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Objectives: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Assessment of glomerular filtration rate (GFR) is necessary for dose adjustments of beta-lactam that are excreted by the kidneys, such as meropenem. The aim of this study was to compare the daily dose of 24 h-continuous infusion (CI) meropenem when GFR was calculated by means of measured creatinine clearance (mCLCR) or estimated by the CKDEPI (eGFRCKDEPI), Cockcroft–Gault (eGFRCG), and MDRD (eGFRMDRD) equations. Adult critically ill patients who underwent therapeutic drug monitoring (TDM) for the assessment of 24 h-CI meropenem steady state concentration (Css) and for whom a 24 h-urine collection was performed were retrospectively enrolled. Meropenem clearance (CLM) was regressed against mCLCR, and meropenem daily dose was calculated based on the equation infusion rate = daily dose/CLM. eGFRCKDEPI, eGFRCG, and eGFRCKDEPI were regressed against mCLCR in order to estimate CLM. Forty-six patients who provided 133 meropenem Css were included. eGFRCKDEPI overestimated mCLCR up to 90 mL/min, then mCLCR was underestimated. eGFRCG and eGFRMDRD overestimated mCLCR across the entire range of GFR. In critically ill patients, dose adjustments of 24 h-CI meropenem should be based on mCLCR. Equations for estimation of GFR may lead to gross under/overestimates of meropenem dosages. TDM may be highly beneficial, especially for critically ill patients with augmented renal clearance.

The increasing use of mobile broadband requires new acoustic filtering technologies that can operate efficiently at frequencies above 6 GHz. Previous research has shown that AlN Super High Frequency (SHF) Cross-Sectional Lamé Mode resonators (CLMRs) can address this challenge, but their performance is limited by the piezoelectric strength of AlN. In this work, we explore the use of substitutional doping of Al in AlN with Sc to enhance the kt2 values of SHF CLMRs. Our results showed that the measured kt2·Qm product of Al72Sc28N CLMRs was four times greater than that of AlN CLMRs operating at the same frequency. Additionally, the measured fractional bandwidth (FWB) of Al72Sc28N 2nd order ladder filters was 4.13%, a fourfold improvement over AlN filters with the same design. We also discuss other aspects of the technology, such as power handling, losses, and spurious mode suppression, and identify potential areas for future research.

Introduction: optimal treatment of Gram-negative infections in critically ill patients is challenged by changing pathophysiological conditions, reduced antimicrobial susceptibility and limited therapeutic options. The aim of this study was to assess the impact of maximizing Css/MIC ratio on efficacy of continuous infusion (CI) meropenem in treating documented Gram-negative infections in critically ill patients and to perform a population pharmacokinetic/pharmacodynamic analysis to support treatment optimization.Materials and Methods: Classification and regression tree (CART) analysis was used to identify whether a cutoff of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) (Css/MIC) ratio correlated with favorable clinical outcome. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. The probability of target attainment (PTA) of the identified Css/MIC ratio was calculated by means of Monte Carlo simulations. Cumulative fraction of response (CFRs) were calculated against common Enterobacterales, P. aeruginosa and A. baumannii as well.Results: a total of 74 patients with 183 meropenem Css were included. CART analysis identified a Css/MIC ratio ≥4.63 as cutoff value significantly associated with favorable clinical outcomes. Multivariate regression analysis confirmed the association [OR (95%CI): 20.440 (2.063–202.522); p < 0.01]. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that, across different classes of renal function, dosages of meropenem ranging between 0.5 and 2 g q6h over 6 h (namely by CI) may grant PTAs of Css/MIC ratios ≥4.63 against susceptible pathogens with an MIC up to the EUCAST clinical breakpoint of 2 mg/L. The CFRs achievable with these dosages were very high (>90%) against Enterobacterales across all the classes of renal function and against P. aeruginosa among patients with CLCR < 30 ml/min/1.73 m2, and quite lower against A. baumannii.Discussion: our findings suggest that Css/MIC ratio ≥4.63 may be considered the pharmacodynamic target useful at maximizing the efficacy of CI meropenem in the treatment of Gram-negative infections in critically ill patients. Dosages ranging between 0.5 g q6h and 2 g q6h by CI may maximize the probability of favorable clinical outcome against meropenem-susceptible Gram-negative pathogens among critically ill patients having different degrees of renal function.

Objectives: To perform a pharmacokinetic/pharmacodynamic (PK/PD) analysis of continuous-infusion (CI) fosfomycin combined with extended-infusion (EI) cefiderocol or CI ceftazidime-avibactam in a case series of severe difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections. Methods: A single-center retrospective study of patients who were treated with CI fosfomycin plus EI cefiderocol or CI ceftazidime-avibactam for severe DTR-PA infections and who underwent therapeutic drug monitoring (TDM), from 1 September 2021 to 30 June 2022 was performed. Concentrations were measured at steady-state (Css) for CI fosfomycin and ceftazidime-avibactam and at trough (Cmin) for EI cefiderocol. Joint PK/PD targets of combination therapy were analyzed (thresholds: area-under-the curve to minimum inhibitory concentration (AUC/MIC) ratio > 40.8 for fosfomycin; ceftazidime Css/MIC ratio ≥ 4 coupled with avibactam Css > 4 mg/L for ceftazidime-avibactam; Cmin/MIC ratio ≥ 4 for cefiderocol). Joint PK/PD targets of the combination therapy were analyzed and defined as optimal when both were achieved, quasi-optimal if only one of the two was achieved, and suboptimal if none of the two was achieved). The relationship between joint PK/PD target attainment and microbiological response was assessed. Results: Six patients (three pneumonia, two BSI + pneumonia, and one BSI) were included. The joint PK/PD targets were optimal in four cases and quasi-optimal in the other two. Microbiological eradication (ME) occurred in 4/4 of patients with optimal joint PK/PD targets and in one of the two patients with quasi-optimal joint PK/PD targets. Conclusions: Attaining optimal joint PK/PD targets with a combo-therapy of CI fosfomycin plus EI cefiderocol or CI ceftazidime-avibactam could represent an effective strategy for granting favorable microbiological outcomes in patients with DTR-PA pneumonia and/or BSI.

Meconium peritonitis (MP) is a rare cause of nonimmune hydrops and only few of those cases have been reported in literature. Here is to report on a case of FH secondary to perforated midgut volvulus and MP with special interest in the discussion of pathophysiology and clinical strategies. We report on a preterm male neonate diagnosed with FH at 29th week of gestational age (WGA) and EXIT at 30 WGA. In addition, he presented with abdominal mass, respiratory distress syndrome and hypoglycemia. Emergent endotracheal intubation and mechanical ventilation rescued the baby. All maternal and infant viral panel, Toxoplasmosis, Sars-Covid 2 and indirect/direct coombs tests were negative. . At laparotomy, we found a midgut volvulus interesting nearly all the jejunum but sparing the ileum which appeared hypoplastic. One of intestinal loop was completely perforated with diffuse MP. Distal to the first jejunal loop, the jejunum appeared necrotic and then resected with bowel exteriorization (terminal jejunostomy and ileostomy). The postoperative course was complicated by worsening of respiratory distress, acute tubular necrosis and renal failure unresponsive to medical therapy and fatal outcome. In conclusion, we believe that hydrops secondary to midgut volvulus and meconium peritonitis has its own pathophysiological and clinical characteristics that make this disease at high risk of unfavourable outcome when compared with prenatal cases of midgut and/or meconium peritonitis without hydrops.

Abstract We consider double parton distribution functions (dPDFs), essential quantities in double parton scattering (DPS) studies, which encode novel non perturbative insight on the partonic proton structure. We develop the formalism to extract this information from dPDFs and present results by using constituent quark model calculations within the Light-Front approach, focusing on radiatively generated gluon dPDFs. Moreover, we generalize the relation between the mean transverse partonic distance between two active partons in a DPS process and the so called σ eff to include partonic correlations and the so called 2v1 mechanism contribution. Finally we investigate the impact of relativistic effects on digluon distributions and study the structure of the corresponding longitudinal and transverse correlations.

Loeys–Dietz syndrome (LDS) is a rare autosomal-dominant disorder of the connective tissue with some typical vascular findings, skeletal manifestations, craniofacial features, and cutaneous findings with a wide phenotypic spectrum. Six different genes are involved in LDS and the diagnosis is based on the identification of a heterozygous pathogenic variant in TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, or SMAD2 in children with suggestive findings. These genes distinguish LDS into six classes (LDS1–LDS6, respectively). Delay in diagnosis of Loeys–Dietz syndrome may be associated with an adverse prognosis due to a very high augmented risk of early complications such as aortic or vascular rupture. The present report describes a case of an early diagnosis of LDS in a neonate with cleft soft palate and aortic root dilatation.

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients’ characteristics.

Sc-doped aluminum nitride is emerging as a new piezoelectric material which can substitute undoped aluminum nitride (AlN) in radio-frequency MEMS applications, thanks to its demonstrated enhancement of the piezoelectric coefficients. Furthermore, the recent demonstration of the ferroelectric-switching capability of the material gives AlScN the possibility to integrate memory functionalities in RF components. However, its high-coercive field and high-leakage currents are limiting its applicability. Residual stress, growth on different substrates, and testing-temperature have already been demonstrated as possible knobs to flatten the energy barrier needed for switching, but no investigation has been reported yet on the whole impact on the dielectric and ferroelectric dynamic behavior of a single process parameter. In this context, we analyze the complete spectrum of variations induced by the applied substrate-RF, from deposition characteristics to dielectric and ferroelectric properties, proving its effect on all of the material attributes. In particular, we demonstrate the possibility of engineering the AlScN lattice cell to properly modify leakage, breakdown, and coercive fields, as well as polarization charge, without altering the crystallinity level, making substrate-RF an effective and efficient fabrication knob to ease the limitations the material is facing.

The RHAPS (Redox-Activity And Health-Effects Of Atmospheric Primary And Secondary Aerosol) project was launched in 2019 with the major objective of identifying specific properties of the fine atmospheric aerosol from combustion sources that are responsible for toxicological effects and can be used as new metrics for health-related outdoor pollution studies. In this paper, we present the overall methodology of RHAPS and introduce the phenomenology and the first data observed. A comprehensive physico-chemical aerosol characterization has been achieved by means of high-time resolution measurements (e.g., number size distributions, refractory chemical components, elemental composition) and low-time resolution analyses (e.g., oxidative potential, toxicological assays, chemical composition). Preliminary results indicate that, at the real atmospheric conditions observed (i.e., daily PM1 from less than 4 to more than 50 μg m−3), high/low mass concentrations of PM1, as well as black carbon (BC) and water soluble Oxidative Potential (WSOP,) do not necessarily translate into high/low toxicity. Notably, these findings were observed during a variety of atmospheric conditions and aerosol properties and with different toxicological assessments. Findings suggest a higher complexity in the relations observed between atmospheric aerosol and toxicological endpoints that go beyond the currently used PM1 metrics. Finally, we provide an outlook to companion papers where data will be analyzed in more detail, with the focus on source apportionment of PM1 and the role of source emissions on aerosol toxicity, the OP as a predictive variable for PM1 toxicity, and the related role of SOA possessing redox-active capacity, exposure-response relationships for PM1, and air quality models to forecast PM1 toxicity.

Abstract Two-parton correlations in the pion are investigated in terms of double parton distribution functions. A Poincaré covariant light-front framework has been adopted. As non perturbative input, the pion wave function obtained within the so-called soft-wall AdS/QCD model has been used. Results show how novel dynamical information on the structure of the pion, not accessible through one-body quantities, are encoded in double parton distribution functions.

Theoretical predictions as well as experiments performed at storage rings have shown that the lifetimes of β-radionuclides can change significantly as a function of the ionization state. In this paper we describe an innovative approach, based on the use of a compact plasma trap to emulate selected stellar-like conditions. It has been proposed within the PANDORA project (Plasmas for Astrophysics, Nuclear Decay Observation and Radiation for Archaeometry) with the aim to measure, for the first time in plasma, nuclear β-decay rates of radionuclides involved in nuclear-astrophysics processes. To achieve this task, a compact magnetic plasma trap has been designed to reach the needed plasma densities, temperatures, and charge-states distributions. A multi-diagnostic setup will monitor, on-line, the plasma parameters, which will be correlated with the decay rate of the radionuclides. The latter will be measured through the detection of the γ-rays emitted by the excited daughter nuclei following the β-decay. An array of 14 HPGe detectors placed around the trap will be used to detect the emitted γ-rays. For the first experimental campaign three isotopes, 176Lu, 134Cs, and 94Nb, were selected as possible physics cases. The newly designed plasma trap will also represent a tool of choice to measure the plasma opacities in a broad spectrum of plasma conditions, experimentally poorly known but that have a great impact on the energy transport and spectroscopic observations of many astrophysical objects. Status and perspectives of the project will be highlighted in the paper.

Colistin is a last-resort agent for the treatment of infections due to Gram-negative bacteria with difficult-to-treat resistance. The primary objective of this post hoc analysis of a cross-sectional study conducted in 22 Italian hospitals was to assess factors associated with inadequate intravenous colistin dosage. Overall, 187 patients receiving intravenous colistin were included in the analyses. Inadequate colistin dosages were administered in 27% of cases (50/187). In multivariable analysis, AKI (dummy variable with KDIGO stage 0 as a reference, odds ratio (OR) 3.98 with 95% confidence interval (CI) 1.48–10.74 for stage 1, OR 4.44 with 95% CI 1.17–16.93 for stage 2, OR 9.41 with 95% CI 1.59–55.70 for stage 3; overall p = 0.001) retained an independent association with inadequate colistin dosage, whereas the presence of a central venous catheter was associated with adequate colistin dosage (OR: 0.34 for inadequate dosage, 95% CI: 0.16–0.72, p = 0.004). These results were confirmed in an additional multivariable model with the center as a random effect. The association between AKI and inadequate dosage may reflect the perception of an increased risk of nephrotoxicity in patients with impaired renal function, which nonetheless should not be accompanied by dosage reductions beyond those recommended and could represent the target of dedicated antimicrobial stewardship efforts.

We study Generalized Parton Distribution functions (GPDs) usually measured in hard exclusive processes and encoding information on the three dimensional partonic structure of hadrons and their spin decomposition, for non-zero skewness within the AdS/QCD formalism. To this aim the canonical scheme to calculate GPDs at zero skewness has been properly generalized. Furthermore, we show that the latter quantities, in this non-forward regime, are sensitive to non-trivial details of the hadronic light front wave function, such as a kind of parton correlations usually not accessible in studies of form factors and GPDs at zero skewness. Keywords: Phenomenological models, Deep inelastic scattering (phenomenology)

The miniaturization of antennas beyond a wavelength is limited by designs which rely on electromagnetic resonances. Here, Nan et al. have developed acoustically actuated antennas that couple the acoustic resonance of the antenna with the electromagnetic wave, reducing the antenna footprint by up to 100.

Abstract Climate warming affects the development and distribution of sea ice, but at present the evidence of polar ecosystem feedbacks on climate through changes in the atmosphere is sparse. By means of synergistic atmospheric and oceanic measurements in the Southern Ocean near Antarctica, we present evidence that the microbiota of sea ice and sea ice-influenced ocean are a previously unknown significant source of atmospheric organic nitrogen, including low molecular weight alkyl-amines. Given the keystone role of nitrogen compounds in aerosol formation, growth and neutralization, our findings call for greater chemical and source diversity in the modelling efforts linking the marine ecosystem to aerosol-mediated climate effects in the Southern Ocean.

A first attempt to apply the AdS/QCD framework for a bottom–up approach to the evaluation of the effective cross section for double parton scattering in proton–proton collisions is presented. The main goal is the analytic evaluation of the dependence of the effective cross section on the longitudinal momenta of the involved partons, obtained within the holographic Soft-Wall model. If measured in high-energy processes at hadron colliders, this momentum dependence could open a new window on 2-parton correlations in a proton.

Nature-based solutions can represent beneficial tools in the field of urban transformation for their contribution to important environmental services such as air quality improvement. To evaluate the impact on urban air pollution of a CityTree (CT), an innovative wall-type green infrastructure in passive (deposition) and active (filtration) modes of operation, a study was conducted in a real urban setting in Modena (Italy) during 2017 and 2018, combining experimental measurements with modelling system evaluations. In this work, relying on the computational resources of CRESCO (Computational Centre for Research on Complex Systems)/ENEAGRID High Performance Computing infrastructure, we used the air pollution microscale model PMSS (Parallel Micro-SWIFT-Micro SPRAY) to simulate air quality during the experimental campaigns. The spatial characteristics of the impact of the CT on local air pollutants concentrations, specifically nitrogen oxides (NOx) and particulate matter (PM10), were assessed. In particular, we used prescribed bulk deposition velocities provided by the experimental campaigns, which tested the CT both in passive (deposition) and in active (filtration) mode of operation. Our results showed that the PM10 and NOx concentration reductions reach from more than 0.1% up to about 0.8% within an area of 10 × 20 m2 around the infrastructure, when the green infrastructure operates in passive mode. In filtration mode the CT exhibited higher performances in the abatement of PM10 concentrations (between 1.5% and 15%), within approximately the same area. We conclude that CTs may find an application in air quality hotspots within specific urban settings (i.e., urban street canyons) where a very localized reduction of pollutants concentration during rush hours might be of interest to limit population exposure. The optimization of the spatial arrangement of CT modules to increment the “clean air zone” is a factor to be investigated in the ongoing development of the CT technology.

Plasmonic metasurfaces can provide exciting optical functionalities. Here, Hui et al. demonstrate an infrared sensor by combining plasmonic and piezoelectric electromechanical resonances, demonstrating efficient transduction of vibration with a strong and polarization-independent absorption over an ultrathin thickness.

We present a calculation of the effective cross section σeff, an important ingredient in the description of double parton scattering in proton–proton collisions. Our theoretical approach makes use of a Light-Front quark model as a framework to calculate the double parton distribution functions at low-resolution scale. QCD evolution is implemented to reach the experimental scale. The obtained values of σeff in the valence region are consistent with the present experimental scenario, in particular with the sets of data which include the same kinematical range. However the result of the complete calculation shows a dependence of σeff on xi, a feature not easily seen in the available data, probably because of their low accuracy. Measurements of σeff in restricted xi regions are addressed to obtain indications on double parton correlations, a novel and interesting aspect of the three dimensional structure of the nucleon.