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Betelgeuse, the nearest red supergiant, dimmed to an unprecedented level in early 2020. The star emerged from this “Great Dimming” episode with its typical, roughly 400 days pulsation cycle halved, and a new dominant period of around 200 days. The dimming event has been attributed to a surface mass ejection, in which rising material drove shocks through the stellar atmosphere and expelled some material, partially obscuring the star as it formed molecules and dust. In this paper, we use hydrodynamic simulations to reveal the connections between Betelgeuse's vigorously convective envelope, the surface mass ejection, and the pulsation mode switching that ensued. An anomalously hot convective plume, generated rarely but naturally in the star's turbulent envelope, can rise and break free from the surface, powering an upwelling that becomes the surface mass ejection. The rising plume also breaks the phase coherence of the star's pulsation, causing the surface to keep expanding even as the deeper layers contract. This drives a switch from the 400 days fundamental mode of pulsation, in which the whole star expands and contracts synchronously, to the 200 days first overtone, where a radial node separates the interior and exterior of the envelope moving in opposite phase. We predict that the star's convective motions will damp the overtone oscillation and Betelgeuse will return to its previous, 400 days fundamental-mode pulsation in the next 5–10 yr. With its resolved surface and unprecedentedly detailed characterization, Betelgeuse opens a window to episodic surface mass ejection in the late-stage evolution of massive stars.

The engulfment of substellar bodies (SBs), such as brown dwarfs and planets, by giant stars is a possible explanation for rapidly rotating giants, lithium-rich giants, and the presence of SBs in close orbits around subdwarfs and white dwarfs. We perform three-dimensional hydrodynamical simulations of the flow in the vicinity of an engulfed SB. We model the SB as a rigid body with a reflective surface because it cannot accrete. This reflective boundary changes the flow morphology to resemble that of engulfed compact objects with outflows. We measure the drag coefficients for the ram-pressure and gravitational drag forces acting on the SB, and use them to integrate its trajectory inside the star. We find that engulfment can increase the luminosity of a 1 M _⊙ star by up to a few orders of magnitude. The time for the star to return to its original luminosity is up to a few thousand years when the star has evolved to ≈10 R _⊙ and up to a few decades at the tip of the red giant branch (RGB). No SBs can eject the envelope of a 1 M _⊙ star before it evolves to ≈10 R _⊙ if the orbit of the SB is the only energy source contributing to the ejection. In contrast, SBs as small as ≈10 M _Jup can eject the envelope at the tip of the RGB. The numerical framework we introduce here can be used to study planetary engulfment in a simplified setting that captures the physics of the flow at the scale of the SB.

Stellar-mass black holes can become embedded within the disks of active galactic nuclei (AGNs). Afterwards, their interactions are mediated by their gaseous surroundings. Here, we study the evolution of stellar-mass binary black holes (BBHs) embedded within AGN disks using three-dimensional hydrodynamic simulations and analytic methods, focusing on environments where the AGN disk scale height H is ≳ the BBH sphere of influence. We model the local surroundings of the embedded BBHs using a wind tunnel formalism and characterize different accretion regimes based on the local properties of the disk. We develop prescriptions for accretion and drag for embedded BBHs. Using these prescriptions with AGN disk models that can represent the Toomre-unstable outer regions of AGN disks, we study the long-term evolution of BBHs as they migrate through the disk. We find that BBHs typically merge within ≲1–30 Myr, increasing their mass significantly in the process, allowing BBHs to enter (or cross) the pair-instability supernova mass gap. The BBH accretion rate often exceeds the Eddington limit, sometimes by several orders of magnitude. Many embedded BBHs will merge before migrating significantly in the disk. We also discuss possible electromagnetic signatures during and following the inspiral, finding that it is generally unlikely for the bolometric luminosity of the BBH to exceed the AGN luminosity.

Background. Pompe disease is a rare, severe, autosomal recessive genetic disorder caused by GAA gene mutations, which cause α-1,4-glucosidase enzyme deficiency. There are two forms of Pompe disease based on the age of onset, the infantile and the adult form (LOPD). Cardiac involvement, previously recognized only in infantile cases, is now also reported in adults. Cardiomyopathy remains an exceptional finding while heart rhythm disorders appear to be more frequent. Methods. We retrospectively evaluated cardiac involvement in 12 patients with late-onset Pompe disease (LOPD) followed for an overall period of 143 years (mean 12.7 ± 7.7) using ECG, Holter ECG, and echocardiography. Results. The mean age of patients (M8:F4) at the first visit was 40.7 ± 16.1 (range 14–63) and 53.7 ± 16.9 (range 21–76) at last visit. Conduction delay was present in three patients; one patient developed ascending aorta ectasia but had a history of hypertension, and one patient showed right heart enlargement on echocardiography, probably due to pulmonary hypertension. No patient died during the FU, nor developed cardiomyopathy. Ectopic supraventricular beats and repeated episodes of ablation-resistant atrial fibrillation were observed in only one patient (8.3%) who required PMK implantation. Conclusions. Benefitting from the long follow-up, this study allows us to state that primary myocardial involvement is rare in patients with LOPD, while rhythm disorders are more frequent and require monitoring to avoid the risk of possible life-threatening complications.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Benign Prostatic Hyperplasia (BPH) is the most frequent cause of Lower Urinary Tract Symptoms (LUTSs) in elderly populations. Minimally invasive treatments of BPH are safe and effective and are gaining popularity among both professionals and patients. Prostate Artery Embolization (PAE) has proven to be effective in Trans-Urethral Resection of the Prostate (TURP) in terms of prostate volume reduction and LUTS relief. PAE entails the selective catheterization of the prostatic artery and later embolization of distal vessels with beads of various calibers. Universal consensus regarding the ideal particle size is yet to be defined. We retrospectively evaluated 24 consecutive patients (median age: 75 years; range: 59–86 years) treated with PAE at our institution from October 2015 to November 2022. Particles of different sizes were employed; 12 patients were treated with 40–120 µm particles, 5 with 100 µm, 5 with 100–300 µm and 2 with 250 µm. Technical success, defined as selective prostate artery catheterization and controlled release of embolizing beads, was achieved in all patients. Removal vs. retention of the urinary catheter at the first post-procedural urological visit was the main clinical objective. No major peri-procedural complications were recorded, with 56% of patients successfully removing the urinary catheter.

This work presents the design and implementation of an operational infrastructure for the monitoring of atmospheric parameters at sea through GNSS meteorology sensors installed on liners operating in the north-west Mediterranean Sea. A measurement system, capable of operationally and continuously providing the values of surface parameters, is implemented together with software procedures based on a float-PPP approach for estimating zenith path delay (ZPD) values. The values continuously registered over a three year period (2020–2022) from this infrastructure are compared with the data from a numerical meteorological reanalysis model (MERRA-2). The results clearly prove the ability of the system to estimate the ZPD from ship-based GNSS-meteo equipment, with the accuracy evaluated in terms of correlation and root mean square error reaching values between 0.94 and 0.65 and between 18.4 and 42.9 mm, these extreme values being from the best and worst performing installations, respectively. This offers a new perspective on the operational exploitation of GNSS signals over sea areas in climate and operational meteorological applications.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antiradical capacity (AC), anthocyanins and non-anthocyanin PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits received the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to incorporate components like PCs and dietary fiber into traditional consumers’ diets.

In this work we describe the implementation of a processing chain for a fully automatic modeling of the seismic source parameters and its slip distribution through the inversion of the InSAR displacements generated from the EPOSAR service. This processing chain consists of a suite of procedures and algorithms handling a sequence of steps: selection of the highest quality InSAR datasets, definition of the area of interest, image sampling, non-linear and linear inversions to get, respectively, the source geometry and its slip distribution. A set of side procedures and interfaces also allows an interactive refinement and the publication of results, consisting of scientific data and graphical outputs. The whole procedure has been developed, tested and validated by considering 100 events with magnitudes between 5.5 and 8.2, worldwide distributed and covering an exhaustive range of mechanisms and tectonic contexts.Main aim of this work is describing the implementation of the automatic modeling procedures, used to produce solutions in real time, already during the emergency phase. These sources, validated by experts before their publication, can be a reference for operational purposes and initial scientific analyses. The creation of this repository sets also the framework to store, out of the emergency time, more sophisticated solutions, manually revised and/or with peer-review quality.

BackgroundThere are little data on remote monitoring (RM) of implantable loop recorders (ILRs) in patients with unexplained syncope and whether it confers enhanced diagnostic power.ObjectiveTo evaluate the effect of RM in ILR recipients for unexplained syncope for early detection of clinically relevant arrhythmias by comparison with a historical cohort with no RM.MethodsSyncRM is a propensity score (PS)-matched study prospectively including 133 consecutive patients with unexplained syncope and ILR followed up by RM (RM-ON group). A historical cohort of 108 consecutive ILR patients with biannual in-hospital follow-up visits was used as control group (RM-OFF group). The primary endpoint was the time to the clinician's evaluation of clinically relevant arrhythmias (types 1, 2, and 4 of the ISSUE classification).ResultsThe primary endpoint of arrhythmia evaluation was reached in 38 patients (28.6%) of the RM-ON group after a median time of 46 days (interquartile range, 13–106) and in 22 patients (20.4%) of the RM-OFF group after 92 days (25–368). The PS-matched adjusted ratio of rates of arrhythmia evaluation was 2.53 (95% confidence interval, 1.32–4.86) in the RM-ON vs. RM-OFF group (p = 0.005).ConclusionIn our PS-matched comparison with a historical cohort, RM of ILR patients with unexplained syncope was associated with a 2.5-fold higher chance of evaluations of clinically relevant arrhythmias as compared with biannual in-office follow-up visits.

This review is a brief overview of the current status and the potential role of robotics in interventional radiology. Literature published in the last decades, with an emphasis on the last 5 years, was reviewed and the technical developments in robotics and navigational systems using CT-, MR- and US-image guidance were analyzed. Potential benefits and disadvantages of their current and future use were evaluated. The role of fusion imaging modalities and artificial intelligence was analyzed in both percutaneous and endovascular procedures. A few hundred articles describing results of single or several systems were included in our analysis.

Understanding and monitoring the ecological quality of coastal waters is crucial for preserving marine ecosystems. Eutrophication is one of the major problems affecting the ecological state of coastal marine waters. For this reason, the control of the trophic conditions of aquatic ecosystems is needed for the evaluation of their ecological quality. This study leverages space-based Sentinel-3 Ocean and Land Color Instrument imagery (OLCI) to assess the ecological quality of Mediterranean coastal waters using the Trophic Index (TRIX) key indicator. In particular, we explore the feasibility of coupling remote sensing and machine learning techniques to estimate the TRIX levels in the Ligurian, Tyrrhenian, and Ionian coastal regions of Italy. Our research reveals distinct geographical patterns in TRIX values across the study area, with some regions exhibiting eutrophic conditions near estuaries and others showing oligotrophic characteristics. We employ the Random Forest Regression algorithm, optimizing calibration parameters to predict TRIX levels. Feature importance analysis highlights the significance of latitude, longitude, and specific spectral bands in TRIX prediction. A final statistical assessment validates our model’s performance, demonstrating a moderate level of error (MAE of 0.51) and explanatory power (R2 of 0.37). These results highlight the potential of Sentinel-3 OLCI imagery in assessing ecological quality, contributing to our understanding of coastal water ecology. They also underscore the importance of merging remote sensing and machine learning in environmental monitoring and management. Future research should refine methodologies and expand datasets to enhance TRIX monitoring capabilities from space.

Breast cancer (BC) is the most frequently diagnosed malignancy among women. In the past two decades, new technologies and BC screening have led to the diagnosis of smaller and earlier-stage BC (ESBC). Therefore, percutaneous minimally invasive techniques (PMIT) were adopted to treat patients unfit for surgery, women who refuse it, or elderly patients with comorbidities that could make surgery a difficult and life-threatening treatment. The target of PMIT is small-size ESBC with the scope of obtaining similar efficacy as surgery. Minimally invasive treatments are convenient alternatives with promising effectiveness, lower morbidity, less cost, less scarring and pain, and more satisfying cosmetic results. Ablative techniques used in BC are cryoablation, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound (US), and laser ablation. The aim of our study is to discuss the current status of percutaneous management of BC, evaluate the clinical outcomes of PMIT in BC, and analyze future perspectives regarding ablation therapy in BC.

The increasing frequency and severity of forest fires necessitate early detection and rapid response to mitigate their impact. This project aims to design a cyber-physical system for early detection and rapid response to forest fires using advanced technologies. The system incorporates Internet of Things sensors and autonomous unmanned aerial and ground vehicles controlled by the robot operating system. An IoT-based wildfire detection node continuously monitors environmental conditions, enabling early fire detection. Upon fire detection, a UAV autonomously surveys the area to precisely locate the fire and can deploy an extinguishing payload or provide data for decision-making. The UAV communicates the fire’s precise location to a collaborative UGV, which autonomously reaches the designated area to support ground-based firefighters. The CPS includes a ground control station with web-based dashboards for real-time monitoring of system parameters and telemetry data from UAVs and UGVs. The article demonstrates the real-time fire detection capabilities of the proposed system using simulated forest fire scenarios. The objective is to provide a practical approach using open-source technologies for early detection and extinguishing of forest fires, with potential applications in various industries, surveillance, and precision agriculture.

The importance of lead analysis in environmental matrices becomes increasingly relevant due to the anthropogenic spread of toxic species in nature. Alongside the existing analytical methods to detect lead in a liquid environment, we propose a new dry approach for lead detection and measurement based on its capture from a liquid solution by a solid sponge and subsequent quantification based on X-ray analyses. The detection method exploits the relationship between the electronic density of the solid sponge, which depends on the captured lead, and the critical angle for total reflection of the X-rays. For this purpose, gig-lox TiO2 layers, grown by modified sputtering physical deposition, were implemented for their branched multi-porosity spongy structure that is ideal for capturing lead atoms or other metallic ionic species in a liquid environment. The gig-lox TiO2 layers grown on glass substrates were soaked into aqueous solutions containing different concentrations of Pb, dried after soaking, and finally probed through X-ray reflectivity analyses. It has been found that lead atoms are chemisorbed onto the many available surfaces within the gig-lox TiO2 sponge by establishing stable oxygen bonding. The infiltration of lead into the structure causes an increase in the overall electronic density of the layer and, thus, an increment of its critical angle. Based on the established linear relationship between the amount of lead adsorbed and the augmented critical angle, a standardized quantitative procedure to detect Pb is proposed. The method can be, in principle, applied to other capturing spongy oxides and toxic species.

Abstract Three-dimensional models are considered a powerful tool for improving the concordance between in vitro and in vivo phenotypes. However, the duration of spheroid culture may influence the degree of correlation between these counterparts. When using immortalised cell lines as model systems, the assumption for consistency and reproducibility is often made without adequate characterization or validation. It is therefore essential to define the biology of each spheroid model by investigating proteomic dynamics, which may be altered relative to culture duration. As an example, we assessed the influence of culture duration on the relative proteome abundance of HepG2 cells cultured as spheroids, which are routinely used to model aspects of the liver. Quantitative proteomic profiling of whole cell lysates labelled with tandem-mass tags was conducted using liquid chromatography-tandem mass spectrometry (LC–MS/MS). In excess of 4800 proteins were confidently identified, which were shared across three consecutive time points over 28 days. The HepG2 spheroid proteome was divergent from the monolayer proteome after 14 days in culture and continued to change over the successive culture time points. Proteins representing the recognised core hepatic proteome, cell junction, extracellular matrix, and cell adhesion proteins were found to be continually modulated.

BackgroundFor head and neck reconstructive procedures, free flap survival depends on microsurgical and anatomical choices besides multimodal clinical management. The aim of the present study is to identify relevant variables for flap survival in our initial consecutive series.MethodsA single-center, novel reconstructive team consecutive surgical series was revised. The outcome was analyzed in terms of flap survival observing variables considered more relevant: flap type, recipient artery, vein(s), and graft interposition were discussed for facial thirds to be reconstructed. Statistical analysis was performed with Chi-square, Mann–Whitney, and Odds ratio.ResultsA total of 118 free flaps were performed in 115 microsurgical procedures (93.9% for malignancies) on 109 patients, with a flap survival rate of 91.5%. For reconstruction of the middle and lower third of the face, the facial artery was privileged, because it was already transected during lymph node dissection in order to save the superior thyroid artery for further microsurgical needs. Flap failure was 50% venous. Double vein anastomosis was not related to flap survival. Deep venous drainage (as the internal jugular vein system) required fewer revisions. Half of the re-explorations saved the flap. Grafts were a risk for flap survival. Bony flaps were more critical.ConclusionAt comparable reconstructive quality, flap choice should avoid a vascular graft. The facial artery is a preferable recipient vessel, since it saves other arteries both in the case of an arterial revision and in the case of recurrence, for further free flap reconstruction. For venous anastomosis, a deep venous recipient is safer, since it offers the possibility to choose the level of anastomosis optimizing the vascular pedicle geometry. A close postsurgical flap monitoring is advisable up to 7 days postoperatively to allow for timely flap salvage.

IntroductionIn the context of randomized clinical trials, subcutaneous implantable cardiac defibrillators (S-ICDs) are non-inferior to transvenous ICDs (T-ICDs) concerning device-related complications or inappropriate shocks in patients with an indication for defibrillator therapy and not in need of pacing. We aimed at describing the clinical features of patients who underwent S-ICD implantation in our clinical practice, as well as the ICD-related complications and the inappropriate therapies among S-ICD vs. T-ICD recipients during a long-term follow-up.Materials and MethodsAll patients undergoing ICD, both S-ICD and TV-ICD, at Monaldi Hospital from January 1, 2015 to January 1, 2019 and followed up at our institution were included in the present analysis. The clinical variables associated with S-ICD implantation were evaluated by logistic regression analyses. We collected the ICD inappropriate therapies, ICD-related complications (including both pulse generator and lead-related complications), ICD-related infections, appropriate ICD therapies, and overall mortality. Kaplan-Meier (KM) analyses were performed to assess the risk of clinical outcome events between the two subgroups. A time-dependent Cox regression analysis was performed to adjust the results.ResultsTotal 607 consecutive patients (mean age 53.8 ± 16.8, male 77.8%) with both TV-ICD (n: 290, 47.8%) and S-ICD (n: 317, 52.2%), implanted and followed at our center for a mean follow-up of 1614 ± 1018 days, were included in the study. At multivariate logistic regression analysis, an independent association between S-ICD implantation and ionic channel disease [OR: 6.01 (2.26–15.87); p < 0.0001] and ischemic cardiomyopathy [OR: 0.20 (0.12–0.35); p < 0.0001] was shown. The KM analysis did not show a significantly different risk of the inappropriate ICD therapies (log rank p = 0.64) between the two subgroups; conversely, a significant increase in the risk of ICD-related complications (log rank p = 0.02) and infections (log rank p = 0.02) in TV-ICD group was shown. The adjusted risk for ICD-related infections [OR: 0.07 (0.009–0.55), p = 0.01] and complications [0.31 (0.12–0.81), p = 0.01] was significantly lower among patients with S-ICD.ConclusionsThe choice to implant S-ICD was mainly driven by younger age and the presence of ionic channel disease; conversely ischemic cardiomyopathy reduces the probability to use this technology. No significant differences in inappropriate ICD therapies were shown among S-ICD vs. TV-ICD group; moreover, S-ICD is characterized by a lower rate of infectious and non-infectious complications leading to surgical revision or extraction.

The goal of this work was to investigate the morphological and chemical–physical changes induced by adding ZnO nanoparticles to bio-based polymeric materials based on polylactic acid (PLA) and polyamide 11 (PA11). Precisely, the photo- and water-degradation phenomena of nanocomposite materials were monitored. For this purpose, the formulation and characterization of novel bio-nanocomposite blends based on PLA and PA11 at a ratio of 70/30 wt.% filled with zinc oxide (ZnO) nanostructures at different percentages were performed. The effect of ZnO nanoparticles (≤2 wt.%) within the blends was thoroughly explored by employing thermogravimetry (TGA), size exclusion chromatography (SEC), matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) and scanning and transmission electron microscopy (SEM and TEM). Adding up to 1% wt. of ZnO resulted in a higher thermal stability of the PA11/PLA blends, with a decrement lower than 8% in terms of molar masses (MMs) values being obtained during blend processing at 200 °C. ZnO promoted trans-ester-amide reactions between the two polymers, leading to the formation of PLA/PA11 copolymers. These species could work as compatibilisers at the polymer interface, improving thermal and mechanical properties. However, the addition of higher quantities of ZnO affected such properties, influencing the photo-oxidative behaviour and thus thwarting the material’s application for packaging use. The PLA and blend formulations were subjected to natural aging in seawater for two weeks under natural light exposure. The 0.5% wt. ZnO sample induced polymer degradation with a decrease of 34% in the MMs compared to the neat samples.

A novel measurement concept specifically tuned to monitoring tropospheric water vapour’s vertical distribution has been demonstrated on a theoretical basis and is currently under development for space deployment. The NDSA (Normalised Differential Spectral Attenuation) technique derives the integrated water vapour (IWV) along the radio link between a transmitter and a receiver carried by two LEO satellites, using the linear correlation between the IWV and a parameter called spectral sensitivity. This is the normalised incremental ratio of the spectral attenuation at two frequencies in the Ku and K bands, with the slope of the water vapour absorption line at 22.235 GHz. Vertical profiles of WV can be retrieved by inverting a set of IWV measurements acquired in limb geometry at different tangent altitudes. This paper provides a comprehensive insight into the NDSA approach for sounding lower tropospheric WV, from the theoretical investigations in previous ESA studies, to the first experimental developments and testing, and to the latest advancements achieved with the SATCROSS project of the Italian Space Agency. The focus is on the new results from SATCROSS activities; primarily, on the upgrading of the instrument prototype, with improved performance in terms of its power stability and the time resolution of the measurements. Special emphasis is also placed on discussing tomographic inversion methods capable of retrieving tropospheric WV content from IWV measurements, i.e., the least squares and the external reconstruction approaches, showing results with different spatial features when applied to a given atmospheric scenario. The ultimate goal of deploying the NDSA measurement technique from space is thoroughly examined and conclusions are drawn after presenting the results of an Observing System Simulation Experiment conducted to assess the impact of NDSA data assimilation on environmental model simulations.

It is well known that skin wound healing could be severely impaired in space. In particular, the skin is the tissue at risk of injury, especially during human-crewed space missions. Here, we propose a hybrid system based on the biocompatible poly 2-hydroxyethyl methacrylate (pHEMA) to actively support a nanocontainer filled with the drug. Specifically, during the cryo-polymerization of HEMA, halloysite nanotubes (HNTs) embedded with thymol (Thy) were added as a component. Thy is a natural pharmaceutical ingredient used to confer wound healing properties to the material, whereas HNTs were used to entrap the Thy into the lumen to ensure a sustained release of the drug. The as-obtained material was characterized by chemical–physical methods, and tests were performed to assess its ability for a prolonged drug release. The results showed that the adopted synthetic procedure allows the formation of a super absorbent system with good swelling ability that can contain up to 5.5 mg of Thy in about 90 mg of dried sponge. Releasing tests demonstrated the excellent material’s ability to perform a slow controlled delivery of 62% of charged Thy within a week. As humans venture deeper into space, with more extended missions, limited medical capabilities, and a higher risk of skin wounds, the proposed device would be a versatile miniaturized device for skin repair in space.

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased thromboembolic risk. The impact of the female sex as an independent risk factor for thromboembolic events in AF is still debated. Background and Objectives: The aim of this review is to evaluate the gender-related differences in cardioembolic risk and response to anticoagulants among AF patients. Materials and Methods: The PubMed database is used to review the reports about gender differences and thromboembolic risk in atrial fibrillation. Results: Non-vitamin K oral anticoagulants (NOACs) represent the gold standard for thromboembolic risk prevention in patients with non-valvular atrial fibrillation (NVAF). Despite a similar rate of stroke and systemic embolism (SE) among men and women in NOACs or vitamin K antagonists (VKAs) treatment, the use of NOACs in AF women is associated with a lower risk of intracranial bleeding, major bleeding, and all-cause mortality than in men. Conclusions: The female sex can be defined as a stroke risk modifier rather than a stroke risk factor since it mainly increases the thromboembolic risk in the presence of other risk factors. Further studies about the efficacy and safety profile of NOACs according to sex are needed to support clinicians in performing the most appropriate and tailored anticoagulant therapy, either in male or female AF patients.

Introduction:Little is known about the clinical performance of single-chamber leadless pacemaker (LLPM) in patients without atrial fibrillation (AF) as pacing indication. The aim of this study was to describe the clinical characteristics of patients who underwent single chamber LLPM implantation at three tertiary referral centers and to compare the safety and effectiveness of the single-chamber LLPM among patients with or without AF.Materials and Methods:All the consecutive patients who underwent LLPM implantation at three referral centers were analyzed. The indications to LLPM in a real-world setting were described. The study population was divided into two groups according to AF as pacing indication. We assessed the procedure-related complications; moreover, we compared syncope, cardiac hospitalization, pacemaker syndrome, and all-cause death recurrence during the follow-up between patients with and without AF as pacing indication.Results:A total of 140 consecutive patients (mean age, 76.7 ± 11.24 years, men 64.3%) were included in the study. The indication to implantation of LLPM was permanent AF with slow ventricular response (n: 67; 47.8%), sinus node dysfunction (n: 25; 17.8%), third atrioventricular block (AVB) (n: 20; 14.2%), second-degree AVB (n: 18; 12.8%), and first degree AVB (n: 10; 7.1%). A total of 7 patients (5%) experienced perioperative complications with no differences between the AF vs. non-AF groups. During a mean follow-up of 606.5 ± 265.9 days, 10 patients (7.7%) died and 7 patients (5.4%) were reported for cardiac hospitalization; 5 patients (3.8%) experienced syncope; no patients showed pacemaker syndrome. No significant differences in the clinical events between the groups were shown. The Kaplan–Meier analysis for the combined endpoints did not show significant differences between the AF and non-AF groups [hazard ratio (HR): 0.94, 95% CI: 0.41–2.16; p = 0.88].Conclusion:Our real-world data suggest that LLPM may be considered a safe and reasonable treatment in patients without AF in need of pacing. Further studies are needed to confirm these preliminary results.

Objectives: The prognostic significance of adenosine-mediated pulmonary vein (PV) dormant conduction is unclear. We prospectively followed patients with adenosine-mediated PV reconduction with a subsequent repeated ablation until there was no reconduction inducible with patients without reconduction after PV isolation. Method and Results. Consecutive patients (n=179) with paroxysmal atrial fibrillation (AF) without prior catheter ablation (CA) were enlisted in the study. We used a point-by-point CA and general anesthesia in all patients. Twenty minutes after PV isolation we administered adenosine in a dose sufficient to produce an atrioventricular block. If a dormant conduction was present (n=54) we performed additional ablation until there was no adenosine mediated reconduction inducible. During 36 months of follow-up, all patients were examined for eight 7-day ECG recordings. There was no difference in arrhythmia recurrence rate between patients with and without dormant conduction (29.6 vs. 24.8% at 12 months, P=0.500; 31.5 vs. 30.4% at 36 months, P=1.000), for any echocardiographic parameter or any parameter of the ablation procedure. Conclusion: The patients with dormant conduction after adenosine during catheter ablation of paroxysmal atrial fibrillation with complete elimination of the dormant conduction by additional extensive ablation have the same outcome in the long term as patients without a dormant conduction.

Aridity and drought, which are determined by climatic and temporary water scarcity, respectively, are important limiting factors for plant gross primary production. These phenomena are commonly assessed and/or monitored by means of weather indices, most of which are based on observations of precipitation and potential evapotranspiration. The estimation of such indices over large areas can be carried out using multiple datasets, i.e., those derived from weather stations, satellite images, and ground radars. The possibility of using interpolated or remotely sensed datasets in place of ground measurements was currently investigated for Tuscany, a region in Central Italy, showing complex and heterogeneous environmental features. The former weather datasets were first evaluated versus corresponding ground measurements. Next, the basic weather variables were combined and cumulated over 30–60 days to yield synthetic indicators of water deficit, which were assessed in the same way. Finally, these indicators were evaluated to predict the soil water conditions of a meadow and an olive grove during the 2021 summer period. The results obtained indicate that the use of the multi-source weather datasets induces only a minor deterioration of the water stress indicators and is therefore efficient to monitor the water status of different ecosystems with high spatial (200 m) and temporal (daily) details.

In situ measurements of precipitation are typically obtained by tipping bucket or weighing rain gauges or by disdrometers using different measurement principles. One of the most critical aspects of their operational use is the calibration, which requires the characterization of instrument responses both in laboratory and in real conditions. Another important issue with in situ measurements is the coverage. Dense networks are desirable, but the installation and maintenance costs can be unaffordable with most of the commercial conventional devices. This work presents the development of a prototype of an impact rain gauge based on a very low-cost piezoelectric sensor. The sensor was developed by assembling off-the-shelf and reused components following an easy prototyping approach; the calibration of the relationship between the different properties of the voltage signal, as sampled by the rain drop impact, and rainfall intensity was established using machine-learning methods. The comparison with 1-minute rainfall obtained by a co-located commercial disdrometer highlights the fairly good performance of the low-cost sensor in monitoring and characterizing rainfall events.

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin (≤500 µm) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV (eFOV) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV-microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV-microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV-microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.

The capacity for social media to influence the utilization of re-purposed medicines to manage COVID-19, despite limited availability of safety and efficacy data, is a cause for concern within health care systems. This study sought to ascertain links between social media reports and utilization for three re-purposed medicines: hydroxychloroquine (HCQ), ivermectin and colchicine. A combined retrospective analysis of social media posts for these three re-purposed medicines was undertaken, along with utilization and clinical trials data, in South Africa, between January 2020 and June 2021. In total, 77,257 posts were collected across key social media platforms, of which 6884 were relevant. Ivermectin had the highest number of posts (55%) followed by HCQ (44%). The spike in ivermectin use was closely correlated to social media posts. Similarly, regarding chloroquine (as HCQ is not available in South Africa), social media interest was enhanced by local politicians. Sentiment analysis revealed that posts regarding the effectiveness of these repurposed medicines were positive. This was different for colchicine, which contributed only a small number of mentions (1%). Of concern is that the majority of reporters in social media (85%) were unidentifiable. This study provides evidence of social media as a driver of re-purposed medicines. Healthcare professionals have a key role in providing evidence-based advice especially with unidentifiable posts.

Progressive cardiac conduction disease (PCCD) is a relatively common condition in young and elderly populations, related to rare mutations in several genes, including SCN5A, SCN1B, LMNA and GJA5, TRPM4. Familial cases have also been reported. We describe a family with a large number of individuals necessitating pacemaker implantation, likely due to varying degrees of PCCD. The proband is a 47-year-old-patient, whose younger brother died at 25 years of unexplained sudden cardiac death. Three paternal uncles needed a pacemaker (PM) implantation between 40 and 65 years for unspecified causes. At the age of 42, he was implanted with a PM for two episodes of syncope and the presence of complete atrioventricular block (AVB). NGS analysis revealed the missense variation c. 2351G>A, p.Gly844Asp in the exon 17 of the TRPM4 gene. This gene encodes the TRPM4 channel, a calcium-activated nonselective cation channel of the transient receptor potential melastatin (TRPM) ion channel family. Variations in TRPM4 have been shown to cause an increase in cell surface current density, which results in a gain of gene function. Our report broadens and supports the causative role of TRPM4 gene mutations in PCCD. Genetic screening and identification of the causal mutation are critical for risk stratification and family counselling.

La gestión de la información para representar distancias y altimetrías encontradas en los mapas de ruta permite visibilizar datos por medio de tablas, gráficas, fotografías, perfiles e imágenes. A partir de lo anterior surge el siguiente interrogante: ¿Es clara la información de distancias y altimetría en los mapas de ruta para un grupo de usuarios de varios niveles? Para dar respuesta en este artículo se propone un ejercicio investigativo de tipo mixto, en el que se utilizó material cartográfico en formato análogo de cuadros de distancias y perfiles de altimetría de los mapas de ruta Bogotá-Medellín y una encuesta semiestructurada. El objetivo de la investigación fue analizar la lectura en los mapas de ruta de la vía Bogotá-Medellín de 1997, 2006 y 2010 realizada por un grupo de usuarios e indagar la claridad, dificultad y formas de lectura de los cuadros de distancias y perfiles de altimetría.

Learning styles attempt to describe individual differences among students by identifying students’ preferences in how they learn, and adapting their learning to accommodate that style. Since their inception, learning styles have gained mass popularity among teachers, researchers, and the public. Numerous assessments and self-help books are available to discover one’s individual learning style. Learning styles, however, have been heavily criticized by researchers who contend that learning styles lack evidence supporting their effectiveness and possess unreliable diagnostic tools. I posit that the case against learning styles is not limited to those two claims; in addition, that learning styles outcomes can be associated with confounding factors, and that learning styles may lead to ineffective teaching practices that negatively affect students and teachers. Through evidence-based practices, we can move forward from learning styles and create learning environments that have a greater probability of positive effects.

During the night between 9 and 10 September 2017, multiple flash floods associated with a heavy-precipitation event affected the town of Livorno, located in Tuscany, Italy. Accumulated precipitation exceeding 200 mm in two hours was recorded. This rainfall intensity is associated with a return period of higher than 200 years. As a consequence, all the largest streams of the Livorno municipality flooded several areas of the town. We used the limited-area weather research and forecasting (WRF) model, in a convection-permitting setup, to reconstruct the extreme event leading to the flash floods. We evaluated possible forecasting improvements emerging from the assimilation of local ground stations and X- and S-band radar data into the WRF, using the configuration operational at the meteorological center of Tuscany region (LaMMA) at the time of the event. Simulations were verified against weather station observations, through an innovative method aimed at disentangling the positioning and intensity errors of precipitation forecasts. A more accurate description of the low-level flows and a better assessment of the atmospheric water vapor field showed how the assimilation of radar data can improve quantitative precipitation forecasts.

The high relevance of satellites for collecting information regarding precipitation at global scale implies the need of a continuous validation of satellite products to ensure good data quality over time and to provide feedback for updating and improving retrieval algorithms. However, validating satellite products using measurements collected by sensors at ground is still a challenging task. To date, the Dual-frequency Precipitation Radar (DPR) aboard the Core Satellite of the Global Precipitation Measurement (GPM) mission is the only active sensor able to provide, at global scale, vertical profiles of rainfall rate, radar reflectivity, and Drop Size Distribution (DSD) parameters from space. In this study, we compare near surface GPM retrievals with long time series of measurements collected by seven laser disdrometers in Italy since the launch of the GPM mission. The comparison shows limited differences in the performances of the different GPM algorithms, be they dual- or single-frequency, although in most cases, the dual-frequency algorithms present the better performances. Furthermore, the agreement between satellite and ground-based estimates depends on the considered precipitation variable. The agreement is very promising for rain rate, reflectivity factor, and the mass-weighted mean diameter (Dm), while the satellite retrievals need to be improved for the normalized gamma DSD intercept parameter (Nw).

The active collision of the Apulian continental lithosphere with the Eurasian plate characterizes the tectonics of the Epirus region in northwestern Greece, invoking crustal shortening. Epirus has not experienced any strong earthquakes during the instrumental era and thus there is no detailed knowledge of the way the active deformation is being expressed. In March 2020, a moderate size (Mw 5.8) earthquake sequence occurred close to the Kanallaki village in Epirus. The mainshock and major aftershock focal mechanisms are compatible with reverse faulting, on NNW-ESE trending nodal planes. We measure the coseismic surface deformation using radar interferometry and investigate the possible fault geometries based on seismic waveforms and InSAR data. Slip distribution models provide good fits to both nodal planes and cannot resolve the fault plane ambiguity. The results indicate two slip episodes for a 337° N plane dipping 37° to the east and a single slip patch for a 137° N plane dipping 43° to 55° to the west. Even though the area of the sequence is very close to the triple junction of western Greece, the Kanallaki 2020 activity itself seems to be distinct from it, in terms of the acting stresses.

Thermal degradation processes of poly(ether sulfone) random copolymers having different molar amount of diphenolic acid (DPA) units were studied by direct-pyrolysis/mass spectrometry, stepwise pyrolysis-gas chromatography/mass spectrometry and thermogravimetric techniques. Results highlighted that thermal degradation processes occur in the temperature range from 370 to 650 °C, yielding a char residue of 32–35 wt%, which decreases as the mol% of DPA units rises. The pyrolysis/mass spectra data allowed us to identify the thermal decomposition products and to deduce the possible thermal degradation mechanisms. Thermal degradation data suggest that the decarboxylation process of the pendant acid moiety mainly occurs in the initial step of the pyrolysis of the copolymers studied. Successively, the scission of the generated isobutyl groups occurs in the temperature range between 420 and 480 °C. Known processes involving the main chain random scission of the diphenyl sulfone and diphenyl ether groups were also observed.