Toward Autonomous Guidance and Control: A Robust AI-Based Solution for Low-Thrust Orbit Transfers

The focus of our initial application scenario centers around a low-thrust orbit transfer in Low-Earth Orbit (LEO). This specific use-case has been chosen due to its inherent challenges, including the requirements for robustness and real-time computation. We propose an AI-based solution capable of autonomous and robust on-board G&C. The core of our approach leverages a Deep Neural Network (DNN) trained through Reinforcement Learning (RL) techniques. Our method aims at enhancing a traditional guidance approach by managing environmental perturbations, it processes the on-board navigation coordinates and provides the thrust to be imposed by the propulsion subsystem. Our approach demonstrates effectiveness in performing maneuvers changing semi-major axis (SMA), eccentricity (ECC), and inclination (INC), operating continuously with a control horizon of several days. Robustness is tested by using physical model uncertainties, introducing disturbances in the mission coordinates, and injecting perturbations in subsystems

Multi-year prevalence and macrolide resistance of Mycoplasma genitalium in clinical samples from a southern Italian hospital

The use of azithromycin for the treatment of Mycoplasma genitalium infections has led to resistance to macrolides. From July 2014 to July 2020, 7150 samples were analysed for the detection of sexually transmitted infections at the Policlinico of Bari. A total of 67/7150 samples (0.93%) were positive for MG DNA and 47 samples were analysed for the evaluation of six azithromycin resistance-associated mutations. In 5/47 samples, the A2058G mutation was detected (10.63%). Although the cases of positive MG samples and mutations are low in our reality, diagnostic tests to detect azithromycin resistant-associated genes may provide a convenient way to monitor resistance rate

In vitro activity of ceftazidime/avibactam alone and in combination with fosfomycin and carbapenems against KPC-producing Klebsiella pneumoniae

KPC-producing Klebsiella pneumonia (KPC-Kp) represents a major therapeutic challenge in critically ill patients. Ceftazidime-avibactam (CAZ-AVI) is a new effective drug against KPC-Kp but, due to emerging resistant strains during monotherapy, the association with a second antibiotic has been advocated. Therefore, intravenous fosfomycin may be a possible choice for combination therapy. The aim of this study was to evaluate the in vitro susceptibility of CAZ-AVI alone and in combination with fosfomycin and carbapenems against KPC-Kp clinical isolates by E-test method. The combination of CAZ-AVI with carbapenems showed synergistic activity, whereas with fosfomycin showed addictive activity, suggesting that fosfomycin may be a carbapenem-sparing strategy in antimicrobial stewardship programs

MEAD: A Multi-Armed Approach for Evaluation of Adversarial Examples Detectors

This paper has been accepted to appear in the Proceedings of the 2022 European Conference on Machine Learning and Data Mining (ECML-PKDD), 19th to the 23rd of September, Grenoble, FranceInternational audienceDetection of adversarial examples has been a hot topic in the last years due to its importance for safely deploying machine learning algorithms in critical applications. However, the detection methods are generally validated by assuming a single implicitly known attack strategy, which does not necessarily account for real-life threats. Indeed, this can lead to an overoptimistic assessment of the detectors' performance and may induce some bias in the comparison between competing detection schemes. We propose a novel multi-armed framework, called MEAD, for evaluating detectors based on several attack strategies to overcome this limitation. Among them, we make use of three new objectives to generate attacks. The proposed performance metric is based on the worst-case scenario: detection is successful if and only if all different attacks are correctly recognized. Empirically, we show the effectiveness of our approach. Moreover, the poor performance obtained for state-of-the-art detectors opens a new exciting line of research

Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nano-particles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lac-tic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Inter-nalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanofor-mulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here

Salvage stereotactic body radiotherapy for isolated lymph node recurrent prostate cancer : single institution series of 94 consecutive patients and 124 lymph nodes

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Annali storici di Principato Citra, A. 9, n. 1.1 (2011)

A.9, n.1.1(2011): G. Guardia, Editoriale, P. 3 ; A. Botti, D.L. Thurmond, F. La Greca, Un palmento ben conservato a Novi Velia ed altri palmenti nel territorio del Cilento. Osservazioni ed ipotesi, P. 5 ; G. Aromando, Una dipendenza cavense: Sant'Arsenio e la badia della SS. Trinità di Cava, P. 53 ; C. Schiavo, Avventure etimologiche in forma di prosa nelle terre del Cilento, P. 81 ; A. Capano, Caselle in Pittari: note storiche e il catasto murattiano del 1815, P. 104 ; A. Di Gennaro, Il porto romano di San Marco di Castellabate, P. 134 ; F. De Nigris, I comunisti in parrocchia: il Sessantotto cattolico in Italia, P. 147 ; S. De Divitiis, Il '68 dei cattolici: l'Azione cattolica a Salerno, P. 165 ; C. Schiavo, Santa Maria di Vito a Fogna, P. 176 ; P. Romanelli, La cappella dei SS. Pietro e Paolo nel palazzo vescovile di Novi Velia, P. 182 ; A. Tesauro, Vietri. Dalla guerra alla vigilia della Costituzione, P. 188

Drug Survival of Interleukin (IL)‑17 and IL‑23 Inhibitors for the Treatment of Psoriasis: A Retrospective Multi‑country, Multicentric Cohort Study

Background: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. Objective: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. Methods: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. Results: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. Conclusion: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription