Precessing jet nozzle connecting to a spinning black hole in M87.

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

P-IOTA: A Cloud-Based Geographically Distributed Threat Alert System That Leverages P4 and IOTA.

The recent widespread novel network technologies for programming data planes are remarkably enhancing the customization of data packet processing. In this direction, the Programming Protocol-independent Packet Processors (P4) is envisioned as a disruptive technology, capable of configuring network devices in a highly customizable way. P4 enables network devices to adapt their behaviors to mitigate malicious attacks (e.g., denial of service). Distributed ledger technologies (DLTs), such as blockchain, allow secure reporting alerts on malicious actions detected across different areas. However, the blockchain suffers from major scalability concerns due to the consensus protocols needed to agree on a global state of the network. To overcome these limitations, new solutions have recently emerged. IOTA is a next-generation distributed ledger engineered to tackle the scalability limits while still providing the same security capabilities such as immutability, traceability, and transparency. This article proposes an architecture that integrates a P4-based data plane software-defined network (SDN) and an IOTA layer employed to notify about networking attacks. Specifically, we propose a fast, secure, and energy-efficient DLT-enabled architecture that combines the IOTA data structure, named Tangle, with the SDN layer to detect and notify about network threats.

Design, Implementation, and Characterization of a Signal Acquisition Chain for SADino: The Precursor of the Italian Low-Frequency Telescope Named the Sardinia Aperture Array Demonstrator (SAAD).

Low-frequency aperture arrays represent sensitive instruments to detect signals from radio astronomic sources situated in the universe. In Italy, the Sardinia Aperture Array Demonstrator (SAAD) consists of an ongoing project of the Italian National Institute for Astrophysics (INAF) aimed to install an aperture array constituted of 128 dual-polarized Vivaldi antennas at the Sardinia Radio Telescope (SRT) site. The originally envisaged 128 elements of SAAD were re-scoped to the 16 elements of its precursor named SADino, with the aim to quickly test the system with a digital beam-former based on the Italian Tile Processing Module (iTPM) digital back-end. A preliminary measurements campaign of radio frequency interference (RFI) was performed to survey the less contaminated spectral region. The results of these measurements permitted the establishment of the technical requirements for receiving a chain for the SADino telescope. In this paper, the design, implementation, and characterization of this signal acquisition chain are proposed. The operative frequency window of SAAD and its precursor, SADino, sweeps from 260 MHz to 420 MHz, which appears very attractive for radio astronomy applications and radar observation in space and surveillance awareness (SSA) activities.

The Impact of COVID-19 on Universal Newborn Hearing Screening.

OBJECTIVES: To report the direct and indirect impact of coronavirus disease 2019 pandemic on the Universal Newborn Hearing Screening program of our institution (Azienda Ospedaliero Universitaria di Sassari). DESIGN: Monocentric retrospective study whose target population included all the newborns born in or referred to our hospital in 2019 and 2020. RESULTS: There is no statistically significant difference in time to retest or loss to follow-up rate between the 2 years considered (2019 to 2020). Referral rate is not higher for newborns born to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction positive mothers. CONCLUSIONS: In relation to the analyzed variables, coronavirus disease 2019 seems to have a limited impact on our screening program. Severe acute respiratory syndrome coronavirus 2 did not behave as an audiological risk factor in our series.

P4DM: Measure the Link Delay with P4.

Network management strategies depend on a timely and accurate knowledge of the network performance measures. Among these, one of the most relevant is the delay of the links, which unfortunately is not easy to measure with accuracy, especially when considering multi-hop paths. This is a classical networking problem, for which several solutions have been proposed. Nonetheless, we argue in this manuscript that there is still some room for improving accuracy and effectiveness in the measurement. This paper proposes a new solution based on the exploitation of the P4 data plane programming language. The basic idea is to handle lightweight probe packets that are forged ad-hoc at the edge of a link and processed at the other edge. Hosts generate the probe packets that are then exploited by the P4 programs in the switches to implement the measure. This approach provides an accurate and reliable measure of the link transit time, also effective in multi-hop links. In this latter case, we show that the measurement is not influenced much by the packet loss when the network is overloaded, thus providing more reliable results with respect to more conventional tools such as the classical ping utility. The manuscript explains the proposed P4 solution; then, it provides a comparison with several other approaches found in the literature, showing that outperform most of them, and finally show the behavior of the proposed methodology when facing a multi hop network path on a congested network to prove its robustness.

Microwave Spectroscopy Investigation of Carasau Bread Doughs: Effects of Composition up to 8.5 GHz.

Carasau bread is a flat bread, typical of Sardinia (Italy). The market of this food product has a large growth potential, and its industry is experiencing a revolution, characterized by digitalization and automation. To monitor the quality of this food product at different manufacturing stages, microwave sensors and devices could be a cost-effective solution. In this framework, knowledge of the microwave response of Carasau dough is required. Thus far, the analysis of the microwave response of Carasau doughs through dielectric spectroscopy has been limited to the dynamics of fermentation. In this work, we aim to perform complex dielectric permittivity measurements up to 8.5 GHz, investigating and modeling the role of water amount, salt and yeast concentrations on the spectra of this food product. A third-order Cole-Cole model was used to interpret the microwave response of the different samples, resulting in a maximum error of 1.58% and 1.60% for the real and imaginary parts of permittivity, respectively. Thermogravimetric analysis was also performed to support the microwave spectroscopy investigation. We found that dielectric properties of Carasau bread doughs strongly depend on the water content. The analysis highlighted that an increase in water quantity tends to increase the bounded water fraction at the expense of the free water fraction. In particular, the free water amount in the dough is not related to the broadening parameter γ2 of the second pole, whereas the bound water weight fraction is more evident in the γ2 and σdc parameters. An increase in electrical conductivity was observed for increasing water content. The microwave spectrum of the real part of the complex permittivity is slightly affected by composition, while large variation in the imaginary part of the complex dielectric permittivity can be identified, especially for frequencies below 4 GHz. The methodology and data proposed and reported in this work can be used to design a microwave sensor for retrieving the composition of Carasau bread doughs through their dielectric signature.

Microservice security: a systematic literature review.

Microservices is an emerging paradigm for developing distributed systems. With their widespread adoption, more and more work investigated the relation between microservices and security. Alas, the literature on this subject does not form a well-defined corpus: it is spread over many venues and composed of contributions mainly addressing specific scenarios or needs. In this work, we conduct a systematic review of the field, gathering 290 relevant publications-at the time of writing, the largest curated dataset on the topic. We analyse our dataset along two lines: (a) quantitatively, through publication metadata, which allows us to chart publication outlets, communities, approaches, and tackled issues; (b) qualitatively, through 20 research questions used to provide an aggregated overview of the literature and to spot gaps left open. We summarise our analyses in the conclusion in the form of a call for action to address the main open challenges.

Audiological Risk Factors, Referral Rates and Dropouts: 9 Years of Universal Newborn Hearing Screening in North Sardinia.

Background: Objectives of the present work were to analyze the prevalence of hearing loss in our population of screened newborns during the first 9 years of the universal newborn hearing screening (UNHS) program at University Hospital Sassari (Italy) (AOU Sassari), to analyze the risk factors involved, and to analyze our effectiveness in terms of referral rates and dropout rates. Methods: Monocentric retrospective study whose target population included all the newborns born or referred to our hospital between 2011 and 2019. Results: From 2011 to 2019, a total of 11,688 babies were enrolled in our screening program. In total, 3.9‱ of wellborn babies and 3.58% of neonatal intensive care unit (NICU) babies had some degree of hearing loss. The most frequently observed risk factors among non-NICU babies were family history of hearing loss (3.34%) and craniofacial anomalies (0.16%), among NICU babies were low birth weight (54.91%) and prematurity (24.33%). In the multivariate analysis, family history of hearing loss (p < 0.001), NICU (p < 0.001), craniofacial anomalies (p < 0.001), low birth weight (<1500 g) (p = 0.04) and HIV (p = 0.03) were confirmed as risk factors. Conclusions: Our data are largely consistent with the literature and most results were expected, one relevant exception being the possible role of NICU as a confounding factor and the limited number of risk factors confirmed in the multivariate analysis.

CD4 T cell-intrinsic STING signaling controls the differentiation and effector functions of TH1 and TH9 cells.

BACKGROUND: While stimulator of interferon genes (STING) activation in innate immune cells of the tumor microenvironment can result in CD8 T cell-dependent antitumor immunity, whether STING signaling affects CD4 T-cell responses remains elusive. METHODS: Here, we tested whether STING activation modulated the effector functions of CD4 T cells in vivo by analyzing tumor-infiltrating CD4 T cells and evaluating the contribution of the CD4 T cell-derived cytokines in the antitumor activity of the STING ligand 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) in two mouse tumor models. We performed ex vivo experiments to assess the impact of STING activation on CD4 T-cell differentiation and investigate the underlying molecular mechanisms. Finally, we tested whether STING activation enhances TH9 cell antitumor activity against mouse melanoma upon adoptive transfer. RESULTS: We found that activation of STING signaling cell-intrinsically enhances the differentiation and antitumor functions of TH1 and TH9 cells by increasing their respective production of interferon gamma (IFN-γ) and interleukin-9. IRF3 and type I interferon receptors (IFNARs) are required for the STING-driven enhancement of TH1 cell differentiation. However, STING activation favors TH9 cell differentiation independently of the IFNARs/IRF3 pathway but through mammalian target of rapamycin (mTOR) signaling, underscoring that STING activation differentially affects the fate of distinct CD4 T-cell subsets. The therapeutic effect of STING activation relies on TH1 and TH9-derived cytokines, and STING activation enhances the antitumor activity of TH9 cells upon adoptive transfer. CONCLUSION: Our results reveal the STING signaling pathway as a therapeutic target to boost CD4 T-cell effector functions and antitumor immunity.

A prospective pilot study on the effects of endoscopic sinus surgery on upper and lower airway performance.

OBJECTIVE: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease. METHODS: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated. RESULTS: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1st second (FEV1) significantly improved after surgery from 3.23 to 3.45 L/s. CONCLUSIONS: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.

Audiovestibular symptoms and sequelae in COVID-19 patients.

BACKGROUND: since the beginning of COVID-19 outbreak a growing number of symptoms and deficits associated with the new pathology have emerged, among them cochlear damage in otherwise asymptomatic COVID-19 patients has been described. OBJECTIVE: to investigate general and audiovestibular symptoms and sequelae in healed patients, and to seek for any sign of residual or permanent hearing or vestibular loss. METHODS: we reviewed the data coming from 48 Covid-19 patients whose nasopharyngeal swabs have turned negative, all employed at our facility, that opted in for a free screening of audiovestibular symptoms offered by our hospital after the aforementioned report was published. The screening included a tonal pure tone audiometry, a vHIT and SHIMP test, as well as a survey including known symptoms and audiovestibular symptoms. RESULTS: general symptoms as reported by our patients largely reflect what reported by others in the literature. 4 (8.3%) patients reported hearing loss, 2 (4.2%) tinnitus, 4 dizziness (8.3%), 1 spinning vertigo (2%), 1 dynamic imbalance (2%), 3 static imbalance (6.3%). Most audiovestibular symptoms have regressed. Thresholds at pure tone audiometry and vHIT gain were within normality range in all post-Covid-19 patients. CONCLUSIONS: even if some patients suffer from audiovestibular symptoms, these are mostly transitory and there is no clear evidence of clinically relevant persistent cochlear or vestibular damage after recovery.

Relationship between calcium metabolism and benign paroxysmal positional vertigo in north Sardinia population.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) has a reported recurrence ranging from 26.8 to 50%. Osteoporosis and Vitamin D deficiency seems to have an impact on recurrence of BPPV. OBJECTIVE: to evaluate the impact of osteoporosis and Vitamin D deficiency on recurrence of BPPV. METHODS: 73 consecutive patients were divided in two groups according to the presence (group 1) or absence (group 0) of a recurrent episode. BMD, femoral and lumbar T-scores and Vitamin D levels were recorded. Statistical analysis was performed to investigate correlations. RESULTS: patients in group 1 had statistically significant lower values of both femoral (-1,62±1,06 vs. -0,53±1,51; p = 0,001), lumbar T-score (-2,10±1,19 vs -0, 53±1.51, p = 0.001) and Vitamin D (19.53±15.33). The values of femoral T-score and Vitamin D could be combined in a model able to properly classify 65.8% of the cases (p = 0.002) as isolated or recurrent BPPV, with high accuracy (AUC 0.710 [0.590 -0.830]). CONCLUSION: present data show a probable correlation between osteoporosis and Vitamin D with recurrent BPPV.

Medical-surgical management and clinical outcome in cervical abscesses.

INTRODUCTION: This study aims at defining through a retrospective evaluation, the clinical parameters affecting the clinical course and consequently the management of patients presenting with cervicofacial abscesses. METHODOLOGY: A total of 394 patients diagnosed with abscess at the University of Sassari Otorhinolaryngology Division between 2009 and 2017 were included; among these, eleven patients were diagnosed with necrotizing fasciitis. Personal and clinical parameters including the LRINEC score and the medical and/or surgical treatment used were analyzed for each patient. The most frequently affected site was the peritonsillar space (76.9%), followed by the parapharyngeal space. RESULTS: Mean age was 41(±17) years, the male population was slightly overrepresented (68%). An average of 6 (±7) days of hospitalization duration was recorded. The mortality rate was confirmed to be relatively low (1/349 patients) and was reported only in one patient diagnosed with necrotizing fasciitis (1/11). CONCLUSION: Diagnosis, correct clinical definition and early medical-surgical treatment of neck abscesses were crucial to reduce complications; LRNEC score, C-reactive protein, glycemia and creatininemia proved to be reliable prognostic indicators of difficult patient management and risk of complications.

Does the involvement of first-year residents have a negative impact on the performance of a newborn hearing screening program?

OBJECTIVES: We aimed to evaluate the efficiency of our hearing screening program, prior to hospital discharge, together with the consistency of our teamwork including first year residents by assessing a learning curve for the operators involved. METHODS: We evaluated all the data collected during the first stage of the screening program of all non-NICU neonates from March 2009 to July 2013, analyzing by means of a linear regression model, the monthly referral rate for the whole period of activity of each group of residents. RESULTS: performances of each group of screeners were statistically different (chi square test p < 0.005). The nptrend test showed that group 2 (p = 0.01) and group 4 (p = 0.01) reached a statistical significance in higher and lower referral rates respectively. No statistical differences were found in other groups (Group 1 p = 0.161; Group 3 p = 0.853). CONCLUSION: Despite a statistically significant difference in the performances between the groups of residents, the referral rates for each group (range 6.18%-9.29%) and the overall referral rate for the whole period (7.84%) agree with the values commonly reported for TEOAEs in the literature. It means that our screening program is reasonably effective despite a yearly turnover of operators.

Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study.

BACKGROUND: Objective data on chemosensitive disorders during COVID-19 are lacking in the Literature. METHODS: Multicenter cohort study that involved four Italian hospitals. Three hundred and forty-five COVID-19 patients underwent objective chemosensitive evaluation. RESULTS: Chemosensitive disorders self-reported by 256 patients (74.2%) but the 30.1% of the 89 patients who did not report dysfunctions proved objectively hyposmic. Twenty-five percentage of patients were seen serious long-lasting complaints. All asymptomatic patients had a slight lowering of the olfactory threshold. No significant correlations were found between the presence and severity of chemosensitive disorders and the severity of the clinical course. On the contrary, there is a significant correlation between the duration of the olfactory and gustatory symptoms and the development of severe COVID-19. CONCLUSIONS: Patients under-report the frequency of chemosensitive disorders. Contrary to recent reports, such objective testing refutes the proposal that the presence of olfactory and gustatory dysfunction may predict a milder course, but instead suggests that those with more severe disease neglect such symptoms in the setting of severe respiratory disease.

Author Correction: Crizotinib-induced immunogenic cell death in non-small cell lung cancer.

The original version of this Article contained an error in the spelling of the author Lin Xia, which was incorrectly given as Xia Lin. This has now been corrected in both the PDF and HTML versions of the Article.

Crizotinib-induced immunogenic cell death in non-small cell lung cancer.

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.

Immunotherapeutic properties of chemotherapy.

Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations. In this review, we will summarize which immunological processes are involved in the anticancer action of some cytotoxic agents and discuss the recently unraveled contribution of the gut microbiota into the immunogenicity of anticancer drugs. We will eventually introduce the scientific rationale for therapeutic strategies combining chemotherapeutic drugs and immune checkpoint blockers.

Influence of metals on rhinosinusal polyposis in Sardinian population (Italy).

Metals have strong toxic effects in humans and can act as immunoregulatory factors. The purpose of our study was to determine whether the concentrations of metals are associated with the clinical course of nasal polyposis (NP). We measured the concentrations of 10 metals and non-metal (Zn, Mn, Se, Fe, Cr, Ni, Pb, Al, Cd, and Cu) in 58 patients with NP, and 29 controls with a healthy nasal mucosa. We used electron microscopy to compare the ultrastructural features of the nasal mucosa between NP patients and healthy controls. Concentrations of metals in nasal polyps and healthy mucosa were determined by mass spectrometry. Transmission electron microscopic (TEM) and scanning electron microscopic (SEM) images of the nasal mucosa were obtained. The mean tissue concentrations of all 10 metals and non-metal were significantly lower in NP patients than in healthy controls (P < 0.05).TEM and SEM revealed changes in the mucosal ultrastructure in NP with progressive fibrosis, devascularisation, and inflammation. Tissue concentrations of metals were lower in NP patients than in healthy controls, and this was particularly evident in massive polyposis.

Comparison of three different polyvinyl alcohol packs following functional endoscopic Nasal surgery.

OBJECTIVES/HYPOTHESIS: To compare the extent of bleeding and patient discomfort during packing removal of three different polyvinyl alcohol (PVA) packs: 1) a standard PVA sponge (s-PVA) (Mondocel Standard 10 cm; Mondomed NV, Hamont-Achel, Belgium); 2) a PVA sponge with oxidized cellulose (oc-PVA) (Merocel Hemox 10 cm; Medtronic Xomed Surgical Products, Jacksonville, FL); and 3) a PVA sponge with polyethylene film (pf-PVA) (Merocel 2000 8 cm; Medtronic Xomed Surgical Products, Jacksonville, FL), after functional endoscopic sinus surgery and inferior turbinoplasty. STUDY DESIGN: A prospective, randomized, blinded, controlled trial. METHODS: Ninety consecutive patients were enrolled and randomized to receive in each side one pack in the middle meatus and another pack of the same material in the nasal fossa. The patients were equally divided in three groups of 30 patients each. Group A received the pf-PVA; group B received oc-PVA; and group C received s-PVA. Postoperatively, bleeding after removal of the entire nasal packing was evaluated by an observer, whereas the severity of pain was rated by patients with visual analog scales. RESULTS: Our study evaluated three nasal packing materials, demonstrating that the pf-PVA is less painful than the others but with intermediate bleeding ratio. However, the oc-PVA has an intermediate pain score but minimum bleeding. The s-PVA showed the worst pain and bleeding results. CONCLUSIONS: Considering that removal of the second pack (middle meatus) is more painful than the first (nasal fossa), our results suggest that a pf-PVA can be placed in the middle meatus and a oc-PVA in the nasal fossa in order to reduce patient's discomfort in terms of pain and bleeding. LEVEL OF EVIDENCE: 1b.