for binary Consensus in such model, thus establishing an exponential gap between the number of rounds necessary for Consensus versus Broadcast. We also prove a new O(ε −2 n log n) upper bound for Broadcast in this model

Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases

The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80-98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease

Higher resolution physical numerical model of the Mediterranean Sea in the Copernicus Marine Service

INGV is responsible for the operational production of the physical component of the Mediterranean Sea Monitoring and Forecasting Centre (Med-MFC) of the Copernicus Marine Service Monitoring System (CMEMS). The system was implemented in 2000 by the INGV National Group of Operational oceanography (GNOO) and has been developed in years thanks to a number of European projects. The Med-MFC is a coupled hydrodynamic-wave model with data assimilation component with a resolution of 1/16°. The model solutions are corrected by the variational assimilation (based on a 3DVAR scheme) of Temperature and Salinity vertical profiles (from ARGO, CTD, XBT and Gliders observations) and along track satellite Sea Level Anomaly (SLA) observations. In order to meet the requirements for Copernicus Marine Service Phase I the increase of the horizontal (to 1/24°) and vertical resolution of the hydrodynamic component of Med-MFC has been planned. The major improvements expected from this development are the following: 1) to better resolve the mesoscale processes in the Mediterranean region where the Rossby radius of deformation is about 12-15 km (1/24° is about 4-5 km); 2) to resolve the tidal forcing at Gibraltar, entering from the Atlantic into the Mediterranean, known to provide about 30% amplitude of the tidal signal in the Mediterranean; 3) to better resolve vertical mixing processes.UnpublishedIstituto Nazionale di Geofisica e Vulcanologia. Sede Centrale. Roma3SR. AMBIENTE - Servizi e ricerca per la Societ

ICG fluorescence imaging in colorectal surgery: a snapshot from the ICRAL study group

Background: Fluorescence-guided visualization is a recently proposed technology in colorectal surgery. Possible uses include evaluating perfusion, navigating lymph nodes and searching for hepatic metastases and peritoneal spread. Despite the absence of high-level evidence, this technique has gained considerable popularity among colorectal surgeons due to its significant reliability, safety, ease of use and relatively low cost. However, the actual use of this technique in daily clinical practice has not been reported to date. Methods: This survey was conducted on April 2020 among 44 centers dealing with colorectal diseases and participating in the Italian ColoRectal Anastomotic Leakage (iCral) study group. Surgeons were approximately equally divided based on geographical criteria from multiple Italian regions, with a large proportion based in public (89.1%) and nonacademic (75.7%) centers. They were invited to answer an online survey to snapshot their current behaviors regarding the use of fluorescence-guided visualization in colorectal surgery. Questions regarding technological availability, indications and techniques, personal approaches and feelings were collected in a 23-item questionnaire. Results: Questionnaire replies were received from 37 institutions and partially answered by 8, as this latter group of centers do not implement fluorescence technology (21.6%). Out of the remaining 29 centers (78,4%), fluorescence is utilized in all laparoscopic colorectal resections by 72.4% of surgeons and only for selected cases by the remaining 27.6%, while 62.1% of respondents do not use fluorescence in open surgery (unless the perfusion is macroscopically uncertain with the naked eye, in which case 41.4% of them do). The survey also suggests that there is no agreement on dilution, dosing and timing, as many different practices are adopted based on personal judgment. Only approximately half of the surgeons reported a reduced leak rate with fluorescence perfusion assessment, but 65.5% of them strongly believe that this technique will become a minimum requirement for colorectal surgery in the future. Conclusion: The survey confirms that fluorescence is becoming a widely used technique in colorectal surgery. However, both the indications and methods still vary considerably; furthermore, the surgeons' perceptions of the results are insufficient to consider this technology essential. This survey emphasizes the need for further research to reach recommendations based on solid scientific evidence. Keywords: Colon cancer; Fluorescence guided surgery; ICG; Laparoscopy; Rectal cancer

Colorectal surgery in Italy during the Covid19 outbreak: a survey from the iCral study group

Background The COVID19 pandemic had a deep impact on healthcare facilities in Italy, with profound reorganization of surgical activities. The Italian ColoRectal Anastomotic Leakage (iCral) study group collecting 43 Italian surgical centers experienced in colorectal surgery from multiple regions performed a quick survey to make a snapshot of the current situation. Methods A 25-items questionnaire was sent to the 43 principal investigators of the iCral study group, with questions regard- ing qualitative and quantitative aspects of the surgical activity before and after the COVID19 outbreak. Results Two-thirds of the centers were involved in the treatment of COVID19 cases. Intensive care units (ICU) beds were partially or totally reallocated for the treatment of COVID19 cases in 72% of the hospitals. Elective colorectal surgery for malignancy was stopped or delayed in nearly 30% of the centers, with less than 20% of them still scheduling elective colo- rectal resections for frail and comorbid patients needing postoperative ICU care. A significant reduction of the number of colorectal resections during the time span from January to March 2020 was recorded, with significant delay in treatment in more than 50% of the centers. Discussion Our survey confirms that COVID19 outbreak is severely affecting the activity of colorectal surgery centers partici- pating to iCral study group. This could impact the activity of surgical centers for many months after the end of the emergency

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections