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Abstract Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2

Abstract The study proposes an approach to elucidate spatiotemporal mesoscale variations of seawater Dimethylsulfide (DMS) concentrations, the largest natural source of atmospheric sulfur aerosol, based on the Gaussian Process Regression (GPR) machine learning model. Presently, the GPR was trained and evaluated by nested cross-validation across the warm-oligotrophic Mediterranean Sea, a climate hot spot region, leveraging the high-resolution satellite measurements and Mediterranean physical reanalysis together with in-situ DMS observations. The end product is daily gridded fields with a spatial resolution of 0.083° × 0.083° (~9 km) that spans 23 years (1998–2020). Extensive observations of atmospheric methanesulfonic acid (MSA), a typical biogenic secondary aerosol component from DMS oxidation, are consistent with the parameterized high-resolution estimates of sea-to-air DMS flux (FDMS). This represents substantial progress over existing coarse-resolution DMS global maps which do not accurately depict the seasonal patterns of MSA in the Mediterranean atmospheric boundary layer.

Background: Functional Gastrointestinal Disorders (FGIDs) can pose a great burden on affected children, their families, and the healthcare system. Due to the lack of knowledge about the precise pathophysiology of FGIDs, a proper identification of children at risk to develop FGIDs has never been attempted. The research aims to identify early-life risk factors for FGIDs such as infantile colic, regurgitation, and functional constipation, within the first year of life. Methods: This prospective observational cohort study enrolled both term and preterm infants from a tertiary care university hospital between January 1, 2020, and December 31, 2022. The study employed both traditional statistical methods and artificial intelligence (AI) techniques, specifically a random forest classification model, to identify key risk factors associated with the development of FGIDs. Based on these findings, an AI-based predictive model will be developed, along with a user-friendly, web-based interface designed for practical risk assessment. Results: 6060 infants were enrolled. 8.1 % were born preterm. According to random forest classification model by AI, birth weight (BW), cord blood pH, and maternal age were the most relevant variables linked to development of FGIDs in the first year of life. Some discrepancies between potential risk factors identified through conventional statistics and AI were detected. Conclusion: For the first time machine learning allowed to identify BW, cord blood pH and maternal age as important variable for risk prediction of FGIDs in the first year of life. This practical risk assessment tool would help clinicians to identify infants at risk of FGIDs who would benefit from a tailored preventive approach.

Carbonaceous aerosols (CA), composed of black carbon (BC) and organic matter (OM), significantly impact the climate. Light absorption properties of CA, particularly of BC and brown carbon (BrC), are crucial due to their contribution to global and regional warming. We present the absorption properties of BC (bAbs,BC) and BrC (bAbs,BrC) inferred using Aethalometer data from 44 European sites covering different environments (traffic (TR), urban (UB), suburban (SUB), regional background (RB) and mountain (M)). Absorption coefficients showed a clear relationship with station setting decreasing as follows: TR > UB > SUB > RB > M, with exceptions. The contribution of bAbs,BrC to total absorption (bAbs), i.e. %AbsBrC, was lower at traffic sites (11–20 %), exceeding 30 % at some SUB and RB sites. Low AAE values were observed at TR sites, due to the dominance of internal combustion emissions, and at some remote RB/M sites, likely due to the lack of proximity to BrC sources, insufficient secondary processes generating BrC or the effect of photobleaching during transport. Higher bAbs and AAE were observed in Central/Eastern Europe compared to Western/Northern Europe, due to higher coal and biomass burning emissions in the east. Seasonal analysis showed increased bAbs, bAbs,BC, bAbs,BrC in winter, with stronger %AbsBrC, leading to higher AAE. Diel cycles of bAbs,BC peaked during morning and evening rush hours, whereas bAbs,BrC, %AbsBrC, AAE, and AAEBrC peaked at night when emissions from household activities accumulated. Decade-long trends analyses demonstrated a decrease in bAbs, due to reduction of BC emissions, while bAbs,BrC and AAE increased, suggesting a shift in CA composition, with a relative increase in BrC over BC. This study provides a unique dataset to assess the BrC effects on climate and confirms that BrC can contribute significantly to UV–VIS radiation presenting highly variable absorption properties in Europe.

ABSTRACT Cytomegalovirus (CMV) colitis is a serious concern worsening the prognosis of patients with ulcerative colitis (UC). We aimed to assess risk factors and prognostic impact of CMV colitis in patients with moderate-to-severe UC flare. We conducted a retrospective, observational, single-center study. Consecutive adult patients hospitalized for moderate-to-severe UC from January 2020 to June 2023 were included. The primary endpoint was a diagnosis of CMV-colitis according to immunohistochemistry on tissue biopsies. The secondary endpoint was the need for colectomy within 30 days. Overall, 135 patients were included. CMV colitis was diagnosed in n = 37 (27.4%): n = 19 (51.4%) endoscopically, the remaining on surgical specimens. Of them, n = 23 (62.2%) had positive CMV-DNAemia with a median value of 1,008 cp/mL (interquartile range 318–2,980). Differences between the two groups (CMV colitis vs non-CMV) included age (60 vs 41 years, P = 0.004), Charlson Comorbidity Index (1 vs 0, P = 0.003), steroid refractoriness (86.5% vs 62.2%, P = 0.007), and positive CMV-DNAemia (62.2% vs 10.1%, P < 0.001). At multivariable analysis, steroid-refractory disease, Charlson Comorbidity Index, and CMV-DNAemia were associated with CMV colitis. Overall, n = 54 (39.7%) patients underwent colectomy, and this was significantly more common in patients with CMV colitis vs non-CMV group (54.1% vs 34.4%, P = 0.049). Kaplan-Meier showed that antiviral therapy seems to have a relevant impact on colectomy (P < 0.001). CMV-DNA blood detection is independently associated with CMV-positive refractory UC. Since CMV colitis may increase the risk of colectomy and antiviral treatment seems to reduce such risk, prospective studies are needed to confirm the role of CMV-DNA blood detection to early diagnose CMV colitis.IMPORTANCECytomegalovirus (CMV) colonic reactivation worsens the prognosis of patients with active ulcerative colitis. Blood CMV-DNA reactivation is strongly associated with CMV colitis. Prompt diagnosis and treatment of CMV colitis can avoid surgery in most cases.

Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Abstract Optical frequency combs, featuring evenly spaced spectral lines, have been extensively studied and applied to metrology, signal processing, and sensing. Recently, frequency comb generation has been also extended to MHz frequencies by harnessing nonlinearities in microelectromechanical membranes. However, the generation of frequency combs at radio frequencies (RF) has been less explored, together with their potential application in wireless technologies. In this work, we demonstrate an RF system able to wirelessly and passively generate frequency combs. This circuit, which we name quasi-harmonic tag (qHT), offers a battery-free solution for far-field ranging of unmanned vehicles (UVs) in GPS-denied settings, and it enables a strong immunity to multipath interference, providing better accuracy than other RF approaches to far-field ranging. Here, we discuss the principle of operation, design, implementation, and performance of qHTs used to remotely measure the azimuthal distance of a UV flying in an uncontrolled electromagnetic environment. We show that qHTs can wirelessly generate frequency combs with μWatt-levels of incident power by leveraging the nonlinear interaction between an RF parametric oscillator and a high quality factor piezoelectric microacoustic resonator. Our technique for frequency comb generation opens new avenues for a wide range of RF applications beyond ranging, including timing, computing and sensing.

Abstract Background Bloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients’ outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients. Methods Pre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist. Results Overall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58–75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p

To assess the clinical usefulness of teicoplanin optimized by means of a therapeutic drug monitoring (TDM)-guided approach for treating secondary bloodstream infections (BSIs) caused by Enterococcus faecium. Hospitalized patients having in the period 1 March 2021–31 October 2024 a documented BSI caused by glycopeptide-susceptible Enterococcus faecium being treated with teicoplanin as definitive targeted therapy optimized by means of a real-time TDM-guided expert clinical pharmacological advice (ECPA) program were retrospectively included. Teicoplanin trough concentrations (Cmin) ranging from 20 to 30 mg/L were defined as the desired target of efficacy based on international guidelines. Univariate analysis was performed for assessing variables potentially associated with microbiological failure (defined as persistence at the infection site of the index Enterococcus faecium strain after more than 7 days from starting treatment as documented by follow-up blood cultures). Overall, 67 patients (median age 70 years; male 55.2%) were included. Catheter-related BSIs (50.7%) and intrabdominal/biliary tract (29.9%) infections were the main sources of Enterococcus faecium BSI. The desired target of teicoplanin Cmin was attained in 62.7% of patients at the first TDM assessment and significantly increased to 85.1% (p = 0.003) at subsequent TDM-guided ECPA instances during the overall treatment course. Microbiological eradication was obtained in 95% of cases (63/67). In the univariate analysis, failing effective source control was the only variable associated with an increased risk of microbiological failure (75.0% vs. 12.7%; p = 0.01). Targeted TDM-guided teicoplanin therapy, coupled with effective source control of the primary infection site by granting microbiological eradication in the vast majority of cases, may be considered a reasonable strategy for managing glycopeptide-susceptible Enterococcus faecium secondary BSIs.

Abstract The Atomic Cluster Expansion (ACE) provides a formally complete basis for the local atomic environment. ACE is not limited to representing energies as a function of atomic positions and chemical species, but can be generalized to vectorial or tensorial properties and to incorporate further degrees of freedom (DOF). This is crucial for magnetic materials with potential energy surfaces that depend on atomic positions and atomic magnetic moments simultaneously. In this work, we employ the ACE formalism to develop a non-collinear magnetic ACE parametrization for the prototypical magnetic element Fe. The model is trained on a broad range of collinear and non-collinear magnetic structures calculated using spin density functional theory. We demonstrate that the non-collinear magnetic ACE is able to reproduce not only ground state properties of various magnetic phases of Fe but also the magnetic and lattice excitations that are essential for a correct description of finite temperature behavior and properties of crystal defects.

Abstract Over recent years, the surge in mobile communication has deepened global connectivity. With escalating demands for faster data rates, the push for higher carrier frequencies intensifies. The 7–20 GHz range, located between the 5G sub-6 GHz and the mm-wave spectra, provides an excellent trade-off between network capacity and coverage, and constitutes a yet-to-be-explored range for 5G and 6G applications. This work proposes a technological platform able to deliver CMOS-compatible, on-chip multi-frequency, low-loss, wide-band, and compact filters for cellular radios operating in this range by leveraging the micro-to-nano scaling of acoustic electromechanical resonators. The results showcase the first-ever demonstrated low insertion loss bank of 7 nanoacoustic passband filters in the X-band. Most of the filters showcase fractional bandwidths above 3% and sub-dB loss per stage in an extremely compact form factor, enabling the manufacturing of filters and duplexers for the next generation of mobile handsets operating in the X-band and beyond.

Abstract Exposures to fine particulate matter (PM $$_1$$ 1 ) have been associated with health impacts, but the understanding of the PM $$_1$$ 1 concentration-response (PM $$_1$$ 1 -CR) relationships, especially at low PM $$_1$$ 1 , remains incomplete. Here, we present novel data using a methodology to mimic lung exposure to ambient air (2 $$

Abstract Purpose To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort. Methods Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome. Results Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59–82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 [2–4] days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 [95%CI 0.14–0.70], p = 0.005]). No difference in hospitalization rates in early treatment compared to late treatment were found. Conclusions No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.

The light-front formalism for a covariant description of the European Muon Collaboration (EMC) effect, already applied to He3, is formally extended to any nucleus, and used for actually calculating the 3H and He4 cases. The realistic and accurate nuclear description of few-nucleon bound systems, obtained with both phenomenological and chiral potentials, has been properly combined with the Poincaré covariance and macroscopic locality, automatically satisfying both number of particles and momentum sum rule. While retaining the on-mass-shell nucleon structure functions, one is then able to predict a sizable EMC effect for He4, as already observed for He3. Moreover, the impact on the EMC effect of both i) the short-range correlations, such as those generated by modern nuclear interactions, and ii) the ratio between the neutron and proton structure functions has been studied. The short-range correlations generated by retaining only the standard nuclear degrees of freedom act on the depth of the minimum in the EMC ratio, while the uncertainties linked to the ratio of neutron to proton structure functions are found to be very small. These light-front results facilitate ascribing deviations from experimental data due to genuine QCD effects, not included in a standard nuclear description, and initiating unbiased investigations.

Background & Aims: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT). Methods: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG). Results: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients. Conclusions: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis. Impact and implications: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted.

Numerous studies have shown negative health effects related to exposure to ambient particulate matter (PM), likely due to induced oxidative stress. In this study, we have examined ambient PM samples from Birr, a small (~5000 inhabitants) town in central Ireland, for their water-soluble DTT-based oxidative potential (OP_DTT) with a resolution of 6 h, together with online chemical characterization measurements, to assess the OP of organic aerosols, in particular from residential solid fuel burning. The OP_DTT normalized by the volume of sampled air shows a high variability, ranging from −1 m−3, and a high correlation with PM mass. A lower variability was associated with the mass-normalized OP. Nevertheless, both tended to present higher values during night-time pollution episodes. Simple and multivariate linear regression approaches linked OP_DTT to residential solid fuel burning, and in particular to wood (~87%) and peat (~13%) combustion. The results of the present study show how residential solid fuel burning can have a severe impact on air quality, even in small towns, with potential negative health effects on the exposed population.

ABSTRACT: Objective: To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI). Methods: Multicentre retrospective study of patients diagnosed with SWI from January 2016 to December 2019 at two cardiac surgery facilities treated with dalbavancin, teicoplanin or daptomycin. Patients with SWI treated with dalbavancin were compared with SoC to evaluate resolution of infection at 90 and 180 days from infection diagnosis, length of stay (LoS) and management costs. Results: 48 patients with SWI were enrolled, 25 (50%) male, median age 67 (60–73) years, Charlson index score 5 (4–7). Fifteen patients were treated with dalbavancin (31%) and 33 with SoC (69%): teicoplanin in 21 (63%), and daptomycin in 12 (37%). Staphylococcus species were the most frequent isolates (44, 92%), mostly (84%) resistant to methicillin. All patients were treated with surgical debridement followed by negative pressure wound therapy. Wound healing at day 90 and 180 was achieved in 46 (95.8%) and 34 (82.9%) of patients, respectively. A shorter length of hospitalization in patients treated with dalbavancin compared with SoC [12 (7–18) days vs 22 (12–36) days, p:0.009] was found. Treatment with dalbavancin resulted in total cost savings of €16 026 (95% CI 5976–26 076, P < 0.001). Savings were mainly related to the LoS that was significantly shorter in the dalbavancin group, generating significantly lower cost compared to SoC group. Conclusion: Dalbavancin treatment of sternal wound infections is effective and seems to reduce hospitalization length, leading to significantly lower costs.

Abstract The holographic graviton soft-wall model, introduced to describe the spectrum of scalar and tensor glueballs, is improved to incorporate the realization of chiral-symmetry as in QCD. Such a goal is achieved by including the longitudinal dynamics of QCD into the scheme. Using the relation between AdS/QCD and light-front dynamics, we construct the appropriate wave function for the pion which is used to calculate several pion observables. The comparison of our results with phenomenology is remarkably successful.

Abstract Agricultural sensors are powerful tools to optimize crop productivity while conserving natural resources. Here we report a crop water-stress detector based on a plasmonically-enhanced micromechanical photoswitch capable of detecting water content in leaves that is lower than a predetermined threshold without consuming electrical power when the leaf is healthy. The detection mechanism exploits the energy in a specific narrow-spectral band of solar radiation reflected off leaves that is strongly correlated to the water content in plants. This biosensor relies on a spectrally selective infrared plasmonic absorber and a thermally sensitive micro-cantilever to harvest the reflected solar energy and further produce a digitized wakeup-bit only when the monitored leaf is water-stressed. In particular, we demonstrate that the detector activates a commercial water pump when a soybean plant is water-stressed. The 10-year battery lifetime of the proposed detector pave the way for the development of high-granularity, maintenance-free sensor networks for large-scale smart-farms.

(1) Background: Piperacillin-tazobactam represents the first-line option for treating infections caused by full- or multi-susceptible Enterobacterales and/or Pseudomonas aeruginosa in critically ill patients. Several studies reported that attaining aggressive pharmacokinetic/pharmacodynamic (PK/PD) targets with beta-lactams is associated with an improved microbiological/clinical outcome. We aimed to assess the relationship between the joint PK/PD target attainment of continuous infusion (CI) piperacillin-tazobactam and the microbiological/clinical outcome of documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP) of critically ill patients treated with CI piperacillin-tazobactam monotherapy. (2) Methods: Critically ill patients admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 treated with CI piperacillin-tazobactam monotherapy optimized by means of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program for documented Gram-negative BSIs and/or VAP were retrospectively retrieved. Steady-state plasma concentrations (Css) of piperacillin and of tazobactam were measured, and the free fractions (f) were calculated according to respective plasma protein binding. The joint PK/PD target was defined as optimal whenever both the piperacillin fCss/MIC ratio was >4 and the tazobactam fCss/target concentration (CT) ratio was > 1 (quasi-optimal or suboptimal whenever only one or none of the two weas achieved, respectively). Multivariate logistic regression analysis was performed for testing variables potentially associated with microbiological outcome. (3) Results: Overall, 43 critically ill patients (median age 69 years; male 58.1%; median SOFA score at baseline 8) treated with CI piperacillin-tazobactam monotherapy were included. Optimal joint PK/PD target was attained in 36 cases (83.7%). At multivariate analysis, optimal attaining of joint PK/PD target was protective against microbiological failure (OR 0.03; 95%CI 0.003–0.27; p = 0.002), whereas quasi-optimal/suboptimal emerged as the only independent predictor of microbiological failure (OR 37.2; 95%CI 3.66–377.86; p = 0.002). (4) Conclusion: Optimized joint PK/PD target attainment of CI piperacillin-tazobactam could represent a valuable strategy for maximizing microbiological outcome in critically ill patients with documented Gram-negative BSI and/or VAP, even when sustained by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. In this scenario, implementing a real-time TDM-guided ECPA program may be helpful in preventing failure in attaining optimal joint PK/PD targets among critically ill patients. Larger prospective studies are warranted to confirm our findings.

(1) Objectives: To describe the attainment of optimal pharmacokinetic/pharmacodynamic (PK/PD) targets in orthotopic liver transplant (OLT) recipients treated with continuous infusion (CI) beta-lactams optimized using a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program during the early post-surgical period. (2) Methods: OLT recipients admitted to the post-transplant intensive care unit over the period of July 2021–September 2023, receiving empirical or targeted therapy with CI meropenem, piperacillin-tazobactam, meropenem-vaborbactam, or ceftazidime-avibactam optimized using a real-time TDM-guided ECPA program, were retrospectively retrieved. Steady-state beta-lactam (BL) and/or beta-lactamase inhibitor (BLI) plasma concentrations (Css) were measured, and the Css/MIC ratio was selected as the best PK/PD target for beta-lactam efficacy. The PK/PD target of meropenem was defined as being optimal when attaining a fCss/MIC ratio > 4. The joint PK/PD target of the BL/BLI combinations (namely piperacillin-tazobactam, ceftazidime-avibactam, and meropenem-vaborbactam) was defined as being optimal when the fCss/MIC ratio > 4 of the BL and the fCss/target concentration (CT) ratio > 1 of tazobactam or avibactam, or the fAUC/CT ratio > 24 of vaborbactam were simultaneously attained. Multivariate logistic regression analysis was performed for testing potential variables that were associated with a failure in attaining early (i.e., at first TDM assessment) optimal PK/PD targets. (3) Results: Overall, 77 critically ill OLT recipients (median age, 57 years; male, 63.6%; median MELD score at transplantation, 17 points) receiving a total of 100 beta-lactam treatment courses, were included. Beta-lactam therapy was targeted in 43% of cases. Beta-lactam dosing adjustments were provided in 76 out of 100 first TDM assessments (76.0%; 69.0% decreases and 7.0% increases), and overall, in 134 out of 245 total ECPAs (54.7%). Optimal PK/PD target was attained early in 88% of treatment courses, and throughout beta-lactam therapy in 89% of cases. Augmented renal clearance (ARC; OR 7.64; 95%CI 1.32–44.13) and MIC values above the EUCAST clinical breakpoint (OR 91.55; 95%CI 7.12–1177.12) emerged as independent predictors of failure in attaining early optimal beta-lactam PK/PD targets. (4) Conclusion: A real-time TDM-guided ECPA program allowed for the attainment of optimal beta-lactam PK/PD targets in approximately 90% of critically ill OLT recipients treated with CI beta-lactams during the early post-transplant period. OLT recipients having ARC or being affected by pathogens with MIC values above the EUCAST clinical breakpoint were at high risk for failure in attaining early optimal beta-lactam PK/PD targets. Larger prospective studies are warranted for confirming our findings.

This paper demonstrates Lithium Niobate based Piezoelectric Micromachined Ultrasonic Transducers. The devices allow activation of multiple vibration modes, achieve a high communication link, and monitor an implanted medical device up to 13.5 cm inside the body.

Abstract In this investigation an holographic description of the deconfined phase transition of scalar and tensor glueballs is presented within the so called hard-wall model. The spectra of these bound states of gluons have been calculated from the linearized Einstein equations for a graviton propagating from a thermal $$AdS_5$$ A d S 5 space to an AdS Black-Hole. In this framework, the deconfined phase is reached via a two steps mechanism. We propose that the transition between the AdS thermal sector to the BH is described via a first order phase transition, with discontinuous masses at the critical temperature, which has been determined by Herzog’s method of regulating the free energy densities. Then, the glueball masses diverge with increasing T in the BH phase and thus lead to deconfined states à la Hagedorn.

A new and rigorous light-front formalism for electron deep inelastic scattering on unpolarized nuclei, in Bjorken limit, is proposed. It preserves Poincaré covariance, macroscopic locality, both number of particles and momentum sum rules. The approach is applied to the A=3 iso-doublet, very relevant for the flavor decomposition of the parton distribution functions and in view of the planned operation with unpolarized and polarized beams at the Electron-Ion Collider. At variance with previous light-front estimates, our procedure, including a realistic nuclear description and free-nucleon structure functions, predicts a sizable European Muon Collaboration effect for 3He. This will allow to analyze deviations from the proposed baseline in terms of genuine QCD effects. The extension to heavier nuclei is straightforward, although numerically challenging.

Bacteremia and ventilator-associated pneumonia due to a pan-resistant Klebsiella pneumoniae strain co-producing KPC and OXA-48 carbapenemases was successfully treated in a COVID-19 critically ill patient with a combination therapy of a high-dose continuous infusion of meropenem (up to 3 g every 6 h, daily) plus fosfomycin (up to 24 g/daily) that was guided by real-time therapeutic drug monitoring. Clinical pharmacological advice was helpful in maximizing, over time, the pharmacodynamic target attainment of both antibiotics.

Objectives: Ceftazidime-avibactam (CAZ-AVI) is a promising novel agent with activity against carbapenem-resistant Enterobacteriaceae. Here, we describe the dynamic evolution of a Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infection in a critically ill patient treated with CAZ-AVI-tigecycline combination therapy. Methods: Whole-genome sequencing was performed on longitudinal intrapatient KPC-Kp strains isolated from different sites during CAZ-AVI treatment. The pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed on the basis of therapeutic drug monitoring of ceftazidime. Results: The development of resistance due to mutations in the blaKPC gene was observed in KPC-Kp strains isolated from bronchoalveolar lavage and blood during CAZ-AVI treatment. PK/PD analysis demonstrated that during the first days of treatment CAZ- AVI blood exposure was suboptimal (steady-state concentration/minimum inhibitory concentration ratio 2.85). Of note, the low antibiotic pressure may have selected hybrid subpopulations harboring blaKPC-3 and T243M mutation in KPC-Kp isolated from bronchoalveolar lavage and D179Y mutation in those isolated from blood. Conclusion: These results suggest the high adaptability of KPC to CAZ-AVI due to the rapid evolution of resistance and highlight the importance of identifying the optimal PK/PD target to prevent such an event from occurring again in a critically ill patient with pneumonia due to KPC-Kp.

(1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022–May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fCss) were calculated. Meropenem total clearance (CLtot) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CLtot was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fCss/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fCss was 19.9 mg/L (17.4–28.0 mg/L). Median (IQR) CLtot was 3.89 L/h (3.28–5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8–44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h.

(1) Objectives: To describe the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin–tazobactam or meropenem monotherapy and microbiological outcome in a case series of urological patients with documented Gram-negative infections. (2) Methods: Patients admitted to the urology ward who were treated with CI piperacillin–tazobactam or meropenem monotherapy for documented Gram-negative infections and underwent real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program from June 2021 to May 2023 were retrospectively retrieved. Average steady-state (Css) piperacillin–tazobactam and meropenem concentrations were determined, and the free fractions (fCss) were calculated. Optimal PK/PD target attainments were defined as an fCss/MIC ratio >4 for CI meropenem and an fCss/MIC ratio of piperacillin >4 coupled with an fCss/CT ratio for tazobactam >1 for piperacillin–tazobactam (joint PK/PD target). The relationship between beta-lactam PK/PD targets and microbiological outcome was explored. (3) Results: Sixteen urologic patients with documented Gram-negative infections (62.5% complicated urinary tract infections (cUTI)) had 30 TDM-guided ECPAs. At first TDM assessment, beta-lactam dosing adjustments were recommended in 11 out of 16 cases (68.75%, of which 62.5% decreases and 6.25% increases). Overall, beta-lactam dosing adjustments were recommended in 14 out of 30 ECPAs (46.6%). Beta-lactam PK/PD target attainments were optimal in 100.0% of cases. Microbiological failure occurred in two patients, both developing beta-lactam resistance. (4) Conclusion: A TDM-guided ECPA program may allow for optimizing beta-lactam treatment in urologic patients with documented Gram-negative infections, ensuring microbiological eradication in most cases.

Organic aerosol (OA) is a key component of total submicron particulate matter (PM1), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013–2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30–240 min) and long-term data coverage (9–36 months), providing essential information to improve/validate air quality, health impact, and climate models.

Abstract The atomic cluster expansion is a general polynomial expansion of the atomic energy in multi-atom basis functions. Here we implement the atomic cluster expansion in the performant C++ code PACE that is suitable for use in large-scale atomistic simulations. We briefly review the atomic cluster expansion and give detailed expressions for energies and forces as well as efficient algorithms for their evaluation. We demonstrate that the atomic cluster expansion as implemented in PACE shifts a previously established Pareto front for machine learning interatomic potentials toward faster and more accurate calculations. Moreover, general purpose parameterizations are presented for copper and silicon and evaluated in detail. We show that the Cu and Si potentials significantly improve on the best available potentials for highly accurate large-scale atomistic simulations.

Abstract Massive deployments of wireless sensor nodes (WSNs) that continuously detect physical, biological or chemical parameters are needed to truly benefit from the unprecedented possibilities opened by the Internet-of-Things (IoT). Just recently, new sensors with higher sensitivities have been demonstrated by leveraging advanced on-chip designs and microfabrication processes. Yet, WSNs using such sensors require energy to transmit the sensed information. Consequently, they either contain batteries that need to be periodically replaced or energy harvesting circuits whose low efficiencies prevent a frequent and continuous sensing and impact the maximum range of communication. Here, we report a new chip-less and battery-less tag-based WSN that fundamentally breaks any previous paradigm. This WSN, formed by off-the-shelf lumped components on a printed substrate, can sense and transmit information without any need of supplied or harvested DC power, while enabling full-duplex transceiver designs for interrogating nodes rendering them immune to their own self-interference. Also, even though the reported WSN does not require any advanced and expensive manufacturing, its unique parametric dynamical behavior enables extraordinary sensitivities and dynamic ranges that can even surpass those achieved by on-chip sensors. The operation and performance of the first implementation of this new WSN are reported. This device operates in the Ultra-High-Frequency range and is capable to passively and continuously detect temperature changes remotely from an interrogating node.

Sea spray aerosol (SSA) formation plays a major role in the climate system. The Antarctic Peninsula (AP) is affected by the greatest warming occurring in the Southern Ocean; changes in cryospheric and biological processes are being observed. Whilst there is some evidence that organic material produced by ice algae and/or phytoplankton in the high Arctic contributes to SSA, less is known about Antarctic Sea ice (sympagic) regions. To gain insight into the influence of Antarctic Sea ice biology and biogeochemistry on atmospheric aerosol, we report simultaneous water-air measurements made by means of in situ aerosol chamber experiments. For the first time, we present a methodology showing that the controlled plunging jet aerosol chamber settings do not cause major cell disruption on the studied sea ice ecosystems. Larger sea ice phytoplankton cells (>20 µm; mainly diatoms) tend to sediment at the bottom of the chamber (during the 24h experiment) and likely have a minor role on SSA production. When comparing four chamber experiments - we find that the two producing more SSA are the ones with highest abundance of nanophytoplankton cells (

Abstract Double parton distribution functions (dPDFs), entering the double parton scattering (DPS) cross section, are unknown fundamental quantities encoding new interesting properties of hadrons. Here, the pion dPDFs are investigated within different holographic QCD quark models in order to access their basic features. Results of the calculations obtained within the AdS/QCD soft-wall approach, have been compared with predictions of lattice QCD evaluations of the pion two-current correlation functions. The present analysis confirms that double parton correlations, affecting dPDFs, are very important and not direct accessible from generalised parton distribution functions and electromagnetic form factors. The comparison between lattice data and quark model calculations unveils the relevance of the contributions of high partonic Fock states in the pion. Nevertheless, by using a complete general procedure, results of lattice QCD have been used, for the first time, to estimate the mean value of the so called $$\sigma _{eff}$$ σeff , a relevant experimental observable for DPS processes. In addition, the results of the first calculations of the $$\rho $$ ρ meson dPDFs are discussed in order to make predictions.